- Email: [email protected]
Calcium, dairy products, and osteoporosis: Implications of lactose intolerance
CALCIUM DAIRY PRODUCTS, AND OSTlkOPOROSIS: IMPLICATIONS OF LACTOSE INTOLERANCE Patricia M. Bannan, RD, and Michael
A high calcium intake reduces the severity of osteoporosis. Although dairy products are rich and inexpensive sources of calcium, these products contain large quantities of lactose, a sugar that is digested with di$cuIty by an appreciable fraction of the population. The resultant malabsorption of lactose may produce abdominal symptoms, a condition known as lactose intolerance. To prevent these symptoms, many individuals mistakenly believe they must either avoid all dairy products or use commercial digestive aids. This article reviews the role of calcium and dairy products in osteoporosis with particular emphasis on the importance of lactose intolerance as a deterrent to ingestion of dairy products. We conclude that problems resulting from lactose intolerance have been overemphasized, and virtually all subjects can ingest atleast I cup of milkper day with breakfast without recognizable symptoms. Thus, lactose digestive aids should be reserved for higher doses of milk. Alternatively, lactose intolerant subjects who wish to ingest large quantities of dairy products can eat yogurt (which contains bacterial lactase) or hard cheeses (which contain minimal amounts of lactose). (Prim Care Update
Ob/Gyns
1996;
3:146-151)
From Washington, Veteran’s Affairs Minnesota.
146
DC, and the *Department of Medical Center, Minneapolis,
0 1996 Elsevier
Science
D. Levitt, MD*
ELSEVIER
Bone fractures represent a common and serious health problem in the elderly. Although many factors contribute to the high frequency of these fractures, decreased bone mass secondary to osteoporosis is of major importance in postmenopausal women. Osteoporosis affects 20-25 million Americans over the age of 45,* and osteoporosis is the rule for elderly white women who suffer about 1.3 million fractures per year.’ The development of osteoporosis is, in part, related to inadequate calcium intake, and a high calcium intake may slow the decrement in bone mass observed in postmenopausal women. The simplest and most readily accepted way to ingest calcium is via normal dietary constituents. Although milk and milk products are the single richest dietary source of calcium, these products also contain lactose, a disaccharide that is poorly digested by a large fraction of the population. The symptoms that result from maldigestion of this sugar (lactose intolerance) have received enormous publicity both in lay and medical publications. As a result, the public is extremely knowledgeable concerning lactose-induced symptoms, and real or imagined problems following lactose ingestion have caused many individuals to avoid dairy products. A diet devoid of milk and milk products seldom contains the quantity of calcium recommended to minimize osteoporosis. In this report we briefly review the pathophysiology of osteoporosis and the role of dietary calcium in Inc., all rights
reserved.
1066-607X/96/$15.00
l
this condition and then discuss the importance of ingestion of dairy products with particular emphasis on the problem of lactose intolerance.
Pathophysiology of Osteoporosis Bone mass increases rapidly during childhood and adolescence followed by a more gradual increase until about age 30.~ An obligatory bone loss begins in the mid 30s, and this loss is enhanced by the superimposition of estrogen deficiency in the postmenopausal state.4 A fraction of the body’s calcium is lost via the digestive tract, urine, and skin (sweat and desquamated cells).5 This excretion cannot be prevented or regulated. In addition, the gut and kidneys excrete additional calcium in response to a high-calcium intake. When losses exceed absorption from the diet, extracellular calcium tends to fall. Extracellular ionized calcium concentration is defended at the expense of bone via mobilization of calcium from bone. It follows that maintenance of normal serum calcium levels from ingested calcium minimizes the “borrowing” of bone calcium and maximizes bone mass.
Relationship of Calcium Intake and Osteoporosis Maximal bone mass is determined in part by genetic factors, eg, African American females have a much
PII SlO68-607X(96)00022-8
Prim Care Update
Ob/Gyns
greater maximal bone density than do Caucasians. In addition, the consumption of adequate calcium during childhood, adolescence, and young adulthood is thought to result in a greater maximal bone mass. There also is evidence that subsequent high calcium intake can slow the progression of osteoporosis and the incidence of fractures in postmenopausal women. For example, a controlled study of 300 postmenopausal women showed that increasing calcium intake from 400 to 900 mglday reduced the bone loss otherwise observed in elderly women.6 Another study found that elderly individuals consuming >800 mg/day of calcium had 60% fewer fractures than did subjects ingesting ~400 mg/daye7 A metaanalysis’ of published studies concluded that there was a clear-cut relationship between calcium intake and bone strength.
