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Inflammatory bowel diseases
Chapter 11
Inflammatory bowel diseases Introduction: Adaptive role of the intestines based on an endobiogenic reflection This chapter discusses an Endobiogenic approach to two common inflammatory bowel diseases (IBDs): Crohn’s disease (CD) and ulcerative colitis (UC) also referred to as recto-hemorrhagic colitis. IBDs are disorders expressed in genetically susceptible individuals,1, 2 when the intestines are unable to adapt to local or systemic adaptation. Because the disorder remains latent across generations, across space, and time, one must look beyond genetic mechanisms to include epigenetic factors and adaptability in order to understand the Endobiogenic cause of disease.2, 3 One must place the intestines within the context of their intrinsic function and role in regional and global adaptation. Current thinking in the scientific literature views IBD as a disorder of dismicrobialism in those with a genetic susceptibility.1, 2, 4 The genetic foundation is undeniable. However, we find shortcomings in this approach that have led us to a very different approach to understanding IBD. For example, the risk of developing CD is 50% amongst monozygotic twins and less than 10% for dizygotic twins, indicating that there is even more than a genetic predisposition at play.1, 2 However, there are more than 160 genetic loci that have been correlated with IBD.2 Even if causation was to be shown, as opposed to association, it would still indicate a multifactorial origin to the expression of IBD, requiring a more nuanced approach to diagnosis and treatment, which is our position, as this chapter will detail. Contemporary models of disease focus on the interaction between the microbiota and the intestines as if they exist within a vacuum. The exact relationship of the changes in the microbiota has not been established.5 It is not clear if it is causative, associated, or the result of other local or systemic imbalances. Even when diet and lifestyle issues are considered, such as smoking, they are seen through a narrow lens of downstream physiology viz. oxidation, inflammation, and transcription mechanisms.2–4 IBD is a disease of the intestines, on this we agree. However, the intestinal tract is completely integrated into the global functioning of the terrain and submitted to neuroendocrine regulation. It The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00011-0 © 2019 Elsevier Inc. All rights reserved.
primarily functions to serve the vital organs and tissues of the organism. Its intrinsic metabolic activity of the intestines is disproportionately small given its mass and weight compared to that of the remainder of the body, especially the brain, heart, and kidneys.6 The approach of Endobiogeny is to contextualize this disease of the intestinal tract to genetic, epigenetic, neuroendocrine, dietary, lifestyle and geographic factors, as well as chronobiologic cycles of genetic programming. The small and large intestines are the conduit and apparatus by whish the entire metaorganism of host + commensal flora obtain nutrients for nourishment (cf. The Theory of Endobiogeny, Volume 2, Chapters 5 and 6). However, as tissue, they have their own intrinsic metabolic requirements. Being subjected to constant threat from external agents and aggressions from fluctuations in pH, chemical moieties, etc., the intestinal epithelium has a high rate of turnover. This makes them susceptible to changes in the balance of metabolic demand to nourishment of the nourishing apparatus. Their primary role is to regulate the absorption of nutrients, discharge of potentially toxic waste, and regulation of fluid according to the global needs of the organism. At all times, the local and global needs must be balanced to avoid a state of nutritional excess or deficiency at either level. The role of the commensal flora must also be considered.1, 4 They aid in digestion for their own benefit, the benefit of their local intestinal host, and the global metaorganism of host + flora. They have their own terrain within the metaterrain, and their own response within the metaresponse of the global organism to aggressions. Thus, the regulation of the regulating capabilities of the intestines is capital and is linked to global neuroendocrine demands. Throughout the intestines are areas rich in receptors for central endocrine hormones that ensure the precise regulation of nutrients and electrolytes related to the production or activity of the endocrine glands that they stimulate. Small intestines: They express the quotidian responsibility of absorption of nutrients according to the exogenous presentation of nutrients and the endogenous demands of the organism.7 Ileocecal zone: It is a transition zone between the evagination from villi in the small intestines and the invagination 237
238 The Theory of Endobiogeny
of the colon composed of columnar epithelial cells.7 This zone is a key point in structural adaptation with respect to the management of electrolytes, water, and nutrients (Table 11.1). Large intestines: The role of intestines is to absorb water and residual nutrients from stool.8 The colon is rich in endocrine receptors.9–12 Dr Duraffourd, originator of the theory of Endobiogeny, hypothesized that each segment of the colon is rich in central endocrine receptors based on the nutrient requirements of the end organ that it stimulates (Table 11.1). In other words, the central hormone directly stimulates nutrient absorption from the segment rich in its receptors. Or, it upregulates the receptors of its peripheral hormone in that particular segment of the colon, which then alters nutrient reclamation.12 The global manager finely tunes reclamation of key elements of adaptation and buffering capacity during periods
of oversolicitation and hyperfunctioning (Fig. 11.1). For example, adrenocorticotropic hormone (ACTH) solicits the adrenal cortex for aldosterone excretion during adaptation states. Aldosterone retains water and minerals to improve perfusion pressure within general circulation.12 There is an increase in the reuptake of fluid and electrolytes from the rectosigmoid segment of the distal colon in adaptation states.12 The teleology, we posit, is a second source of electrolytes and fluids during a surge in aldosterone’s actions in a manner independent of its renal actions and intake of fluids or minerals from the diet. According to the theory of Endobiogeny, the distribution of IBD within the intestinal tract, from mouth to anus, is a result of their auto-pathogenic axis and by extension the critical Endobiogenic terrain expressed in the face of an aggression. Evaluating the basic function of each segment of the intestinal tract, the colon in particular, allows
TABLE 11.1 Endo-enteric relationships by location, receptor, hormone, and, metabolites Location
Microbiotic metabolism
Metabolites reclaimed
Central receptor
Peripheral hormone
Ileocecal junction
Fermentation: polysaccharides, cellulose, pectins, oligosaccharides carbohydrates → shortchain fatty acids (SCFA), iodine scavenging
Water Electrolytes
ACTH: structural adaptation
Adrenal cortex: aldosterone
Ascending right colon
As above + Muscle fibers, mucous, desquamated cells Lipid hydrolysis
Proteins
FSH
Gonads: estrogens
Hepatic flexure
Bile acids: enterohepatic recycling
Lipids
TRH/TSH
Pancreas: insulin, glucagon Gallbladder
Right transverse colon
Deamination of proteins SCFA Phenols, indoles Lipid fermentation
Proteins
FSH
Gonads: estrogens
Left transverse colon
Lipid fermentation: desaturated fatty acids, sterols
Proteins
LH
Gonads: androgens
Iron, proteins
TSH
Spleno-humoral immunity
Lipids Trace metals
GH Prolactin
Pancreas: insulin; relaunching of second loop of adaptation and augmentation of ACTH
Water Electrolytes
ACTH: functional adaptation
Adrenal cortex: aldosterone
Splenic flexure Descending colon
Recto-sigmoid
Flora putrification Final reduction of nondigested, nonmetabolized material pH neutral
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g astrointestinal tract from oral mucosa to the anus in contract to UC, which affects only the colon.13, 14 The broad distribution of disease reflects the extent of hypersolicitation of all endocrine axes at the level of pituitary disadaptation (cf. below for a discussion of central endocrine receptors and enteric physiology).
Epidemiology and risk factors Geographic Northern sections of Europe and North America have the greatest incidence.15 In cooler areas of the world, there is a greater demand for adaptability during the change of seasons due to the cold. Because of the role of alpha- sympathetic in relaunching seasonal adaptation, it can also relaunch the critical terrain in late or recidivistic CD patients. ● ● ● ●
FIG. 11.1 The Endobiogenic cartography of global-enteric relationships. Central hormones adapt the rate of functioning of reclamation of elements of nutrition and buffering capacity according to the relative level of demand they have placed on their end organs. See Table 11.1 and text for details. (Modified with permission from Duraffourd and Lapraz, unpublished © 2015 Systems Biology Research Group.)
us to link it to endocrine activity and arrive at a rational understanding of localized inflammation, skip lesions and long-segment affliction in patients with IBD.
Crohn’s disease Introduction CD is a chronic, recurrent inflammatory bowel disorder.1, 13 According to the theory of Endobiogeny, the chronicity of the disease implies that there is a structural factor of initiation (SFI) that is unable to resolve a particular physiologic demand of the organism. An SFI is a factor of dysfunction is a genetically derived, disadapted response the organism’s demand for structural maintenance (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). When the organism has difficulty maintaining or adapting some basic elements of cellular or tissular structure, a series of compensatory responses are installed, which creates the precritical terrain. In the face of an aggressor, the critical terrain is expressed and the symptoms of disease become manifest. The recurrent nature of the disorder implies that there is a disadaptation that occurs in the face of an aggression. Thus, CD is a structuro-functional disorder at the level of the intestinal tract—a difficulty maintaining the integrity of the intestines in the face of an intense adaptation demand. CD is an ulcerative disease that affects all layers of the mucosa. It may affect any part of the mucosal lining of the
Northern Europe: 16 per 100,000 North America: 12 per 100,000 people Southern Europe: 8 per 100,000 All other areas: 5 per 100,000
Industrialization, affluence, and diet Industrialized nations have a greater incidence, but this may be because countries of Northern Europe and North American have been industrialized for longer periods of time than other areas of the world, which brings with it an increased consumption of refined and preserved foods. Also, a large percentage of North America claims descent from Northern Europe. As less industrialized countries become more industrialized, the incidence of CD increases.15 Sex Pediatric ● In childhood onset, boys outnumber girls in diagnosis of new-onset CD. We find that this witnesses the role of the hyperandrogenic terrain that solicits a strong folliclestimulating hormone (FSH) response readapt the level of estrogen production Adult ● In adult onset CD, women outnumber men; women are particularly susceptible in our experience with first incidence in gonadopause in the late 30s or early 40s. This witnesses in our opinion, the greater role of FSH in adult females than in adult males in general, and witnesses the hyperfolliculinic response to a drop in estrogens during gonadopause.
Pathophysiology of CD Precritical terrain FSH has two key functions relevant to CD. First, FSH has a preparatory action on the cells.16–18 There are multiple,
240 The Theory of Endobiogeny
complex actions working at the level of the membrane, nucleus, and other areas of the cell related to transcription and translational modification.16 FSH through its second messengers stimulates growth factors, preparation of cholesterol for conversion into estrogens, upregulation of aromatase enzyme, etc. In general, FSH is known to have extra-gonadal sits of action.18 According to the theory of Endobiogeny, tissue, especially mucosa, become congested during this time in order to augment the amount and duration of exposure of tissue to nutrients. The second action of FSH is its classical vertical stimulation of estrogens. The SFI in CD is an insufficiency of estrogen activity relative to the intestinal requirement for initiation of protein metabolism. The response from FSH is intense due to the threshold of response from the pituitary. Due to an inability of the organism to readapt primary gonadal estrogen production to this level of FSH activity, the FSH response becomes excessive and prolonged (Fig. 11.2). There is an absolute hyper-FSH state and an absolute hyperestrogenism, with FSH >> estrogens. This imbalance in FSHestrogen relationship solicits a parasympathetic response
resulting in a spasmophilia with impaired adaptation arising from exocrine pancreas and parathyroid insufficiency. In our experience, CD patients are vagotonic by nature (Fig. 11.3). The vagus nerve solicits the exocrine pancreas to readapt the level of proteolytic enzyme expression in order to meet the appeal to proteins that FSH makes. The exocrine pancreas, similar to the gonad, is not able to sufficiently response to this appeal. This installs a hypervagal state in the chronic attempt to stimulate the exocrine pancreas. The sympathetic response to the hypervagal state is strong and greater than that of para (red heavy arrow, Fig. 11.3). At the level of metabolism, there is a hypermetabolic state with catabolic predominance thanks to the strong alpha response. In effect, the hypermetabolism brings about a chronic demand for proteins not met due to proteolytic enzyme insufficiency. The catabolic predominance further fragilizes tissue integrity, already congested. The hyperfunctioning sympathetic activity makes an appeal to the parathyroid gland, which becomes exhausted and incompetent in its ability to mobilize calcium for cellular or global adaptation (shown in gray, Fig. 11.3).
FSH
LH
Cortisol
Estrogens
Androgens
Delays anabolis
Protein intake
Protein utilization
Chromosome Nucleus
Impaired adaptation Catabolism > anabolism Proteolytic enzymes Insufficient to demand
Precritical
Disproportional action
Ribosomes Mitochrondnon Golgi apparatus
Delayed action
Endoplastic reticulum
FIG. 11.2 Structural factor of initiation (SFI) in Crohn’s disease. The SFI is a hyperfunctioning FSH, depicted by the heavy black arrow. The precritical terrain (lower left) is one of impaired adaptation in which catabolism exceeds anabolism and there is insufficient proteolytic enzymes to restore tissues (cf. Fig. 11.3 and text). This is the first step in compromising the quality of tissue. The second influence is the generally elevated cortisol activity (upper left) which delays anabolism, further impairing the general regulation of the cell cycle. Estrogen activity is hyperfunctioning, but not relative to the FSH demand. The demand created by estrogens for proteins is not sufficiently adapted (gray box). Estrogens, as is typical, relaunch LH and androgens, which initiate an intense protein utilization (red box) that exceeds the quality of estrogens in protein utilization. This is the final event that impairs the quality of mucosal tissue, resulting in a fragilization of the mucosa. (© 2015 Systems Biology Research Group.)
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FIG. 11.3 Precritical terrain of Crohn’s disease. In addition to the structural factor of initiation (SFI), the precritical terrain fragilizes adaptability and the quality of the intestinal mucosa, in an attempt to compensate for the SFI hyper demand for proteins. In vagotonic patients, there is a hyperfunctioning parasympathetic tone to adapt exocrine pancreatic function (black arrow) to produce more proteolytic enzymes. The insufficiency of the response (gray arrow) makes a reactive appeal (broken green arrow) back to para, resulting in a further rise in vagal tone. There is a reactive alpha-sympathetic surge in response to this (heavy red arrow), which favors catabolism (Cata) over anabolism (Ana). Alpha-sympathetic stimulates the parathyroid glands (black arrow) to adapt the level of calcium activity to assist in the adaptation demand it has installed. The parathyroid hormone response is insufficient, thus, so is calcium response (gray arrow). This results in a reactive appeal (broken green arrow) to the sympathetic nervous system with a further reactive response in an (ultimately unsuccessful) attempt to re-relaunch the parathyroid glands (broken red arrow). In sum, there is a catabolic predominance both due to alpha and insufficient proteolytic enzymes to repair injured intestinal mucosa. In addition, the patient is not prepared to face an aggression due to impaired precritical adaptability at the level of the parathyroid gland. (© 2015 Systems Biology Research Group.)
Returning to the endocrine system, the hypersympathetic state overstimulates the adrenal cortex with a net effect of delaying metabolism (cf. The Theory of Endobiogeny, Volume 1, Chapter 6). There is a strong appeal to luteinizing hormone (LH) primarily from horizontal FSH stimulation and secondarily from radial estrogen stimulation. The androgen activity is relatively strong and greater than estrogens (Fig. 11.2). The net effect of this dysendocrinism is poor quality of protein assemblage be it enzymes, cytoskeleton, or tissular architecture reflected in the dysplastic architecture.19 According to the theory of Endobiogeny, we conclude that CD is a disorder of dysadaptability of protein management in the face of an aggression. Initiating factor of the critical terrain of CD In the face of an aggression, real or perceived, the autonomic nervous system is the initiating factor in Crohn’s colitis. It is the perception of stress that itself is a risk factor installation of the critical terrain.20 The aggression may be from diet or infections or psychic traumas.21, 22 For example, patients with IBD have an internalizing psychological tendency compared to nonaffected siblings, and the severity of internalization of feelings has been correlated to
severity of symptoms.22 Using arbitrary units of function, if the sympathetic-parasympathetic ratio is 3:1.8 (1.66) in the precritical state, it is 8:3 (2.66) in the critical terrain. The sympathetic response includes both alpha and beta. It is the brutality of the sympathetic response to an aggression, be it from the interior or the exterior that installs the intensity of the endocrine response resulting in ulceration of the mucosa.
Critical terrain of CD The critical terrain of CD involves sequential involvement of each axis: corticotropic, gonadotropic, thyrotropic then somatotropic. In the discussion the four axes involved, somatotropic, we review the concept of a special triadic endocrine relationship called a trépied (Fig. 11.4, and Theory of Endobiogeny, Volume 1, Chapter 9). There is a dysfunctional trépied in the CD patients which is key to understanding the degree of inflammation, ulceration and delayed wound healing (Fig. 11.5). Upon conclusion of the discussion of the critical endocrine terrain, the pre- and critical terrains are schematically summarized in Fig. 11.6.
242 The Theory of Endobiogeny
Third axis of solicitation: thyrotropic
FIG. 11.4 Trépied of alpha-sympathetic, prolactin (PL) and growth hormone (GH). Alpha stimulates GH and PL. GH stimulates PL, but PL inhibits GH. This is the trépied relationship. In terms of adaptation, in a first time, alpha initiates adaptation, in a second time, alpha stimulates GH to calibrate nutrient entry (first loop). In a third time, both alpha and GH relaunch PL to progress adaptation (from first to second loop). At a fourth time, once rising PL activity has inhibited GH, alpha’s final peak of PL helps complete adaptation (end of the second loop). (© 2018 Systems Biology Research Group.)
FIG. 11.5 The alpha-prolactin (PL)-growth hormone (GH) trépied in inflammatory bowel disease (IBD). The normal trépied is described in the text and Fig. 11.4. In IBD, the trépied is dysfunctional. Alpha is hyperfuncitoning, leading to a hyperadaptation. It also drives an intense PL that inhibits GH before GH can have its time in calibrating nutrients. Thus there is prolonged adaptation, hyperinsulinism, inflammation, delayed wound healing (in part due to insufficient nutrient accumulation), and ulceration of mucosa. (© 2018 Systems Biology Research Group.)
First axis of solicitation: corticotropic 1. Central: ACTH hyperfunctioning. At the level of the intestines, ACTH receptors are stimulated in the ileocecal junction to augment the absorption of water and electrolytes for structural adaptation, thus the predilection of inflammation of the terminal ileum 2. Peripheral: cortisol and adrenal cortex hyperfunctioning, cortisol > global adrenal activity → hypercatabolic state a. Net imbalance: ACTH > cortisol > adrenal cortex Second axis of solicitation: gonadotropic 1. Central: FSH hyperfunctioning intensified a. Mucosal hypertrophy of colon → increased anabolic demand for proteins 2. Peripheral: gonadal hyperfunctioning, estrogens ≫ androgen → impaired completion of protein anabolism → mucosal ulcerations a. Net imbalance: FSH ≫ estrogens > androgens
1. Central a. Thryotropin-releasing hormone (TRH) hyperfunctioning: i. TRH → gallbladder → excess bile excretion → autodigestion of the small intestines ii. TRH → PL → pancreas → insulin → mistiming of GH-insulin relationship → inflammation b. TSH hyperfunctioning i. FSH → TSH → congestion of mucosal tissues ii. TSH → insufficient T4, parathyroid hormone → insufficient calcium for adaptation 2. Peripheral a. Peripheral thyroid → hyperfunctioning → hypercatabolic, use of fat for energy, insufficient lipid management for cellular reconstruction b. Net imbalance: generally hyperfunctioning axis Fourth axis of solicitation: somatotropic Alpha has a classic trépied relationship with prolactin (PL) and growth hormone (GH) (Fig. 11.4). When this trépied functions normally, in a first time, alpha initiates adaptation. As the first loop of the general adaptation advances, in a second time, alpha stimulates GH to start the process of calibrating nutrients except glucose. This is the role of PL at the end of the second loop. In a third time, alpha also stimulates PL to advance adaptation by turning the first loop to the second. The GH response is initially greater than the PL response. As PL levels rise, be it from alpha, GH, or TRH, in time it inhibits GH in order to end the time nutrient apportionment, thus beginning the time of insulin and glucose to generate adenosine triphosphate (ATP) to fuel metabolism. And with this, in the fourth time, PL (along with somatostatin) ends adaptation. In IBD, the genetic heritage favors both a hyperfunctioning alpha and a hyperfunctioning and early responding PL during adaptation states (Fig. 11.5). Thus, when alpha stimulates GH and PL, the PL response is far greater than GH, and precedes it in time. GH is inhibited too quickly and PL remains in a hyperfunctioning state. This impairs somatotropic synchronization of glucose entry and energy production, resulting in free radical production, inflammation, ulceration, and delayed wound healing. The key to treating this imbalance is to inhibit alpha and relaunch GH. It may seem paradoxical that a medicinal plant such as Lamium album is efficient in IBD, as it stimulates GH and PL from the anterior pituitary. By relaunching GH with Lamium album, one restores the competency of GH in relationship to PL. This gives information to alpha to downregulate its stimulation of the somatotrophs in the pituitary. This is similar to the role of Eleutherococcus senticosus in prostate enlargement (Chapter 7) and acne (Chapter 8) with respect to androgens and LH.
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FIG. 11.6 Summary of precritical and critical terrain and pathophysiology of Crohn’s disease according to the theory of Endobiogeny. The precritical terrain (lower left) fragilizes the intestinal mucosa, meaning that it easily is susceptible to injury during adaptation states (cf. Figs. 11.2 and 11.3). In the critical terrain (upper and middle image), a hyperfunctioning alpha relaunches the entire axial sequence of endocrine activity: ACTH and cortisol, FSH and estrogens, LH and androgens, TRH-TSH-thyroid. Most crucial to the ulceration in a Crohn’s colitis is the disruption of the alpha-PL-GH trépied (Fig. 11.5). The end result in mucosal edema, inflammation, fissures, and ulceration. (© 2015 Systems Biology Research Group.)
1. Central a. PL hyperfunctioning → i. Hyperinsulinism ii. ACTH → relaunching of second loop adaptation, functional adaptation demands, and involvement of rectosigmoid colon iii. Abscess (favored) b. GH delay 2. Peripheral a. Hyperinsulinism proceeding GH with low insulin resistance → i. Elevated free radicals → inflammation → necrosis ii. Delayed wound healing iii. Fistula formation Emunctory congestion The exocrine pancreas continues to be congested. The liver becomes congested at the metabolic level and possibly for circulatory reasons due to the quantity of endocrine metabolites and inflammatory proteins that need to be metabolized as a result of the critical terrain. Tissue pathology With respect to history, the colon in CD shows chronic intestinal inflammation. There is activation of TH1 cells promoting interleukin-2, tissues necrosis factor alpha, arachidonic acid, proteases, platelet activating factor, and
free radicals. The net effect is mucosal ulceration forming crypts in the mucosal endothelium, muscularis layers, and affecting the mesentery and lymph nodes. One can find abscesses with a neutrophilia within the crypts and mucosa.1, 13
Anatomical distribution of CD CD is characterized classically has having “skip” lesions: areas of affected and unaffected areas of ulceration (Fig. 11.7). From the Endobiogenic perspective, it witnesses the role of the various central hormone receptors on the colon and their particular role in the patient’s Endobiogenic terrain (cf. Fig. 11.1). For example, in Fig. 11.7, A (top) represents an ACTH predominance in the critical terrain for maintenance of structure. B (middle) and C (bottom) represent ACTH in structure, LH, TRH, and GH.
