The Salted Food Addiction Hypothesis may explain overeating and the obesity epidemic

Medical Hypotheses 73 (2009) 892–899

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The Salted Food Addiction Hypothesis may explain overeating and the obesity epidemic James A. Cocores a,*, Mark S. Gold a,b a b

Department of Psychiatry, University of Florida College of Medicine & McKnight Brain Institute, Gainesville, FL, USA Departments of Psychiatry, Neuroscience, Anesthesiology, Community Health & Family Medicine, Gainesville, FL, USA

a r t i c l e

i n f o

Article history: Received 24 June 2009 Accepted 28 June 2009

s u m m a r y One plausible explanation for the controversy that surrounds the causes and clinical management of obesity is the notion that overeating and obesity may only be a couple of ‘‘symptoms” associated with a yet to be discovered medical disorder. Objectives: To introduce the Salted Food Addition Hypothesis. This theory proposes that salted food acts in the brain like an opiate agonist, producing a hedonic reward which has been perceived as being only peripherally ‘‘flavorful”, ‘‘tasty” or ‘‘delicious”. The Salted Food Addition Hypothesis also proposes that opiate receptor withdrawal has been perceived as ‘‘preference,” ‘‘urges,” ‘‘craving” or ‘‘hunger” for salted food. Methods: The Salted Food Addiction Hypothesis is made manifest by individually presenting a basic review of its primary coexisting components; the Neurological Component and the Psychosocial Component. We also designed a prospective study in order to test our hypothesis that opiate dependent subjects increase their consumption of salted food during opiate withdrawal. Results: The neuropsychiatric evidence integrated here suggests that salted food acts like an, albeit mild, opiate agonist which drives overeating and weight gain. The opiate dependent group studied (N = 27) developed a 6.6% increase in weight during opiate withdrawal. Conclusions: Salted Food may be an addictive substance that stimulates opiate and dopamine receptors in the brain’s reward and pleasure center more than it is ‘‘tasty”, while salted food preference, urge, craving and hunger may be manifestations of opiate withdrawal. Salted food and opiate withdrawal stimulate appetite, increases calorie consumption, augments the incidence of overeating, overweight, obesity and related illnesses. Obesity and related illnesses may be symptoms of Salted Food Addiction. Ó 2009 Elsevier Ltd. All rights reserved.

Introduction Little is known about the uncontrollable overeating commonly associated with obesity. Much less is known about treatment techniques that can enable ‘‘willing” candidates to transition into ‘‘able” new-lifestyle neophytes, who gradually reach and maintain their ideal weight for the duration of what is purported to be an extended life span. One explanation for the controversy that surrounds the causes and clinical management of obesity is the notion that overeating and obesity may only be a couple of ‘‘symptoms” associated with a yet to be discovered medical disorder. Addictions, or Substance-Related Disorders, have been long thought to be the exclusive province of drugs of abuse, like cocaine or heroin, because they prompt progressive neuro-receptor sensitivity, reward, brain plasticity and tolerance, while drug with-

* Corresponding author. Address: Department of Nutritional Neuropsychiatry, Southcoast Psychotherapy and Education Associates, 5301 N Federal Hwy., Suite 270, Boca Raton, FL 33487, USA. Tel.: +561 989 9393; fax: +561 989 9369. E-mail address: [email protected] (J.A. Cocores). 0306-9877/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2009.06.049

drawal correlates with dysphoria, craving and the priority of seeking, obtaining and consuming more addictive substance. What ensues is a bio-behaviorally based and maladaptive ‘‘need” to use progressively larger quantities of drug(s) in order to quiet physical and neuropsychiatric withdrawal and be re-rewarded with less discomfort or euphoria. This insidious neuropsychiatric cycle defines the fundamental nosological boundaries of ‘‘addiction” or Substance Dependence. More recently, foods have been considered as a substance of abuse because they share common pathways of reward. Articles on ‘‘excess sugar addiction” [1 and ‘‘salt cravings” [2] have appeared in the literature while this article was underway. Specifics regarding how adaptive changes in human neuro-plasticity/consummatory behavior become maladaptive have not been sufficiently fleshed-out in the literature in order to add ‘‘Processed Food-Related Disorders” to the next edition of the Diagnostic and Statistical Manual of Mental Disorders [3], implicating it as a primary cause of overeating, overweight, and obesity. Hence the purpose of this article is to take a nosological first step towards a Hypothesized Processed Food-Related Addictive Disease.

