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Lactose Intolerance
LACTOSE INTOLERANCE
DM Paige, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA r 2013 Elsevier Ltd. All rights reserved.
Overview Lactose maldigestion and intolerance results from an inability to digest varying amounts of the milk sugar, lactose. This is a result of an inadequate amount of the genetically regulated milk sugar enzyme commonly referred to as lactase and more precisely identified as lactase-phlorizin hydrolase. The most common reason for lactose maldigestion is a decline of lactase activity with increasing age. Lactose maldigestion may also occur secondary to intestinal tract infection and diarrhea. A rare form of alactasia, an absence of the milk sugar enzyme, can occur at birth. The symptoms associated with lactose maldigestion are a result of the incomplete hydrolysis, or splitting, of the disaccharide lactose into its absorbable monosaccharide components, glucose and galactose. The most common form of lactose maldigestion observed in the majority of the world’s adult population, is due to genetically determined low lactase levels. Lactose maldigestion may result in abdominal bloating or pain, flatulence, loose stools, and diarrhea, singly or in combination. The symptoms associated with lactose maldigestion result in lactose intolerance. Low lactase levels due to genetic nonpersistence is reported in approximately 70% of the world’s adult population. The prevalence is lowest in individuals of northern European descent (15%) and highest in many Asian populations with reports approaching 100%. The prevalence of lactase nonpersistence in individuals of African descent is approximately 70% to 80%. Similar levels are reported for Latinos and those of Eastern European and South American ancestry. Not all individuals with a reduced level of the enzyme lactase experience symptoms with the ingestion of dietary lactose. The presence or absence of symptoms varies with the amount and type of food consumed, intestinal transit time and level of residual intestinal lactase. Individuals with low lactase levels may tolerate a moderate intake of lactose. Uniform agreement regarding the application and definition of terms identifying lactose nonpersistence has been lacking and has led to confusion and controversy. The 2010 National Institutes of Health Consensus conference on lactose intolerance has underscored the use of an agreed terminology. Hypolactasia is defined as a relative diminution, or very low levels of lactase enzyme activity. Lactose malabsorption, identifies a lactose test result following a lactose challenge resulting in an abnormal rise in breath hydrogen resulting from undigested lactose reaching the colon. The undigested lactose may result in one or more of the following symptoms: bloating, abdominal cramps, flatulence, and diarrhea. Lactose intolerance, is the term used to identify individuals with any
Encyclopedia of Human Nutrition, Volume 3
of the above clinical symptoms resulting from unhydrolyzed lactose. It is a reliable indicator of unhydrolyzed lactose when properly used and interpreted. Milk intolerance, self reported, may be due to lactose maldigestion but may result entirely or partly for other reasons. The most reliable method for diagnosing lactase deficiency is determining lactase activity in the small bowel. The test is invasive and expensive. Lactose maldigestion can generally be identified by a breath hydrogen test, the most commonly used test to measure the level of undigested lactose reaching the colon. Bacterial fermentation of the undigested lactose is responsible for the volume of breath hydrogen production. A lactose tolerance test measuring blood sugar rise is also used. Genetic testing is available. Lactose elimination trials represent a noninvasive, no cost alternative, albeit often difficult to carry out and interpret. Small bowel bacterial overgrowth can confound results. Individuals experiencing discomfort with lactose ingestion can elect to consume commercially hydrolyzed milk that is readily available, milk substitutes or alternative food sources equally rich in calcium.
Historical and Geographic Perspective The first herd animals, sheep, are reported to have been domesticated approximately 10 000 BC. Herd animals were primarily used for meat and perhaps certain other purposes. The historical record suggests that herd animals during this period were not milked. Evidence that humans milked domesticated animals dates to approximately 4000 to 3000 BC, in northern Africa and southwest Asia. Following that time, dairying spread across Eurasia and into sub-Saharan Africa. Dairying was not, however, adopted by all groups in Asia and Africa who had suitable herd animals. Even as late as AD 1500, the beginning of the great European overseas expansion, there were sizable areas occupied by nonmilking groups. In Africa the zone of nonmilking centered on the Congo Basin but extended beyond to cover approximately one-third of the continent. In Asia the zone of nonmilking covered the bulk of the eastern and southeastern portions of the continent, including Thailand, Vietnam, China, and Korea as well as the islands to the east. Dairying remained unknown in the Pacific region and in the Americas in pre-European times. Animal milk was not part of their diet. At that time the nonmilking people of Asia, Africa, and the Americas consumed mother’s milk as infants, but normally ingested no milk after weaning. It was striking that adults of all groups whose origins lay in the traditional zone of nonmilking were predominantly
http://dx.doi.org/10.1016/B978-0-12-375083-9.00169-0
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Lactose Intolerance
maldigesters, usually from 75% to 100% of the individuals tested. Also striking was the fact that the people with low prevalences of lactose maldigestion (northwest Europeans and certain East African pastoral groups) came from a long tradition of consuming milk, much of it in lactose-rich forms. This suggests the geographic or culture–historical hypothesis. The hypothesis is based on the assumption that in the hunting and gathering stage, human groups everywhere were like most other land mammals in their patterns of lactase activity. That is, in the normal individual lactase activity would drop at weaning to low levels, which prevailed throughout life. With the beginning of dairying, however, significant changes occurred in the diets of many human groups. As a result, there may have been a selective advantage for those aberrant individuals who experienced high levels of intestinal lactase throughout life. That advantage would have occurred only in certain situations: Where milk was an especially critical part of the diet, where the group was under dietary stress, and where people did not process all their milk into low lactose products such as aged cheese. Under those conditions, most likely to occur among pastoral groups, such aberrant individuals would drink more milk, would benefit more nutritionally as a result, and would enjoy increased prospects of survival, wellbeing, and of bearing progeny and supporting them. In classic evolutionary terms, the condition of high intestinal lactase activity throughout life, or lactase persistence, would come to be typical of such a group.
Lactase Nonpersistence In its pure form, lactose can not be transported across the mucosa of the small intestine. To be absorbed, it must be hydrolyzed by lactase to yield glucose and galactose. These two simple sugars are rapidly and completely absorbed in the normal small intestine. The rate of lactase synthesis is high from birth until the age of 3–5 years. However, between ages 5 and 14 years, many people undergo a genetically programmed reduction in lactase synthesis resulting in only 5–10% of the lactase levels in infancy. This reduction, known as lactase nonpersistence or primary lactase deficiency, is not related to the continued intake of milk or lactose. As noted, less than one-third of the world’s adult population is genetically predisposed to maintain a high degree of lactase activity or lactase persistence throughout adulthood. Lactase persistence in the human population is inherited as a dominant genetic trait. It has been observed that low lactase level is ‘‘ancient and globally distributed’’ predating the appearance of a persistent lactase variant that was naturally selected in dairying regions. Hollox et al. report, ‘‘the continued adult production of lactase results from the persistent expression of the protein lactase-phlorizin hydrolase which is encoded by the lactase gene (LCT) on chromosome 2’’. Swallow notes, ‘‘the distribution of different lactase phenotypes in human populations is highly variable and is controlled by a polymorphic element cis-acting to the lactase gene. A putative causal nucleotide change has been identified and occurs on the background of a very extended haplotype that is frequent in northern Europeans, where lactase persistence is frequent’’.
Lactase persistence is a likely result of the advent of dairying and the result of natural selection. Samples of ancient human mitochondrial deoxyribonucleic acid (DNA) sequences from ancient skeletons in the early Neolithic Europeans support the hypothesis. Investigators did not observe the allele most often identified with lactase persistence in Europeans suggesting lactase persistence was uncommon in early European farmers thereby reinforcing the cultural– historical hypothesis.