Pediatric In children, the onset of CD is 12–15 years,5, 21, 23 in the gonadic metabolic and tissular phases of chronobiologic unfolding (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). This is a time of intense demand for estrogens for structural growth. The areas of frequency of presentation are presented below with comments with respect to the Endobiogenic significance of these findings.
244 The Theory of Endobiogeny
● ●
Small intestine alone: 30% Mouth, esophagus, stomach: rare but possible: 20%
Clinical presentation CD presenting in childhood tends to be more severe and progresses more rapidly.5 Symptoms are presented below by system.
Gastrointestinal Abdominal pain ● Right lower quadrant or periumbilical, often relieved with defecation ● Lower left quadrant pain may be more prevalent if there is a greater affectation of rectosigmoid colon Bowel habits ●
● ●
Diarrhea, intermittent, typically not bloody, or mucopurulent unless rectosigmoid colon involved Urgency to defecate Foul stool (rectal involvement with abscess)
Fistula-related presentations ● Recurrent urinary tract infections ● Feculent vaginal discharge ● Feculent soiling of skin ● Retroperitoneal abscess FIG. 11.7 Skip lesions in Crohn’s disease. (A) Isolated lesion (red) at the distal ileum, (B) skip lesions (red), affecting, with endobiogenic significance in parentheses: ileum, ileocecal junction (ACTH), ascending colon (FSH), hepatic flexure (TRH/TSH), mid-transverse colon (LH), mid to distal descending colon (GH), and (C) skip lesions (red) exclusively affecting the colon, whose Endobiogenic significance is noted in (B). (Reproduced from Samir, vectorized by Fvasconcellos [CC-BY-SA-3.0] via Wikimedia Commons.)
●
●
●
Terminal ileum: 50%–70% ● It witnesses the role of structural disadaptation by ACTH, possibly installed during adrenarche from 11 to 12 years of age Colon (typically ascending colon): 50%–60% ● It witnesses the role of FSH as a SFI and oversolicitation during Crohn’s colitis Gastric and duodenum: 30%–40%
Systemic ● Anorexia ● Weight loss ● Growth delay (in children may precede diagnosis of disease by 1 year or more)
Review of systems ●
●
●
Keen on sports, which improves the discharge of alpha, reducing the violent explosion of beta Vivid dreams, witnessing the inflammatory, fragilizing role of TRH in its stimulation of the endocrine pancreas Diet: tends to be rich in animal proteins, refined carbohydrates, animal fats, processed fats, which present daily insult and injury to the intestinal epithelium
Adult In adults, expression of CD is more evenly distributed, reflecting the settling of the organism into its adult Endobiogenic endocrine equilibrium.24 ● ●
Ileocecum: 30% Colon (rectosigmoid most prominent): 20%
Physical examination Morphology ● ●
Pale skin, darker hair in fair-skinned patients Feminine face with a masculine body (all ethnic origins)
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Pertinent findings Head, ears, eyes, nose, and throat (HEENT) ● Dilated veins on eyelids, nasal bridge, forehead ● Dark eyebrows, possibly bushy ● Long eyelashes ● Enlarged parotid and submandibular glands ● Dilated canal of Stensen ● Sublingual veins dilated, dark blue Abdominal ● Hepatic congestion, portal congestion ● Small intestine/dysbiosis: often tender ● Colon tender on palpation: all areas Extremities ● Right leg, tender on palpation at inferior and medial to tibial tuberosity, indicative of gallbladder congestion
Laboratory studies Fecal calprotectin and serum C-reactive protein (CRP) can serve as helpful markers of remission of the critical terrain.25, 26 Studies suggest that they may be superior to remission determined by clinical symptoms.27 This mirrors our experience with the biology of functions (Tables 11.2–11.5). Patients can be symptomatically in remission but still have numerous elements of the critical terrain, which keep the patient fragilized and susceptible to flare-up. In addition, labs for the biology of functions (including vitamin D) are recommended to follow the evolution of the terrain based on the integrative physiologic principles.
Biology of functions Once a patient has been diagnosed with CD, there are essentially three terrains one can view. The first is the critical terrain proper during an active flare-up (Tables 11.3–11.6). The second is a patient in remission with elements of the
critical terrain present, but not sufficiently elevated to bring about active disease. We refer to this as the suppressed critical terrain. We hypothesize that based on the genetically inherited terrain, there are various phenotypic subtypes of CD. For example, in some patients who are clinically asymptomatic in a suppressed critical terrain may have elevated brain stem activation, or inflammation, a hyperoxidative state, etc. Finally, there is the true correction of the critical terrain to a precritical state, typically with some Endobiogenic treatment. In the critical terrain, most of the elements will be deranged (high or low). In the suppressed critical terrain, the patient is asymptomatic and some of the elements of the critical terrain will remain deranged but less so than in the critical terrain. In the precritical terrain, the patient is asymptomatic and has derangements consistent with the precritical terrain. Some aspects, such as the exocrine pancreas, need to be assessed by physical exam. Table 11.2 summarizes the criteria we propose for number of deranged indexes per axis. There is overlap between the number of deranged indexes across the three categories. For example, the criteria for thyrotropic axis and immunity are 7–9 deranged indexes. For the same group, the suppressed critical terrain is 4–7. The reason for this that even there are not a substantial reduction in the number of positive signs in one axis, there will be in the two or more of the other axes. The one that continues to be the most deranged is likely to be the autopathogenic axis of the patient (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). The first group of indexes is grouped together as “neurocorticotropic” because of the implication of sympathetic activation of the corticotropic axis (Table 11.3). In order to discuss terrain, we introduce new indexes not previously discussed. The immediate adaptation score #2 witnesses the global peripheral catabolic neuroendocrine activity during immediate adaptation: alpha, beta, and the adrenal cortex. It witnesses alpha-sympathetic engagement of the entire adrenal unit: medulla (adrenaline) and cortex (cortisol). There is also the adaptation entrainment score adjusted index. It witnesses, in the face of the relative degree of entrainment of sequential axial function starting with corticotropic axis the
TABLE 11.2 Criteria of indexes deranged per stage of terrain of Crohn’s disease Axis
Critical
Suppressed critical
Precritical
Neuro-corticotropic
>5/11
3–5/11
<3/11
Gonadotropic
>3/7
2–4/7
<3/7
Thyrotropic-immunity
>6/9
4–7/9
<4/9
Somatotropic
>6/9
4–7/9
<5/9
Psychological
>3/5
2–3/5
1–2/5
Total indexes deranged
28–41
15–28
<15
246 The Theory of Endobiogeny
TABLE 11.3 Neuro-corticotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
ANS
Leukocyte mobilization
↑↑ or ↓↓
↑ or ↓
Normal
Platelet mobilization
↑↑, typically
↑
Normal
Starter
↑↑ or ↓↓
↑ or ↓
Normal
Immediate adaptation score 2
↑↑
↑
Normal
Adaptation entrainment score adj.
↑↑
↑
Normal
Vasopressin corrected
↑↑
↑ or ↓
Varies
ACTH
↑↑
↑ or ↓
Varies
Cortisol
↑↑
↑
Normal or ↓
Adaptation permissivity of the adrenal cortex
↑↑, may be negative
↑
Normal
Aldosterone comparative
↑↑, may be negative
↑, may be negative
Normal or slightly elevated
Structure/function
↑↑
↑
Normal
Neuro-corticotropic
Corticotropic
TABLE 11.4 Gonadotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
Gonadotropic
LH
↑↑
↑ or ↓
Normal
FSH
↑↑
↑ or ↓
Varies, tends to be slightly elevated
Organotissular estrogen yield
↓↓
↓
Varies, may be slightly low
Estrogen index
Normal or ↓ for age
Normal or ↓ for age
Normal or ↓ for age
Estrogen index corrected
Normal or ↓ for age
Normal or ↓ for age
Normal or ↓ for age
Genital androgens
Normal or ↓ for age
Normal or ↓ for age
Normal or ↓ for age
Genito-thyroid
↑↑
↑
Normal
Gonado-thyrotropic
degree of liminal tissular expression of estrogens to witness both the solicitation and anabolic achievement from the gonadotropic axis, specifically from estrogens. By extension, it evaluates the ability of the organism to evolve the adaptation response throughout the phases of the adaptation syndromes. By extension, the higher the value, the greater the persistence of immediate and mediate adaptation and by extension of inflammation and catabolism. By extension, the lower the value is, the greater the progression of the adaptation syndromes is anticipated to be toward restitutio ad integrum. In CD, during a flare-up, the index is elevated as the corti-
cotropic axis as a whole is intensely stimulated (as noted in the immediate adaptation score #2) but so are estrogens in an attempt to compensate for the intensity of the catabolic response through endocrine coupling. What is notable is that often even in the suppressed critical terrain and even in remission, the index remains elevated. This indicates that the organism is not able to resolve the adaptation response and enter in an anabolic phase of restoration. This is especially the case if the structure/function index also remains elevated. The structure/function index expresses the solicitation of adaptative tissular mechanisms of structure relative to those of
Inflammatory bowel diseases Chapter | 11 247
TABLE 11.5 Thyrotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
Thyrotropic
βMSH/αMSH
↑↑↑
↑↑ or ↓↓
Normal to low
Thyroid relaunching
↑↑
↑
Normal to slightly elevated
Thyroid relaunching corrected
↑↑↑
↑↑
Normal to slightly elevated
Thyroid
↑↑↑
↑↑ or ↓↓
Normal to slightly low
Thyroid efficiency
↑
Normal or ↓ for age
Normal or slightly ↑ for age
PTH
Varies
Varies
Varies
Vitamin D adaptation index
↓, negative or both
Varies
Varies
Mobilization of immunity
↑↑
↑
Varies, may be negative
Interleukin 1
↓↓
↓
Varies, may remain low
Thyro-immune
TABLE 11.6 Somatotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
Somatotropic
Prolactin
↓↓↓
↓↓
Varies, may be slightly elevated
GH growth score
↓↓↓
↓↓
Varies, may be slightly elevated
Somatostatin
↓
Varies, often high
Varies, often high
Insulin
↑↑↑
Varies
Varies, may be slightly elevated
Insulin resistance
↓↓
Varies, often low
Varies, may be slightly low
Expansivity #2
↑↑
Varies
Varies
Redox
↑↑ to ↑↑↑
↑ to ↑↑
Varies, may be slightly elevated
Noxious free radicals
↑↑↑
↑↑
Varies, often elevated
Autophagy 1 adjusted
↑↑↑
↑↑
Varies, often elevated
function. The higher the index, the more tissue solicit structural mechanisms of adaptation. It is elevated in CD. Finally, there is the vasopressin index corrected. It witnesses the strictly central effects of vasopressin, as opposed to the net central and peripheral actions of vasopressin. In the critical terrain of CD, vasopressin may be paradoxically elevated because the feedback of cortisol on ACTH is impaired. Thus, vasopressin attempts to relaunch ACTH from the anterior pituitary,28 despite elevated cortisol activity. The gonadotropic axis (Table 11.4) shows elements of the SFI deranged to a greater degree. Not all of the estrogen indexes will be deranged. It is sufficient for one to be deranged. The number of estrogen indexes deranged partly depends on the age of the patient and their stage in their
lifestyle. NB: normal values differ for adolescents compared to adults. The activity of the thyrotropic axis is presented in Table 11.5. We have placed the βMSH/αMSH index in the thyrotropic axis because the elevated value reflects the role of βMSH and TRH in stimulating the axis. An elevated index in the critical terrain indicates that βMSH is acting to (over-) stimulate the thyroid gland outside of central regulation, and by extension, that there is insufficient central endorphins to end this process. During the suppressed critical phase, it may dip low, favoring αMSH, which would be beneficial in allowing for the long programmatic and sequential passage of endocrine activity to occur in order to complete the adaptation response. αMSH regulates energy homeostasis.29 It is antipyretic, antiinflammatory, cicatrizing, and
248 The Theory of Endobiogeny
anorexigenic, all actions that help the patient recovery from the critical terrain of a Crohn’s flare-up.30 If the index remains elevated, favoring βMSH and an insufficiency of endorphins, it is a cause for concern that the patient remains fragilized and quite at risk of a subsequent flare-up, despite their current level of treatment. This index tracks with the thyroid index. The thyroid efficiency index expresses the tissular activity of the thyroid in its participation in structural activity. In other words, it evaluates how effectively thyroid response to and contributes to the energy required for structural assemblage of cellular elements such as enzymes and organelles initiated by estrogens. In the critical terrain of CD, an elevated index is problematic because estrogen activity is insufficient. Thus, an elevated value indicates that thyroid is providing a catabolic action that is greater than the anabolic activity initiated by estrogens. This favors friable mucosa and risk of further bleeding. It may be advantageous for the index to be lower than normal then return to normal or even slightly elevated once other aspects of the terrain have normalized as well. In this case, a slightly elevated index in the face of elevated estrogens would be favorable as an indication of tissular thyroid activity dedicated to restoration of tissue integrity, one cell at a time. The parathyroid hormone (PTH) index may or may not be elevated because the index evaluates the general level of endocrinometabolic activity of the gland, not its specific role in adaptation. The vitamin D adaptation index witnesses the relative insufficiency of vitamin D in mitigating the intensity of the central adaptation response. The higher the index, the less efficient vitamin D is in mitigating the adaptation response and the more likely high dose, shortterm vitamin D therapy may be in CD.31 The benefit of this therapy is not related to reduction in inflammation as measured by CRP,31 which reinforces the notion of the index of evaluating vitamin D’s role in adaptation. Finally, the mobilization of immunity index evaluates the relative efficiency of mobilization of elements of immunity from the macrophage-activating system relative to the rate of sequestration. It is a composite of the effects of cortico-thyrotropic and immune factors: vitamin D, splanchnic mobilization of leukocytes, splenic mobilization of platelets, adrenal cortex yield, and interleukin activity. When the index is elevated, as it is in CD, it witnesses the risk of a hyper- or dysregulated immune response, despite the fact that interleukin activity is low.32 In other words, the notion of dysregulation refers to poor management of immune activity as reflected by excessive intensity and/or duration of inflammation but inappropriate type of immune cell or timing of function. Within the somatotropic axis (Table 11.6), one notes the low Prolactin index indicates a hyperfunctioning PL. The low GH growth score index indicates that GH is delayed and/or inhibited in its role of calibrating timing and quality of nutrient entry. Thus, we see a corresponding
d esynchronization of peripheral glucose delivery timing to cells with an elevated insulin index and low insulin resistance index. To further characterize the tissular and cellular disturbances in IBD, we introduce a number of new indexes. In our discussion of the Endobiogenic critical terrain of CD, we mentioned the cellular disorganization.19 This refers to the topology of cell arrangement and morphology in threedimensional (3D) space. The expansivity #2 index characterizes the degree of risk of anarchic cellular development based within the adaptative modalities of metabolism in their consequences of structural implication. Autophagy is the process in which lysosomes within cells destroy damaged organelles, proteins, other material, etc. This process has been found to be aberrant in IBD.33, 34 The autophagy index evaluates the relative risk of insufficient autophagy due to the intrinsic metabolic functioning of the cell and thus the accumulation of biologic toxins of endogenous origin. The autophagy 1 adjusted index evaluates the risk of insufficient autophagy and is adjusted by the potentially beneficial role of free radicals in stimulating autophagy genes.35 However, if the noxious free radicals index is more than 10-fold above normal, the role of free radicals is dysregulated and harmful, which is the case in IBD.36 When the autophagy 1 adjusted index and the noxious free radicals index are both elevated, free radical scavengers should be considered, such as α-lipoic acid.37 One may also evaluate certain psychological states in the CD patient using the biology of functions (Table 11.7). CD patients are noted to have an internalizing coping style. In addition, we find, as others have, that the perception of stress is key given their psychosocial milieu and coping style.20, 38, 39 We can speak about a general IBD
TABLE 11.7 Psychological indexes related to Crohn’s disease Critical terrain
Suppressed critical
Remission
Closed off from receiving
↑↑
↑
Normal
Permeability adjusted
↑↑↑
↑↑
Normal to ↑
Traumatic memory
↑↑
↑
Normal
Acceptancecontentment
↓↓
↓
Slightly ↓, normal, or ↑,
Frustration index
↑↑↑, may be negative
↑↑, may be negative
Slightly ↑ to normal, negative value may persist
Index
Inflammatory bowel diseases Chapter | 11 249
p sychological type according to the theory of Endobiogeny. Variations in the UC patient are discussed in the appropriate section (cf. Table 11.20). We continue to evaluate the structure value of the psychological indexes, which favor challenges in the relationship with intimates, family members, and close friends, as opposed to acquaintances (cf. UC). The IBD patient feels unloved, reflected in the closed off from receiving index. The closed off from receiving index evaluates the tendency to feel defensive and closed off from receiving emotional support from others. When it is elevated, it witnesses a greater tendency to feel defensive and create a defensive barrier to protect one self, which can involve internalization of feelings. The frustration index witnesses the tendency to have a moralistic or perfectionist attitude and feel frustrated by one’s inability bring to fruition what one has envisioned. By extension, it favors the tendency to be frustrated toward the perceived failings of others. When the index is elevated and negative—often the case during a CD flare-up—it indicates that the frustration does not lead to productive changes in the patient’s life. It only leads to more frustration. When both indexes are elevated, the patient is more like to internalize their feelings. There is an underlying sense of emotional vulnerability, reflected in the permeability adjusted index. The higher the index, the greater the feeling of emotional vulnerability. Perceived or real insults or criticism “cut” into the self-esteem of the patient, mirroring the ulceration of the mucosa. As CD is a deeper level of ulceration, one also notes a deeper level of emotional vulnerability. It is elevated during a flare-up and may persist even in remission, but certainly in the suppressed critical terrain. In fact, from remission to a fragilization and risk of flare-up, one is likely to see this index rise, even before the onset of clinical symptoms. From the feeling of not being loved and the feelings of emotional vulnerability, one notes that UC patients have traumatic rumination during their crisis, reflected in the traumatic memory index. IBD patients are generally discontent with their situation, reflected in the acceptance-contentment index, which when low indicates this feeling of discontent and searching from answers that one cannot find. This tends to persist, even in the precritical terrain. If the patient has an elevated index in the precritical terrain, it indicates that they tend to rationalize their discontent. This increases the risk of a flare-up even more than a slightly low score. Finally, UC patients tend to be critical of others, sometimes projecting their own internal frustration. This is reflected in the critical tendency score, which evaluates the tendency to be critical against oneself and other people.
Treatment: General considerations The Endobiogenic approach to Crohn’s colitis is to initiate symptomatic treatment, alter diet, and then address the
issues of terrain. The choice of symptomatic treatment is dictated by the degree of decompensation of the patient and the probability of spontaneous or supported recovery without surgical intervention or pharmaceutical intervention. There is no inappropriate treatment, only an inappropriate utilization of a treatment due to its aggressiveness or lack of effectiveness, or excessive or insufficient duration of treatment for the given state of decompensation. Standard of care treatments with pharmaceutical agents is the most well-researched approach to suppression of downstream pathophysiologic factors and clinical symptoms. It is part of the Endobiogenic approach to the treatment of IBD. The use of medicinal plants may be supportive or primary based on a number of considerations. The more severe the clinical symptoms, the higher the biomarkers (e.g., calprotectin, CRP), and the more passive the patient is in disease management, the greater the imperative for the pharmaceutical treatments to be the primary treatment.
Treatment: Standard of care All classical biomedical approaches are symptomatic and suppressive in nature. They offer reduction in the inflammation and dysregulated immune damage to the cell. Nonbiological agents do not necessarily change the outcome of disease.27, 40 They reduce inflammation and symptoms of disease41 but may not prevent relapse either.42 Thus, reinforces the Endobiogenic theory of a critical terrain that must be treated as opposed to suppression of mechanisms of pathophysiology. The step-up approach uses increasingly targeted therapy commensurate with severity of disease. The less severe the presentation of symptoms, the less aggressive the pharmaceutical agent. The first “step” in ascending treatment is the mucosal antiinflammatory 5-aminosalicyclic acid (5ASA).41 It is prepared in various prodrug forms so as to be released in the small intestines (mesalamine) or colon (sulfasalazine) based on the area of inflammation. The second step is glucocorticoids. When systemic symptoms are present, oral glucocorticoids such as prednisone can be used. When symptoms are primarily enteric, budesonide is favored, as it does not have systemic absorption.41, 42 The third step is immunosuppression: 6-mercaptopurine (6-MP), or its prodrug azathioprine. Methotrexate is another option for children and adults, especially when 6-MP is not successful.43 Other options include tacrolimus and mycophenolate. The fourth step is biological therapy. These medications inhibit downstream mechanisms of disease and/or constitutively expressed regulators of cell function, often with increasingly consequential side effects.27 Currently, there are two general classes: antitumor necrosis factor agents (e.g., adalimumab), and leukocyte adhesion and migration inhibitors (e.g., natalizumab). There are risk of rare lymphomas and opportunistic infections.41 New classes of
250 The Theory of Endobiogeny
drugs in development include inhibitors of interleukin 23 and Janus kinase 1.27 Antibacterial treatment can be added as indicated.41
Diet and lifestyle during a crisis ● ●
Symptomatic treatment: An endobiogenic approach An Endobiogenic symptomatic treatment is aimed at reducing inflammation, diarrhea, and sympathetic hyperfunctioning, favoring astringent plants (Table 11.8). These plants are all polyvalent for symptomatic treatment and elements of the terrain.44–46 Many elements listed under symptomatic treatment also treat the critical or precritical terrain. The primary difference is dose and frequency of administration.
Diet: high purine protein, low fat, low fiber Lifestyle: calming activities: meditation, breath work, yoga, Tai chi, prayer, etc.