J.A. Cocores, M.S. Gold / Medical Hypotheses 73 (2009) 892–899 Table 1 Hypothesized processed food–related disorders. Amino Acid Use Disorders – Food(s) with an increased A–O (free Amino acid availability to Oral mesolimbic receptors) Index  Amino Acid Abuse (i.e. previously skinned and soaked roasted chicken breast)  Amino Acid and Fatty Acid Abuse (i.e. rib eye steak)  Amino Acid and Monosaccharide Abuse and Dependence (i.e. certain whey, soy, cottage cheese preparations) Fatty Acid Use Disorders – Food(s) with an increased F–O (free Fatty acid availability to Oral-mesolimbic-receptors) Index  Fatty Acid Abuse (i.e. broiled fresh pork rind)  Fatty Acid and Monosaccharide Abuse and Dependence (i.e. milk chocolate, ice cream) Monosaccharide Use Disorders – Food(s) with an increased M–O (Monosaccharide availability to Oral-mesolimbic-receptors) Index. Monosaccharide Abuse and Dependence (i.e. bread, soda, candy, certain breakfast cereals) MIXED PROCESSED FOOD – RELATED DISORDERS Non–Nutritive Sweetener (NNS) Use Disorders – Aspartame, sucralose or saccharin combined with: NNS-Amino Acid Abuse (i.e. unsweetened gelatin) NNS-Fatty Acid Abuse (i.e. sugarless cheese cake) NNS-Monosaccharide Abuse and Dependence (i.e. certain cereals, pudding, gelatin, gum, mints) NNS-Other (i.e. certain flavored water) Salted Food Use Disorders – Moderate to high sodium chloride added to: Salted Protein Abuse and Dependence – protein with a high A-O Index (i.e. beef jerky) Salted Lipid Abuse and Dependence – lipid with a high F-O Index (i.e. butter, certain non-butter spreads) Sodium Salted Mixed Food Abuse and Dependence (i.e. pizza, hamburger, cheese, French fries, bacon, certain canned soups, certain frozen meals, chips, energy bars, eatery food, complete nutrition drinks) Potassium Salted Mixed Food Abuse (i.e. ‘‘no sodium added” foods) Salted Carbohydrate Abuse and Dependence – carbohydrate with a high M–O Index (i.e. pretzels) Mixed Unsalted Food Use Disorders (i.e. dry roasted peanuts)

The subject of this article is, in our opinion, one of the most commonly occurring subcategories of the Hypothesized Processed Food-Related Disorders (Table 1), developed from a research outline completed in 2006 [4], in industrialized regions; Sodium Salted Mixed Food Dependence, or for our purposes ‘‘Salted Food Addiction”. The Salted Food Addition Hypothesis (SFAH) proposes that salted food acts in the brain like an opiate agonist, thereby producing a hedonic reward, which has been perceived as being only peripherally ‘‘flavorful,” ‘‘tasty” or ‘‘delicious.” The SFAH also theorizes that opiate receptor withdrawal has been perceived as ‘‘preference,” ‘‘urges,” ‘‘craving” or ‘‘hunger” for salted food. The SFAH also claims that the daily use of salted food produces Salted Food Addiction, which in turn progressively escalates (opioid ‘‘tolerance”) to overeating, an increase in the number of calories consumed daily, overweight, a sedentary lifestyle, obesity and the numerous medical illnesses stemming from obesity. The Salted Food Addiction Hypothesis (SFAH) is made manifest by individually presenting a brief review of its primary coexisting components; the Neurological Component and the Psychosocial Component. The neuropsychiatric evidence integrated here coupled with new data showing increased consumption of salted food and weight gain in opiate dependent patients during withdrawal support the hypothesis that salted food acts like an opiate agonist and existence of Salted Food Addictive Disease.