Lactose Digestion and Gastrointestinal Function Lactose is hydrolyzed at the intestinal jejunal brush border by the enzyme lactase into its absorbable monosaccharides glucose and galactose. Lactase activity is robust during infancy and as is the case in humans along with most mammals declines after weaning. Accordingly, the general pattern of lactase nonpersistence is a continuous decline in genetically programmed populations. A shifting pattern of lactose digestion and gastrointestinal function are the result of lactase nonpersistence. The pattern can be described and monitored during three distinct clinical phases. First, there is a decreasing ability to digest the large lactose load consumed during the screening test. It is important to recognize that this is not an all or nothing phenomenon but rather a slowly progressive decline in available lactase activity, and that this decline, as earlier noted, can be influenced by transit time, the vehicle in which the lactose is consumed, and the intake of additional foods along with lactose. Next, with the continued decline of lactase activity, a point is reached when available lactase activity is no longer sufficient to hydrolyze more modest levels of lactose. Therefore, the consumption of a glass of milk or another product containing the equivalent level of lactose will result in incomplete hydrolysis of the lactose consumed. The individuals so tested frequently do not recognize signs or symptoms associated with the incomplete digestion of lactose. Finally, with the continued decline of lactase activity with increasing age, individuals become symptomatic as a result of the undigested lactose. The decline in available lactase activity reaches a recognizable clinical threshold with increasing age. Initially, many reports had treated the population studied as a single unit and had paid incomplete attention to age-specific considerations. Distinctions between secondary lactose malabsorption due to short-term intestinal injury, and primary lactose malabsorption that has a genetic basis, were not always made. This introduced additional confounding variables. Differences in an individual’s capacity to hydrolyze and tolerate a lactose challenge dose compared to his or her ability to utilize lesser amounts of lactose found in usually consumed amounts of milk created additional areas of confusion. When attention is paid to the many factors associated with lactose digestion from infancy to old age, it is possible to place many of the seeming contradictions into perspective. What may have appeared to be incongruities in reported data appear to merge into a relatively predictable pattern of lactose digestion. Lactose maldigestion and intolerance are influenced by age, infection, size of the lactose bolus, gastric emptying time, intestinal transit time, individual sensitivities, eating habits,
Lactose Intolerance
genetics, environment, food ideologies, and cultural patterns. Further, symptoms of lactose malabsorption may also be the result of bacterial fermentation of undigested carbohydrate in the colon. The type and extent of the colonic bacterial profile and the absorption of hydrogen and the volatile fatty acids will influence individual reports of symptoms associated with lactose intolerance. Clearly, lactose malabsorption is not a homogeneous event. Neither is it an all or nothing phenomenon having its origins in a single etiology. Clinical expressions of lactose malabsorption, lactose intolerance, and milk rejection find their origins in one or more of the causes outlined above (Figure 1).
Prevalence
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the ability to hydrolyze a lactose challenge was observed in children of both high and low socioeconomic status. Studies in white children 1–12 years of age identified only 17% of children maldigesting a lactose challenge. Signs and symptom production associated with a reduction in lactose digestion in a child population is difficult to measure due to the nature of the symptoms being reported and the signs observed and the subjective nature of the reports. This is reinforced by a report of 21 African-American girls of 11–15 years of age indicating 82% had evidence of lactose maldigestion with reports of gastrointestinal symptoms being negligible and breath hydrogen excretion, while remaining high, varied between two time periods. Consistent with the above data, milk consumption studies, both observed and reported, suggest a progressive decline in milk intake with increasing age in the African-American population of children and parallel reports
Children A review of reported data on diverse populations support the conclusion that in later childhood and adolescence an important transition in lactose digestion occurs. Below 3 years of age there is lactase persistence. Between 3 and 11 years of age the beginning of a genetically controlled lactose nonpersistence is recognized. Older children and young adults are increasingly unable to digest even modest amounts of lactose. This results in increased symptom production, recognition of discomfort, and avoidance of lactose-containing products that provoke symptoms (Table 1). A progressive decrease in lactase is noted from approximately 1–5 years of age through adolescence. Reported rates in United States African-American children ranged from 27% lactose maldigestion following lactose testing using a lactose load equivalent to two 8-ounce glasses of milk at 1–2 years to 74% in 11–12-year-old children. The progressive decrease in
Table 1 Genetically determined lactase levels in healthy individuals by age and lactase persistence Age
Fetal period Birth Weaning 3–12-year-old child Adolescent Adult Elderly
Lactase level Low lactase nonpersistent individual
High lactase persistent individual
Low High Decline Reduced
Low High High High
Low Lower Lowest
High Average Decline
Lactose digestion, lactase persistence and associated symptoms Lactase persistent
Small intestine
High lactase
Lactase phlorizin hydrolase
Results
Glucose Dietary lactose
Galactose
Net fluid Absorption
Hydrolysis
Lactase non-persistent Low lactase
Lactase phlorizin hydrolase Lactose malabsorption
Dietary lactose
Hydrolysis
Modifying factors Lactose quantity Fat content Stomach emptying Intestinal transport Colon bacterial fermentation Subjective factors
Net fluid Luminal
Symptoms
Mild
Moderate
Severe
Flatulence Abdominal bloating Loose stools Abdominal cramps Diarrhea Figure 1 Lactose digestion, lactase persistence, and associated symptoms.
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Lactose Intolerance
in children from other populations with a high prevalence of lactose maldigestion (Table 2). Phenotypic lactase nonpersistence needs to be distinguished from secondary lactose maldigestion and intolerance as a result of a variety of other conditions. Secondary lactose maldigestion can be observed with diarrheal disease and infection, celiac disease, allergic enteropathy, Crohns’ disease, chemotherapy, radiation, and small bowel resection.
Adults The progressive increase in prevalence of lactose maldigestion increases with age reaching reported adult levels of approximately 70% of the world’s adult population. The exceptions are populations of northern and central Europeans and some Middle Eastern populations as well as groups of primarily European descent in Australia, New Zealand, and North America. Thus, minority populations in North America and Europe, as well as adult populations in most developing countries are lactose maldigesters (Table 3). Reported milk drinking patterns of individuals classified as maldigesters vary considerably in adults. Data range from 50% reporting symptoms with one 8-ounce glass of milk, to 75% reporting symptoms with two 8-ounce glasses of milk and 30% reporting not drinking any milk. Nevertheless, caution must be exercised in interpreting reported symptoms and making the diagnosis of lactose intolerance. There can be considerable crossover between individuals who self-identify Table 2
as intolerant to lactose and are not diagnosed as lactose maldigesters versus those in whom the diagnosis was carefully established. More attention to identifying and categorizing symptoms more precisely may help. A recent Finnish study notes flatulence as the most severe symptom in maldigesters whereas abdominal bloating is most frequently reported by individuals self-identifying as lactose maldigesters. Moreover, microbiota may play a role in the presence and intensity of lactose-related symptoms. Data suggest that increased levels of colonic bacteria, as well as their diversity, may play a role, as a result of increased fermentative capacity in reducing the symptoms associated with lactose intolerance.
Pregnant Women The role of lactose digestion in pregnant women is of special interest. Despite the nutritional value of milk during pregnancy, the lactase levels in some individuals in a number of racial and ethnic groups may be insufficient to hydrolyze commonly consumed amounts of lactose resulting in lactose maldigestion and possibly milk intolerance. The Institute of Medicine report notes, that ‘‘lactose intolerance among pregnant African-American women may result in their subsequent avoidance of milk’’. Other populations may also experience lactose maldigestion and intolerance to milk during pregnancy. Lactose maldigestion, in pregnant women in our studies as measured by breath hydrogen response to 240 ml of low fat
Patterns of lactose digestion by lactase status
Lactase status
Test results
Symptoms
Lactose intolerance
Milk consumption
Adequate Marginal lactase Deficiency Moderate lactase Deficiency Severe lactase Deficiency
Normal ( ) þ þ
0 0/ þ
Average ( þ ) þ
0/ þ
þþþ
þþ
0 0/ þ 0/ þ þþ
þ
Sidney, Phillips, Paige & Bayless.