Case study in acute management of CD
Diatomaceous earth is efficient in inflammatory bowel disorders. It is antihemorrhagic, antiinflammatory, cicatrizing, antimicrobial, absorbent, and adsorbent.44–48 Based on our research, we have found the green Illite clay to be the most efficient. Green Illite clay: 1–2 tbsp every 2–3 h
A 16-year-old boy of Indian descent, born and raised in the United States, was being treated with Humira for CD. He spent the summer visiting relatives in India. Since he felt well eating traditional fermented and vegetarian foods of south India, he let his prescription run out. Two weeks later, he returned home to the United States. Four weeks later he presented 1 week of abdominal pain and 6 bloody stools per day. He had hemoglobin evaluated in urgent care, which showed anemia: 9 mg/dL (12.5–17 mg/dL). Before summer vacation, his hemoglobin was 12.7 mg/dL. The patient was started on acute, symptomatic treatment without performing a biology of functions. On exam, the patient was noted to have a beautiful face with large almond eyes. The abdominal exam was significant for tenderness of the exocrine and endocrine pancreas, ascending colon (FSH), mid- and distal descending colon (GH, PL), and rectosigmoid area (ACTH).
Sample treatments of Crohn’s colitis
General treatment
Preparing the Illite clay with a tisane, or adding a tincture offers the highly efficient symptomatic treatment of CD. Clay + tisane Matricaria recutita 30 g, Fragaria vesca 30 g, Alchemilla vulgaris 30 g, Poterium sanguisorba 30 g: 1 tbsp steeped 12 min in 200 mL water, strain and add to 1 tbsp clay. Let sit for 30 min, mix and administer. Prepare next tisane and hydration of clay. Clay + tincture with essential oils Matricaria recutita 30 mL, Fragaria vesca 30 mL, Alchemilla vulgaris 30 mL, Poterium sanguisorba 30 mL, Lavandula angustifolia EO 2 mL: 6 mL every 4 h added to prepared clay. In more severe cases of hemorrhagic disease, especially when the prominent site is the rectosigmoid area, a microlavage infusion can be used. The same preparations noted above can be lavaged into the rectum. The method is as follows: Tincture + clay: add ½ tsp. clay to 10 mL water. Let sit 15 min. Shake tincture well (if it contains essential oils), add 5–6 mL to the clay preparation, stir well, draw up with a rectal administration bulb, and slowly administer over 5–10 min. Do not use muco-caustic essential oils such as oregano, cinnamon, or clove. Tincture + clay: add ½ tsp. clay to 10 mL of a tisane prepared from 1 tbsp of mixture steeped 15 min in 100 mL water. Let sit 15 min. Stir and administer as above.
Since he was already vegetarian, he was started on the following empirical treatment: 1-Astringent-adsorbant: tisane-EO-clay mixture every 4 h while awake until bloody diarrhea has resolved
Diatomaceous earth
● ● ● ●
1 tbsp Illite clay 1 drop Carum carvi (caraway) EO 1 drop Mentha piperita (peppermint) EO 200 mL tisane of Juglans regia: 1 heaping tsp. leaf steeped 8 min in hot water; strain
2-Astringent, antihemorrhagic cicatrizant tincture: Lamium album MT 30 mL, Poterium sanguisorba MT 30 mL, Malva sylvestris MT 30 mL, Hamamelis virginiana MT 30 mL: 3 mL 4 times per day in clay water. 3-ANS-cortico-gonado-thyrotropic tincture: Salvia sclarea MT 80 mL, Lithospermum officinale MT 80 mL, Leonurus cardiaca MT 80 mL + petitgrain EO 2 mL, eucalyptus EO 2 mL, clove EO 0.5 mL 4 mL twice per day in clay water. The number of blood stools reduced to 4 per day in 24 h, then 2 per day in 48 h and resolved by the third day of treatment.
Treatment of terrain: An endobiogenic approach There are a number of medicinal plants that can be used to treat the terrain of CD. Those that are the most efficient due
TABLE 11.8 Symptomatic treatment of Crohn’s colitis Medicinal plant
Alpha-lytic
Antiinflam.
Alchemilla vulgaris
•
Angelica archangelica
•
Arnica montana
•
• indirect
Artemisia dracunculus
•
Fragaria vesca
•
Lamium album
•
Astringent
Antihemorrhagic
Endocrine
Intestinal tropism
•
Aldosterone antagonist
Antispasmodic, antimicrobial
Estrogenic (−), FSH
Antispasmodic, antimicrobial
a
Delays insulin activity
•
a
Hemostatic
Estrogenic (mild)
Antispasmodic, antimicrobial
•
(−) ACTH, (−) conversion of androgens to estrogens
Antimicrobial
•
Improve growth factors
•
•
(−) Adrenal cortex
Hepatobiliary drainer Cicatrizing Antimicrobial
Matricaria recutita
•
•
(−) ACTH
Antispasmodic, antimicrobial, cicatrizant Decongestant: hepatic, splanchnic, pelvic
Plantago major
Poterium sanguisorba
•
•
a
Antispasmodic, antimicrobial, antiulcerative Hepato-pancreatic drainer •
(−) PL and by extension hyperinsulinism and inflammation, and corticotropic relaunching
By delaying the actions of insulin in the cell membrane, Arnica montana diminishes inflammation rooted in somatotropic desynchronization.
Antiinflam.: Antiinflammatory.
Antiseptic
Inflammatory bowel diseases Chapter | 11 251
Lavandula angustifolia
252 The Theory of Endobiogeny
to their polyvalent action are listed in Table 11.9, followed by a discussion of the plants by axis and action within the axis. Most of the plants in Table 11.9 share the properties of coupling or linking (cf. The Theory of Endobiogeny, Volume 1, Chapter 10). Plants that affect coupling simultaneously alter adjacent endocrine axes, for example, corticogonadotropic, gonado-thyrotropic, somato- corticotropic, etc. Plants that affect linking affect the two anabolic axes: gonado-somatotropic or somato-gonadotropic, such as PL’s effect on GnRH or estrogen activity.
Corticotropic Support adrenal activity while reducing ACTH44, 45, 47 ● ● ●
Ribes nigrum leaf > bud Fragaria vesca Salvia sclarea
Adrenal support with hepato-splanchnic drainage44, 45 ●
Quercus pedunculata
Gonadotropic Reduce central overactivity44, 45 ● ● ●
Angelica archangelica Lithospermum officinale Borago officinalis
Support peripheral tissular estrogen activity44, 45 ● ● ●
Avena sativa Angelica archangelica Salvia sclarea
Central: GH Relaunch GH to restore the chronologic relationship with insulin44, 45 ●
Lamium album Peripheral: Insulin Delay effects of insulin on cell membrane44, 45
● ●
Arnica montana Malva sylvestris
Lamium album (White deadnettle) Parts used: leaf, flower44, 45 Galenic: MT, FE, MS, bulk herb Summary: supports hypophyso-pancreatic axis, use in children with failure to thrive, in adults with wasting or ulcerative disorders, in chronic fatigue states with brain fog Actions: GU: uterine vasoconstrictor, antimetrorrhagic, antihemmoragic by vasoconstriction, pelvic decongestant by venous stimulation. Endo: somatotropic: supports hypophysopancreatic axis, prolactogenic, increases GH and growth factors. Neuro: relaunches dopamine. GI: antidiarrheal, astringent. ID: urinary antiinfectious. Derm: vulnery, stimulates fibroblasts. HEME: antianemic. Pulm: expectorant, bronchial fluidifier. CV: venoconstrictive, venotonic, antiinflammatory. Use: GU: uterine bleeding, cystitis, vaginitis, leukorrhea, pelvic congestion, prostatitis. GI: colitis. Vascular: hemorrhoids, phlebitis, varicose veins. Metabolic: failure to thrive in children, chronic fatigue. Neurologic: brain fog. HEME: hemorrhagic anemia. Pulm: bronchitis, emphysema. Method: Tisane: 2 tsp./cup; infuse 8 min; Douche: of tisane for vaginal infections
Thyrotropic Reduce central hyperthyroidism44, 45 ● ● ●
Lithospermum officinale Lycopus europaeus Leonurus cardiaca
Modulate peripheral thyroid terrain according to the Endobiogenic state of the patient and support PTH ● ●
Calcium (ascorbate, glycinate, malate) Vitamin D (10,000 IU in AM × 4 days, then 5000–6000 IU in AM × 3 days, then reassess)
Arnica montana (Arnica) Parts used: flower44, 45 Galenic: MT, MS, bulk herb Summary: helpful in allergic/anxiety states with tachycardia, insomnia, etc. and in all disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization. Actions: Oil infusion ● Neuro: antalgic, antimyalgic, antineuralgic, antispasmodic, spasmolytic Actions: Other galenic forms ●
Somatotropic Central: PL Inhibit PL activity, favoring plants with tropism for the intestines44, 45 ● ●
Fragaria vesca Poterium sanguisorba
● ●
Endo: ● Somatotropic: hyperglycemant (reduces the insulin activity at the level of cell) ● Posterior pituitary: oxytocic Immune: reduces histamine release from platelets CV: bathmotrope negative, strongly chronotrope negative, dromotrope negative, inotrope positive, facilitates coronary circulation, coronary vasodilator
TABLE 11.9 Overview of treatment of terrain of Crohn’s disease by polyvalent action of key medicinal plants Medicinal plant
Corticogonado
Gonado-thyro
Thyro-somato
Poterium sanguisorba Fragaria vesca
•
Salvia sclarea
•
Somato-cortico
Somato-gonado
Thyro-cortico
Other
• indirect
• indirect
Astringent, antihemorrhagic Antiseptic
•
•
Astringent, antihemorrhagic Antimicrobial Hepatobiliary-pancreatic support Astringent Antimicrobial
Avena sativa
•
Exocrine pancreas
Lithospermum officinale
•
• indirect
Lycopus europaeus
•
• indirect
Leonurus cardiaca
•
•a
Cortico-gonado, corticotropic-gonadotropic; Gonado-thyro, gonadotropic-thyrotropic; Thyro-somato, thyrotropic-somatotropic; Somato-gonado, somatotropic-gonadotropic. a
Reduces fixation of cortisol.
Inflammatory bowel diseases Chapter | 11 253
•
254 The Theory of Endobiogeny
●
● ●
HEME: anticoagulant, antiecchymotic, eutrophic, hemostatic ANS: sympatholytic GI: hepatoprotective49
Use: hyperthyroid conditions with low insulin resistance, anxiety with insomnia, diurnal chronic fatigue and recurrent hypoglycemia, allergic diseases, cardiovascular disease, chronic fatigue, any disorder of inflammation rooted in a hyperinsulinism with somatotropic desynchronization. Cautions: cardiotoxic and hallucinogenic at high doses, can diminish the activity of antihypotensive and anticoagulant medications. Avoid during pregnancy and nursing
Malva sylvestris (Mallow) 44, 45
Parts used: flower Galenic: MT, MS, bulk herb Summary: all disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially recurrent infections and genitourinary disorders. Actions: Immune: antiinflammatory: digestive and pulmonary tropisms. CV: decongestant: tropisms: ear, nose, throat, pelvic, urinary. ID: antiinfectious: tropisms: ear, nose, throat, lungs. GI: emollient, antigastritic, laxative, anticolitic. Endo: somatotropic: hyperglycemiant (reduces effects of insulin on cell; increases insulin resistance). Use: Any disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially where inflammation has led to passive congestion with impaired drainage, GI: UC, small intestinal dysbiosis, ID: recurrent or prolonged bronchitis—especially dry, GU: pelvic congestion states: PMS, menorrhagia, menometrorrhagia, prostatitis, prostatic adenomas where inflammation plays a more prominent role.
Arnica vs mallow Arnica and mallow are interchangeable with respect to their actions on insulin activity. However, they are not equivalent. Arnica’s spheres of influence are primarily CNS and heart, especially in a person with a personality trait of anxiety. Malva’s spheres of influence are chest, abdomen, and pelvis, especially where inflammation of the mucosa is implicated in the disorder.
● ●
Intestines: support cicatrization of mucosal tissue and tonification of mucosa44, 45 ● ● ● ● ●
Medicinal plants ●
● ● ●
● ●
Alchemilla vulgaris Carduus marianus Agrimonia eupatoria Plantago major Pancreas: support exocrine function44, 45
●
Avena sativa
Maintain central inhibition of endocrine activity, especially FSH and TSH Hepato-pancreatic drainage Re-equilibrate enteric flora Pediatric Crohn: ensure good mineralization of bones and adequate vertical growth and weight gain 31 ● Vitamin D 2000–5000 IU per day in combination with calcium and magnesium and trace boron, vanadium, and phosphorous. ● Bone mineralization tincture: Sequoia gigantea GM 60 mL, Abies pectinata GM 60 mL, Rubus fruticosus GM 60 mL, Betula alba GM 60 mL: 3–4 mL twice per day ● Bone mineralization dry extract: Equisetum arvense 1 capsule twice per day
Sample treatment ● ●
●
●
●
Fragaria vesca Lamium album Plantago major Poterium sanguisorba Green Illite clay
Treatment: Management of the terrain
Drainage Liver: ensure good hepatic drainage44, 45 ●
Plantago major Digestive enzymes
Vitamin D 5000 IU in AM with calcium and magnesium Illite clay 1 tbsp in evenings before bed—soak all day in a tisane of Anthemis nobilis tisane: 1 heaping teaspoon of flowering tops steeped 15–20 min in 200 mL water. Strain and add to clay, mix well, let sit all day. Mix again in evening before bed and consume. ANS-cortico-somato-intestine: Matricaria recutita MT 60 mL, Poterium sanguisorba MT 40 mL, Fragaria vesca MT 60 mL, Malva sylvestris MT 80 mL, Lavandula angustifolia EO 4 mL, Dose: 3 mL TID before meals Gonado-thyrotropic-pancreas: Lycopus europaeus MT, Borago officinalis MT, Angelica archangelica MT, Agrimonia eupatoria MT, Eucalyptus globulus EO 2.5 mL, Cupressus sempervirens EO 1.5 mL, Dose: 3 mL TID before meals
Diet ● ● ●
Pancreas sparing diet Vegetarian or pescatarian diet in general Fermented foods
Inflammatory bowel diseases Chapter | 11 255
Lifestyle ● ●
Regular aerobic exercise, de-stressing techniques Pediatric Crohn’s: be sure to address psychosocial issues related to body image, altered lifestyle, and compliance with treatment regimen
Case study in Crohn’s flare-up and treatment We present the case of a 14-year-old boy with CD who underwent a major flare-up in part due to noncompliance. We follow his recovery from critical to suppressed critical to remission terrain. He was diagnosed at 11.4 years. His CD was under management by a pediatric gastroenterologist, who started him on adalimumab. The family had a long tradition of use of medicinal plants and was referred to our practice for management. The primary gastroenterologist was open to collaboration with us. In addition to adalimumab, he was started on a decoction, tisane, clay, and vitamin D. The family stopped adalimumab after 9 months—1 year before flare-up and did not inform the gastroenterologist. They stopped the Endobiogenic treatments 6 months before flare-up and had not informed us of this. He had been scheduled for biology of functions blood drawn for routine Endobiogenic follow-up. The symptoms of CD flareup started hours after blood drawn, resulting in hospitalization. After stabilization, he was discharged home on adalimumab once again. His Endobiogenic treatment was as follows: ●
Adaptation decoction of Eleutherococcus senticosus root 1 tbsp decocted in 4 cups of water for 15 min. This decoction was used to steep 2 tbsp of the following tisane for 8–10 min
TABLE 11.10 Neuro-corticotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
●
● ●
Cortico-gonado-enteric tisane of Lamium album, Poterium sanguisorba, Fragaria vesca, and Inula helenium equal parts Vitamin D 10,000 IU in the morning Calcium-magnesium supplement
Tables 11.10–11.14 demonstrate the recovery of his terrain over a 12-month period of time from critical to remission terrain. The neuro-corticotropic activity (Table 11.10), most susceptible to acute changes, also showed the clearest return to remission by 8 months and more so by 1 year after his flare-up. The gonadotropic axis (Table 11.11) is perhaps the most complex to interpret for two reasons. First, it contains the SFI, which is the hyper-FSH response. Second, this boy was in puberty and at an age where this axis is the most implicated in the development of secondary sexual characteristics and increases tissue mass in general. In general, the patient experienced a favorable correction of central and peripheral gonadotropic activity by 8 months postflare-up. This was probably part of the process of recovery toward restitutio ad integrum. However, 1 year on, the terrain showed the precritical imbalance of slightly elevated FSH activity due to insufficient estrogen activity and an appeal to LH which is also elevated. In the biology of functions, the FSH to LH indexes should have a ratio of approximately 2:1. One notes that while both are elevated in the critical terrain. FSH is 10-fold more elevated than LH, supporting the notion of the SFI being FSH and a graver increase in its activity in the critical terrain drives a number of key aspects of the pathophysiology.
256 The Theory of Endobiogeny
TABLE 11.11 Gonadotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
TABLE 11.12 Thyrotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
The thyrotropic axis and immune function (Table 11.12), is yoked along with the corticotropic axis to alpha-sympathetic activity. While not deterministically linked, they are interrelated and integrated. We note a similar and clear improvement in thyrotropic function and immunity by 1-year postflare-up. The somatotropic axis (Table 11.13), while showing improvement overtime, has indexes with the greatest degree of derangement away from the normal values. This is not surprising since CD is a structuro-functional disorder. As with the gonadotropic axis, since this adolescent was in puberty, there were fluctuations in GH growth score activity. First, we note it to be elevated as a compensatory response to the injury to the colon. Then, 1 year after the flare-up, it is low again, representing a fundamental elevation of PL and alpha delaying GH timing.
The psychological profile of CD is not well understood. We are not aware of specific, validated psychotherapeutic interventions. We did offer advice to the family and supported a more communicative style between the patient and his father. The mother and patient already had a very open style of communication. While the two indexes we have discussed were less severe 1 year on than they were during the flare-up, they were worse than they were at 8 months postflare-up (Table 11.14). In effect, we concluded that at the psychological level, the patient came out of a remission into a suppressed critical phase. Fortunately, since the physiologic terrain was sufficiently improved, we did not consider the patient to be at risk of a further flare-up as long as he stayed on his treatments.
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TABLE 11.13 Somatotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
TABLE 11.14 Psychological indexes related to Crohn’s disease
High low values presented in red/blue respectively.
Ulcerative colitis Introduction UC is a chronic, recurrent inflammatory bowel disorder of the left distal descending and rectosigmoid colon.2, 14 It is an ulcerative disease that affects the superficial mucosal layer of the distal colon. In contrast, CD affects all layers of the bowel. According to the theory of Endobiogeny, UC is a functional disorder of adaptation at the level of the distal colon, where CD is a structuro-functional disorder of intestinal integrity. With regard to UC, we make three observations: 1. Chronicity implicates a SFI unable to resolve a physiologic demand 2. Recurrence implicates disadaptation each time the organism faces an aggression 3. Localization to the distal colon indicates a functional disadaptation of cortico-somatotropic activity (ACTH in adaptation, GH for tissue repair) It can be concluded that from the perspective of Endobiogeny, CD and UC are not on a “spectrum” of IBD with respect to the fundamental elements of precritical terrain, SFI and hence the fullness of the genetic and epigenetic
heritage. They do share phenotypic expression of inflammation and mucosal ulceration and hence symptomatic pharmacologic treatment will have commonalities. If one wishes to treat beyond suppression of symptoms, if one wishes to prevent the onset of disease in those at risk or truly bring the patient into remission, the distinction in the terrain must be noted, respected, and addressed in the long-term treatment.
Epidemiology and risk factors Genetic Family history is associated with higher risk of disease.1, 2
Immunity The immune system is dysregulated with autoimmune tendency. One finds dysbiosis with hyperimmune response to noncommensal organisms, with an increase in anaerobic sulfate-reducing bacteria (oxidize hydrogen [H2] and reduce sulfates [SO 4 2− ] from decaying organic material). This increases the general inflammatory terrain of the intestines.50 According to the theory of Endobiogeny, dysbiosis is not causative but predilecting and itself a downstream event of immune dysregulation and the precritical terrain.
258 The Theory of Endobiogeny
Diet Consumption of dairy products is associated with UC exacerbation. Again, this needs to be seen in the light of the genetic inheritance and dysbiosis.3
Nutritional Vitamin A regulates T-helper cell differentiation. Patients with UC have lower levels of vitamins A than controls.51, 52 Supplementation may improve the state of immune dysregulation and clinical symptoms such as blood in stool.51
Psychological UC is a disorder of adaptability and adaptation. The perception of stress more than any “objective” evaluation of stress is key in the risk of flare-ups.38, 39, 53 UC patients suffer from a higher incidence than the general population of anxiety and depression. Depression, according to the theory of Endobiogeny, is also a disorder of dysadaptability. Both disorders share commonalities. In the precritical terrain, both are vagotonics with dysfunction of the exocrine pancreas (Fig. 11.8). In the critical terrain is exaggerated alpha- sympathetic response and overfunctioning corticotropic axis (Fig. 11.9). Psychological and psychosocial stressors are associated with UC e xacerbation. According to a systematic review of trials to date, psychotherapy is
helpful in improving subjective assessment of mood, and psychopharmacology therapy improves both mood and symptoms of UC.54
Comorbidities Adults and children with IBD have a higher incidence than age-matched controls of autoimmune and other inflammatory conditions.55–57 Incidence risk is twofold, commensurate to severity of disease and inversely related to use of salicylates in therapy.57 Most commonly occurring are uveitis and sclerosing cholangitis. Other manifestations include ankylosing spondylitis, spondyloarthropathies, pyoderma gangrenosum, pleuritis, erythema nodosum, and multiple sclerosis. Chronic UC is associated with a 2.4-fold increased risk in colon cancer.58
Epidemiology Similar to CD with respect to age, sex, geographic clime, and industrialization. UC tends to occur more commonly than CD, up to 3 times more often.15
Pathophysiology Precritical terrain UC occurs in vagotonic individuals (Fig. 11.8). The SFI is a general insufficiency of exocrine pancreatic enzymes. This
FIG. 11.8 Precritical terrain of ulcerative colitis. In vagotonic patients, there is an oversolicitation of the exocrine pancreas for general augmentation of digestive enzymes (black arrow). The response is insufficient (gray arrow), which solicits a reactive appeal (broken green arrow) which puts the patient in a hyperfunctioning parasympathetic state. This solicits a rise in alpha-sympathetic (black arrow) to match its tone. Alpha (αΣ) makes an appeal to beta-sympathetic (βΣ) which is delayed or blocked (gray broken arrow). This has two consequences: (1) blocked adaptation, (2) spasmophilia. Alpha also stimulates ACTH, and ACTH’s stimulation of the adrenal cortex is insufficient as well (broken gray arrow). This, along with a level of peripheral thyroid activity not sufficiently adaptated to alpha-sympathetic tone results in a total sympathetico-cortico-thyrotropic incompetence to adapt to future aggressions. The rising alpha tone that attempts to (unsuccessfully) readapt beta and adrenal cortex activity leads to a further reactive rise in parasympathetic tone (broken green arrow). (© 2015 Systems Biology Research Group.)