Recommended Dietary Allowances (RDA) of Calcium In childhood, the retention of calcium for bone growth is about 100 mglday and obligatory excretory losses are 100-150 mg/day; thus, about 250 mg/day of calcium is required for optimal bone formation3 Because only about 40% of ingested calcium is absorbed, children should ingest about 800 mg of calcium per day to ensure adequate calcium absorption, Similar calculations for adolescents and young adults indicate that calcium intakes should be about 1,000 mglday and 800 mg/day, respectively.” For postmenopausal women, an National Institutes of Health Consensus Conference recommended an intake of 1,0oo-I ,500 mg/day.g Data from phase one of the third National Health and Nutrition Examination Survey indicated that Volume
3. Number
4. lsofi
Table
1. Calcium Content of Average Servings of Various Foeds’O Usual Serving
Food
Milk, fresh Cheese, American process Salmon, pink, canned Turnip greens, cooked Clams or oysters Mustard greens, cooked Shrimp Ice cream Cottage cheese, uncreamed Kale, cooked Soybeans, mature, cooked Broccoli, cooked Orange, whole Sweet potato, boiled Molasses, light Egg, whole Carrots, cooked Cabbage, raw, shredded Bread, 4% nonfat dry milk * Assuming
recommended
dietary
lc 1 oz 3 oz
%c %c %c 3 oz
V8 q 3 oz
%c l/2 c v2 c 1 medium 1 medium 1 tbsp 1 medium l/z c ‘h c 1 slice allowance
of calcium
teenage girls consume an average of only 68% of the RDA for calcium, and adult women roughly 85% of the RDA.’
Sources of Dietary Calcium The preferred source of calcium is calcium-rich foods, particularly dairy foods. In addition to calcium, dairy products provide nutrients, such as zinc and protein, that are important for bone metabolism. As demonstrated in Table 1, it is extremely difficult to ingest the recommended daily requirement of calcium (800 to 1,500 mg) solely via conventional (unfortified) foods if dairy products are excluded from the diet. Calcium-fortified foods and calcium supplements are other means by which optimal calcium intake can be reached in those who cannot meet this need via conventional foods. Fortified orange juice or cereals contain lo-20% of the RDA per serving. Calcium contain-
Calcium (mgl 288 198 167 126 113 97 98 87 77 74 73 66 54 47 33 27 24 22 21
% of Adult Daily Allowance* 36 25 21 16 14 12 12 11 10 9 9 8 7 6 4 3 3 3 3
of 800 mg.
ing tablets provide RDA per tablet.
about 50% of the
Pathophysiology of lactase Deficiency Lactose is an unusual sugar that is found naturally in high concentrations only in milk and milk products (see Table 2). Cow’s milk contains about 11 g per cup (8 oz); human’s milk about 17 g per cup. Hard cheeses contain minimal lactose (cl g/ounce). Lactose is a disaccharide consisting of glucose bound to galactose. Absorption requires hydrolysis to the component monosaccharides, a reaction catalyzed by the intestinal enzyme lactase. Mammals are born with abundant lactase, a necessity for survival given the enormous exposure to lactose that occurs in the newborn. Following weaning, all nonhuman mammals are genetically programmed to reduce lactase synthesis. Lactase levels of adult animals are only about l/10 that of 147
BANNAN & LEVITT 2. Lactose and Calcium Content of Average Servings of Various Dairy Products
Table
Dairy
Product
Milk Human
Lactose’l (g)
Serving
Calcium’z (mg)
lc
17
80
lc
11 11 10 6
290 300 285 80
9
90
2 5
52 300-400 1
cow
Whole Low fat Buttermilk Ice cream Ice milk Sherbet, orange Yogurt, low fat Butter Cheese Swiss American Cheddar, sharp Parmesan Blue
lc IC
l/2 c 1%c %c lc 1 tsp
Trace
oz oz oz oz oz
1 2 o-1 1 1
1 1 1 1 1
infancy, and neither exposure to milk nor lactose prevents the development of this low lactase state. Since weaned animals never encounter milk (unless fed to them by humans), this reduction in lactase has no significance in nature.