Table 3
Prevalence of lactose maldigestion in selected populations
Population
Country
% Lactose maldigestion
Population
Country
% Lactose maldigestion
African-American 18–54 years Asian 23–39 years Native American 18–54 years African-American 13–19 years Mexican 18–94 years Vietnamese 22–63 years Sicilian 25 years average Northern 28.7 years average Central 36 years average Romai Austrian 22 years average General 20.3 years average Aboriginal
USA USA USA USA USA USA Italy Italy Italy Hungary Austria Finland Australia
75 100 81 69 53 100 71 52 18 56 20 17 84
General 21–65 years General 20.3 years General 16–54 years Non Caucasian General 38–49 years Arab adult General male 14–34 years General 15–78 years Bantu 13–43 years Yoruba 13–70 years General adult General 17–83 years General 15–64 years
Finland Germany Chile Peru Brazil Israel Egypt Greece Uganda Nigeria India Korea Japan
15 70 80 94 80 81 73 45 100 83 61 75 100
Lactose Intolerance Table 4 Lactose maldigestiona in pregnant and nonpregnant African-American women African-American women
% Lactose maldigestion
Early pregnancy (13–16 weeks) Late pregnancy (30–35 weeks) Postpartum (8 weeks) Nonpregnant
66 69 75 80
a
Breath hydrogen rise 420ppm following the consumption of 240 ml of low fat (1%) milk containing 12 g of lactose following an overnight fast.
(1%) milk, reinforces the Institute of Medicine’s concern with lactose digestion among pregnant African-American women. We report the prevalence of lactose maldigestion in early (13–16 weeks), late (30–35 weeks) and 8 weeks postpartum as 66%, 69%, and 75% respectively. The prevalence in nonpregnant control women was 80% (Table 4). Accordingly, healthcare providers instructing AfricanAmerican women on the optimal dietary pattern during pregnancy need to be mindful of a high rate of lactose maldigestion. Implications for fetal growth and development remain to be answered by further study. Furthermore, health providers need to be aware that the presence or absence of symptoms may be unevenly reported by pregnant AfricanAmerican women; and symptoms do not represent a reliable guide to lactose digestion. Less than 25% of pregnant lactose maldigesting women reported any symptoms with 240 ml of low fat (1%) milk. Symptoms may be further reduced when milk is consumed with other foods. Unanswered is the level of digestion and absorption of a range of nutrients in the consumed milk. Health care providers should discuss with the pregnant woman, her ability to tolerate milk, and where and when appropriate, should educate her as to other food options. In this regard, Kingfisher and Millard report that ‘‘Euroamerican staff tended to give advice that was biologically appropriate for them but not for many of their patients, a process reflecting biocentrism’’.
Secondary Lactase Deficiency Secondary lactase deficiency is distinct from genetically determined loss of lactase with age. Secondary lactase deficiency is frequently associated with diseases of the small intestine. Enteric viruses such as rotavirus and Norwalk agent can induce lactase deficiency by penetration of the enterocyte in the small intestine Rotaviruses are a principal cause of diarrhea and lactose intolerance in infancy. Denudation of the brush border of the jejunal mucosa associated with diarrhea can lead to the loss of the other two disaccharides, maltase and sucrose. Continued diarrhea may also lead to severe complications such as monosaccharide intolerance. Giardiasis and Ascaris lumbricoides have also been implicated as contributing to lactose maldigestion. Severe protein malnutrition is frequently associated with lactose maldigestion. Other disease conditions that give rise to secondary lactose maldigestion are celiac disease, gluten-induced enteropathy, and tropical and non–tropical sprue. The mucosal brush border of the small intestine is severely damaged in each case.
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Lactose Digestion and Diet Calcium Dietary calcium is an important element in skeletal development. Dairy products can account for up to three-quarters of dietary calcium in some populations. Milk is a rich source of calcium. Nevertheless, many minorities in the United States and population groups throughout the world drink decreasing amounts of milk after early childhood and little milk as adults. Given the high prevalence of lactose intolerance, alternatives to cow’s milk should be identified for those who cannot tolerate lactose and desire a milk alternative. Lactose-intolerant individuals ultimately attribute their discomfort to lactosecontaining foods and voluntarily reduce or eliminate their milk intake. Data from National Studies in the United States indicate African-American and Hispanic women have lower intakes of calcium compared with non Hispanic women. An Institute of Medicine Report concludes that the disparity in calcium intake ‘‘may be explained in part by the much higher prevalence of lactose intolerance among African-Americans and Hispanics, sometimes resulting in their subsequent avoidance of milk’’. In general, populations at risk for lactose intolerance report a lower calcium intake as a result of the decline in the intake of milk and milk products. One solution to this problem is to educate lactose-intolerant groups as to alternative calcium-containing foods, reinforce appropriate cultural patterns and dietary practices that include alternatives to milk and identify other culturally acceptable calciumcontaining foods. Meeting the calcium requirement with an alternative diet is a challenge but nevertheless is required for many in the community. Although milk may serve as a primary source of calcium, appreciable quantities of calcium can be found in nondairy foods (Table 5). Clearly it is more difficult to meet the published calcium recommendation with a diet low in whole cow’s milk. A review of the tables of food composition reveals a variety of foods that contain acceptable levels of calcium per 100-g portion or other standard portions. Other lactose-modified dairy products including hard cheeses, yogurts, and lactosemodified milk are good calcium sources. In addition, lactose digestive aids are available and are increasingly used. The digestive aids commercially available include lactase tablets, lactase preparations, lactose-free milk, and prehydrolyzed milk. Live culture yogurt is another alternative to milk. Lactose in yogurt is better digested than lactose in milk. Tolerance to yogurt is thought to be due to the microbial beta-galactosidase activity that digests the lactose.
Osteoporosis The role of lactose maldigestion, calcium intake and osteoporosis has been studied. Osteoporosis and osteoporitic fractures are major public health problems. The role of lactose maldigestion and osteoporosis remains unsettled. For example, minority populations consuming small amounts of milk should be at greater risk for osteoporosis. Nevertheless, African-American and Hispanic populations in the United States appear to have a lower risk of developing osteoporosis. Caucasian and Asian women were found to have the highest
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Table 5 noteda
Lactose Intolerance
Calcium content in milligrams per 100 g portion or as
Canned sardines (3 oz.) Buckwheat pancakes Kale (raw) Mustard greens Muffinsb Wafflesb Figs (dry) Canned salmon (3 oz. with bones) Collard greens
372 249 225 220 206 192 186 167
Brewer’s yeast (2 tbs) Lobster Green beans Flounder Bran flakes Canned apricots (1 cup) Gingerbread (1 piece) Plain rolls
66 65 63 61 61 57 57 55
162
54
Oat breakfast cerealb Wheat pancakes Almonds Tofu (8 oz.) Egg yolk Corn breadb Kale (frozen) Filberts Beet greens Oysters (½ cup) Whole cow’s milk (100 g) Swiss chard Rhubarb (cooked ½ cup) Canned shrimp (3 oz.) Okra Soy beans (1 cup) Sunflower seeds Broccoli Sauerkraut (1 cup) Potato salad (1 cup) Peanut butter Spinach Dates (dry)
160 158 152 143 147 139 134 120 118 113 113
Toaster pastry (1 piece)b Prunes (dry) Orange Whole egg Peanuts Artichokes Cod Brussels sprouts Clams (3 oz.) Lima beans Puffed wheatb Whole wheat bread (2 slices) Sweet potato Fruit cocktail (1 cup)
54 54 54 54 51 50 50 47 47 46 46
should be an important consideration in developing a suitable policy regarding the use of milk and dairy products by the lactose malabsorber and by ethnic or racial groups, among whom high rates of malabsorption prevail. Accordingly, a balance must be struck between dietary guidance and the interests of a diverse population with a large number of lactose maldigesters. For many the continued use of a limited amount of milk may be appropriate and comfortable. For others dietary modification and lactose reduction or elimination may be warranted. The substitution of low-lactose products or alternative foods may be successful. Traditional diets among lactose-maldigesting populations, using little or no milk or dairy products should be respected.