Neurological perspective The peripheral gustatory system Taste Receptors may actually be referred to as ‘‘external’ afferents of the central nervous system because they are open to the environ-

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ment - the precise density of sodium-specific receptors and their distribution within the oral cavity varies from species to species and subject to subject [5–7]. Sodium-specific taste receptors rely on the innervating nerve for their nutrients [5,8]. It is for this reason that in most cases salt-specific taste receptors degenerate when their respective innervating nerve is transected [8]. Atrophic receptors innervated by cranial nerve seven or nine readily regenerate after its corresponding nerve is reinnervated. Receptors innervated by cranial nerve twelve do not appear to show the same resilience [9]. Dietary sodium manipulations have been shown to alter peripheral taste receptors and serve as a model for sensory plasticity [10], which may also be reflective of a more central neuronal progression of sensitization, tolerance, and addiction. The Chorda Tympani Nerve (CT), a branch of the facial (cranial nerve 7), innervates the taste buds or receptors in the anterior two-thirds of the tongue. Almost half of taste receptors in this field are highly sodium sensitive [11]. Transection of the CT severely disrupts the ability to taste the difference between NaCl and KCl [12], and reduces salt intake even during sodium depletion, perhaps making the taste bud an example of an external receptor. Amiloride decreases the responsiveness of taste receptors that are important in sodium and non-sodium salt discernment [13]. An intact CT is critically important to salt craving even during sodium depletion [14]. Though speculative, the contemporary role of the CT may have changed in humans from an ancestral need for detecting salt during sodium depletion, to one of detecting poisonous levels of salt in food or beverage (i.e. rejection of a cold glass of sea water or over-salted food) and optimally salted food while sodium-replete. The lingual tonsilar nerve, a branch of cranial nerve number nine, the glossopharyngeal nerve (GN), innervates taste receptors in the tongue’s posterior field. This field has less sodium-specific receptors when compared to the CT innervated anterior field [15]. It has been postulated that the GN compensates by becoming more sodium-sensitive following resection of the CT [16]. This is yet another demonstration of receptor plasticity, which is inherent to the central nervous system [17] and may explain salted food-induced peripheral receptor super-sensitivity [18,19] as well as escalation of salted food intake and tolerance. Amiloride does not block glossopharyngeal sodium taste response as it does in the CT perhaps due to the presence of less sodium-specific receptor subtypes [20]. The Greater Superficial Petrosal Nerve (GSP), a branch of the hypoglossal (cranial nerve 12), innervates the taste receptors clustered in three distinct areas of the palate. The first field of taste receptors is in the anterior hard palate immediately behind the upper incisors. The second field is in the form of a strip of receptors straddling the hard and soft palates and the third area is found towards the rostral aspect of the soft palate. GSP afferents are third in line regarding the quantity and quality of sodium-specific taste receptors [21] in the oral cavity. Palatal sodium afferents are strongly reduced by amiloride [22]. Amiloride reduces salt appetite to a greater extent than CT transection alone [23], which suggests sodium selective taste receptors similar to the ones found on the surface of the posterior tongue are also present on the palate. This suggests that the GSP is second to the GN with regard to the density of salted food receptors occupying the oral cavity. The Superior Laryngeal Nerve (SL), a branch of the vagus (cranial nerve 10), innervates taste receptors in the laryngeal epithelium. These receptors contain water fibers that influence dieresis [24]. Urine flow increases when water is applied to the larynx, while this response is decreased by sodium [25]. The role of these receptors is to maintain isotonicity while consuming a hypertonic meal or snack. Monosaccharide, amino acid [26], fatty acid [27] and other taste receptor types have been identified and known to be interspersed