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FIG. 11.9 Critical terrain of ulcerative colitis. It can be understood in three parts. The first is autonomic. Hyperfunctioning alpha (top center) stimulates a hyperfunctioning beta (adrenaline, top left), which favors hyperglycemia and inflammation. The second is the relaunching of the catabolic axes (center), again, by alpha. Central functioning exceeds peripheral gland response (gray, small print). The third is a disruption of the alpha-prolactin (PL)-growth hormone (GH) trépied (top right), discussed in Fig. 11.5. This participates in ulceration of distal colon mucosa. (© 2015 Systems Biology Research Group.)
entrains a hypervagal state which in turn solicits a reactive hypersympathetic response. This installs a spasmophilia, resulting in blocked adaptation. The adaptation dysfunction is rooted in dysfunctional yoking of alpha to the corticothyrotropic response. There is a hyper-ACTH response with insufficient adrenal cortex response. In the thyrotropic axis, peripheral thyroid activity is weak. In summary, the precritical terrain is a blocked neuroendocrine adaptation response with exocrine pancreatic insufficiency.
Aggressor and critical terrain: Ulcerative, hemorrhagic colitis
TABLE 11.15 ANS changes in the precritical and critical terrains of ulcerative colitis ANS
Precritial
Critical terrain
πΣ
++
++
αΣ
++
++++
βΣ
Blocked (spasmophilia)
+++
αΣ, alpha-sympathetic; βΣ, beta sympathetic; πΣ, parasympathetic. + Refers to the intensity of hyperfunctioning, the more pluses, the greater the hyperfunctioning.
Sympathetic In the face of some type of aggressors: a perceived stressor, an exaggerated response to a true aggressor,38, 39, 53 change of seasons, infection, diet, etc., the sympathetic nervous system is the initiating factor of a hemorrhagic UC. Ultimately, it is all three branches of the autonomic nervous system that are entrained into a hyperresponse in the face of an aggression. Table 11.15 summarizes the difference in the ANS between the precritical and critical terrains. Similar to CD, global sympathetic tone is elevated and far exceeds the parasympathetic response.
Endocrine response The endocrine response is detailed below and summarized in Fig. 11.9.
Corticotropic: First axis of solicitation 1. Central: ACTH in hyperfunctioning in adaptation: a. ACTH ≫ glucocorticoids, with adaptive cortisol blocking anabolism
b. Hypermetabolism of rectosigmoid colon to augment absorption of water and electrolytes for adaptation 2. Peripheral: insufficient adrenal cortex a. Cortisol > global adrenal cortex (relative): blocked anabolism in the face of mucosa proliferates → ulceration → hemorrhage
Thyrotropic: Second axis of solicitation 1. Central a. TRH hyperfunctioning: relaunches PL b. TSH hyperfunctioning: Expansion of cell membranes beyond anabolic capacity due to cortisol’s blockage of anabolism 2. Peripheral a. Peripheral thyroid insufficiency: absolute or relative to central functioning → insufficient lipid incorporation into growing and repairing cells → hemorrhage, blocked wound healing
260 The Theory of Endobiogeny
Somatotropic: Third axis of solicitation
Physical examination
The dysfunction of the alpha-PL-GH trépied is similar to that discussed in CD.
Abdominal exam similar to Crohn’s with respect to colon, liver, and pancreas; greater likelihood of pain on palpation of the distal colon from the splenic flexure distal to the rectosigmoid region
1. Central a. PL hyperfunctioning → i. Hyperinsulinism → inflammation of mucosa ii. ACTH relaunching → prolonged hypermetabolism of distal colon iii. Abscess formation favored iv. GH delay → impaired wound healing b. GH delay i. Insufficient insulin resistance → desynchronized nutrient entry in relationship to insulin → impaired cicatrization → ulceration, hemorrhage 2. Peripheral a. Hyperinsulinism proceeding GH with low insulin resistance → i. Elevated free radicals → inflammation → necrosis ii. Delayed wound healing iii. Fistula formation
Tissue pathology On biopsy of the distal colon, one notes a hyperimmune pattern with chronic inflammation. Cytotoxic T cells infiltrate the epithelium of colon. There are B-lymphocytes and increased IgG and IgE. Antibodies to the colon, smooth muscle, and cytoskeleton have been documented. Abscesses, granulomatous tissue, and pseudo-polyps may be present.59
Anatomical distribution of UC The most common areas of expression of UC are the anal verge, rectum, and rectosigmoid segments. Less common is pancolitis and least common is ileocecal involvement.60
Clinical presentation Similar to the colorectal symptoms associated with CD.
Laboratory studies: Critical terrain It is identical to that of CD with respect to CRP, fecal calprotectin, stool lactoferrin, and biology of function labs. Fecal calprotectin is the most sensitive and specific test in IBD in general of those listed, but is more targeted for UC than CD.25
Biology of functions: Critical terrain A similar consideration will be made in evaluating UC using the biology of functions as with CD. We start with a series of criteria to determine the critical vs suppressed critical vs precritical terrain (Table 11.16). It is important to note that as a functional disorder of adaptation, it is the adaptation indexes that will be the area of focus. And, most typically, it is the adaptation indexes that will be more deranged than those of structure. The first group of indexes is grouped together as “neuro- corticotropic” because of the implication of sympathetic activation of the corticotropic axis (Table 11.17). In order to discuss terrain, we introduce new indexes not previously discussed in other chapters or with respect to CD. The immediate adaptation index witnesses the relative role of the peripheral adrenal gland in the immediate adaptation syndrome. It will be elevated in both critical terrains. The CRH index evaluates the central activity of CRH. The greater the index, the greater the intensity of solicitation of the corticotropic axis is, and by extension, the less effective cortisol and aldosterone are in their negative feedback capacity. Treatment favors alpha-sympatholytics and central oxytocics such as Arnica montana or Taraxacum officinale to downregulate the amplifying role of vasopressin in ACTH relaunching and by extension vasopressin inhibitors (e.g., Taraxacum officinale).44, 45 Thus, one must also
TABLE 11.16 Criteria of indexes deranged per stage of terrain of ulcerative colitis Axis
Critical
Suppressed critical
Precritical
Neuro-corticotropic
>6/11
3–6/11
<4/11
Thyrotropic-immunity
3–5/5
2–4/5
<3/5
Somatotropic
>6/9
4–7/9
<4/9
Psychological
4–5/5
2–3/5
1–2/5
Total indexes deranged
21–30
11–20
8–10
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TABLE 11.17 Neuro-corticotropic terrains of ulcerative colitis Axis
Index
Critical terrain
Suppressed critical
Remission
ANS
Starter
↑↑ or ↓↓
↑ or ↓
Normal
Neuro-corticotropic
Immediate adaptation
↑↑
↑
Normal
Adaptation entrainment score adj.
↑↑
↑
Normal
Oxytocin
↓↓
↓
Normal
Vasopressin corrected
↑↑
↑ or ↓
Varies
CRH
↑↑
↑
Varies
ACTH
↑↑
↑ or ↓
Varies
Cortisol
↑↑
↑
Normal or ↓
Adaptation permissivity of the adrenal cortex
↑↑, may be negative
↑
Normal
Aldosterone comparative
↑↑, may be negative
↑, may be negative
Normal or slightly elevated
Adrenal yield
↑↑
↑
Normal
Corticotropic
evaluate the oxytocin index, which expresses the central effects of oxytocin. The index tends to be low in UC, which represents a dysfunction in posterior pituitary regulation of the corticotropic axis’ response to an aggression. This has not been well studied, however, peripheral use of oxytocin is antiinflammatory in experimental models of colitis, and may also be insufficient in UC patients during a flare-up.61 The lower the oxytocin index, the greater the difficulty in managing stress and the greater the tendency is to forming memories of stressful events. This last aspect of the index’s interpretation is germane to the psychological profile of the UC patient according to our experience. Finally, we introduce the adrenal yield index. It witnesses the relative efficiency of adrenal function in adaptation in relationship to the degree of stimulation. The higher the yield, the more exaggerated the output of the adrenal cortex will be in relationship to that of demand. Elevated cortisol is correlated with chronic psychosocial stress, and elevated cortisol is linked to dysfunction of the intestinal tract.39 In UC, the demand is elevated from the sympathetic nervous system, CRH, vasopressin, and ACTH. In addition, the feedback on central factors by peripheral corticotropic factors is impaired. It should be noted that the leukocyte and platelet mobilization indexes are not as reliable to evaluate alpha-sympathetic activity as other indexes. Thus, only the starter index is focused on here. That is because the global expression of sympathetic activity originating in the central, cognitive perception of stress is more relevant here than the solicitation of the splanchnic bed.
The activity of the thyrotropic axis is presented in Table 11.18. The thyrotropic axis is largely reactive and implicated in two ways. The first is yoking in the general catabolic response to an aggression. This is primarily expressed in the thyroid relaunching indexes and the thyroid index, and vitamin D adaptation index. And as with CD, when elevated, it favors treatment with high dose, short-term vitamin D.31 The other is in somatotropic desynchronization, most closely linked to the low serum TSH in both critical terrains. It is hard to define precisely a low TSH, because it must be
TABLE 11.18 Thyrotropic terrains of ulcerative colitis Index
Critical terrain
Suppressed critical
Remission
TSH serum
↓↓
↓
Normal
Thyroid relaunching
↑↑
↑
Normal to slightly elevated
Thyroid relaunching corrected
↑↑↑
↑↑
Normal to slightly elevated
Thyroid
↑↑↑
↑↑ or ↓↓
Normal to slightly low
Vitamin D adaptation index
↓, negative or both
Varies
Varies
262 The Theory of Endobiogeny
considered in relationship to osteocalcin and the cortisol index, amongst others. The higher the cortisol index, the more likely that even a low-normal TSH will exacerbate suppression of GH and thus somatotropic desynchronization. In general, we can say that an optimal TSH in healthy patients will be 1–4, with 0.51–0.99 considered low, and values less than or equal to 0.5 as very low. The somatotropic axis and its relationship to the corticotropic axis are important for two reasons. The first is in turning the loops and prolonging the corticotropic response to an aggression. The second is delayed wound healing and blocked anabolism (Table 11.19) The alpha-GH-PL trépied was previously discussed and can be observed in the indexes of the biology of functions: low Prolactin and low GH growth score index. Cellular architecture is disrupted, as with CD. With respect to autophagy, it is disrupted as well.33, 34 However, the origin of it is system dysfunction, not intrinsic cellular dysfunction. This is reflected in the autophagy 2 index. It evaluates the relative risk of insufficient cellular autophagy in the face of oversolicited organotissular metabolism imposed by global metabolic demands. An elevated index, as one notes in UC, favors the use of intermittent fasting for 1–3 days during the critical phase of hemorrhagic colitis. Observational studies in UC, and general observations of improvement in chronic, degenerative disorders support this approach.62, 63 More studies in the IBD population needs to be conducted, especially when the patient is in the critical terrain. One also sees similar disruptions in insulin and insulin resistance and hence a hyperoxidative state with elevated free radicals. Thus, free radical scavengers such as α-lipoic acid can also be considered during the acute phases of the critical terrain or to help abort hemorrhage with prodromic expressions of dysadaptation.37 Naturally, necrosis will be elevated.
One may also evaluate the psychological states in the UC patient using the biology of functions, as one does in CD (Table 11.7). UC psychological profile is similar to CD with a few exceptions. In UC, again, one evaluates the function values (Table 11.20). In the psychological indexes, this represents the relationship of these patients with nonfamiliar people: colleagues, classmates, and the general public. The indexes tend to be less elevated and less likely to be negative, as opposed to CD. In addition, it is the frustration score 2 rather than the frustration index that is elevated. The frustration score 2 evaluates the tendency to feel frustrated due to a reactivity of the organism lying within the thyrotropic axis, which participates in intense but fugacious expressions of negative imagination and worry. When the index is elevated it favors a phlegmatic personality type. Our characterization of the UC psychological typology has not been elucidated in the literature. What has been established is that perception of stressors and the patient’s belief in their capability to respond are relevant, especially if they are chronic stressors.38, 39, 53 One need not be a psychotherapist to appreciate the importance of evaluating chronic psychosocial stressors in IBD patients. Perceived stress and its physiologic response impair wound healing and perpetuate a low-grade chronic stress response that fragilizes the buffering capacity and increases the risk of relapse when patients are in remission.39, 53, 64 The IBD patient feels unloved, reflected in the closed off from receiving index. There is an underlying sense of emotional vulnerability, reflected in the permeability adjusted index. The higher the index, the greater the feeling of emotional vulnerability. It is elevated during a flare-up and may persist even in remission, but certainly in the suppressed critical terrain. In fact, from remission to a fragilization and risk of flare-up, one is likely to see this index rise, even before the onset of clinical symptoms. From the feeling of
TABLE 11.19 Somatotropic terrains of ulcerative colitis Axis
Index
Critical terrain
Suppressed Critical
Remission
Somatotropic
Prolactin
↓↓↓
↓↓
Normal
GH growth score
↓↓↓
↓↓
Normal
Somatostatin
↓↓
↓
Normal
Insulin
↑↑↑
Varies
Normal
Insulin resistance
↓↓
Varies, often low
Normal
Expansivity #2
↑↑
Varies
Normal
Redox
↑↑ to ↑↑↑
↑ to ↑↑
Normal
Necrosis corrected
↑↑↑
↑↑
Normal
Autophagy 2
↑↑↑
↑↑
Normal
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TABLE 11.20 Psychological indexes related to ulcerative colitis Critical terrain
Suppressed critical
Remission
Closed off from receiving
↑↑
↑
Normal
Permeability adjusted
↑↑↑
↑↑
Normal to ↑
Traumatic memory
↑↑
↑
Normal
Acceptancecontentment
↓↓
↓
Slightly ↓, normal, or ↑
Frustration score 2
↑↑
↑
Slightly ↑ to normal
Index
not being loved and the feelings of emotional vulnerability, one notes that UC patients have traumatic rumination during their crisis, reflected in the traumatic memory index. UC patients are generally discontent with their situation, reflected in the acceptance-contentment index, which when low indicates this feeling of discontent and searching from answers that one cannot find. This tends to persist, even in the precritical terrain. If the patient has an elevated index in the precritical terrain, it indicates that they tend to rationalize their discontent. This increases the risk of a flare-up even more than a slightly low score. With this comes a great sense of frustration with themselves and their situation, reflected in the frustration score 2 (as opposed to the frustration index in CD). Finally, UC patients tend to be critical of others, sometimes projecting their own internal frustration. This is reflected in the critical tendency score, which evaluates the tendency to be critical against oneself and other people.
The gonadotropic axis (Table 11.21) is not part of the assessment of the critical terrain of UC per se except for the genito-thyroid index, which is elevated. It is a nonspecific indicator of hyperimmune, pro-inflammatory terrain. However, we present values to demonstrate how distinct the terrains of CD and UC are. NB: normal values differ for adolescents compared to adults.
Treatment: General considerations according to an endobiogenic reflection The Endobiogenic approach to the treatment of hemorrhagic UC is similar to that of CD: treat symptomatically at first, alter diet, and then address the issues of terrain. The same considerations of appropriateness of treatment and severity of presentation pertain here as in the discussion of CD. Considering the nature of UC, there will be a greater Endobiogenic emphasis on managing the autonomic nervous system, corticotropic and somatotropic activity than in CD.
Treatment: Standard of care The same considerations apply to the role of pharmaceutical treatments, their advantages, and limitations. The standard approach to UC is to characterize severity of the flare-up by the number of bloody stools per day, and the presence of one or more of the following: fever, anemia, tachycardia, elevated markers of inflammation.60 The general progression of stepped-up therapy is also similar. There are some particularities to UC. Mild disease is defined colitis limited to the rectum, with less than 6 hemorrhagic stools per day. Mesalamine suppository is more effective than oral dosing. If the colitis is mild but includes more proximal segments of the intestine, lower-dose oral mesalamine is favored.2 Oral steroids will be reserved for treatment failure of mesalamine.
TABLE 11.21 Gonadotropic terrains of ulcerative colitis Axis
Index
Critical terrain
Suppressed critical
Remission
Gonadotropic
LH
↓↓
↓
Normal
FSH
↓↓
↓
Normal
Organotissular estrogen yield
↑↑
↑
Normal
Estrogen index
↑↑
↑
Normal
Estrogen index corrected
↑↑
↑
Normal
Genital androgens
↑↑
↑
Normal
Genito-thyroid
↑↑
↑
Normal
Gonado-thyrotropic
264 The Theory of Endobiogeny
Severe disease is defined as 6 or more bloody stools per day with fever, anemia, tachycardia, and/or elevated inflammatory markers elevated, such as fecal calprotectin, CRP, etc. Current treatment standards include starting with intravenous glucocorticoids, high dose. The other immunosuppressive and biological agents discussed in CD can also be used based on various considerations.
TABLE 11.22 Sources of vitamin A Food
Vitamin A per 1 cup
Sweet potato
1900
Carrots
1000
Spinach
940
Kale
885
Mustard greens
865
Collard greens
770
Squash
535
ANS
Cantaloupe
270
Reduce global autonomic activity, favoring plants that are spasmolytic and/or with an intestinal tropism (cf. Crohn’s disease). In addition, the following medicinal plants are quite efficient in UC:
Papaya
130
Apricots
33
Symptomatic treatment: An endobiogenic approach Cf. Crohn’s disease.
● ● ●
Passiflora incarnata Melissa officinalis Ilex acquafolium GM
Diet and lifestyle during a crisis ●
●
Diet: avoid dairy products; high purine protein, low fat, low fiber Lifestyle: calming activities: meditation, breath work, yoga, Tai chi, prayer, etc.
Treatment of terrain: An endobiogenic approach
●
We recommend 2000–4000 IU per day for the first 2 weeks of recovery is recommended, followed by 1000–4000 IU per day based on preference of the patient for these types of foods Vitamin E is best obtained through diet as well (Table 11.23). For the first 1–2 weeks of recovery, encourage 300–400 mg of vitamin E from the diet
Somatotropic Cf. Crohn’s disease.
Drainage
Corticotropic
Cf. Crohn’s disease
Support adrenal activity while reducing ACTH (cf. Crohn’s disease).
1. Liver: ensure good hepatic drainage 2. Pancreas: support exocrine function 3. Intestines and colon: support cicatrization of mucosal tissue and tonification of mucosa
Thyrotropic Reduce central hyperthyroidism (cf. Crohn’s disease) Modulate peripheral thyroid terrain according to the Endobiogenic state of the patient and support PTH ● ●
● ●
●
Avena sativa Selenium oligo (also reduces inflammation, supports hepatic detoxification activity) Calcium (chronic use) Vitamin D 5000–10,000 IU in the morning, reduced to 3000–4000 maintenance or according to the Endobiogenic terrain and quality of vitamin D’s management of adaptation response Vitamin A is best obtained through diet (Table 11.22). Vegetables are the richest sources. Some fruits p rovide moderate amounts of vitamin A. While animal sources also provide retinol, they are not recommended in UC.
TABLE 11.23 Sources and servings of vitamin E Source
Per 100 g serving (mg)
Wheat germ oil
150
Almond oil
95
Canola oil
44
Sunflower oil
41
Hazelnuts
20
Almonds
15
Olive oil
14
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Treatment: After hemorrhagic flare-up Medicinal plants ● ● ● ●
Improve adaptability of the organism Maintain central inhibition ACTH, TRH, TSH, PL Hepatopancreatic drainage Re-equilibrate enteric flora
Diet ●
● ●
Pancreas sparing diet, in particular avoiding dairy products Vegetarian or pescatarian diet Fermented foods
Sample treatment ●
●
● ●
●
Vegetarian diet emphasizing foods rich in vitamins A and E (Tables 11.22 and 11.23) Illite clay 1 tbsp + 1 drop Carum carvi (caraway) EO + 1 drop Mentha piperita EO every 4 h prepared with Juglans regia leaf tisane until bloody diarrhea resolved ● 200 mL tisane of Juglans regia leaf tisane: 1 heaping tsp. Juglans regia (walnut) leaf: steep 8 min in hot water; strain ● Let clay mixture sit 15 min or longer, mix again, then consume Vitamin D 5000 IU in AM Somatotropic: astringent, antihemorrhagic cicatrizant tincture: Lamium album MT 30 mL, Poterium sanguisorba MT 30 mL, Malva sylvestris MT 30 mL, Hamamelis virginiana MT 30 mL: 3 mL q8 a.m., noon, 4 p.m., 8 p.m. until bleeding has resolved ANS-cortico-thyrotropic tincture: Passiflora incarnata MT, 60 mL, Sequoia gigantea GM 60 mL, Zea mays GM 60 mL, Viburnum lantana GM 60 mL + eucalyptus EO 3.5 mL, clove EO 0.5 mL: 4 mL twice per day
Conclusions Crohn’s disease (CD) and ulcerative colitis (UC) are both classified as inflammatory bowel disorders. According to the theory of Endobiogeny, they are not on a spectrum of the same general type of disorder, as they differ in their structural factors of initiation (SFI). CD is a structuro-functional disorder rooted in a faulty FSH-estrogen relationship and an impaired adaptation response due to an exhausted parathyroid gland. It is a disorder of the intrinsic ability of the bowel to maintain its integrity in the face of an aggression. The response is exaggerated and brutal, resulting in ulceration and delayed wound healing. The ulceration in CD is deeper than UC, and all areas from mouth to anus may be affected.
UC is a functional disorder rooted in a faulty autonomiccorticotropic relationship. It is a systemic disorder that happens to be expressed at the level of the bowel because the bowel is a metabolically active tissue because it constantly faces aggressions in the form or diet and other genetic variables that fragilize the intestines. The level of ulceration is superficial and is limited to the colon, and most often to the distal rectosigmoid region and anus. The symptomatic treatment of both types of IBD is similar, be it pharmaceutical or nonpharmaceutical. It involves reducing inflammation, hyperimmunity and the adaptation response, and stimulating bowel restoration. The treatment in remission and goals for treatment of the precritical terrain vary as they have unique origins from the perspective of Endobiogeny. In both conditions, the Endobiogenist should pay careful attention to the psychological component of the patient and their experience of stressors and the disease itself, as it has been shown to play a role in the severity and course of disease.