Summary
risk for osteoporosis, with fracture rates of 140.7/1 00 000 and 85.4/1 00 000, respectively. Hispanic and African-American females had lower age-adjusted rates, at 49.7/1 00 000 and 57.3/1 00 000, respectively. A study of gene-identified lactose intolerance in a Dutch Caucasian elderly population is associated with lower dietary Calcium intake and serum Calcium levels but not associated with bone mineral density or fractures. The paradox reinforces the complexity of the disease and the importance of biologic, genetic and as yet undetermined factors in the etiology of osteoporosis.
In summary, the principles of genetics and evolution help to explain the emergence of continued lactase activity beyond weaning. Darwin referred to food as a major factor in selective pressures. Lactose digestion illustrates how a certain food, by indirectly favoring the survival of those able to digest that substance, can influence the evolutionary process. Clinical and nutritional consequences of lactose digestion in adults must be examined in relation to digestion, intolerance, milk rejection, symptoms, and their recognition. Estimates of how frequently milk intolerance is a clinically significant problem in adults vary. The protocol of individual scientific studies can influence interpretation. A balance of factors tend to prevent or minimize symptoms when the stomach, small intestine, and colon can compensate for an increased solute load, but abdominal discomfort or diarrhea occur when these small intestinal and colonic physiologic mechanisms are loaded beyond their capacity. The role of the colonic flora in metabolizing unabsorbed sugar and the importance of colonic salvage of unabsorbed carbohydrate is an important variable in the symptom complex. Secondary lactase deficiency due to infectious gastroenteritis and malnutrition represents a distinct clinical syndrome and must be distinguished from lactose intolerance. Dietary recommendations must take account of lactose maldigestion. Milk and dairy product consumption will vary among lactose-maldigesting and milk-intolerant individuals. Lactose-reduced or lactose-free products are available to lactose-maldigesting and – intolerant individuals who wish to drink milk and milk-based products. Nevertheless, dietary recommendations must be modified and respectful of those who do not drink milk. Accordingly, appropriate alternatives to milk and other lactose-containing foods must be identified and guidance provided in developing nutritionally equivalent diets.
Nutrition policy
Further Reading
Apart from the nutritional implications outlined above, there are policy considerations that require attention. Clearly milk has important economic, nutritional, and emotional significance in Western culture, a culture strongly committed to the concept that milk is an ideal food. Yet, lactose digestion
Bayless TM and Paige DM (1978) Lactose tolerance by lactose-malabsorbing Indians. Gastroenterology 74: 153. Bayless TM and Rosensweig NS (1966) A racial difference in the incidence of lactase deficiency: A survey of milk tolerance and lactase deficiency in healthy males. The Journal of the American Medical Association 197: 968–972.
105 105 98 92 90 88 88 85 80 74 73 72
Raisins (1/2 cup) Apricots Farina (1 cup) Fig bars (4 cookies) Pecans White bread (2 slices) Pecans White bread (2 slices) Tangerine Raspberries (raw) Apple sauce
46 46 45 44 44 44 43 42 43 42 40 40 21
a
Oski and Paige modified from Krause and Mahan & Burton. Enriched, fortified, or restored to legal standard when one exists.
b
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Burger J, Kirchner M, Bramanti B, Haak W, and Thomas MG (2007) Absence of the lactase-persistence-associated allele in early Neolithic Europeans. Proceedings of the Nationall Academy of Sciences of the United States of America 6 104(10): 3736–3741. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, and Jarvela I (2002) Identification of a variant associated with adult-type hypolactasia. Nature Genetics 30(2): 233–237. Goldberg JP and Folta SC (2002) Milk: Can a ‘‘good’’ food be so bad? Pediatrics 110(4): 826–832. Hollox EJ, Poulter M, Zvarik M, et al. (2001) Lactase haplotype diversity in the Old World. The American Journal of Human Genetics 68(1): 160–172. Institute of Medicine (U.S.) (1990) Subcommittee on Nutritional Status and Weight Gain During Pregnancy. Nutrition During Pregnancy, National Academy of Sciences. Itan Y, Jones BL, Ingram CJ, Swallow DM, and Thomas MG (2010) A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evolutionary Biology 10: 36. Itan Y, Powell A, Beaumont MA, Burger J, and Thomas MG (2009) The origins of lactase persistence in Europe. PLoS Computational Biology 5(8). Jackson RT and Latham MC (1979) Lactose malabsorption among Masai children of East Africa. The American Journal of Clinical Nutrition 32: 779–782. Kingfisher CP and Millard AV (1998) Milk makes me sick but my body needs it: Conflict and contradiction in the establishment of authoritative knowledge. Medical Anthropology Quarterly 12(4): 447–466. Koek WN, van Meurs JB, van der Erden BC, et al. (2010) The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake. Journal of Bone and Mineral Research 9: 1980–1987. Kretchmer N (1972) Lactose and lactase. Scientific American 227: 70–78. Labayen I, Forga L, Gonzalez A, Lenoir-Wijnkoop I, Nutr R, and Martinez JA (2001) Relationship between lactose digestion, gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption. Alimentary Pharmacology and Therapeutics 15(4): 543–549. Law D, Conklin J, and Pimentel M (2010) Lactose Intolerance and the Role of the Lactose Breath Test. The American Journal of Gastroenterology 105(8): 1726–1728. Mendel LB and Mitchell PH (1907) Chemical studies on growth: I The inverting enzymes of the alimentary tract, especially in the embryo. American Journal of Physiology 20: 81–96. Novillo A, Peralta D, Dima G, Besasso H, and Soifer L (2010) Frequency of bacterial overgrowth in patients with clinical lactose intolerance. Acta Gastroenterol Latinoam 40(3): 221–224. Nutrition Reviews (1969) Lactase deficiency in Thailand. Nutrition Reviews 27: 278–280. Omenn GS (2010) Evolution in health and medicine Sackler colloquium: Evolution and public health. Proceedings of the National Academy of Sciences of the United States of America Jan 26 107(supplement 1): 1702–1709. Oski FA and Paige DM (1994) Cow’s milk is a good food for some and a poor choice for others: Eliminating the hyperbole. Archives of Pediatrics and Adolscent Medicine 148: 104–107. Paige DM (1981) Lactose malabsorption in children: Prevalence, symptoms, and nutritional considerations. In: Paige DM and Bayless TM (eds.) Lactose Digestion: Clinical and Nutritional Implications, pp. 151–161. Baltimore, MD: The Johns Hopkins University Press. Paige DM (1982) Milk intolerance in human populations. In Animal Products in Human Nutrition. In: Beitz DC (ed.) Nutrition Foundation Monograph Series. New York: Academic Press. Paige DM and Bayless TM (eds.) (1981) Lactose Digestion: Clinical and Nutritional Implications. Baltimore, MD: Johns Hopkins University Press. Paige DM, Bayless TM, Ferry GD, and Graham GG (1971) Lactose malabsorption and milk rejection in Negro children. Johns Hopkins Medical Journal 129: 163–169. Paige DM, Bayless TM, and Graham GG (1973) Pregnancy and lactose intolerance. The American Journal of Clinical Nutrition 26: 238–240.