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in varying densities among salt receptors on the lingual-palatal fields. However, a review of each macronutrient and macro-nonnutritive substance is beyond the scope of this article and remains the topic of a different article. Research from this point forward on the oral-mesolimbic trail becomes comparatively sparse. Geniculate and petrosal ganglia The somata of the CT (anterior tongue) and GSP (palate) are located in the geniculate ganglion (GG). Sodium chloride elicits high response frequencies in a subset of CT neurons and moderate response frequencies in relatively larger proportion of GSP neurons [28]. This disparity goes along with the belief that receptors innervated by the CT are more sodium specific, while the sodium receptors occupying the GSP fields contain proportionately more widely tuned neurons, which are more likely to be dedicated to other macrominerals, and macronutrients such as glucose. Neurons in the GG also respond to 5HT and GABA, but not Ach and substance P [29], which may correspond with reports of the presence of amino acid or protein-specific taste buds [30] on the anterior tongue and palate. Taste receptors on the posterior field of the tongue (GN) have cell bodies in the petrosal ganglion (PG). Neurons in the PG exhibit both sharp and humped action potentials. Neurons with humped action potentials have been linked to pain via nociceptors, while neurons with sharp action potentials innervate taste receptors. In this way, neurons of the PG are less homogenous than those of the GG, and respond to acetylcholine, 5HT, SP, and GABA [29]. The larger variety of transmitters parallels the greater density of macronutrient to sodium receptors, salted food, found on the posterior aspect of the tongue. A speculation with regard to the peripheral gustatory system is that it is mostly stimulated by the macronutrient(s), and macromineral(s) deficiencies present within the mammal, thereby maintaining homeostasis. If this were the case, it may support the view that optimal nutrition is best achieved by eating a variety of wholesome foods throughout the day a la ancestral foraging, rather than one to three meals per day along with supplements. More research is needed here. The central gustatory system The delineation from peripheral to the central gustatory system can be made where salted food triggered impulses originating in the oral cavity/ganglia converge on the nucleus of the solitary tract (NST) in the brainstem. Gustatory neurons employ glutamate as a messenger at their central synapses in the rostral portion of the NST [31] and AMPA type glutamate receptors are thought to be targeted to synapses within taste receptors [32]; this may partially explain why monosodium glutamate is a more powerful flavor enhancer compared to sodium chloride. GABA and SP are thought to function as inhibitory and excitatory neurotransmitters at the NST relay [33]. More research is needed along this pathway. Mesoaccumbens pathways Salt-specific taste receptors travel through the ganglia and NST and continue into mesolimbic structures. Discernment between either ‘‘aversive,” ‘‘safe” [34] or ‘‘preferred” peripheral signals occurs in this region of the brain. Aversive signals appear to be diverted to the mesocortical pathways connecting the VTA to cortical areas in the frontal lobes when the anterior field of the tongue detects high concentrations of salt; stimulating dopaminergic and glutamatergic pathways may prompt instantaneous mobilization away from potentially toxic salt sources. We hypothesize that mu governed rapid increases in extracellular dopamine receptors, which are activated by

delta (1)-opioid receptors and not delta (2) [35] are responsible for sudden retraction from sea water or overly salted food and salted food seeking behavior during hunger. Conversely, low sodium, moderate and deliciously salted food signals originating from the lingual-palatal fields are recognized as homeostatically ‘‘safe” and immobilize the organism by instilling an instantaneous central reward in the form of euphoria from mesolimbic pathways connecting the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and the ventral pallidum. It has been known for a long time that organisms will actively work to restore sodium levels if depleted [36]. Furthermore, it has been demonstrated that a history of sodium depletion (and perhaps ‘‘relative” sodium depletion in sodium sensitized over eaters) results in long lasting increases in sodium consumption, even when currently sodium ‘‘need-free” or replete [37–39], and that these changes are accompanied by neurobiological alterations [40]. In these instances, the mesolimbic opioid system becomes engaged and actively participates in activating salt intake, reward and continued salted food consumption [41,42] even while satiated. A particularly interesting finding is that the aversiveness of high sodium solutions can be switched to a ‘‘pleasant” taste in animals with a history of sodium deprivation, and that the neural activity in the ventral pallidum (a brain region with extensive connections to e.g., the nucleus accumbens) switches to a pattern associated with other reinforcers (e.g., saccharin) [43,44]. These findings may explain why continued consumption/reward with immobility, overeating, may be brought about by mu moderated slow onset increases in extracellular dopamine (mu-s), which occurs by inhibiting delta (1) or delta (2) stimulation. The direct connection between salt receptors (in the presence of various macronutrient receptors or salted food) on the tongue and the mesoaccumbens brain regions associated with reward establishes a neuropsychiatric explanation for overeating salted food in sodium replete individuals, as well as the more established findings of increases in sodium-seeking and consumption of hypertonic liquids and foods in sodium-depleted individuals. Along these lines, it is of interest that mu opioid receptor stimulation in the nucleus accumbens results in increased salt drinking and intake in never-deprived, sodium-replete animals [45,46], and opioid antagonists block saline intake in animals deprived of water [47]. Because Addictive Diseases are neuropsychiatric entities, we now turn to the psychosocial perspective, integrating the briefly reviewed neurologic perspective as we proceed.