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Inflammatory bowel diseases Introduction: Adaptive role of the intestines based on an endobiogenic reflection This chapter discusses an Endobiogenic approach to two common inflammatory bowel diseases (IBDs): Crohn’s disease (CD) and ulcerative colitis (UC) also referred to as recto-hemorrhagic colitis. IBDs are disorders expressed in genetically susceptible individuals,1, 2 when the intestines are unable to adapt to local or systemic adaptation. Because the disorder remains latent across generations, across space, and time, one must look beyond genetic mechanisms to include epigenetic factors and adaptability in order to understand the Endobiogenic cause of disease.2, 3 One must place the intestines within the context of their intrinsic function and role in regional and global adaptation. Current thinking in the scientific literature views IBD as a disorder of dismicrobialism in those with a genetic susceptibility.1, 2, 4 The genetic foundation is undeniable. However, we find shortcomings in this approach that have led us to a very different approach to understanding IBD. For example, the risk of developing CD is 50% amongst monozygotic twins and less than 10% for dizygotic twins, indicating that there is even more than a genetic predisposition at play.1, 2 However, there are more than 160 genetic loci that have been correlated with IBD.2 Even if causation was to be shown, as opposed to association, it would still indicate a multifactorial origin to the expression of IBD, requiring a more nuanced approach to diagnosis and treatment, which is our position, as this chapter will detail. Contemporary models of disease focus on the interaction between the microbiota and the intestines as if they exist within a vacuum. The exact relationship of the changes in the microbiota has not been established.5 It is not clear if it is causative, associated, or the result of other local or systemic imbalances. Even when diet and lifestyle issues are considered, such as smoking, they are seen through a narrow lens of downstream physiology viz. oxidation, inflammation, and transcription mechanisms.2–4 IBD is a disease of the intestines, on this we agree. However, the intestinal tract is completely integrated into the global functioning of the terrain and submitted to neuroendocrine regulation. It The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00011-0 © 2019 Elsevier Inc. All rights reserved.
primarily functions to serve the vital organs and tissues of the organism. Its intrinsic metabolic activity of the intestines is disproportionately small given its mass and weight compared to that of the remainder of the body, especially the brain, heart, and kidneys.6 The approach of Endobiogeny is to contextualize this disease of the intestinal tract to genetic, epigenetic, neuroendocrine, dietary, lifestyle and geographic factors, as well as chronobiologic cycles of genetic programming. The small and large intestines are the conduit and apparatus by whish the entire metaorganism of host + commensal flora obtain nutrients for nourishment (cf. The Theory of Endobiogeny, Volume 2, Chapters 5 and 6). However, as tissue, they have their own intrinsic metabolic requirements. Being subjected to constant threat from external agents and aggressions from fluctuations in pH, chemical moieties, etc., the intestinal epithelium has a high rate of turnover. This makes them susceptible to changes in the balance of metabolic demand to nourishment of the nourishing apparatus. Their primary role is to regulate the absorption of nutrients, discharge of potentially toxic waste, and regulation of fluid according to the global needs of the organism. At all times, the local and global needs must be balanced to avoid a state of nutritional excess or deficiency at either level. The role of the commensal flora must also be considered.1, 4 They aid in digestion for their own benefit, the benefit of their local intestinal host, and the global metaorganism of host + flora. They have their own terrain within the metaterrain, and their own response within the metaresponse of the global organism to aggressions. Thus, the regulation of the regulating capabilities of the intestines is capital and is linked to global neuroendocrine demands. Throughout the intestines are areas rich in receptors for central endocrine hormones that ensure the precise regulation of nutrients and electrolytes related to the production or activity of the endocrine glands that they stimulate. Small intestines: They express the quotidian responsibility of absorption of nutrients according to the exogenous presentation of nutrients and the endogenous demands of the organism.7 Ileocecal zone: It is a transition zone between the evagination from villi in the small intestines and the invagination 237
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of the colon composed of columnar epithelial cells.7 This zone is a key point in structural adaptation with respect to the management of electrolytes, water, and nutrients (Table 11.1). Large intestines: The role of intestines is to absorb water and residual nutrients from stool.8 The colon is rich in endocrine receptors.9–12 Dr Duraffourd, originator of the theory of Endobiogeny, hypothesized that each segment of the colon is rich in central endocrine receptors based on the nutrient requirements of the end organ that it stimulates (Table 11.1). In other words, the central hormone directly stimulates nutrient absorption from the segment rich in its receptors. Or, it upregulates the receptors of its peripheral hormone in that particular segment of the colon, which then alters nutrient reclamation.12 The global manager finely tunes reclamation of key elements of adaptation and buffering capacity during periods
of oversolicitation and hyperfunctioning (Fig. 11.1). For example, adrenocorticotropic hormone (ACTH) solicits the adrenal cortex for aldosterone excretion during adaptation states. Aldosterone retains water and minerals to improve perfusion pressure within general circulation.12 There is an increase in the reuptake of fluid and electrolytes from the rectosigmoid segment of the distal colon in adaptation states.12 The teleology, we posit, is a second source of electrolytes and fluids during a surge in aldosterone’s actions in a manner independent of its renal actions and intake of fluids or minerals from the diet. According to the theory of Endobiogeny, the distribution of IBD within the intestinal tract, from mouth to anus, is a result of their auto-pathogenic axis and by extension the critical Endobiogenic terrain expressed in the face of an aggression. Evaluating the basic function of each segment of the intestinal tract, the colon in particular, allows
TABLE 11.1 Endo-enteric relationships by location, receptor, hormone, and, metabolites Location
Microbiotic metabolism
Metabolites reclaimed
Central receptor
Peripheral hormone
Ileocecal junction
Fermentation: polysaccharides, cellulose, pectins, oligosaccharides carbohydrates → shortchain fatty acids (SCFA), iodine scavenging
Water Electrolytes
ACTH: structural adaptation
Adrenal cortex: aldosterone
Ascending right colon
As above + Muscle fibers, mucous, desquamated cells Lipid hydrolysis
Proteins
FSH
Gonads: estrogens
Hepatic flexure
Bile acids: enterohepatic recycling
Lipids
TRH/TSH
Pancreas: insulin, glucagon Gallbladder
Right transverse colon
Deamination of proteins SCFA Phenols, indoles Lipid fermentation
Proteins
FSH
Gonads: estrogens
Left transverse colon
Lipid fermentation: desaturated fatty acids, sterols
Proteins
LH
Gonads: androgens
Iron, proteins
TSH
Spleno-humoral immunity
Lipids Trace metals
GH Prolactin
Pancreas: insulin; relaunching of second loop of adaptation and augmentation of ACTH
Water Electrolytes
ACTH: functional adaptation
Adrenal cortex: aldosterone
Splenic flexure Descending colon
Recto-sigmoid
Flora putrification Final reduction of nondigested, nonmetabolized material pH neutral
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g astrointestinal tract from oral mucosa to the anus in contract to UC, which affects only the colon.13, 14 The broad distribution of disease reflects the extent of hypersolicitation of all endocrine axes at the level of pituitary disadaptation (cf. below for a discussion of central endocrine receptors and enteric physiology).
Epidemiology and risk factors Geographic Northern sections of Europe and North America have the greatest incidence.15 In cooler areas of the world, there is a greater demand for adaptability during the change of seasons due to the cold. Because of the role of alpha- sympathetic in relaunching seasonal adaptation, it can also relaunch the critical terrain in late or recidivistic CD patients. ● ● ● ●
FIG. 11.1 The Endobiogenic cartography of global-enteric relationships. Central hormones adapt the rate of functioning of reclamation of elements of nutrition and buffering capacity according to the relative level of demand they have placed on their end organs. See Table 11.1 and text for details. (Modified with permission from Duraffourd and Lapraz, unpublished © 2015 Systems Biology Research Group.)
us to link it to endocrine activity and arrive at a rational understanding of localized inflammation, skip lesions and long-segment affliction in patients with IBD.
Crohn’s disease Introduction CD is a chronic, recurrent inflammatory bowel disorder.1, 13 According to the theory of Endobiogeny, the chronicity of the disease implies that there is a structural factor of initiation (SFI) that is unable to resolve a particular physiologic demand of the organism. An SFI is a factor of dysfunction is a genetically derived, disadapted response the organism’s demand for structural maintenance (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). When the organism has difficulty maintaining or adapting some basic elements of cellular or tissular structure, a series of compensatory responses are installed, which creates the precritical terrain. In the face of an aggressor, the critical terrain is expressed and the symptoms of disease become manifest. The recurrent nature of the disorder implies that there is a disadaptation that occurs in the face of an aggression. Thus, CD is a structuro-functional disorder at the level of the intestinal tract—a difficulty maintaining the integrity of the intestines in the face of an intense adaptation demand. CD is an ulcerative disease that affects all layers of the mucosa. It may affect any part of the mucosal lining of the
Northern Europe: 16 per 100,000 North America: 12 per 100,000 people Southern Europe: 8 per 100,000 All other areas: 5 per 100,000
Industrialization, affluence, and diet Industrialized nations have a greater incidence, but this may be because countries of Northern Europe and North American have been industrialized for longer periods of time than other areas of the world, which brings with it an increased consumption of refined and preserved foods. Also, a large percentage of North America claims descent from Northern Europe. As less industrialized countries become more industrialized, the incidence of CD increases.15 Sex Pediatric ● In childhood onset, boys outnumber girls in diagnosis of new-onset CD. We find that this witnesses the role of the hyperandrogenic terrain that solicits a strong folliclestimulating hormone (FSH) response readapt the level of estrogen production Adult ● In adult onset CD, women outnumber men; women are particularly susceptible in our experience with first incidence in gonadopause in the late 30s or early 40s. This witnesses in our opinion, the greater role of FSH in adult females than in adult males in general, and witnesses the hyperfolliculinic response to a drop in estrogens during gonadopause.
Pathophysiology of CD Precritical terrain FSH has two key functions relevant to CD. First, FSH has a preparatory action on the cells.16–18 There are multiple,
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complex actions working at the level of the membrane, nucleus, and other areas of the cell related to transcription and translational modification.16 FSH through its second messengers stimulates growth factors, preparation of cholesterol for conversion into estrogens, upregulation of aromatase enzyme, etc. In general, FSH is known to have extra-gonadal sits of action.18 According to the theory of Endobiogeny, tissue, especially mucosa, become congested during this time in order to augment the amount and duration of exposure of tissue to nutrients. The second action of FSH is its classical vertical stimulation of estrogens. The SFI in CD is an insufficiency of estrogen activity relative to the intestinal requirement for initiation of protein metabolism. The response from FSH is intense due to the threshold of response from the pituitary. Due to an inability of the organism to readapt primary gonadal estrogen production to this level of FSH activity, the FSH response becomes excessive and prolonged (Fig. 11.2). There is an absolute hyper-FSH state and an absolute hyperestrogenism, with FSH >> estrogens. This imbalance in FSHestrogen relationship solicits a parasympathetic response
resulting in a spasmophilia with impaired adaptation arising from exocrine pancreas and parathyroid insufficiency. In our experience, CD patients are vagotonic by nature (Fig. 11.3). The vagus nerve solicits the exocrine pancreas to readapt the level of proteolytic enzyme expression in order to meet the appeal to proteins that FSH makes. The exocrine pancreas, similar to the gonad, is not able to sufficiently response to this appeal. This installs a hypervagal state in the chronic attempt to stimulate the exocrine pancreas. The sympathetic response to the hypervagal state is strong and greater than that of para (red heavy arrow, Fig. 11.3). At the level of metabolism, there is a hypermetabolic state with catabolic predominance thanks to the strong alpha response. In effect, the hypermetabolism brings about a chronic demand for proteins not met due to proteolytic enzyme insufficiency. The catabolic predominance further fragilizes tissue integrity, already congested. The hyperfunctioning sympathetic activity makes an appeal to the parathyroid gland, which becomes exhausted and incompetent in its ability to mobilize calcium for cellular or global adaptation (shown in gray, Fig. 11.3).
FSH
LH
Cortisol
Estrogens
Androgens
Delays anabolis
Protein intake
Protein utilization
Chromosome Nucleus
Impaired adaptation Catabolism > anabolism Proteolytic enzymes Insufficient to demand
Precritical
Disproportional action
Ribosomes Mitochrondnon Golgi apparatus
Delayed action
Endoplastic reticulum
FIG. 11.2 Structural factor of initiation (SFI) in Crohn’s disease. The SFI is a hyperfunctioning FSH, depicted by the heavy black arrow. The precritical terrain (lower left) is one of impaired adaptation in which catabolism exceeds anabolism and there is insufficient proteolytic enzymes to restore tissues (cf. Fig. 11.3 and text). This is the first step in compromising the quality of tissue. The second influence is the generally elevated cortisol activity (upper left) which delays anabolism, further impairing the general regulation of the cell cycle. Estrogen activity is hyperfunctioning, but not relative to the FSH demand. The demand created by estrogens for proteins is not sufficiently adapted (gray box). Estrogens, as is typical, relaunch LH and androgens, which initiate an intense protein utilization (red box) that exceeds the quality of estrogens in protein utilization. This is the final event that impairs the quality of mucosal tissue, resulting in a fragilization of the mucosa. (© 2015 Systems Biology Research Group.)
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FIG. 11.3 Precritical terrain of Crohn’s disease. In addition to the structural factor of initiation (SFI), the precritical terrain fragilizes adaptability and the quality of the intestinal mucosa, in an attempt to compensate for the SFI hyper demand for proteins. In vagotonic patients, there is a hyperfunctioning parasympathetic tone to adapt exocrine pancreatic function (black arrow) to produce more proteolytic enzymes. The insufficiency of the response (gray arrow) makes a reactive appeal (broken green arrow) back to para, resulting in a further rise in vagal tone. There is a reactive alpha-sympathetic surge in response to this (heavy red arrow), which favors catabolism (Cata) over anabolism (Ana). Alpha-sympathetic stimulates the parathyroid glands (black arrow) to adapt the level of calcium activity to assist in the adaptation demand it has installed. The parathyroid hormone response is insufficient, thus, so is calcium response (gray arrow). This results in a reactive appeal (broken green arrow) to the sympathetic nervous system with a further reactive response in an (ultimately unsuccessful) attempt to re-relaunch the parathyroid glands (broken red arrow). In sum, there is a catabolic predominance both due to alpha and insufficient proteolytic enzymes to repair injured intestinal mucosa. In addition, the patient is not prepared to face an aggression due to impaired precritical adaptability at the level of the parathyroid gland. (© 2015 Systems Biology Research Group.)
Returning to the endocrine system, the hypersympathetic state overstimulates the adrenal cortex with a net effect of delaying metabolism (cf. The Theory of Endobiogeny, Volume 1, Chapter 6). There is a strong appeal to luteinizing hormone (LH) primarily from horizontal FSH stimulation and secondarily from radial estrogen stimulation. The androgen activity is relatively strong and greater than estrogens (Fig. 11.2). The net effect of this dysendocrinism is poor quality of protein assemblage be it enzymes, cytoskeleton, or tissular architecture reflected in the dysplastic architecture.19 According to the theory of Endobiogeny, we conclude that CD is a disorder of dysadaptability of protein management in the face of an aggression. Initiating factor of the critical terrain of CD In the face of an aggression, real or perceived, the autonomic nervous system is the initiating factor in Crohn’s colitis. It is the perception of stress that itself is a risk factor installation of the critical terrain.20 The aggression may be from diet or infections or psychic traumas.21, 22 For example, patients with IBD have an internalizing psychological tendency compared to nonaffected siblings, and the severity of internalization of feelings has been correlated to
severity of symptoms.22 Using arbitrary units of function, if the sympathetic-parasympathetic ratio is 3:1.8 (1.66) in the precritical state, it is 8:3 (2.66) in the critical terrain. The sympathetic response includes both alpha and beta. It is the brutality of the sympathetic response to an aggression, be it from the interior or the exterior that installs the intensity of the endocrine response resulting in ulceration of the mucosa.
Critical terrain of CD The critical terrain of CD involves sequential involvement of each axis: corticotropic, gonadotropic, thyrotropic then somatotropic. In the discussion the four axes involved, somatotropic, we review the concept of a special triadic endocrine relationship called a trépied (Fig. 11.4, and Theory of Endobiogeny, Volume 1, Chapter 9). There is a dysfunctional trépied in the CD patients which is key to understanding the degree of inflammation, ulceration and delayed wound healing (Fig. 11.5). Upon conclusion of the discussion of the critical endocrine terrain, the pre- and critical terrains are schematically summarized in Fig. 11.6.
242 The Theory of Endobiogeny
Third axis of solicitation: thyrotropic
FIG. 11.4 Trépied of alpha-sympathetic, prolactin (PL) and growth hormone (GH). Alpha stimulates GH and PL. GH stimulates PL, but PL inhibits GH. This is the trépied relationship. In terms of adaptation, in a first time, alpha initiates adaptation, in a second time, alpha stimulates GH to calibrate nutrient entry (first loop). In a third time, both alpha and GH relaunch PL to progress adaptation (from first to second loop). At a fourth time, once rising PL activity has inhibited GH, alpha’s final peak of PL helps complete adaptation (end of the second loop). (© 2018 Systems Biology Research Group.)
FIG. 11.5 The alpha-prolactin (PL)-growth hormone (GH) trépied in inflammatory bowel disease (IBD). The normal trépied is described in the text and Fig. 11.4. In IBD, the trépied is dysfunctional. Alpha is hyperfuncitoning, leading to a hyperadaptation. It also drives an intense PL that inhibits GH before GH can have its time in calibrating nutrients. Thus there is prolonged adaptation, hyperinsulinism, inflammation, delayed wound healing (in part due to insufficient nutrient accumulation), and ulceration of mucosa. (© 2018 Systems Biology Research Group.)
First axis of solicitation: corticotropic 1. Central: ACTH hyperfunctioning. At the level of the intestines, ACTH receptors are stimulated in the ileocecal junction to augment the absorption of water and electrolytes for structural adaptation, thus the predilection of inflammation of the terminal ileum 2. Peripheral: cortisol and adrenal cortex hyperfunctioning, cortisol > global adrenal activity → hypercatabolic state a. Net imbalance: ACTH > cortisol > adrenal cortex Second axis of solicitation: gonadotropic 1. Central: FSH hyperfunctioning intensified a. Mucosal hypertrophy of colon → increased anabolic demand for proteins 2. Peripheral: gonadal hyperfunctioning, estrogens ≫ androgen → impaired completion of protein anabolism → mucosal ulcerations a. Net imbalance: FSH ≫ estrogens > androgens
1. Central a. Thryotropin-releasing hormone (TRH) hyperfunctioning: i. TRH → gallbladder → excess bile excretion → autodigestion of the small intestines ii. TRH → PL → pancreas → insulin → mistiming of GH-insulin relationship → inflammation b. TSH hyperfunctioning i. FSH → TSH → congestion of mucosal tissues ii. TSH → insufficient T4, parathyroid hormone → insufficient calcium for adaptation 2. Peripheral a. Peripheral thyroid → hyperfunctioning → hypercatabolic, use of fat for energy, insufficient lipid management for cellular reconstruction b. Net imbalance: generally hyperfunctioning axis Fourth axis of solicitation: somatotropic Alpha has a classic trépied relationship with prolactin (PL) and growth hormone (GH) (Fig. 11.4). When this trépied functions normally, in a first time, alpha initiates adaptation. As the first loop of the general adaptation advances, in a second time, alpha stimulates GH to start the process of calibrating nutrients except glucose. This is the role of PL at the end of the second loop. In a third time, alpha also stimulates PL to advance adaptation by turning the first loop to the second. The GH response is initially greater than the PL response. As PL levels rise, be it from alpha, GH, or TRH, in time it inhibits GH in order to end the time nutrient apportionment, thus beginning the time of insulin and glucose to generate adenosine triphosphate (ATP) to fuel metabolism. And with this, in the fourth time, PL (along with somatostatin) ends adaptation. In IBD, the genetic heritage favors both a hyperfunctioning alpha and a hyperfunctioning and early responding PL during adaptation states (Fig. 11.5). Thus, when alpha stimulates GH and PL, the PL response is far greater than GH, and precedes it in time. GH is inhibited too quickly and PL remains in a hyperfunctioning state. This impairs somatotropic synchronization of glucose entry and energy production, resulting in free radical production, inflammation, ulceration, and delayed wound healing. The key to treating this imbalance is to inhibit alpha and relaunch GH. It may seem paradoxical that a medicinal plant such as Lamium album is efficient in IBD, as it stimulates GH and PL from the anterior pituitary. By relaunching GH with Lamium album, one restores the competency of GH in relationship to PL. This gives information to alpha to downregulate its stimulation of the somatotrophs in the pituitary. This is similar to the role of Eleutherococcus senticosus in prostate enlargement (Chapter 7) and acne (Chapter 8) with respect to androgens and LH.
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FIG. 11.6 Summary of precritical and critical terrain and pathophysiology of Crohn’s disease according to the theory of Endobiogeny. The precritical terrain (lower left) fragilizes the intestinal mucosa, meaning that it easily is susceptible to injury during adaptation states (cf. Figs. 11.2 and 11.3). In the critical terrain (upper and middle image), a hyperfunctioning alpha relaunches the entire axial sequence of endocrine activity: ACTH and cortisol, FSH and estrogens, LH and androgens, TRH-TSH-thyroid. Most crucial to the ulceration in a Crohn’s colitis is the disruption of the alpha-PL-GH trépied (Fig. 11.5). The end result in mucosal edema, inflammation, fissures, and ulceration. (© 2015 Systems Biology Research Group.)
1. Central a. PL hyperfunctioning → i. Hyperinsulinism ii. ACTH → relaunching of second loop adaptation, functional adaptation demands, and involvement of rectosigmoid colon iii. Abscess (favored) b. GH delay 2. Peripheral a. Hyperinsulinism proceeding GH with low insulin resistance → i. Elevated free radicals → inflammation → necrosis ii. Delayed wound healing iii. Fistula formation Emunctory congestion The exocrine pancreas continues to be congested. The liver becomes congested at the metabolic level and possibly for circulatory reasons due to the quantity of endocrine metabolites and inflammatory proteins that need to be metabolized as a result of the critical terrain. Tissue pathology With respect to history, the colon in CD shows chronic intestinal inflammation. There is activation of TH1 cells promoting interleukin-2, tissues necrosis factor alpha, arachidonic acid, proteases, platelet activating factor, and
free radicals. The net effect is mucosal ulceration forming crypts in the mucosal endothelium, muscularis layers, and affecting the mesentery and lymph nodes. One can find abscesses with a neutrophilia within the crypts and mucosa.1, 13
Anatomical distribution of CD CD is characterized classically has having “skip” lesions: areas of affected and unaffected areas of ulceration (Fig. 11.7). From the Endobiogenic perspective, it witnesses the role of the various central hormone receptors on the colon and their particular role in the patient’s Endobiogenic terrain (cf. Fig. 11.1). For example, in Fig. 11.7, A (top) represents an ACTH predominance in the critical terrain for maintenance of structure. B (middle) and C (bottom) represent ACTH in structure, LH, TRH, and GH.