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Paige DM, Bayless TM, Huang SS, and Wexler R (1975) Lactose hydrolyzed milk. The American Journal of Clinical Nutrition 28: 818–822. Paige DM, Bayless TM, Mellits ED, and Davis L (1977) Lactose malabsorption in preschool black children. The American Journal of Clinical Nutrition 30: 1018–1022. Paige DM, Davis L, Bayless TM, Mellits ED, Dellinger Jr WS, and Kreitner M (1979) The effects of age and lactose tolerance on blood glucose rise with whole cow and lactose hydrolyzed milk. Journal of Agriculture and Food Chemistry 27(4): 667. Paige DM and Davis LR (1986) Nutritional significance of lactose: Nutritional aspects of lactose digestion. In: Fox PR (ed.) In Dairy Chemistry, pp. 111–132. London: Elsevier Press. Paige DM, Leonardo E, Corando A, Nakashima J, Adrianzen TB, and Graham GG (1972) Lactose intolerance in Peruvian children: Effect of age and early nutrition. The American Journal of Clinical Nutrition 25: 297–301. Paige DM, Witter F, Bronner YL, Kessler L, Perman J, and Paige T (2003) Lactose intolerance in pregnant African-Americans. Public Health Nutrition 6(8): 801–807. Perman JA, Barr RB, and Watkins JB (1978) Sucrose malabsorption in children: non-invasive diagnosis by interval breath hydrogen determination. Journal of Pediatrics 93: 17–22. Perman JA and Dudley B (1998) Dairy products: Try them – you’ll like them? The American Journal of Clinical Nutrition 68: 995–996. Pribila BA, Hertzler SR, Martin BR, Weaver CM, and Savaiano DA (2000) Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet. Journal of the American Dietetic Association 100(5): 524–528. Rao DR, Bello H, Warren AP, and Brown GE (1994) Prevalence of lactose maldigestion. Digestive Diseases and Sciences 39: 1519–1524. Romagnuolo J, Schiller D, and Bailey RJ (2002) Using breath tests wisely in a gastroenterology practice: An evidence-based review of indications and pitfalls in interpretation. The American Journal of Gastroenterology 97(5): 1113–1126. Rush D, Sloan N, Leighton J, et al. (1988) The national WIC evaluation: Evaluation of the special supplemental food program for Women, Infants, and Children (WIC). The American Journal of Clinical Nutrition 48: 439–483. Scrimshaw NS and Murray EB (1988) The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. The American Journal of Clinical Nutrition 48: 1083–1159. Simoons FJ (1970) Primary adult lactose intolerance and the milking habit: A problem in biological and cultural interrelations: II. A culture historical hypothesis. The American Journal of Digestive Diseases 15: 695–710. Simoons FJ (1973) The determinants of dairying and milk use in the Old World: Ecological, physiological and cultural. Ecology of Food and Nutrition 2: 83–90. Suarez F, Savaiano D, and Levitt M (1995) A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. New England Journal of Medicine 333: 1–334. Suchy FJ, Brannon PM, Carpenter TO, et al. (2010) National Institutes of Health Consensus Development Conference: Lactose intolerance and health. Annals of Internal Medicine 152(12): 792–796. Swallow DM (2003) Genetics of lactase persistence and lactose intolerance. Annual Review of Genetics 37: 197–219. Tursi A (2004) Factors influencing lactose intolerance. European Journal of Clinical Investigation 34: 314–315. Voelker R (2010) NIH Panel tackles lactose intolerance. The Journal of the American Medical Association 303(13): 1240–1242. Vonk RJ, Priebe MG, Koetse HA, et al. (2003) Lactose intolerance: Analysis of underlying factors. European Journal of Clinical Investigation 33: 70–75. Vonk RJ, Stellaard F, Priebe MG, et al. (2001) The 13C/2H-glucose test for determination of small intestinal lactase activity. The European Journal of Clinical Investigation 31: 226–233. Weiss KM (2004) The unkindest cup. The Lancet 363. Zhong Y, Priebe MG, Vonk RJ, et al. (2004) The role of calonic microbiota in lactose intolerance. Digestive Diseases and Sciences 49(1): 78–83.
DM Paige, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA r 2013 Elsevier Ltd. All rights reserved.
Overview Lactose maldigestion and intolerance results from an inability to digest varying amounts of the milk sugar, lactose. This is a result of an inadequate amount of the genetically regulated milk sugar enzyme commonly referred to as lactase and more precisely identified as lactase-phlorizin hydrolase. The most common reason for lactose maldigestion is a decline of lactase activity with increasing age. Lactose maldigestion may also occur secondary to intestinal tract infection and diarrhea. A rare form of alactasia, an absence of the milk sugar enzyme, can occur at birth. The symptoms associated with lactose maldigestion are a result of the incomplete hydrolysis, or splitting, of the disaccharide lactose into its absorbable monosaccharide components, glucose and galactose. The most common form of lactose maldigestion observed in the majority of the world’s adult population, is due to genetically determined low lactase levels. Lactose maldigestion may result in abdominal bloating or pain, flatulence, loose stools, and diarrhea, singly or in combination. The symptoms associated with lactose maldigestion result in lactose intolerance. Low lactase levels due to genetic nonpersistence is reported in approximately 70% of the world’s adult population. The prevalence is lowest in individuals of northern European descent (15%) and highest in many Asian populations with reports approaching 100%. The prevalence of lactase nonpersistence in individuals of African descent is approximately 70% to 80%. Similar levels are reported for Latinos and those of Eastern European and South American ancestry. Not all individuals with a reduced level of the enzyme lactase experience symptoms with the ingestion of dietary lactose. The presence or absence of symptoms varies with the amount and type of food consumed, intestinal transit time and level of residual intestinal lactase. Individuals with low lactase levels may tolerate a moderate intake of lactose. Uniform agreement regarding the application and definition of terms identifying lactose nonpersistence has been lacking and has led to confusion and controversy. The 2010 National Institutes of Health Consensus conference on lactose intolerance has underscored the use of an agreed terminology. Hypolactasia is defined as a relative diminution, or very low levels of lactase enzyme activity. Lactose malabsorption, identifies a lactose test result following a lactose challenge resulting in an abnormal rise in breath hydrogen resulting from undigested lactose reaching the colon. The undigested lactose may result in one or more of the following symptoms: bloating, abdominal cramps, flatulence, and diarrhea. Lactose intolerance, is the term used to identify individuals with any
Encyclopedia of Human Nutrition, Volume 3
of the above clinical symptoms resulting from unhydrolyzed lactose. It is a reliable indicator of unhydrolyzed lactose when properly used and interpreted. Milk intolerance, self reported, may be due to lactose maldigestion but may result entirely or partly for other reasons. The most reliable method for diagnosing lactase deficiency is determining lactase activity in the small bowel. The test is invasive and expensive. Lactose maldigestion can generally be identified by a breath hydrogen test, the most commonly used test to measure the level of undigested lactose reaching the colon. Bacterial fermentation of the undigested lactose is responsible for the volume of breath hydrogen production. A lactose tolerance test measuring blood sugar rise is also used. Genetic testing is available. Lactose elimination trials represent a noninvasive, no cost alternative, albeit often difficult to carry out and interpret. Small bowel bacterial overgrowth can confound results. Individuals experiencing discomfort with lactose ingestion can elect to consume commercially hydrolyzed milk that is readily available, milk substitutes or alternative food sources equally rich in calcium.