Psychosocial perspective Salt Sodium or salt ‘‘appetite” has been defined as a powerful drive to seek, obtain, and consume sodium [48]. This motivated behavioral state arises as a response to sodium deficiency [49] and tends to vary in magnitude depending on the species studied. The majority of early studies examining salt appetite in sodium-depleted rats showed a marked affinity towards salt. The magnitude of behavioral reward associated with salt consumption in depleted adult rats may be stronger than directly rewarding brain stimulation [50]. However, salt appetite and craving appears to be a phenomenon confined to sodium depleted animals. A strong preference for salt does not consistently accompany experimental sodium depletion in humans [51] and salt appetite has been reported in only about 15% of people suffering from Addison disease [52]. Furthermore, sodium replete-rats choose isotonic saline over water, and prefer unsalted food to salted food [53], while newborn humans are either averse to saline [54] or do not differentiate between saline and water solutions [55]. This disparity changes to a preference for near-isotonic salt solutions relative to water between 4 months and 24 months of age [56]. Children between 31

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and 60 months of age acquire an adult like taste because they reject saline solution and pursue salted soup, a salted food [57]. Salted food Rats fed junk-food during pregnancy have offspring that prefer junk-food (processed and salted), and develop obesity [58]. The paradigm of placenta-mediated brain receptor sensitivity in drug-dependent newborns suggests that childhood overweight and obesity is a function of both genetics and trans-placental over-exposure to salted foods, however, this is speculative. Humans over-exposed to salted food during intrauterine development may conceivably be born in withdrawal from salted food, but this is also speculation. Under circumstances of less excessive exposure to processed salted food prenatally, 4 and 7 month-old infants are indifferent with regard to salted and unsalted food [59]. However, some 4 [60] and 6 month old infants have established preferences based on the amount of salted food consumed during the previous week [61]. This disparity can be explained in part due to variations in the sodium content of milk administered. The sodium content in breast milk is known to vary diurnally, throughout lactation [62], and from mother to mother. Single case reports range from breast milk induced infant hyponatremia [63] to hypernatremia [64]. Tap water used to dilute milk formula varies with regard to sodium content, and can determine if the infant is on a low or high sodium diet [65]. A relatively high concentration of sodium may be one reason why it is wise to delay the introduction of cow’s milk to older infants [66]. Soy formula may present similar inconsistencies, but this has not been adequately studied. Pre-exposure with high-sodium milk or formula and preprocessed baby foods may affect the degree of preference for plain and salted cereal by 6 months of age, and a significant number of 6 month old infants eat more salted than unsalted cereal [61]. Low sodium feeding past 4 months of age produces a generalized preference for low sodium food, while eating salted foods past 6 months of age can result in a generalized salt preference [67]. Low sodium preference may correspond to a ‘‘default” or non-addiction opioid receptor plasticity setting, while moderate to high (delicious) sodium eating may be reflective of opioid receptor sensitization or tolerance manifested behaviorally as the need to consume progressively larger amounts of salted food in order to quiet hunger or withdrawal by obtaining sufficient opioidergic and dopaminergic reward commonly perceived as satiation. Preference for salted food may be evident as late as 2 years of age given availability and a preferred context [57]. Item-specific preference becomes more intense and variable during early preschool as deprivation of a particular salted food for one week results in marked enhancement of preference [68,69], like drug urges or withdrawal. It also is exemplary of how childhood favorites such as pizza, burgers or macaroni and cheese can be viewed as ‘‘drugs of choice”, like heroin or oxycodone over all other opiates. It is interesting to note that middle school students deprived of high sodium (and saturated fat and Glycemic-Index (GI) dough) pizza consumed fewer slices and calories of the low sodium, saturated fat and GI-dough version [70], and left satiated [71], which may be a paradigm for item-specific detoxification using less ‘‘addictive” salted foods or nutraceuticals. Adolescents tend to prefer higher levels of salt compared with adults [72], which parallels the thrill seeking orientation and experimentation with nicotine, alcohol and other drugs characteristic of this age group. In addition to the ongoing (often overly salted) school lunch program, adolescents progressively become more mobile, independent and at liberty to frequent restaurants, with progressively less ‘‘home” cooked meals and supervision. These factors also contribute to experimentation with tobacco, alcohol and other drugs of abuse. The importance of sensory context in item-specific preferences established during childhood