Pediatric In children, the onset of CD is 12–15 years,5, 21, 23 in the gonadic metabolic and tissular phases of chronobiologic unfolding (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). This is a time of intense demand for estrogens for structural growth. The areas of frequency of presentation are presented below with comments with respect to the Endobiogenic significance of these findings.
244 The Theory of Endobiogeny
● ●
Small intestine alone: 30% Mouth, esophagus, stomach: rare but possible: 20%
Clinical presentation CD presenting in childhood tends to be more severe and progresses more rapidly.5 Symptoms are presented below by system.
Gastrointestinal Abdominal pain ● Right lower quadrant or periumbilical, often relieved with defecation ● Lower left quadrant pain may be more prevalent if there is a greater affectation of rectosigmoid colon Bowel habits ●
● ●
Diarrhea, intermittent, typically not bloody, or mucopurulent unless rectosigmoid colon involved Urgency to defecate Foul stool (rectal involvement with abscess)
Fistula-related presentations ● Recurrent urinary tract infections ● Feculent vaginal discharge ● Feculent soiling of skin ● Retroperitoneal abscess FIG. 11.7 Skip lesions in Crohn’s disease. (A) Isolated lesion (red) at the distal ileum, (B) skip lesions (red), affecting, with endobiogenic significance in parentheses: ileum, ileocecal junction (ACTH), ascending colon (FSH), hepatic flexure (TRH/TSH), mid-transverse colon (LH), mid to distal descending colon (GH), and (C) skip lesions (red) exclusively affecting the colon, whose Endobiogenic significance is noted in (B). (Reproduced from Samir, vectorized by Fvasconcellos [CC-BY-SA-3.0] via Wikimedia Commons.)
●
●
●
Terminal ileum: 50%–70% ● It witnesses the role of structural disadaptation by ACTH, possibly installed during adrenarche from 11 to 12 years of age Colon (typically ascending colon): 50%–60% ● It witnesses the role of FSH as a SFI and oversolicitation during Crohn’s colitis Gastric and duodenum: 30%–40%
Systemic ● Anorexia ● Weight loss ● Growth delay (in children may precede diagnosis of disease by 1 year or more)
Review of systems ●
●
●
Keen on sports, which improves the discharge of alpha, reducing the violent explosion of beta Vivid dreams, witnessing the inflammatory, fragilizing role of TRH in its stimulation of the endocrine pancreas Diet: tends to be rich in animal proteins, refined carbohydrates, animal fats, processed fats, which present daily insult and injury to the intestinal epithelium
Adult In adults, expression of CD is more evenly distributed, reflecting the settling of the organism into its adult Endobiogenic endocrine equilibrium.24 ● ●
Ileocecum: 30% Colon (rectosigmoid most prominent): 20%
Physical examination Morphology ● ●
Pale skin, darker hair in fair-skinned patients Feminine face with a masculine body (all ethnic origins)
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Pertinent findings Head, ears, eyes, nose, and throat (HEENT) ● Dilated veins on eyelids, nasal bridge, forehead ● Dark eyebrows, possibly bushy ● Long eyelashes ● Enlarged parotid and submandibular glands ● Dilated canal of Stensen ● Sublingual veins dilated, dark blue Abdominal ● Hepatic congestion, portal congestion ● Small intestine/dysbiosis: often tender ● Colon tender on palpation: all areas Extremities ● Right leg, tender on palpation at inferior and medial to tibial tuberosity, indicative of gallbladder congestion
Laboratory studies Fecal calprotectin and serum C-reactive protein (CRP) can serve as helpful markers of remission of the critical terrain.25, 26 Studies suggest that they may be superior to remission determined by clinical symptoms.27 This mirrors our experience with the biology of functions (Tables 11.2–11.5). Patients can be symptomatically in remission but still have numerous elements of the critical terrain, which keep the patient fragilized and susceptible to flare-up. In addition, labs for the biology of functions (including vitamin D) are recommended to follow the evolution of the terrain based on the integrative physiologic principles.
Biology of functions Once a patient has been diagnosed with CD, there are essentially three terrains one can view. The first is the critical terrain proper during an active flare-up (Tables 11.3–11.6). The second is a patient in remission with elements of the
critical terrain present, but not sufficiently elevated to bring about active disease. We refer to this as the suppressed critical terrain. We hypothesize that based on the genetically inherited terrain, there are various phenotypic subtypes of CD. For example, in some patients who are clinically asymptomatic in a suppressed critical terrain may have elevated brain stem activation, or inflammation, a hyperoxidative state, etc. Finally, there is the true correction of the critical terrain to a precritical state, typically with some Endobiogenic treatment. In the critical terrain, most of the elements will be deranged (high or low). In the suppressed critical terrain, the patient is asymptomatic and some of the elements of the critical terrain will remain deranged but less so than in the critical terrain. In the precritical terrain, the patient is asymptomatic and has derangements consistent with the precritical terrain. Some aspects, such as the exocrine pancreas, need to be assessed by physical exam. Table 11.2 summarizes the criteria we propose for number of deranged indexes per axis. There is overlap between the number of deranged indexes across the three categories. For example, the criteria for thyrotropic axis and immunity are 7–9 deranged indexes. For the same group, the suppressed critical terrain is 4–7. The reason for this that even there are not a substantial reduction in the number of positive signs in one axis, there will be in the two or more of the other axes. The one that continues to be the most deranged is likely to be the autopathogenic axis of the patient (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). The first group of indexes is grouped together as “neurocorticotropic” because of the implication of sympathetic activation of the corticotropic axis (Table 11.3). In order to discuss terrain, we introduce new indexes not previously discussed. The immediate adaptation score #2 witnesses the global peripheral catabolic neuroendocrine activity during immediate adaptation: alpha, beta, and the adrenal cortex. It witnesses alpha-sympathetic engagement of the entire adrenal unit: medulla (adrenaline) and cortex (cortisol). There is also the adaptation entrainment score adjusted index. It witnesses, in the face of the relative degree of entrainment of sequential axial function starting with corticotropic axis the
TABLE 11.2 Criteria of indexes deranged per stage of terrain of Crohn’s disease Axis
Critical
Suppressed critical
Precritical
Neuro-corticotropic
>5/11
3–5/11
<3/11
Gonadotropic
>3/7
2–4/7
<3/7
Thyrotropic-immunity
>6/9
4–7/9
<4/9
Somatotropic
>6/9
4–7/9
<5/9
Psychological
>3/5
2–3/5
1–2/5
Total indexes deranged
28–41
15–28
<15
246 The Theory of Endobiogeny
TABLE 11.3 Neuro-corticotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
ANS
Leukocyte mobilization
↑↑ or ↓↓
↑ or ↓
Normal
Platelet mobilization
↑↑, typically
↑
Normal
Starter
↑↑ or ↓↓
↑ or ↓
Normal
Immediate adaptation score 2
↑↑
↑
Normal
Adaptation entrainment score adj.
↑↑
↑
Normal
Vasopressin corrected
↑↑
↑ or ↓
Varies
ACTH
↑↑
↑ or ↓
Varies
Cortisol
↑↑
↑
Normal or ↓
Adaptation permissivity of the adrenal cortex
↑↑, may be negative
↑
Normal
Aldosterone comparative
↑↑, may be negative
↑, may be negative
Normal or slightly elevated
Structure/function
↑↑
↑
Normal
Neuro-corticotropic
Corticotropic
TABLE 11.4 Gonadotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
Gonadotropic
LH
↑↑
↑ or ↓
Normal
FSH
↑↑
↑ or ↓
Varies, tends to be slightly elevated
Organotissular estrogen yield
↓↓
↓
Varies, may be slightly low
Estrogen index
Normal or ↓ for age
Normal or ↓ for age
Normal or ↓ for age
Estrogen index corrected
Normal or ↓ for age
Normal or ↓ for age
Normal or ↓ for age
Genital androgens
Normal or ↓ for age
Normal or ↓ for age
Normal or ↓ for age
Genito-thyroid
↑↑
↑
Normal
Gonado-thyrotropic
degree of liminal tissular expression of estrogens to witness both the solicitation and anabolic achievement from the gonadotropic axis, specifically from estrogens. By extension, it evaluates the ability of the organism to evolve the adaptation response throughout the phases of the adaptation syndromes. By extension, the higher the value, the greater the persistence of immediate and mediate adaptation and by extension of inflammation and catabolism. By extension, the lower the value is, the greater the progression of the adaptation syndromes is anticipated to be toward restitutio ad integrum. In CD, during a flare-up, the index is elevated as the corti-
cotropic axis as a whole is intensely stimulated (as noted in the immediate adaptation score #2) but so are estrogens in an attempt to compensate for the intensity of the catabolic response through endocrine coupling. What is notable is that often even in the suppressed critical terrain and even in remission, the index remains elevated. This indicates that the organism is not able to resolve the adaptation response and enter in an anabolic phase of restoration. This is especially the case if the structure/function index also remains elevated. The structure/function index expresses the solicitation of adaptative tissular mechanisms of structure relative to those of
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TABLE 11.5 Thyrotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
Thyrotropic
βMSH/αMSH
↑↑↑
↑↑ or ↓↓
Normal to low
Thyroid relaunching
↑↑
↑
Normal to slightly elevated
Thyroid relaunching corrected
↑↑↑
↑↑
Normal to slightly elevated
Thyroid
↑↑↑
↑↑ or ↓↓
Normal to slightly low
Thyroid efficiency
↑
Normal or ↓ for age
Normal or slightly ↑ for age
PTH
Varies
Varies
Varies
Vitamin D adaptation index
↓, negative or both
Varies
Varies
Mobilization of immunity
↑↑
↑
Varies, may be negative
Interleukin 1
↓↓
↓
Varies, may remain low
Thyro-immune
TABLE 11.6 Somatotropic terrains of Crohn’s disease Axis
Index
Critical terrain
Suppressed critical
Remission
Somatotropic
Prolactin
↓↓↓
↓↓
Varies, may be slightly elevated
GH growth score
↓↓↓
↓↓
Varies, may be slightly elevated
Somatostatin
↓
Varies, often high
Varies, often high
Insulin
↑↑↑
Varies
Varies, may be slightly elevated
Insulin resistance
↓↓
Varies, often low
Varies, may be slightly low
Expansivity #2
↑↑
Varies
Varies
Redox
↑↑ to ↑↑↑
↑ to ↑↑
Varies, may be slightly elevated
Noxious free radicals
↑↑↑
↑↑
Varies, often elevated
Autophagy 1 adjusted
↑↑↑
↑↑
Varies, often elevated
function. The higher the index, the more tissue solicit structural mechanisms of adaptation. It is elevated in CD. Finally, there is the vasopressin index corrected. It witnesses the strictly central effects of vasopressin, as opposed to the net central and peripheral actions of vasopressin. In the critical terrain of CD, vasopressin may be paradoxically elevated because the feedback of cortisol on ACTH is impaired. Thus, vasopressin attempts to relaunch ACTH from the anterior pituitary,28 despite elevated cortisol activity. The gonadotropic axis (Table 11.4) shows elements of the SFI deranged to a greater degree. Not all of the estrogen indexes will be deranged. It is sufficient for one to be deranged. The number of estrogen indexes deranged partly depends on the age of the patient and their stage in their
lifestyle. NB: normal values differ for adolescents compared to adults. The activity of the thyrotropic axis is presented in Table 11.5. We have placed the βMSH/αMSH index in the thyrotropic axis because the elevated value reflects the role of βMSH and TRH in stimulating the axis. An elevated index in the critical terrain indicates that βMSH is acting to (over-) stimulate the thyroid gland outside of central regulation, and by extension, that there is insufficient central endorphins to end this process. During the suppressed critical phase, it may dip low, favoring αMSH, which would be beneficial in allowing for the long programmatic and sequential passage of endocrine activity to occur in order to complete the adaptation response. αMSH regulates energy homeostasis.29 It is antipyretic, antiinflammatory, cicatrizing, and
248 The Theory of Endobiogeny
anorexigenic, all actions that help the patient recovery from the critical terrain of a Crohn’s flare-up.30 If the index remains elevated, favoring βMSH and an insufficiency of endorphins, it is a cause for concern that the patient remains fragilized and quite at risk of a subsequent flare-up, despite their current level of treatment. This index tracks with the thyroid index. The thyroid efficiency index expresses the tissular activity of the thyroid in its participation in structural activity. In other words, it evaluates how effectively thyroid response to and contributes to the energy required for structural assemblage of cellular elements such as enzymes and organelles initiated by estrogens. In the critical terrain of CD, an elevated index is problematic because estrogen activity is insufficient. Thus, an elevated value indicates that thyroid is providing a catabolic action that is greater than the anabolic activity initiated by estrogens. This favors friable mucosa and risk of further bleeding. It may be advantageous for the index to be lower than normal then return to normal or even slightly elevated once other aspects of the terrain have normalized as well. In this case, a slightly elevated index in the face of elevated estrogens would be favorable as an indication of tissular thyroid activity dedicated to restoration of tissue integrity, one cell at a time. The parathyroid hormone (PTH) index may or may not be elevated because the index evaluates the general level of endocrinometabolic activity of the gland, not its specific role in adaptation. The vitamin D adaptation index witnesses the relative insufficiency of vitamin D in mitigating the intensity of the central adaptation response. The higher the index, the less efficient vitamin D is in mitigating the adaptation response and the more likely high dose, shortterm vitamin D therapy may be in CD.31 The benefit of this therapy is not related to reduction in inflammation as measured by CRP,31 which reinforces the notion of the index of evaluating vitamin D’s role in adaptation. Finally, the mobilization of immunity index evaluates the relative efficiency of mobilization of elements of immunity from the macrophage-activating system relative to the rate of sequestration. It is a composite of the effects of cortico-thyrotropic and immune factors: vitamin D, splanchnic mobilization of leukocytes, splenic mobilization of platelets, adrenal cortex yield, and interleukin activity. When the index is elevated, as it is in CD, it witnesses the risk of a hyper- or dysregulated immune response, despite the fact that interleukin activity is low.32 In other words, the notion of dysregulation refers to poor management of immune activity as reflected by excessive intensity and/or duration of inflammation but inappropriate type of immune cell or timing of function. Within the somatotropic axis (Table 11.6), one notes the low Prolactin index indicates a hyperfunctioning PL. The low GH growth score index indicates that GH is delayed and/or inhibited in its role of calibrating timing and quality of nutrient entry. Thus, we see a corresponding
d esynchronization of peripheral glucose delivery timing to cells with an elevated insulin index and low insulin resistance index. To further characterize the tissular and cellular disturbances in IBD, we introduce a number of new indexes. In our discussion of the Endobiogenic critical terrain of CD, we mentioned the cellular disorganization.19 This refers to the topology of cell arrangement and morphology in threedimensional (3D) space. The expansivity #2 index characterizes the degree of risk of anarchic cellular development based within the adaptative modalities of metabolism in their consequences of structural implication. Autophagy is the process in which lysosomes within cells destroy damaged organelles, proteins, other material, etc. This process has been found to be aberrant in IBD.33, 34 The autophagy index evaluates the relative risk of insufficient autophagy due to the intrinsic metabolic functioning of the cell and thus the accumulation of biologic toxins of endogenous origin. The autophagy 1 adjusted index evaluates the risk of insufficient autophagy and is adjusted by the potentially beneficial role of free radicals in stimulating autophagy genes.35 However, if the noxious free radicals index is more than 10-fold above normal, the role of free radicals is dysregulated and harmful, which is the case in IBD.36 When the autophagy 1 adjusted index and the noxious free radicals index are both elevated, free radical scavengers should be considered, such as α-lipoic acid.37 One may also evaluate certain psychological states in the CD patient using the biology of functions (Table 11.7). CD patients are noted to have an internalizing coping style. In addition, we find, as others have, that the perception of stress is key given their psychosocial milieu and coping style.20, 38, 39 We can speak about a general IBD
TABLE 11.7 Psychological indexes related to Crohn’s disease Critical terrain
Suppressed critical
Remission
Closed off from receiving
↑↑
↑
Normal
Permeability adjusted
↑↑↑
↑↑
Normal to ↑
Traumatic memory
↑↑
↑
Normal
Acceptancecontentment
↓↓
↓
Slightly ↓, normal, or ↑,
Frustration index
↑↑↑, may be negative
↑↑, may be negative
Slightly ↑ to normal, negative value may persist
Index
Inflammatory bowel diseases Chapter | 11 249
p sychological type according to the theory of Endobiogeny. Variations in the UC patient are discussed in the appropriate section (cf. Table 11.20). We continue to evaluate the structure value of the psychological indexes, which favor challenges in the relationship with intimates, family members, and close friends, as opposed to acquaintances (cf. UC). The IBD patient feels unloved, reflected in the closed off from receiving index. The closed off from receiving index evaluates the tendency to feel defensive and closed off from receiving emotional support from others. When it is elevated, it witnesses a greater tendency to feel defensive and create a defensive barrier to protect one self, which can involve internalization of feelings. The frustration index witnesses the tendency to have a moralistic or perfectionist attitude and feel frustrated by one’s inability bring to fruition what one has envisioned. By extension, it favors the tendency to be frustrated toward the perceived failings of others. When the index is elevated and negative—often the case during a CD flare-up—it indicates that the frustration does not lead to productive changes in the patient’s life. It only leads to more frustration. When both indexes are elevated, the patient is more like to internalize their feelings. There is an underlying sense of emotional vulnerability, reflected in the permeability adjusted index. The higher the index, the greater the feeling of emotional vulnerability. Perceived or real insults or criticism “cut” into the self-esteem of the patient, mirroring the ulceration of the mucosa. As CD is a deeper level of ulceration, one also notes a deeper level of emotional vulnerability. It is elevated during a flare-up and may persist even in remission, but certainly in the suppressed critical terrain. In fact, from remission to a fragilization and risk of flare-up, one is likely to see this index rise, even before the onset of clinical symptoms. From the feeling of not being loved and the feelings of emotional vulnerability, one notes that UC patients have traumatic rumination during their crisis, reflected in the traumatic memory index. IBD patients are generally discontent with their situation, reflected in the acceptance-contentment index, which when low indicates this feeling of discontent and searching from answers that one cannot find. This tends to persist, even in the precritical terrain. If the patient has an elevated index in the precritical terrain, it indicates that they tend to rationalize their discontent. This increases the risk of a flare-up even more than a slightly low score. Finally, UC patients tend to be critical of others, sometimes projecting their own internal frustration. This is reflected in the critical tendency score, which evaluates the tendency to be critical against oneself and other people.
Treatment: General considerations The Endobiogenic approach to Crohn’s colitis is to initiate symptomatic treatment, alter diet, and then address the
issues of terrain. The choice of symptomatic treatment is dictated by the degree of decompensation of the patient and the probability of spontaneous or supported recovery without surgical intervention or pharmaceutical intervention. There is no inappropriate treatment, only an inappropriate utilization of a treatment due to its aggressiveness or lack of effectiveness, or excessive or insufficient duration of treatment for the given state of decompensation. Standard of care treatments with pharmaceutical agents is the most well-researched approach to suppression of downstream pathophysiologic factors and clinical symptoms. It is part of the Endobiogenic approach to the treatment of IBD. The use of medicinal plants may be supportive or primary based on a number of considerations. The more severe the clinical symptoms, the higher the biomarkers (e.g., calprotectin, CRP), and the more passive the patient is in disease management, the greater the imperative for the pharmaceutical treatments to be the primary treatment.
Treatment: Standard of care All classical biomedical approaches are symptomatic and suppressive in nature. They offer reduction in the inflammation and dysregulated immune damage to the cell. Nonbiological agents do not necessarily change the outcome of disease.27, 40 They reduce inflammation and symptoms of disease41 but may not prevent relapse either.42 Thus, reinforces the Endobiogenic theory of a critical terrain that must be treated as opposed to suppression of mechanisms of pathophysiology. The step-up approach uses increasingly targeted therapy commensurate with severity of disease. The less severe the presentation of symptoms, the less aggressive the pharmaceutical agent. The first “step” in ascending treatment is the mucosal antiinflammatory 5-aminosalicyclic acid (5ASA).41 It is prepared in various prodrug forms so as to be released in the small intestines (mesalamine) or colon (sulfasalazine) based on the area of inflammation. The second step is glucocorticoids. When systemic symptoms are present, oral glucocorticoids such as prednisone can be used. When symptoms are primarily enteric, budesonide is favored, as it does not have systemic absorption.41, 42 The third step is immunosuppression: 6-mercaptopurine (6-MP), or its prodrug azathioprine. Methotrexate is another option for children and adults, especially when 6-MP is not successful.43 Other options include tacrolimus and mycophenolate. The fourth step is biological therapy. These medications inhibit downstream mechanisms of disease and/or constitutively expressed regulators of cell function, often with increasingly consequential side effects.27 Currently, there are two general classes: antitumor necrosis factor agents (e.g., adalimumab), and leukocyte adhesion and migration inhibitors (e.g., natalizumab). There are risk of rare lymphomas and opportunistic infections.41 New classes of
250 The Theory of Endobiogeny
drugs in development include inhibitors of interleukin 23 and Janus kinase 1.27 Antibacterial treatment can be added as indicated.41
Diet and lifestyle during a crisis ● ●
Symptomatic treatment: An endobiogenic approach An Endobiogenic symptomatic treatment is aimed at reducing inflammation, diarrhea, and sympathetic hyperfunctioning, favoring astringent plants (Table 11.8). These plants are all polyvalent for symptomatic treatment and elements of the terrain.44–46 Many elements listed under symptomatic treatment also treat the critical or precritical terrain. The primary difference is dose and frequency of administration.
Diet: high purine protein, low fat, low fiber Lifestyle: calming activities: meditation, breath work, yoga, Tai chi, prayer, etc.