Historical and Geographic Perspective The first herd animals, sheep, are reported to have been domesticated approximately 10 000 BC. Herd animals were primarily used for meat and perhaps certain other purposes. The historical record suggests that herd animals during this period were not milked. Evidence that humans milked domesticated animals dates to approximately 4000 to 3000 BC, in northern Africa and southwest Asia. Following that time, dairying spread across Eurasia and into sub-Saharan Africa. Dairying was not, however, adopted by all groups in Asia and Africa who had suitable herd animals. Even as late as AD 1500, the beginning of the great European overseas expansion, there were sizable areas occupied by nonmilking groups. In Africa the zone of nonmilking centered on the Congo Basin but extended beyond to cover approximately one-third of the continent. In Asia the zone of nonmilking covered the bulk of the eastern and southeastern portions of the continent, including Thailand, Vietnam, China, and Korea as well as the islands to the east. Dairying remained unknown in the Pacific region and in the Americas in pre-European times. Animal milk was not part of their diet. At that time the nonmilking people of Asia, Africa, and the Americas consumed mother’s milk as infants, but normally ingested no milk after weaning. It was striking that adults of all groups whose origins lay in the traditional zone of nonmilking were predominantly
http://dx.doi.org/10.1016/B978-0-12-375083-9.00169-0
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maldigesters, usually from 75% to 100% of the individuals tested. Also striking was the fact that the people with low prevalences of lactose maldigestion (northwest Europeans and certain East African pastoral groups) came from a long tradition of consuming milk, much of it in lactose-rich forms. This suggests the geographic or culture–historical hypothesis. The hypothesis is based on the assumption that in the hunting and gathering stage, human groups everywhere were like most other land mammals in their patterns of lactase activity. That is, in the normal individual lactase activity would drop at weaning to low levels, which prevailed throughout life. With the beginning of dairying, however, significant changes occurred in the diets of many human groups. As a result, there may have been a selective advantage for those aberrant individuals who experienced high levels of intestinal lactase throughout life. That advantage would have occurred only in certain situations: Where milk was an especially critical part of the diet, where the group was under dietary stress, and where people did not process all their milk into low lactose products such as aged cheese. Under those conditions, most likely to occur among pastoral groups, such aberrant individuals would drink more milk, would benefit more nutritionally as a result, and would enjoy increased prospects of survival, wellbeing, and of bearing progeny and supporting them. In classic evolutionary terms, the condition of high intestinal lactase activity throughout life, or lactase persistence, would come to be typical of such a group.
Lactase Nonpersistence In its pure form, lactose can not be transported across the mucosa of the small intestine. To be absorbed, it must be hydrolyzed by lactase to yield glucose and galactose. These two simple sugars are rapidly and completely absorbed in the normal small intestine. The rate of lactase synthesis is high from birth until the age of 3–5 years. However, between ages 5 and 14 years, many people undergo a genetically programmed reduction in lactase synthesis resulting in only 5–10% of the lactase levels in infancy. This reduction, known as lactase nonpersistence or primary lactase deficiency, is not related to the continued intake of milk or lactose. As noted, less than one-third of the world’s adult population is genetically predisposed to maintain a high degree of lactase activity or lactase persistence throughout adulthood. Lactase persistence in the human population is inherited as a dominant genetic trait. It has been observed that low lactase level is ‘‘ancient and globally distributed’’ predating the appearance of a persistent lactase variant that was naturally selected in dairying regions. Hollox et al. report, ‘‘the continued adult production of lactase results from the persistent expression of the protein lactase-phlorizin hydrolase which is encoded by the lactase gene (LCT) on chromosome 2’’. Swallow notes, ‘‘the distribution of different lactase phenotypes in human populations is highly variable and is controlled by a polymorphic element cis-acting to the lactase gene. A putative causal nucleotide change has been identified and occurs on the background of a very extended haplotype that is frequent in northern Europeans, where lactase persistence is frequent’’.
Lactase persistence is a likely result of the advent of dairying and the result of natural selection. Samples of ancient human mitochondrial deoxyribonucleic acid (DNA) sequences from ancient skeletons in the early Neolithic Europeans support the hypothesis. Investigators did not observe the allele most often identified with lactase persistence in Europeans suggesting lactase persistence was uncommon in early European farmers thereby reinforcing the cultural– historical hypothesis.
Lactose Digestion and Gastrointestinal Function Lactose is hydrolyzed at the intestinal jejunal brush border by the enzyme lactase into its absorbable monosaccharides glucose and galactose. Lactase activity is robust during infancy and as is the case in humans along with most mammals declines after weaning. Accordingly, the general pattern of lactase nonpersistence is a continuous decline in genetically programmed populations. A shifting pattern of lactose digestion and gastrointestinal function are the result of lactase nonpersistence. The pattern can be described and monitored during three distinct clinical phases. First, there is a decreasing ability to digest the large lactose load consumed during the screening test. It is important to recognize that this is not an all or nothing phenomenon but rather a slowly progressive decline in available lactase activity, and that this decline, as earlier noted, can be influenced by transit time, the vehicle in which the lactose is consumed, and the intake of additional foods along with lactose. Next, with the continued decline of lactase activity, a point is reached when available lactase activity is no longer sufficient to hydrolyze more modest levels of lactose. Therefore, the consumption of a glass of milk or another product containing the equivalent level of lactose will result in incomplete hydrolysis of the lactose consumed. The individuals so tested frequently do not recognize signs or symptoms associated with the incomplete digestion of lactose. Finally, with the continued decline of lactase activity with increasing age, individuals become symptomatic as a result of the undigested lactose. The decline in available lactase activity reaches a recognizable clinical threshold with increasing age. Initially, many reports had treated the population studied as a single unit and had paid incomplete attention to age-specific considerations. Distinctions between secondary lactose malabsorption due to short-term intestinal injury, and primary lactose malabsorption that has a genetic basis, were not always made. This introduced additional confounding variables. Differences in an individual’s capacity to hydrolyze and tolerate a lactose challenge dose compared to his or her ability to utilize lesser amounts of lactose found in usually consumed amounts of milk created additional areas of confusion. When attention is paid to the many factors associated with lactose digestion from infancy to old age, it is possible to place many of the seeming contradictions into perspective. What may have appeared to be incongruities in reported data appear to merge into a relatively predictable pattern of lactose digestion. Lactose maldigestion and intolerance are influenced by age, infection, size of the lactose bolus, gastric emptying time, intestinal transit time, individual sensitivities, eating habits,
Lactose Intolerance
genetics, environment, food ideologies, and cultural patterns. Further, symptoms of lactose malabsorption may also be the result of bacterial fermentation of undigested carbohydrate in the colon. The type and extent of the colonic bacterial profile and the absorption of hydrogen and the volatile fatty acids will influence individual reports of symptoms associated with lactose intolerance. Clearly, lactose malabsorption is not a homogeneous event. Neither is it an all or nothing phenomenon having its origins in a single etiology. Clinical expressions of lactose malabsorption, lactose intolerance, and milk rejection find their origins in one or more of the causes outlined above (Figure 1).