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[57,73] continues into adolescence. Both adolescents and adults are exposed to greater sensory exposure. Restricted sensory exposure decreases appetite [74], while greater sensory exposure can increase appetite [75]. Industrialized societies are also subject to time restrictions lending themselves to increased consumption of commercially prepared salted ‘‘convenience” foods. Adults who frequently consume large amounts of salted food prefer saltier food [75–77]. Increased dietary sodium directly correlates with increased calorie consumption, while decreased sodium consummator habits lowers calorie intake [78,79]. ‘‘Salted food craving” may be a neuropsychiatric manifestation of severe dysphoria resulting from a high tolerance and severe withdrawal at mu-s opioid receptor sites, while overeating may be a neuropsychiatrically based maladaptive attempt to self-medicate mood destabilization. Persistent salted food cravings can vary from patient to patient with regard to duration, however, a fairly consistent increase in craving does generally occur during the transition to reduced sodium diet [80] using abrupt transition to a low sodium diet plan. More specifically, reduced preference and craving has been estimated to occur after about 2– 12 weeks [81,82] of being on a lower sodium diet. This may correspond to the ‘‘detoxification” or receptor desensitization period. Social Preferred taste rapidly develops when salt is introduced to salt impoverished societal food chains [83]. The majority of children and adults consume more salt (from salted food) than they need [84]. Discretionary use of table and cooking salt constitutes less than ten percent of dietary sodium [85]. Over 90% of the sodium ingested by American adults originates from sources other than that added during home preparation or at the table [86] such as processed food. Salted foods make up as much as 40% of the total energy consumed when salt is readily available [87] (this 1985 statistic is likely to be an underestimation as it relates to 2008). In addition to the growing availability, social stress among industrialized cultures increases salted food consumption during childhood [88] and adulthood (while clonidine decreases sodium intake) [89]. These and other factors may explain why the per capita use of salt has increased by about 50% from the mid-1980s to the mid-1990s [90], while the use of cocaine decreased by about 60% during the same time period [91]. The average per capita intake of salt has been estimated to be 10–12 g/d, or about 4000 mg of sodium [92].

Evidence linking opioid dependence to obesity The Salted Food Addiction Hypothesis also postulates that chronic depletion of opioid receptors secondary to opioid dependence concurrently increases salted food intake, calorie consumption and weight during opiate withdrawal and detoxification as an instinctive counter measure to self-medicate an ‘‘opiate deficiency”. Little research has addressed the role of opiate withdrawal in driving the need to consume larger quantities of salted foods. A gating device was bioengineered permitting the delivery of either an opiate agonist or antagonist to animals, enabling precise control over the timing and duration of opiate withdrawal [93]. Body mass index (BMI) rapidly decreased when the opiate agonist was delivered while the BMI increased during opiate withdrawal. One retrospective study reported a 3.9% weight increase from the time of admission until discharge in a group of 17 opiate-addicted women [94]. Five opiate dependent and bulimic women developed an 11% weight gain while undergoing opiate detoxification. We designed a prospective study in order to examine consummatory behavior and weight change in a group of opiate dependent subjects during opiate withdrawal.

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Method A prospective study was conducted in a group of outpatients to evaluate the impact of opiate withdrawal and detoxification on the consumption of salted food and weight. The information collected included the initial evaluation, psychological and psychosocial assessment, consummatory assessments, medical history with supporting data, substance use history, weight upon admission and 60 days (±3 days) later at approximately the same time of day as admission, progress notes and urine drug screens. Data was collected on 27 patients with a primary diagnosis of opiate dependence; there were 14 females and 13 males. The clinical course of each of these patients was examined through both chart review and regular follow-up interviews. Results Eighty-one percent of the subjects (N = 27) were dependent on oxycodone. The balance were dependent on hydrocodone (7%), Buprenex (4%), heroin (4%), and methadone (4%). The majority were detoxified with Suboxone (52%). The remaining patients were detoxified with Subutex (26%), methadone (15%) and gabapentin (7%). Each of the 27 subjects reported consuming larger amounts of salted food, in the form of fast food, during detoxification compared to the quantity consumed during active opiate addiction. All of the subjects gained weight during the detoxification period and no subject lost weight. Overall, the group developed a 6.6% weight increase (t = 8.52, p = .000). The demographic, diagnostic and weight history data for the 14 female patients are summarized in Table 2, and 13 male patients in Table 3. The females gain more weight (7.5%) compared to the male population (5.3%). The impact of the naloxone component of Suboxone was examined by isolating the weight gain associated with the other detoxification methods. Patients detoxified with methadone, gabapentin and Subutex had a percentage weight gain of 6.6%, 6.4% and 5.7% respectively. These results suggest that naloxone did not insulate the females against weight gain but may have helped the male cohort curtail weight gain during detoxification. This data illustrates an association between the chronic depletion of opioid receptors secondary to opioid dependence and increased consummatory behavior of salted food, calorie consumption and weight during opiate withdrawal. This may reflect an instinctive behavioral attempt to self medicate an ‘‘opiate deficiency.” Increased weight during opiate withdrawal parallels other drug withdrawal states such as alcohol [95].