Case study in acute management of CD
Diatomaceous earth is efficient in inflammatory bowel disorders. It is antihemorrhagic, antiinflammatory, cicatrizing, antimicrobial, absorbent, and adsorbent.44–48 Based on our research, we have found the green Illite clay to be the most efficient. Green Illite clay: 1–2 tbsp every 2–3 h
A 16-year-old boy of Indian descent, born and raised in the United States, was being treated with Humira for CD. He spent the summer visiting relatives in India. Since he felt well eating traditional fermented and vegetarian foods of south India, he let his prescription run out. Two weeks later, he returned home to the United States. Four weeks later he presented 1 week of abdominal pain and 6 bloody stools per day. He had hemoglobin evaluated in urgent care, which showed anemia: 9 mg/dL (12.5–17 mg/dL). Before summer vacation, his hemoglobin was 12.7 mg/dL. The patient was started on acute, symptomatic treatment without performing a biology of functions. On exam, the patient was noted to have a beautiful face with large almond eyes. The abdominal exam was significant for tenderness of the exocrine and endocrine pancreas, ascending colon (FSH), mid- and distal descending colon (GH, PL), and rectosigmoid area (ACTH).
Sample treatments of Crohn’s colitis
General treatment
Preparing the Illite clay with a tisane, or adding a tincture offers the highly efficient symptomatic treatment of CD. Clay + tisane Matricaria recutita 30 g, Fragaria vesca 30 g, Alchemilla vulgaris 30 g, Poterium sanguisorba 30 g: 1 tbsp steeped 12 min in 200 mL water, strain and add to 1 tbsp clay. Let sit for 30 min, mix and administer. Prepare next tisane and hydration of clay. Clay + tincture with essential oils Matricaria recutita 30 mL, Fragaria vesca 30 mL, Alchemilla vulgaris 30 mL, Poterium sanguisorba 30 mL, Lavandula angustifolia EO 2 mL: 6 mL every 4 h added to prepared clay. In more severe cases of hemorrhagic disease, especially when the prominent site is the rectosigmoid area, a microlavage infusion can be used. The same preparations noted above can be lavaged into the rectum. The method is as follows: Tincture + clay: add ½ tsp. clay to 10 mL water. Let sit 15 min. Shake tincture well (if it contains essential oils), add 5–6 mL to the clay preparation, stir well, draw up with a rectal administration bulb, and slowly administer over 5–10 min. Do not use muco-caustic essential oils such as oregano, cinnamon, or clove. Tincture + clay: add ½ tsp. clay to 10 mL of a tisane prepared from 1 tbsp of mixture steeped 15 min in 100 mL water. Let sit 15 min. Stir and administer as above.
Since he was already vegetarian, he was started on the following empirical treatment: 1-Astringent-adsorbant: tisane-EO-clay mixture every 4 h while awake until bloody diarrhea has resolved
Diatomaceous earth
● ● ● ●
1 tbsp Illite clay 1 drop Carum carvi (caraway) EO 1 drop Mentha piperita (peppermint) EO 200 mL tisane of Juglans regia: 1 heaping tsp. leaf steeped 8 min in hot water; strain
2-Astringent, antihemorrhagic cicatrizant tincture: Lamium album MT 30 mL, Poterium sanguisorba MT 30 mL, Malva sylvestris MT 30 mL, Hamamelis virginiana MT 30 mL: 3 mL 4 times per day in clay water. 3-ANS-cortico-gonado-thyrotropic tincture: Salvia sclarea MT 80 mL, Lithospermum officinale MT 80 mL, Leonurus cardiaca MT 80 mL + petitgrain EO 2 mL, eucalyptus EO 2 mL, clove EO 0.5 mL 4 mL twice per day in clay water. The number of blood stools reduced to 4 per day in 24 h, then 2 per day in 48 h and resolved by the third day of treatment.
Treatment of terrain: An endobiogenic approach There are a number of medicinal plants that can be used to treat the terrain of CD. Those that are the most efficient due
TABLE 11.8 Symptomatic treatment of Crohn’s colitis Medicinal plant
Alpha-lytic
Antiinflam.
Alchemilla vulgaris
•
Angelica archangelica
•
Arnica montana
•
• indirect
Artemisia dracunculus
•
Fragaria vesca
•
Lamium album
•
Astringent
Antihemorrhagic
Endocrine
Intestinal tropism
•
Aldosterone antagonist
Antispasmodic, antimicrobial
Estrogenic (−), FSH
Antispasmodic, antimicrobial
a
Delays insulin activity
•
a
Hemostatic
Estrogenic (mild)
Antispasmodic, antimicrobial
•
(−) ACTH, (−) conversion of androgens to estrogens
Antimicrobial
•
Improve growth factors
•
•
(−) Adrenal cortex
Hepatobiliary drainer Cicatrizing Antimicrobial
Matricaria recutita
•
•
(−) ACTH
Antispasmodic, antimicrobial, cicatrizant Decongestant: hepatic, splanchnic, pelvic
Plantago major
Poterium sanguisorba
•
•
a
Antispasmodic, antimicrobial, antiulcerative Hepato-pancreatic drainer •
(−) PL and by extension hyperinsulinism and inflammation, and corticotropic relaunching
By delaying the actions of insulin in the cell membrane, Arnica montana diminishes inflammation rooted in somatotropic desynchronization.
Antiinflam.: Antiinflammatory.
Antiseptic
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Lavandula angustifolia
252 The Theory of Endobiogeny
to their polyvalent action are listed in Table 11.9, followed by a discussion of the plants by axis and action within the axis. Most of the plants in Table 11.9 share the properties of coupling or linking (cf. The Theory of Endobiogeny, Volume 1, Chapter 10). Plants that affect coupling simultaneously alter adjacent endocrine axes, for example, corticogonadotropic, gonado-thyrotropic, somato- corticotropic, etc. Plants that affect linking affect the two anabolic axes: gonado-somatotropic or somato-gonadotropic, such as PL’s effect on GnRH or estrogen activity.
Corticotropic Support adrenal activity while reducing ACTH44, 45, 47 ● ● ●
Ribes nigrum leaf > bud Fragaria vesca Salvia sclarea
Adrenal support with hepato-splanchnic drainage44, 45 ●
Quercus pedunculata
Gonadotropic Reduce central overactivity44, 45 ● ● ●
Angelica archangelica Lithospermum officinale Borago officinalis
Support peripheral tissular estrogen activity44, 45 ● ● ●
Avena sativa Angelica archangelica Salvia sclarea
Central: GH Relaunch GH to restore the chronologic relationship with insulin44, 45 ●
Lamium album Peripheral: Insulin Delay effects of insulin on cell membrane44, 45
● ●
Arnica montana Malva sylvestris
Lamium album (White deadnettle) Parts used: leaf, flower44, 45 Galenic: MT, FE, MS, bulk herb Summary: supports hypophyso-pancreatic axis, use in children with failure to thrive, in adults with wasting or ulcerative disorders, in chronic fatigue states with brain fog Actions: GU: uterine vasoconstrictor, antimetrorrhagic, antihemmoragic by vasoconstriction, pelvic decongestant by venous stimulation. Endo: somatotropic: supports hypophysopancreatic axis, prolactogenic, increases GH and growth factors. Neuro: relaunches dopamine. GI: antidiarrheal, astringent. ID: urinary antiinfectious. Derm: vulnery, stimulates fibroblasts. HEME: antianemic. Pulm: expectorant, bronchial fluidifier. CV: venoconstrictive, venotonic, antiinflammatory. Use: GU: uterine bleeding, cystitis, vaginitis, leukorrhea, pelvic congestion, prostatitis. GI: colitis. Vascular: hemorrhoids, phlebitis, varicose veins. Metabolic: failure to thrive in children, chronic fatigue. Neurologic: brain fog. HEME: hemorrhagic anemia. Pulm: bronchitis, emphysema. Method: Tisane: 2 tsp./cup; infuse 8 min; Douche: of tisane for vaginal infections
Thyrotropic Reduce central hyperthyroidism44, 45 ● ● ●
Lithospermum officinale Lycopus europaeus Leonurus cardiaca
Modulate peripheral thyroid terrain according to the Endobiogenic state of the patient and support PTH ● ●
Calcium (ascorbate, glycinate, malate) Vitamin D (10,000 IU in AM × 4 days, then 5000–6000 IU in AM × 3 days, then reassess)
Arnica montana (Arnica) Parts used: flower44, 45 Galenic: MT, MS, bulk herb Summary: helpful in allergic/anxiety states with tachycardia, insomnia, etc. and in all disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization. Actions: Oil infusion ● Neuro: antalgic, antimyalgic, antineuralgic, antispasmodic, spasmolytic Actions: Other galenic forms ●
Somatotropic Central: PL Inhibit PL activity, favoring plants with tropism for the intestines44, 45 ● ●
Fragaria vesca Poterium sanguisorba
● ●
Endo: ● Somatotropic: hyperglycemant (reduces the insulin activity at the level of cell) ● Posterior pituitary: oxytocic Immune: reduces histamine release from platelets CV: bathmotrope negative, strongly chronotrope negative, dromotrope negative, inotrope positive, facilitates coronary circulation, coronary vasodilator
TABLE 11.9 Overview of treatment of terrain of Crohn’s disease by polyvalent action of key medicinal plants Medicinal plant
Corticogonado
Gonado-thyro
Thyro-somato
Poterium sanguisorba Fragaria vesca
•
Salvia sclarea
•
Somato-cortico
Somato-gonado
Thyro-cortico
Other
• indirect
• indirect
Astringent, antihemorrhagic Antiseptic
•
•
Astringent, antihemorrhagic Antimicrobial Hepatobiliary-pancreatic support Astringent Antimicrobial
Avena sativa
•
Exocrine pancreas
Lithospermum officinale
•
• indirect
Lycopus europaeus
•
• indirect
Leonurus cardiaca
•
•a
Cortico-gonado, corticotropic-gonadotropic; Gonado-thyro, gonadotropic-thyrotropic; Thyro-somato, thyrotropic-somatotropic; Somato-gonado, somatotropic-gonadotropic. a
Reduces fixation of cortisol.
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•
254 The Theory of Endobiogeny
●
● ●
HEME: anticoagulant, antiecchymotic, eutrophic, hemostatic ANS: sympatholytic GI: hepatoprotective49
Use: hyperthyroid conditions with low insulin resistance, anxiety with insomnia, diurnal chronic fatigue and recurrent hypoglycemia, allergic diseases, cardiovascular disease, chronic fatigue, any disorder of inflammation rooted in a hyperinsulinism with somatotropic desynchronization. Cautions: cardiotoxic and hallucinogenic at high doses, can diminish the activity of antihypotensive and anticoagulant medications. Avoid during pregnancy and nursing
Malva sylvestris (Mallow) 44, 45
Parts used: flower Galenic: MT, MS, bulk herb Summary: all disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially recurrent infections and genitourinary disorders. Actions: Immune: antiinflammatory: digestive and pulmonary tropisms. CV: decongestant: tropisms: ear, nose, throat, pelvic, urinary. ID: antiinfectious: tropisms: ear, nose, throat, lungs. GI: emollient, antigastritic, laxative, anticolitic. Endo: somatotropic: hyperglycemiant (reduces effects of insulin on cell; increases insulin resistance). Use: Any disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially where inflammation has led to passive congestion with impaired drainage, GI: UC, small intestinal dysbiosis, ID: recurrent or prolonged bronchitis—especially dry, GU: pelvic congestion states: PMS, menorrhagia, menometrorrhagia, prostatitis, prostatic adenomas where inflammation plays a more prominent role.
Arnica vs mallow Arnica and mallow are interchangeable with respect to their actions on insulin activity. However, they are not equivalent. Arnica’s spheres of influence are primarily CNS and heart, especially in a person with a personality trait of anxiety. Malva’s spheres of influence are chest, abdomen, and pelvis, especially where inflammation of the mucosa is implicated in the disorder.
● ●
Intestines: support cicatrization of mucosal tissue and tonification of mucosa44, 45 ● ● ● ● ●
Medicinal plants ●
● ● ●
● ●
Alchemilla vulgaris Carduus marianus Agrimonia eupatoria Plantago major Pancreas: support exocrine function44, 45
●
Avena sativa
Maintain central inhibition of endocrine activity, especially FSH and TSH Hepato-pancreatic drainage Re-equilibrate enteric flora Pediatric Crohn: ensure good mineralization of bones and adequate vertical growth and weight gain 31 ● Vitamin D 2000–5000 IU per day in combination with calcium and magnesium and trace boron, vanadium, and phosphorous. ● Bone mineralization tincture: Sequoia gigantea GM 60 mL, Abies pectinata GM 60 mL, Rubus fruticosus GM 60 mL, Betula alba GM 60 mL: 3–4 mL twice per day ● Bone mineralization dry extract: Equisetum arvense 1 capsule twice per day
Sample treatment ● ●
●
●
●
Fragaria vesca Lamium album Plantago major Poterium sanguisorba Green Illite clay
Treatment: Management of the terrain
Drainage Liver: ensure good hepatic drainage44, 45 ●
Plantago major Digestive enzymes
Vitamin D 5000 IU in AM with calcium and magnesium Illite clay 1 tbsp in evenings before bed—soak all day in a tisane of Anthemis nobilis tisane: 1 heaping teaspoon of flowering tops steeped 15–20 min in 200 mL water. Strain and add to clay, mix well, let sit all day. Mix again in evening before bed and consume. ANS-cortico-somato-intestine: Matricaria recutita MT 60 mL, Poterium sanguisorba MT 40 mL, Fragaria vesca MT 60 mL, Malva sylvestris MT 80 mL, Lavandula angustifolia EO 4 mL, Dose: 3 mL TID before meals Gonado-thyrotropic-pancreas: Lycopus europaeus MT, Borago officinalis MT, Angelica archangelica MT, Agrimonia eupatoria MT, Eucalyptus globulus EO 2.5 mL, Cupressus sempervirens EO 1.5 mL, Dose: 3 mL TID before meals
Diet ● ● ●
Pancreas sparing diet Vegetarian or pescatarian diet in general Fermented foods
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Lifestyle ● ●
Regular aerobic exercise, de-stressing techniques Pediatric Crohn’s: be sure to address psychosocial issues related to body image, altered lifestyle, and compliance with treatment regimen
Case study in Crohn’s flare-up and treatment We present the case of a 14-year-old boy with CD who underwent a major flare-up in part due to noncompliance. We follow his recovery from critical to suppressed critical to remission terrain. He was diagnosed at 11.4 years. His CD was under management by a pediatric gastroenterologist, who started him on adalimumab. The family had a long tradition of use of medicinal plants and was referred to our practice for management. The primary gastroenterologist was open to collaboration with us. In addition to adalimumab, he was started on a decoction, tisane, clay, and vitamin D. The family stopped adalimumab after 9 months—1 year before flare-up and did not inform the gastroenterologist. They stopped the Endobiogenic treatments 6 months before flare-up and had not informed us of this. He had been scheduled for biology of functions blood drawn for routine Endobiogenic follow-up. The symptoms of CD flareup started hours after blood drawn, resulting in hospitalization. After stabilization, he was discharged home on adalimumab once again. His Endobiogenic treatment was as follows: ●
Adaptation decoction of Eleutherococcus senticosus root 1 tbsp decocted in 4 cups of water for 15 min. This decoction was used to steep 2 tbsp of the following tisane for 8–10 min
TABLE 11.10 Neuro-corticotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
●
● ●
Cortico-gonado-enteric tisane of Lamium album, Poterium sanguisorba, Fragaria vesca, and Inula helenium equal parts Vitamin D 10,000 IU in the morning Calcium-magnesium supplement
Tables 11.10–11.14 demonstrate the recovery of his terrain over a 12-month period of time from critical to remission terrain. The neuro-corticotropic activity (Table 11.10), most susceptible to acute changes, also showed the clearest return to remission by 8 months and more so by 1 year after his flare-up. The gonadotropic axis (Table 11.11) is perhaps the most complex to interpret for two reasons. First, it contains the SFI, which is the hyper-FSH response. Second, this boy was in puberty and at an age where this axis is the most implicated in the development of secondary sexual characteristics and increases tissue mass in general. In general, the patient experienced a favorable correction of central and peripheral gonadotropic activity by 8 months postflare-up. This was probably part of the process of recovery toward restitutio ad integrum. However, 1 year on, the terrain showed the precritical imbalance of slightly elevated FSH activity due to insufficient estrogen activity and an appeal to LH which is also elevated. In the biology of functions, the FSH to LH indexes should have a ratio of approximately 2:1. One notes that while both are elevated in the critical terrain. FSH is 10-fold more elevated than LH, supporting the notion of the SFI being FSH and a graver increase in its activity in the critical terrain drives a number of key aspects of the pathophysiology.
256 The Theory of Endobiogeny
TABLE 11.11 Gonadotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
TABLE 11.12 Thyrotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
The thyrotropic axis and immune function (Table 11.12), is yoked along with the corticotropic axis to alpha-sympathetic activity. While not deterministically linked, they are interrelated and integrated. We note a similar and clear improvement in thyrotropic function and immunity by 1-year postflare-up. The somatotropic axis (Table 11.13), while showing improvement overtime, has indexes with the greatest degree of derangement away from the normal values. This is not surprising since CD is a structuro-functional disorder. As with the gonadotropic axis, since this adolescent was in puberty, there were fluctuations in GH growth score activity. First, we note it to be elevated as a compensatory response to the injury to the colon. Then, 1 year after the flare-up, it is low again, representing a fundamental elevation of PL and alpha delaying GH timing.
The psychological profile of CD is not well understood. We are not aware of specific, validated psychotherapeutic interventions. We did offer advice to the family and supported a more communicative style between the patient and his father. The mother and patient already had a very open style of communication. While the two indexes we have discussed were less severe 1 year on than they were during the flare-up, they were worse than they were at 8 months postflare-up (Table 11.14). In effect, we concluded that at the psychological level, the patient came out of a remission into a suppressed critical phase. Fortunately, since the physiologic terrain was sufficiently improved, we did not consider the patient to be at risk of a further flare-up as long as he stayed on his treatments.
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TABLE 11.13 Somatotropic terrains of Crohn’s disease
High low values presented in red/blue respectively.
TABLE 11.14 Psychological indexes related to Crohn’s disease
High low values presented in red/blue respectively.
Ulcerative colitis Introduction UC is a chronic, recurrent inflammatory bowel disorder of the left distal descending and rectosigmoid colon.2, 14 It is an ulcerative disease that affects the superficial mucosal layer of the distal colon. In contrast, CD affects all layers of the bowel. According to the theory of Endobiogeny, UC is a functional disorder of adaptation at the level of the distal colon, where CD is a structuro-functional disorder of intestinal integrity. With regard to UC, we make three observations: 1. Chronicity implicates a SFI unable to resolve a physiologic demand 2. Recurrence implicates disadaptation each time the organism faces an aggression 3. Localization to the distal colon indicates a functional disadaptation of cortico-somatotropic activity (ACTH in adaptation, GH for tissue repair) It can be concluded that from the perspective of Endobiogeny, CD and UC are not on a “spectrum” of IBD with respect to the fundamental elements of precritical terrain, SFI and hence the fullness of the genetic and epigenetic
heritage. They do share phenotypic expression of inflammation and mucosal ulceration and hence symptomatic pharmacologic treatment will have commonalities. If one wishes to treat beyond suppression of symptoms, if one wishes to prevent the onset of disease in those at risk or truly bring the patient into remission, the distinction in the terrain must be noted, respected, and addressed in the long-term treatment.
Epidemiology and risk factors Genetic Family history is associated with higher risk of disease.1, 2
Immunity The immune system is dysregulated with autoimmune tendency. One finds dysbiosis with hyperimmune response to noncommensal organisms, with an increase in anaerobic sulfate-reducing bacteria (oxidize hydrogen [H2] and reduce sulfates [SO 4 2− ] from decaying organic material). This increases the general inflammatory terrain of the intestines.50 According to the theory of Endobiogeny, dysbiosis is not causative but predilecting and itself a downstream event of immune dysregulation and the precritical terrain.
258 The Theory of Endobiogeny
Diet Consumption of dairy products is associated with UC exacerbation. Again, this needs to be seen in the light of the genetic inheritance and dysbiosis.3
Nutritional Vitamin A regulates T-helper cell differentiation. Patients with UC have lower levels of vitamins A than controls.51, 52 Supplementation may improve the state of immune dysregulation and clinical symptoms such as blood in stool.51
Psychological UC is a disorder of adaptability and adaptation. The perception of stress more than any “objective” evaluation of stress is key in the risk of flare-ups.38, 39, 53 UC patients suffer from a higher incidence than the general population of anxiety and depression. Depression, according to the theory of Endobiogeny, is also a disorder of dysadaptability. Both disorders share commonalities. In the precritical terrain, both are vagotonics with dysfunction of the exocrine pancreas (Fig. 11.8). In the critical terrain is exaggerated alpha- sympathetic response and overfunctioning corticotropic axis (Fig. 11.9). Psychological and psychosocial stressors are associated with UC e xacerbation. According to a systematic review of trials to date, psychotherapy is
helpful in improving subjective assessment of mood, and psychopharmacology therapy improves both mood and symptoms of UC.54
Comorbidities Adults and children with IBD have a higher incidence than age-matched controls of autoimmune and other inflammatory conditions.55–57 Incidence risk is twofold, commensurate to severity of disease and inversely related to use of salicylates in therapy.57 Most commonly occurring are uveitis and sclerosing cholangitis. Other manifestations include ankylosing spondylitis, spondyloarthropathies, pyoderma gangrenosum, pleuritis, erythema nodosum, and multiple sclerosis. Chronic UC is associated with a 2.4-fold increased risk in colon cancer.58
Epidemiology Similar to CD with respect to age, sex, geographic clime, and industrialization. UC tends to occur more commonly than CD, up to 3 times more often.15
Pathophysiology Precritical terrain UC occurs in vagotonic individuals (Fig. 11.8). The SFI is a general insufficiency of exocrine pancreatic enzymes. This
FIG. 11.8 Precritical terrain of ulcerative colitis. In vagotonic patients, there is an oversolicitation of the exocrine pancreas for general augmentation of digestive enzymes (black arrow). The response is insufficient (gray arrow), which solicits a reactive appeal (broken green arrow) which puts the patient in a hyperfunctioning parasympathetic state. This solicits a rise in alpha-sympathetic (black arrow) to match its tone. Alpha (αΣ) makes an appeal to beta-sympathetic (βΣ) which is delayed or blocked (gray broken arrow). This has two consequences: (1) blocked adaptation, (2) spasmophilia. Alpha also stimulates ACTH, and ACTH’s stimulation of the adrenal cortex is insufficient as well (broken gray arrow). This, along with a level of peripheral thyroid activity not sufficiently adaptated to alpha-sympathetic tone results in a total sympathetico-cortico-thyrotropic incompetence to adapt to future aggressions. The rising alpha tone that attempts to (unsuccessfully) readapt beta and adrenal cortex activity leads to a further reactive rise in parasympathetic tone (broken green arrow). (© 2015 Systems Biology Research Group.)