Prevalence
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the ability to hydrolyze a lactose challenge was observed in children of both high and low socioeconomic status. Studies in white children 1–12 years of age identified only 17% of children maldigesting a lactose challenge. Signs and symptom production associated with a reduction in lactose digestion in a child population is difficult to measure due to the nature of the symptoms being reported and the signs observed and the subjective nature of the reports. This is reinforced by a report of 21 African-American girls of 11–15 years of age indicating 82% had evidence of lactose maldigestion with reports of gastrointestinal symptoms being negligible and breath hydrogen excretion, while remaining high, varied between two time periods. Consistent with the above data, milk consumption studies, both observed and reported, suggest a progressive decline in milk intake with increasing age in the African-American population of children and parallel reports
Children A review of reported data on diverse populations support the conclusion that in later childhood and adolescence an important transition in lactose digestion occurs. Below 3 years of age there is lactase persistence. Between 3 and 11 years of age the beginning of a genetically controlled lactose nonpersistence is recognized. Older children and young adults are increasingly unable to digest even modest amounts of lactose. This results in increased symptom production, recognition of discomfort, and avoidance of lactose-containing products that provoke symptoms (Table 1). A progressive decrease in lactase is noted from approximately 1–5 years of age through adolescence. Reported rates in United States African-American children ranged from 27% lactose maldigestion following lactose testing using a lactose load equivalent to two 8-ounce glasses of milk at 1–2 years to 74% in 11–12-year-old children. The progressive decrease in
Table 1 Genetically determined lactase levels in healthy individuals by age and lactase persistence Age
Fetal period Birth Weaning 3–12-year-old child Adolescent Adult Elderly
Lactase level Low lactase nonpersistent individual
High lactase persistent individual
Low High Decline Reduced
Low High High High
Low Lower Lowest
High Average Decline
Lactose digestion, lactase persistence and associated symptoms Lactase persistent
Small intestine
High lactase
Lactase phlorizin hydrolase
Results
Glucose Dietary lactose
Galactose
Net fluid Absorption
Hydrolysis
Lactase non-persistent Low lactase
Lactase phlorizin hydrolase Lactose malabsorption
Dietary lactose
Hydrolysis
Modifying factors Lactose quantity Fat content Stomach emptying Intestinal transport Colon bacterial fermentation Subjective factors
Net fluid Luminal
Symptoms
Mild
Moderate
Severe
Flatulence Abdominal bloating Loose stools Abdominal cramps Diarrhea Figure 1 Lactose digestion, lactase persistence, and associated symptoms.
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Lactose Intolerance
in children from other populations with a high prevalence of lactose maldigestion (Table 2). Phenotypic lactase nonpersistence needs to be distinguished from secondary lactose maldigestion and intolerance as a result of a variety of other conditions. Secondary lactose maldigestion can be observed with diarrheal disease and infection, celiac disease, allergic enteropathy, Crohns’ disease, chemotherapy, radiation, and small bowel resection.
Adults The progressive increase in prevalence of lactose maldigestion increases with age reaching reported adult levels of approximately 70% of the world’s adult population. The exceptions are populations of northern and central Europeans and some Middle Eastern populations as well as groups of primarily European descent in Australia, New Zealand, and North America. Thus, minority populations in North America and Europe, as well as adult populations in most developing countries are lactose maldigesters (Table 3). Reported milk drinking patterns of individuals classified as maldigesters vary considerably in adults. Data range from 50% reporting symptoms with one 8-ounce glass of milk, to 75% reporting symptoms with two 8-ounce glasses of milk and 30% reporting not drinking any milk. Nevertheless, caution must be exercised in interpreting reported symptoms and making the diagnosis of lactose intolerance. There can be considerable crossover between individuals who self-identify Table 2
as intolerant to lactose and are not diagnosed as lactose maldigesters versus those in whom the diagnosis was carefully established. More attention to identifying and categorizing symptoms more precisely may help. A recent Finnish study notes flatulence as the most severe symptom in maldigesters whereas abdominal bloating is most frequently reported by individuals self-identifying as lactose maldigesters. Moreover, microbiota may play a role in the presence and intensity of lactose-related symptoms. Data suggest that increased levels of colonic bacteria, as well as their diversity, may play a role, as a result of increased fermentative capacity in reducing the symptoms associated with lactose intolerance.
Pregnant Women The role of lactose digestion in pregnant women is of special interest. Despite the nutritional value of milk during pregnancy, the lactase levels in some individuals in a number of racial and ethnic groups may be insufficient to hydrolyze commonly consumed amounts of lactose resulting in lactose maldigestion and possibly milk intolerance. The Institute of Medicine report notes, that ‘‘lactose intolerance among pregnant African-American women may result in their subsequent avoidance of milk’’. Other populations may also experience lactose maldigestion and intolerance to milk during pregnancy. Lactose maldigestion, in pregnant women in our studies as measured by breath hydrogen response to 240 ml of low fat
Patterns of lactose digestion by lactase status
Lactase status
Test results
Symptoms
Lactose intolerance
Milk consumption
Adequate Marginal lactase Deficiency Moderate lactase Deficiency Severe lactase Deficiency
Normal ( ) þ þ
0 0/ þ
Average ( þ ) þ
0/ þ
þþþ
þþ
0 0/ þ 0/ þ þþ
þ
Sidney, Phillips, Paige & Bayless.
Table 3
Prevalence of lactose maldigestion in selected populations
Population
Country
% Lactose maldigestion
Population
Country
% Lactose maldigestion
African-American 18–54 years Asian 23–39 years Native American 18–54 years African-American 13–19 years Mexican 18–94 years Vietnamese 22–63 years Sicilian 25 years average Northern 28.7 years average Central 36 years average Romai Austrian 22 years average General 20.3 years average Aboriginal
USA USA USA USA USA USA Italy Italy Italy Hungary Austria Finland Australia
75 100 81 69 53 100 71 52 18 56 20 17 84
General 21–65 years General 20.3 years General 16–54 years Non Caucasian General 38–49 years Arab adult General male 14–34 years General 15–78 years Bantu 13–43 years Yoruba 13–70 years General adult General 17–83 years General 15–64 years
Finland Germany Chile Peru Brazil Israel Egypt Greece Uganda Nigeria India Korea Japan
15 70 80 94 80 81 73 45 100 83 61 75 100
Lactose Intolerance Table 4 Lactose maldigestiona in pregnant and nonpregnant African-American women African-American women
% Lactose maldigestion
Early pregnancy (13–16 weeks) Late pregnancy (30–35 weeks) Postpartum (8 weeks) Nonpregnant
66 69 75 80
a
Breath hydrogen rise 420ppm following the consumption of 240 ml of low fat (1%) milk containing 12 g of lactose following an overnight fast.
(1%) milk, reinforces the Institute of Medicine’s concern with lactose digestion among pregnant African-American women. We report the prevalence of lactose maldigestion in early (13–16 weeks), late (30–35 weeks) and 8 weeks postpartum as 66%, 69%, and 75% respectively. The prevalence in nonpregnant control women was 80% (Table 4). Accordingly, healthcare providers instructing AfricanAmerican women on the optimal dietary pattern during pregnancy need to be mindful of a high rate of lactose maldigestion. Implications for fetal growth and development remain to be answered by further study. Furthermore, health providers need to be aware that the presence or absence of symptoms may be unevenly reported by pregnant AfricanAmerican women; and symptoms do not represent a reliable guide to lactose digestion. Less than 25% of pregnant lactose maldigesting women reported any symptoms with 240 ml of low fat (1%) milk. Symptoms may be further reduced when milk is consumed with other foods. Unanswered is the level of digestion and absorption of a range of nutrients in the consumed milk. Health care providers should discuss with the pregnant woman, her ability to tolerate milk, and where and when appropriate, should educate her as to other food options. In this regard, Kingfisher and Millard report that ‘‘Euroamerican staff tended to give advice that was biologically appropriate for them but not for many of their patients, a process reflecting biocentrism’’.