Discussion Salted food almost immediately ‘‘feels good” rather than ‘‘tastes good.” The peripheral central receptor system potentially has the ability to deliver central reward faster than intravenous use or inhalation, making the ‘‘gustatory” method of substance delivery potentially one of the most addictive routes of administration. The ‘‘Oral Mesolimbic Receptor System” might be a more functionally descriptive alternate language. The SFAH is intended to further our understanding of the causes of overeating and obesity. If proven to hold true, the SFAH would have significant nosological implications as salted food use may apply to current criteria for Substance Dependence when consumed in excess and over long periods of time. (Table 4) We compiled a hypothetical classification for Salted Food Addiction (Table 5). From a clinical stand point, if the Salted Food Hypothesis is true, it suggests that our treatment plans have been designed around the symptoms of overeating and obesity. Prevention of Sodium

Table 2 Demographics, education, diagnostic impression, and weight course during outpatient detoxification: patients (N = 14).

Demographics Sex Female Mean age (range 22–64) Race Caucasian Hispanic African American Education 11th grade High school Two years college BA & MA Diagnosis Opiate Dependence Polysubstance abuse Chronic Pain Syndrome Post Traumatic Stress Syndrome Cyclothymic Disorder Bipolar Disorder Dysthymic Disorder Years of Dependence Opiate (mean years) (range 1–16 years) Weight History Weight on admission (mean) (range 108–221 lbs.) Weight after 60 days of detoxification (mean) (range 114–237 lbs.) Percentage weight gain Height (mean) (range 5’3”-5’7”)

N

Percent

14 36

100 –

10 3 1

71 21 7

1 5 4 4

7 36 29 29

14 9 9 6 4 1 1

100 64 64 43 29 7 7

4.7

–

147 lbs.

–

158 lbs.

–

– 5’5”

7.5 –

Table 3 Demographics, Education, Diagnostic Impression, and Weight Course During Outpatient Detoxification: Patients (N = 13).

Demographics Sex Male Mean age (range 19–55) Race Caucasian Hispanic Education 11th grade High school Two years college BA & MA Diagnosis Opiate Dependence Polysubstance abuse Chronic Pain Syndrome Cyclothymic Disorder Adult Attention Deficit Hyperactivity Disorder Years of Dependence Opiate (mean years) (range 1–12 years) Weight History Weight on admission (mean) (range 108–221 lbs.) Weight after 60 days of detoxification (mean) (range 114–237 lbs.) Percentage weight gain Height (mean) (range 50 700 –60 300 )

N

Percent

13 37

100 –

12 1

92 8

2 4 4 3

15 31 31 23

13 9 5 5 2

100 69 38 38 15

4.3

–

188 lbs.

–

198 lbs.

–

–

5.3

50 1000

–

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Salted Mixed Food Dependence might begin with lower sodium eating during pregnancy, sodium breast milk and tap water assays, Table 4 Substance Dependence Criteria (DSM-IV-TR). A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring any time in the same 12-month period: Tolerance, as defined by either of the following: (a) A need for markedly increased amounts of the substance to achieve intoxication or the desired effect (b) Markedly diminished effect with continued use of the same amount of the substance Withdrawal, as manifested by either of the following: (a) The characteristic withdrawal syndrome for the substance (refer to the criteria sets for Withdrawal from the specific substances) (b) The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms. The substance is often taken in larger amounts or over a longer period than intended There is a persistent desire or unsuccessful efforts to cut down or control substance use A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects Important social, occupational, or recreational activities are given up or reduced because of substance use The substance use is continued despite knowledge of having a persistent physical or psychological problem that is likely to have been caused/worsened by the substance