Inflammatory bowel diseases Chapter | 11 259
FIG. 11.9 Critical terrain of ulcerative colitis. It can be understood in three parts. The first is autonomic. Hyperfunctioning alpha (top center) stimulates a hyperfunctioning beta (adrenaline, top left), which favors hyperglycemia and inflammation. The second is the relaunching of the catabolic axes (center), again, by alpha. Central functioning exceeds peripheral gland response (gray, small print). The third is a disruption of the alpha-prolactin (PL)-growth hormone (GH) trépied (top right), discussed in Fig. 11.5. This participates in ulceration of distal colon mucosa. (© 2015 Systems Biology Research Group.)
entrains a hypervagal state which in turn solicits a reactive hypersympathetic response. This installs a spasmophilia, resulting in blocked adaptation. The adaptation dysfunction is rooted in dysfunctional yoking of alpha to the corticothyrotropic response. There is a hyper-ACTH response with insufficient adrenal cortex response. In the thyrotropic axis, peripheral thyroid activity is weak. In summary, the precritical terrain is a blocked neuroendocrine adaptation response with exocrine pancreatic insufficiency.
Aggressor and critical terrain: Ulcerative, hemorrhagic colitis
TABLE 11.15 ANS changes in the precritical and critical terrains of ulcerative colitis ANS
Precritial
Critical terrain
πΣ
++
++
αΣ
++
++++
βΣ
Blocked (spasmophilia)
+++
αΣ, alpha-sympathetic; βΣ, beta sympathetic; πΣ, parasympathetic. + Refers to the intensity of hyperfunctioning, the more pluses, the greater the hyperfunctioning.
Sympathetic In the face of some type of aggressors: a perceived stressor, an exaggerated response to a true aggressor,38, 39, 53 change of seasons, infection, diet, etc., the sympathetic nervous system is the initiating factor of a hemorrhagic UC. Ultimately, it is all three branches of the autonomic nervous system that are entrained into a hyperresponse in the face of an aggression. Table 11.15 summarizes the difference in the ANS between the precritical and critical terrains. Similar to CD, global sympathetic tone is elevated and far exceeds the parasympathetic response.
Endocrine response The endocrine response is detailed below and summarized in Fig. 11.9.
Corticotropic: First axis of solicitation 1. Central: ACTH in hyperfunctioning in adaptation: a. ACTH ≫ glucocorticoids, with adaptive cortisol blocking anabolism
b. Hypermetabolism of rectosigmoid colon to augment absorption of water and electrolytes for adaptation 2. Peripheral: insufficient adrenal cortex a. Cortisol > global adrenal cortex (relative): blocked anabolism in the face of mucosa proliferates → ulceration → hemorrhage
Thyrotropic: Second axis of solicitation 1. Central a. TRH hyperfunctioning: relaunches PL b. TSH hyperfunctioning: Expansion of cell membranes beyond anabolic capacity due to cortisol’s blockage of anabolism 2. Peripheral a. Peripheral thyroid insufficiency: absolute or relative to central functioning → insufficient lipid incorporation into growing and repairing cells → hemorrhage, blocked wound healing
260 The Theory of Endobiogeny
Somatotropic: Third axis of solicitation
Physical examination
The dysfunction of the alpha-PL-GH trépied is similar to that discussed in CD.
Abdominal exam similar to Crohn’s with respect to colon, liver, and pancreas; greater likelihood of pain on palpation of the distal colon from the splenic flexure distal to the rectosigmoid region
1. Central a. PL hyperfunctioning → i. Hyperinsulinism → inflammation of mucosa ii. ACTH relaunching → prolonged hypermetabolism of distal colon iii. Abscess formation favored iv. GH delay → impaired wound healing b. GH delay i. Insufficient insulin resistance → desynchronized nutrient entry in relationship to insulin → impaired cicatrization → ulceration, hemorrhage 2. Peripheral a. Hyperinsulinism proceeding GH with low insulin resistance → i. Elevated free radicals → inflammation → necrosis ii. Delayed wound healing iii. Fistula formation
Tissue pathology On biopsy of the distal colon, one notes a hyperimmune pattern with chronic inflammation. Cytotoxic T cells infiltrate the epithelium of colon. There are B-lymphocytes and increased IgG and IgE. Antibodies to the colon, smooth muscle, and cytoskeleton have been documented. Abscesses, granulomatous tissue, and pseudo-polyps may be present.59
Anatomical distribution of UC The most common areas of expression of UC are the anal verge, rectum, and rectosigmoid segments. Less common is pancolitis and least common is ileocecal involvement.60
Clinical presentation Similar to the colorectal symptoms associated with CD.
Laboratory studies: Critical terrain It is identical to that of CD with respect to CRP, fecal calprotectin, stool lactoferrin, and biology of function labs. Fecal calprotectin is the most sensitive and specific test in IBD in general of those listed, but is more targeted for UC than CD.25
Biology of functions: Critical terrain A similar consideration will be made in evaluating UC using the biology of functions as with CD. We start with a series of criteria to determine the critical vs suppressed critical vs precritical terrain (Table 11.16). It is important to note that as a functional disorder of adaptation, it is the adaptation indexes that will be the area of focus. And, most typically, it is the adaptation indexes that will be more deranged than those of structure. The first group of indexes is grouped together as “neuro- corticotropic” because of the implication of sympathetic activation of the corticotropic axis (Table 11.17). In order to discuss terrain, we introduce new indexes not previously discussed in other chapters or with respect to CD. The immediate adaptation index witnesses the relative role of the peripheral adrenal gland in the immediate adaptation syndrome. It will be elevated in both critical terrains. The CRH index evaluates the central activity of CRH. The greater the index, the greater the intensity of solicitation of the corticotropic axis is, and by extension, the less effective cortisol and aldosterone are in their negative feedback capacity. Treatment favors alpha-sympatholytics and central oxytocics such as Arnica montana or Taraxacum officinale to downregulate the amplifying role of vasopressin in ACTH relaunching and by extension vasopressin inhibitors (e.g., Taraxacum officinale).44, 45 Thus, one must also
TABLE 11.16 Criteria of indexes deranged per stage of terrain of ulcerative colitis Axis
Critical
Suppressed critical
Precritical
Neuro-corticotropic
>6/11
3–6/11
<4/11
Thyrotropic-immunity
3–5/5
2–4/5
<3/5
Somatotropic
>6/9
4–7/9
<4/9
Psychological
4–5/5
2–3/5
1–2/5
Total indexes deranged
21–30
11–20
8–10
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TABLE 11.17 Neuro-corticotropic terrains of ulcerative colitis Axis
Index
Critical terrain
Suppressed critical
Remission
ANS
Starter
↑↑ or ↓↓
↑ or ↓
Normal
Neuro-corticotropic
Immediate adaptation
↑↑
↑
Normal
Adaptation entrainment score adj.
↑↑
↑
Normal
Oxytocin
↓↓
↓
Normal
Vasopressin corrected
↑↑
↑ or ↓
Varies
CRH
↑↑
↑
Varies
ACTH
↑↑
↑ or ↓
Varies
Cortisol
↑↑
↑
Normal or ↓
Adaptation permissivity of the adrenal cortex
↑↑, may be negative
↑
Normal
Aldosterone comparative
↑↑, may be negative
↑, may be negative
Normal or slightly elevated
Adrenal yield
↑↑
↑
Normal
Corticotropic
evaluate the oxytocin index, which expresses the central effects of oxytocin. The index tends to be low in UC, which represents a dysfunction in posterior pituitary regulation of the corticotropic axis’ response to an aggression. This has not been well studied, however, peripheral use of oxytocin is antiinflammatory in experimental models of colitis, and may also be insufficient in UC patients during a flare-up.61 The lower the oxytocin index, the greater the difficulty in managing stress and the greater the tendency is to forming memories of stressful events. This last aspect of the index’s interpretation is germane to the psychological profile of the UC patient according to our experience. Finally, we introduce the adrenal yield index. It witnesses the relative efficiency of adrenal function in adaptation in relationship to the degree of stimulation. The higher the yield, the more exaggerated the output of the adrenal cortex will be in relationship to that of demand. Elevated cortisol is correlated with chronic psychosocial stress, and elevated cortisol is linked to dysfunction of the intestinal tract.39 In UC, the demand is elevated from the sympathetic nervous system, CRH, vasopressin, and ACTH. In addition, the feedback on central factors by peripheral corticotropic factors is impaired. It should be noted that the leukocyte and platelet mobilization indexes are not as reliable to evaluate alpha-sympathetic activity as other indexes. Thus, only the starter index is focused on here. That is because the global expression of sympathetic activity originating in the central, cognitive perception of stress is more relevant here than the solicitation of the splanchnic bed.
The activity of the thyrotropic axis is presented in Table 11.18. The thyrotropic axis is largely reactive and implicated in two ways. The first is yoking in the general catabolic response to an aggression. This is primarily expressed in the thyroid relaunching indexes and the thyroid index, and vitamin D adaptation index. And as with CD, when elevated, it favors treatment with high dose, short-term vitamin D.31 The other is in somatotropic desynchronization, most closely linked to the low serum TSH in both critical terrains. It is hard to define precisely a low TSH, because it must be
TABLE 11.18 Thyrotropic terrains of ulcerative colitis Index
Critical terrain
Suppressed critical
Remission
TSH serum
↓↓
↓
Normal
Thyroid relaunching
↑↑
↑
Normal to slightly elevated
Thyroid relaunching corrected
↑↑↑
↑↑
Normal to slightly elevated
Thyroid
↑↑↑
↑↑ or ↓↓
Normal to slightly low
Vitamin D adaptation index
↓, negative or both
Varies
Varies
262 The Theory of Endobiogeny
considered in relationship to osteocalcin and the cortisol index, amongst others. The higher the cortisol index, the more likely that even a low-normal TSH will exacerbate suppression of GH and thus somatotropic desynchronization. In general, we can say that an optimal TSH in healthy patients will be 1–4, with 0.51–0.99 considered low, and values less than or equal to 0.5 as very low. The somatotropic axis and its relationship to the corticotropic axis are important for two reasons. The first is in turning the loops and prolonging the corticotropic response to an aggression. The second is delayed wound healing and blocked anabolism (Table 11.19) The alpha-GH-PL trépied was previously discussed and can be observed in the indexes of the biology of functions: low Prolactin and low GH growth score index. Cellular architecture is disrupted, as with CD. With respect to autophagy, it is disrupted as well.33, 34 However, the origin of it is system dysfunction, not intrinsic cellular dysfunction. This is reflected in the autophagy 2 index. It evaluates the relative risk of insufficient cellular autophagy in the face of oversolicited organotissular metabolism imposed by global metabolic demands. An elevated index, as one notes in UC, favors the use of intermittent fasting for 1–3 days during the critical phase of hemorrhagic colitis. Observational studies in UC, and general observations of improvement in chronic, degenerative disorders support this approach.62, 63 More studies in the IBD population needs to be conducted, especially when the patient is in the critical terrain. One also sees similar disruptions in insulin and insulin resistance and hence a hyperoxidative state with elevated free radicals. Thus, free radical scavengers such as α-lipoic acid can also be considered during the acute phases of the critical terrain or to help abort hemorrhage with prodromic expressions of dysadaptation.37 Naturally, necrosis will be elevated.
One may also evaluate the psychological states in the UC patient using the biology of functions, as one does in CD (Table 11.7). UC psychological profile is similar to CD with a few exceptions. In UC, again, one evaluates the function values (Table 11.20). In the psychological indexes, this represents the relationship of these patients with nonfamiliar people: colleagues, classmates, and the general public. The indexes tend to be less elevated and less likely to be negative, as opposed to CD. In addition, it is the frustration score 2 rather than the frustration index that is elevated. The frustration score 2 evaluates the tendency to feel frustrated due to a reactivity of the organism lying within the thyrotropic axis, which participates in intense but fugacious expressions of negative imagination and worry. When the index is elevated it favors a phlegmatic personality type. Our characterization of the UC psychological typology has not been elucidated in the literature. What has been established is that perception of stressors and the patient’s belief in their capability to respond are relevant, especially if they are chronic stressors.38, 39, 53 One need not be a psychotherapist to appreciate the importance of evaluating chronic psychosocial stressors in IBD patients. Perceived stress and its physiologic response impair wound healing and perpetuate a low-grade chronic stress response that fragilizes the buffering capacity and increases the risk of relapse when patients are in remission.39, 53, 64 The IBD patient feels unloved, reflected in the closed off from receiving index. There is an underlying sense of emotional vulnerability, reflected in the permeability adjusted index. The higher the index, the greater the feeling of emotional vulnerability. It is elevated during a flare-up and may persist even in remission, but certainly in the suppressed critical terrain. In fact, from remission to a fragilization and risk of flare-up, one is likely to see this index rise, even before the onset of clinical symptoms. From the feeling of
TABLE 11.19 Somatotropic terrains of ulcerative colitis Axis
Index
Critical terrain
Suppressed Critical
Remission
Somatotropic
Prolactin
↓↓↓
↓↓
Normal
GH growth score
↓↓↓
↓↓
Normal
Somatostatin
↓↓
↓
Normal
Insulin
↑↑↑
Varies
Normal
Insulin resistance
↓↓
Varies, often low
Normal
Expansivity #2
↑↑
Varies
Normal
Redox
↑↑ to ↑↑↑
↑ to ↑↑
Normal
Necrosis corrected
↑↑↑
↑↑
Normal
Autophagy 2
↑↑↑
↑↑
Normal
Inflammatory bowel diseases Chapter | 11 263
TABLE 11.20 Psychological indexes related to ulcerative colitis Critical terrain
Suppressed critical
Remission
Closed off from receiving
↑↑
↑
Normal
Permeability adjusted
↑↑↑
↑↑
Normal to ↑
Traumatic memory
↑↑
↑
Normal
Acceptancecontentment
↓↓
↓
Slightly ↓, normal, or ↑
Frustration score 2
↑↑
↑
Slightly ↑ to normal
Index
not being loved and the feelings of emotional vulnerability, one notes that UC patients have traumatic rumination during their crisis, reflected in the traumatic memory index. UC patients are generally discontent with their situation, reflected in the acceptance-contentment index, which when low indicates this feeling of discontent and searching from answers that one cannot find. This tends to persist, even in the precritical terrain. If the patient has an elevated index in the precritical terrain, it indicates that they tend to rationalize their discontent. This increases the risk of a flare-up even more than a slightly low score. With this comes a great sense of frustration with themselves and their situation, reflected in the frustration score 2 (as opposed to the frustration index in CD). Finally, UC patients tend to be critical of others, sometimes projecting their own internal frustration. This is reflected in the critical tendency score, which evaluates the tendency to be critical against oneself and other people.
The gonadotropic axis (Table 11.21) is not part of the assessment of the critical terrain of UC per se except for the genito-thyroid index, which is elevated. It is a nonspecific indicator of hyperimmune, pro-inflammatory terrain. However, we present values to demonstrate how distinct the terrains of CD and UC are. NB: normal values differ for adolescents compared to adults.
Treatment: General considerations according to an endobiogenic reflection The Endobiogenic approach to the treatment of hemorrhagic UC is similar to that of CD: treat symptomatically at first, alter diet, and then address the issues of terrain. The same considerations of appropriateness of treatment and severity of presentation pertain here as in the discussion of CD. Considering the nature of UC, there will be a greater Endobiogenic emphasis on managing the autonomic nervous system, corticotropic and somatotropic activity than in CD.
Treatment: Standard of care The same considerations apply to the role of pharmaceutical treatments, their advantages, and limitations. The standard approach to UC is to characterize severity of the flare-up by the number of bloody stools per day, and the presence of one or more of the following: fever, anemia, tachycardia, elevated markers of inflammation.60 The general progression of stepped-up therapy is also similar. There are some particularities to UC. Mild disease is defined colitis limited to the rectum, with less than 6 hemorrhagic stools per day. Mesalamine suppository is more effective than oral dosing. If the colitis is mild but includes more proximal segments of the intestine, lower-dose oral mesalamine is favored.2 Oral steroids will be reserved for treatment failure of mesalamine.
TABLE 11.21 Gonadotropic terrains of ulcerative colitis Axis
Index
Critical terrain
Suppressed critical
Remission
Gonadotropic
LH
↓↓
↓
Normal
FSH
↓↓
↓
Normal
Organotissular estrogen yield
↑↑
↑
Normal
Estrogen index
↑↑
↑
Normal
Estrogen index corrected
↑↑
↑
Normal
Genital androgens
↑↑
↑
Normal
Genito-thyroid
↑↑
↑
Normal
Gonado-thyrotropic
264 The Theory of Endobiogeny
Severe disease is defined as 6 or more bloody stools per day with fever, anemia, tachycardia, and/or elevated inflammatory markers elevated, such as fecal calprotectin, CRP, etc. Current treatment standards include starting with intravenous glucocorticoids, high dose. The other immunosuppressive and biological agents discussed in CD can also be used based on various considerations.
TABLE 11.22 Sources of vitamin A Food
Vitamin A per 1 cup
Sweet potato
1900
Carrots
1000
Spinach
940
Kale
885
Mustard greens
865
Collard greens
770
Squash
535
ANS
Cantaloupe
270
Reduce global autonomic activity, favoring plants that are spasmolytic and/or with an intestinal tropism (cf. Crohn’s disease). In addition, the following medicinal plants are quite efficient in UC:
Papaya
130
Apricots
33
Symptomatic treatment: An endobiogenic approach Cf. Crohn’s disease.
● ● ●
Passiflora incarnata Melissa officinalis Ilex acquafolium GM
Diet and lifestyle during a crisis ●
●
Diet: avoid dairy products; high purine protein, low fat, low fiber Lifestyle: calming activities: meditation, breath work, yoga, Tai chi, prayer, etc.
Treatment of terrain: An endobiogenic approach
●
We recommend 2000–4000 IU per day for the first 2 weeks of recovery is recommended, followed by 1000–4000 IU per day based on preference of the patient for these types of foods Vitamin E is best obtained through diet as well (Table 11.23). For the first 1–2 weeks of recovery, encourage 300–400 mg of vitamin E from the diet
Somatotropic Cf. Crohn’s disease.
Drainage
Corticotropic
Cf. Crohn’s disease
Support adrenal activity while reducing ACTH (cf. Crohn’s disease).
1. Liver: ensure good hepatic drainage 2. Pancreas: support exocrine function 3. Intestines and colon: support cicatrization of mucosal tissue and tonification of mucosa
Thyrotropic Reduce central hyperthyroidism (cf. Crohn’s disease) Modulate peripheral thyroid terrain according to the Endobiogenic state of the patient and support PTH ● ●
● ●
●
Avena sativa Selenium oligo (also reduces inflammation, supports hepatic detoxification activity) Calcium (chronic use) Vitamin D 5000–10,000 IU in the morning, reduced to 3000–4000 maintenance or according to the Endobiogenic terrain and quality of vitamin D’s management of adaptation response Vitamin A is best obtained through diet (Table 11.22). Vegetables are the richest sources. Some fruits p rovide moderate amounts of vitamin A. While animal sources also provide retinol, they are not recommended in UC.
TABLE 11.23 Sources and servings of vitamin E Source
Per 100 g serving (mg)
Wheat germ oil
150
Almond oil
95
Canola oil
44
Sunflower oil
41
Hazelnuts
20
Almonds
15
Olive oil
14
Inflammatory bowel diseases Chapter | 11 265
Treatment: After hemorrhagic flare-up Medicinal plants ● ● ● ●
Improve adaptability of the organism Maintain central inhibition ACTH, TRH, TSH, PL Hepatopancreatic drainage Re-equilibrate enteric flora
Diet ●
● ●
Pancreas sparing diet, in particular avoiding dairy products Vegetarian or pescatarian diet Fermented foods
Sample treatment ●
●
● ●
●
Vegetarian diet emphasizing foods rich in vitamins A and E (Tables 11.22 and 11.23) Illite clay 1 tbsp + 1 drop Carum carvi (caraway) EO + 1 drop Mentha piperita EO every 4 h prepared with Juglans regia leaf tisane until bloody diarrhea resolved ● 200 mL tisane of Juglans regia leaf tisane: 1 heaping tsp. Juglans regia (walnut) leaf: steep 8 min in hot water; strain ● Let clay mixture sit 15 min or longer, mix again, then consume Vitamin D 5000 IU in AM Somatotropic: astringent, antihemorrhagic cicatrizant tincture: Lamium album MT 30 mL, Poterium sanguisorba MT 30 mL, Malva sylvestris MT 30 mL, Hamamelis virginiana MT 30 mL: 3 mL q8 a.m., noon, 4 p.m., 8 p.m. until bleeding has resolved ANS-cortico-thyrotropic tincture: Passiflora incarnata MT, 60 mL, Sequoia gigantea GM 60 mL, Zea mays GM 60 mL, Viburnum lantana GM 60 mL + eucalyptus EO 3.5 mL, clove EO 0.5 mL: 4 mL twice per day
Conclusions Crohn’s disease (CD) and ulcerative colitis (UC) are both classified as inflammatory bowel disorders. According to the theory of Endobiogeny, they are not on a spectrum of the same general type of disorder, as they differ in their structural factors of initiation (SFI). CD is a structuro-functional disorder rooted in a faulty FSH-estrogen relationship and an impaired adaptation response due to an exhausted parathyroid gland. It is a disorder of the intrinsic ability of the bowel to maintain its integrity in the face of an aggression. The response is exaggerated and brutal, resulting in ulceration and delayed wound healing. The ulceration in CD is deeper than UC, and all areas from mouth to anus may be affected.
UC is a functional disorder rooted in a faulty autonomiccorticotropic relationship. It is a systemic disorder that happens to be expressed at the level of the bowel because the bowel is a metabolically active tissue because it constantly faces aggressions in the form or diet and other genetic variables that fragilize the intestines. The level of ulceration is superficial and is limited to the colon, and most often to the distal rectosigmoid region and anus. The symptomatic treatment of both types of IBD is similar, be it pharmaceutical or nonpharmaceutical. It involves reducing inflammation, hyperimmunity and the adaptation response, and stimulating bowel restoration. The treatment in remission and goals for treatment of the precritical terrain vary as they have unique origins from the perspective of Endobiogeny. In both conditions, the Endobiogenist should pay careful attention to the psychological component of the patient and their experience of stressors and the disease itself, as it has been shown to play a role in the severity and course of disease.
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