Secondary Lactase Deficiency Secondary lactase deficiency is distinct from genetically determined loss of lactase with age. Secondary lactase deficiency is frequently associated with diseases of the small intestine. Enteric viruses such as rotavirus and Norwalk agent can induce lactase deficiency by penetration of the enterocyte in the small intestine Rotaviruses are a principal cause of diarrhea and lactose intolerance in infancy. Denudation of the brush border of the jejunal mucosa associated with diarrhea can lead to the loss of the other two disaccharides, maltase and sucrose. Continued diarrhea may also lead to severe complications such as monosaccharide intolerance. Giardiasis and Ascaris lumbricoides have also been implicated as contributing to lactose maldigestion. Severe protein malnutrition is frequently associated with lactose maldigestion. Other disease conditions that give rise to secondary lactose maldigestion are celiac disease, gluten-induced enteropathy, and tropical and non–tropical sprue. The mucosal brush border of the small intestine is severely damaged in each case.
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Lactose Digestion and Diet Calcium Dietary calcium is an important element in skeletal development. Dairy products can account for up to three-quarters of dietary calcium in some populations. Milk is a rich source of calcium. Nevertheless, many minorities in the United States and population groups throughout the world drink decreasing amounts of milk after early childhood and little milk as adults. Given the high prevalence of lactose intolerance, alternatives to cow’s milk should be identified for those who cannot tolerate lactose and desire a milk alternative. Lactose-intolerant individuals ultimately attribute their discomfort to lactosecontaining foods and voluntarily reduce or eliminate their milk intake. Data from National Studies in the United States indicate African-American and Hispanic women have lower intakes of calcium compared with non Hispanic women. An Institute of Medicine Report concludes that the disparity in calcium intake ‘‘may be explained in part by the much higher prevalence of lactose intolerance among African-Americans and Hispanics, sometimes resulting in their subsequent avoidance of milk’’. In general, populations at risk for lactose intolerance report a lower calcium intake as a result of the decline in the intake of milk and milk products. One solution to this problem is to educate lactose-intolerant groups as to alternative calcium-containing foods, reinforce appropriate cultural patterns and dietary practices that include alternatives to milk and identify other culturally acceptable calciumcontaining foods. Meeting the calcium requirement with an alternative diet is a challenge but nevertheless is required for many in the community. Although milk may serve as a primary source of calcium, appreciable quantities of calcium can be found in nondairy foods (Table 5). Clearly it is more difficult to meet the published calcium recommendation with a diet low in whole cow’s milk. A review of the tables of food composition reveals a variety of foods that contain acceptable levels of calcium per 100-g portion or other standard portions. Other lactose-modified dairy products including hard cheeses, yogurts, and lactosemodified milk are good calcium sources. In addition, lactose digestive aids are available and are increasingly used. The digestive aids commercially available include lactase tablets, lactase preparations, lactose-free milk, and prehydrolyzed milk. Live culture yogurt is another alternative to milk. Lactose in yogurt is better digested than lactose in milk. Tolerance to yogurt is thought to be due to the microbial beta-galactosidase activity that digests the lactose.
Osteoporosis The role of lactose maldigestion, calcium intake and osteoporosis has been studied. Osteoporosis and osteoporitic fractures are major public health problems. The role of lactose maldigestion and osteoporosis remains unsettled. For example, minority populations consuming small amounts of milk should be at greater risk for osteoporosis. Nevertheless, African-American and Hispanic populations in the United States appear to have a lower risk of developing osteoporosis. Caucasian and Asian women were found to have the highest
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Table 5 noteda
Lactose Intolerance
Calcium content in milligrams per 100 g portion or as
Canned sardines (3 oz.) Buckwheat pancakes Kale (raw) Mustard greens Muffinsb Wafflesb Figs (dry) Canned salmon (3 oz. with bones) Collard greens
372 249 225 220 206 192 186 167
Brewer’s yeast (2 tbs) Lobster Green beans Flounder Bran flakes Canned apricots (1 cup) Gingerbread (1 piece) Plain rolls
66 65 63 61 61 57 57 55
162
54
Oat breakfast cerealb Wheat pancakes Almonds Tofu (8 oz.) Egg yolk Corn breadb Kale (frozen) Filberts Beet greens Oysters (½ cup) Whole cow’s milk (100 g) Swiss chard Rhubarb (cooked ½ cup) Canned shrimp (3 oz.) Okra Soy beans (1 cup) Sunflower seeds Broccoli Sauerkraut (1 cup) Potato salad (1 cup) Peanut butter Spinach Dates (dry)
160 158 152 143 147 139 134 120 118 113 113
Toaster pastry (1 piece)b Prunes (dry) Orange Whole egg Peanuts Artichokes Cod Brussels sprouts Clams (3 oz.) Lima beans Puffed wheatb Whole wheat bread (2 slices) Sweet potato Fruit cocktail (1 cup)
54 54 54 54 51 50 50 47 47 46 46
should be an important consideration in developing a suitable policy regarding the use of milk and dairy products by the lactose malabsorber and by ethnic or racial groups, among whom high rates of malabsorption prevail. Accordingly, a balance must be struck between dietary guidance and the interests of a diverse population with a large number of lactose maldigesters. For many the continued use of a limited amount of milk may be appropriate and comfortable. For others dietary modification and lactose reduction or elimination may be warranted. The substitution of low-lactose products or alternative foods may be successful. Traditional diets among lactose-maldigesting populations, using little or no milk or dairy products should be respected.
Summary
risk for osteoporosis, with fracture rates of 140.7/1 00 000 and 85.4/1 00 000, respectively. Hispanic and African-American females had lower age-adjusted rates, at 49.7/1 00 000 and 57.3/1 00 000, respectively. A study of gene-identified lactose intolerance in a Dutch Caucasian elderly population is associated with lower dietary Calcium intake and serum Calcium levels but not associated with bone mineral density or fractures. The paradox reinforces the complexity of the disease and the importance of biologic, genetic and as yet undetermined factors in the etiology of osteoporosis.
In summary, the principles of genetics and evolution help to explain the emergence of continued lactase activity beyond weaning. Darwin referred to food as a major factor in selective pressures. Lactose digestion illustrates how a certain food, by indirectly favoring the survival of those able to digest that substance, can influence the evolutionary process. Clinical and nutritional consequences of lactose digestion in adults must be examined in relation to digestion, intolerance, milk rejection, symptoms, and their recognition. Estimates of how frequently milk intolerance is a clinically significant problem in adults vary. The protocol of individual scientific studies can influence interpretation. A balance of factors tend to prevent or minimize symptoms when the stomach, small intestine, and colon can compensate for an increased solute load, but abdominal discomfort or diarrhea occur when these small intestinal and colonic physiologic mechanisms are loaded beyond their capacity. The role of the colonic flora in metabolizing unabsorbed sugar and the importance of colonic salvage of unabsorbed carbohydrate is an important variable in the symptom complex. Secondary lactase deficiency due to infectious gastroenteritis and malnutrition represents a distinct clinical syndrome and must be distinguished from lactose intolerance. Dietary recommendations must take account of lactose maldigestion. Milk and dairy product consumption will vary among lactose-maldigesting and milk-intolerant individuals. Lactose-reduced or lactose-free products are available to lactose-maldigesting and – intolerant individuals who wish to drink milk and milk-based products. Nevertheless, dietary recommendations must be modified and respectful of those who do not drink milk. Accordingly, appropriate alternatives to milk and other lactose-containing foods must be identified and guidance provided in developing nutritionally equivalent diets.
Nutrition policy
Further Reading
Apart from the nutritional implications outlined above, there are policy considerations that require attention. Clearly milk has important economic, nutritional, and emotional significance in Western culture, a culture strongly committed to the concept that milk is an ideal food. Yet, lactose digestion
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Raisins (1/2 cup) Apricots Farina (1 cup) Fig bars (4 cookies) Pecans White bread (2 slices) Pecans White bread (2 slices) Tangerine Raspberries (raw) Apple sauce
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Oski and Paige modified from Krause and Mahan & Burton. Enriched, fortified, or restored to legal standard when one exists.
b
Lactose Intolerance
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