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and feeding lower sodium containing milk, formula, baby food, ingredients for home prepared meals, and school and work lunches. Additional preventative measures might include frequent low sodium snacking throughout the day and decreased patronage or lower sodium (and potassium chloride) ordering at eateries. Sodium Salted Food Abuse and Dependence detoxification might be initiated by introducing progressively more low sodium consumption days each week for several weeks ending in a one to two salted food-days/week maintenance program. Pharmaceutical agents might include potassium sparing diuretic, opiate antagonist, clonidine or non-stimulants such as varenicline [106] contained within minimally oxidized multi-nutraceutical based breath sprays, lozenges, orally dissolving wafers, tablets, and beverages or foods containing minimally processed macronutrients [107] to supplement the regular consumption of minimally processed mini-snacks. The possibility of partial resection of the nerve branches innervating the lingual mesolimbic receptor system could be explored in cases of salted mixed food dependence with severe medical symptomatology such as morbid obesity. Conclusions Salted Food may be an addictive substance that stimulates opiate and dopamine receptors in the brain’s reward and pleasure

Table 5 Hypothesized Classification of Sodium Salted Mixed Food Dependence (see Table-2 for criteria). Dependence is associated with excessive buying and consumption of large amounts of food, and frequent overeating or binging, especially when hurt, angry, stressed, at an eatery, being entertained, from 5 PM until 12 M on weekdays, and when celebrating. Other associated symptoms include one (or more) of the following: (1) Obesity [96] (2) Sedentary lifestyle [97] (3) Mood disorders [98] (4) Sleep and awakening disturbances [99] (5) Attention deficit disorder [100] (6) Bulimic symptoms [101] (7) Cholesterol ratio imbalance [102] (8) Cardiac disease [102] (9) Type 2 diabetes [102] (10) Mild cognitive impairment or Alzheimer’s [103] (11) Hypertension [102] (12) History of cerebral vascular accident [103] (13) Osteoporosis [104] (14) Menstrual or menopausal dysphoria [105] (15) Increased systemic oxidative stress and risk of several cancer types [103] Sodium Salted Mixed Food-Induced Disorders Sodium Salted Mixed Food Intoxication A. Recent use of salted foods B. Clinically significant maladaptive behavior or psychological changes (e.g., initial euphoria followed by apathy, or impaired social or occupational functioning) that develop during, or shortly after, overeating salted mixed food C. One (or more) of the following signs, developing during, or shortly after, overeating salted mixed food (1) Dysphoria (2) Gastrointestinal discomfort, nausea, dyspepsia (3) Compromised cognition, speech, or coordination (4) Decreased psychomotor activity (5) Feelings of disappointment, disgust, or depression (6) Impairment in attention or memory (7) Fatigue, decreased ambition or drive D. The symptoms are not due to a general medical condition, a psychotropic medication, and are not better accounted for by another mental disorder (i.e. nicotine withdrawal) Sodium Salted Mixed Food Withdrawal A. Cessation of (or reduction in calories from) sodium salted-mixed food consumption that has been excessive and prolonged (several weeks or longer) B. Three (or more) of the following, developing within hours to several days after cessation or reduction: (1) Hunger for salted food (2) Difficulty concentrating, lack of motivation or loss of interest in activity (3) Irritability, agitated or tense (4) Low energy, fatigue, trouble sleeping or muscle aches (5) Headache (6) Gastrointestinal discomfort (i.e. Nausea) (7) Dizzy, faint or light-headed (8) Tremulous or increased perspiration C. The symptoms in Criteria B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D. The symptoms are not due to a general medical condition or appetite suppressants, and are not better accounted for by another mental disorder (i.e. opiate dependence)

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center more than it is ‘‘tasty,” while salted food preference, urge, craving and hunger may be manifestations of opiate and dopamine withdrawal. Salted food stimulates appetite, increases calorie consumption, augments the incidence of overeating, overweight, obesity and related illnesses. The data presented here suggests that there is an association between opiate dependence and overeating and weight gain during opiate withdrawal. Obesity and related illnesses may be symptoms of Salted Food Addiction.

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