Prevalence of lactase Deficiency The majority of humans follow the animal pattern and are genetically programmed to lose the ability to synthesize lactase.13 However, a mutation in some population groups allows the infantile level of lactase to persist throughout adulthood. Such subjects are said to be lactase persistent, whereas their counterparts who lose the ability to produce lactase are termed lactase nonpersistent (lactase deficient in older terminology). Table 3 shows the percentage of adults of various ethnic origin who are lactase persistent.14 In general, only individuals of northern or middle European extraction, or about 75% of the adult U.S. population, are likely to be lactase persistent. The remaining 25% tend to be lactase nonpersis148
272 124 204
69 150
tant and maldigest and malabsorb lactose. Roughly 75% of the world’s population is lactase nonpersistent; thus, the inability to digest lactose in adulthood is the norm rather than the exception. Familiarity with the relationship between national origin and intestinal lactase levels has clinical utility for the physician. For example, an adult of Asian, Mediterranean, or African origin is very
3. Ethnic Background and Prevalence of Lactase Nonpersistence
Table
Ethnic
Group
Northern European Scandinavians Middle European Native English Native German Mediterranean Northern Italians Southern Italians Most Africans Masai Asians Latinos Semites (Jews) United States African-Americans Alaska Innuits Asian-Americans Native Americans Caucasians
% Lactose Nonpersistent l-5 3 10-20 11
5 60-90 11
85 80-100 <5
>90 64
90 20-25 70-100 80 80-100
>90 12
likely to have low lactase levels and testing ordinarily is not required to confirm the existence of lactose maldigestion.
Diagnosis of lactose Malabsorption The ability to digest lactose usually is assessed via breath hydrogen (H,) testing. Malabsorbed lactose is fermented to H, by the colonic bacteria. This H, is absorbed, transported by the blood to the lungs and then excreted in expired air. Thus, an increase in breath H, after ingestion of lactose provides a simple, noninvasive indicator that lactose was incompletely absorbed.‘” This technique has shown that even small quantities of lactose (for example 6 g, or the quantity in I/Z cup of milk) are incompletely absorbed by lactase nonpersistent individuals.”
Symptoms Resulting from lactose Malabsorption Malabsorbed lactose holds water in the lumen via its osmotic activity, and diarrhea will result if lactose reaches the rectum. Although lactose, per se, cannot be absorbed from the colon, this sugar is rapidly fermented to organic acids such as acetate and butyrate by the colonic bacteria, and these products are efficiently absorbed and/or metabolized by the colonic mucosa.17 Diarrhea is prevented if most of the osmotic activity of lactose is removed via this mechanism. There are limits, however, to the ability of the colonic bacteria to ferment lactose and the colonic mucosa to remove the fermentation products. Ingestion of large, unphysiological lactose loads may cause diarrhea. Large quantities of gas (CO,, H,, and CH,) are produced during lactose fermentation, and the accumulation of these gases may produce bloatPrim
Care Update
ObiGyns
ing, abdominal discomfort and flatulence. However, these gases are consumed by other bacteria and absorbed across the mucosa.18 Symptoms occur only when these removal mechanisms are exceeded. Thus, it is important to recognize that lactose malabsorption and lactose intolerance are not necessarily synonymous. While all lactose nonpersistent subjects malabsorb lactose, with limited doses this malabsorption may not cause perceptible symptoms, ie, there is no lactose intolerance.
When Is Treatment of lactose Intolerance Indicated? There is controversy about the dosage of lactose that can be tolerated by lactase nonpersistent individuals and the need for lactose digestive aids. This topic has major commercial as well as health implications. For example, if each of the roughly XI million lactase nonpersistent Americans used lactase tablets just once per day, annual sales would be about $3 billion. Initial unblinded studies in which subjects were asked if they had symptoms following milk ingestion suggested that the quantity of lactose in one 8 oz cup of milk (12 g) induced appreciable symptoms in the majority of lactase nonpersistent subjects.lg However, the symptoms of lactose intolerance (mild bloating and gas) are notoriously susceptible to suggestion and readily modified by the placebo effect. Determination of the true ability of lactose to induce symptoms requires rigorous double-blind testing in which symptoms are compared following administration of a lactose containing food verses an identical placebo. There is a taste difference between conventional (lactose Volume
3. Number
4, ISDF,
containing) milk and lactose prehydrolyzed milk because the hydrolysis products, glucose and galactose, are sweeter than lactose. However, this difference can be disguised by sweetening conventional milk with aspartame.” Well-controlled studies carried out prior to 1995 generally concluded that symptoms with one 8 oz cup of conventional milk were no greater than those with one 8 oz cup of lactose-hydrolyzed milk.21.22 However, this conclusion is contrary to the belief of an enormous group of individuals who are certain that trivial quantities of milk, such as that used with cereal and coffee, cause symptoms. It seemed possible to us that there might be a subset of extremely lactose intolerant individuals who had not been adequately represented in previous investigations. Therefore, we” recently studied 30 subjects who considered themselves to be extremely lactose intolerant, ie, they routinely developed symptoms after ingestion of less than an 8 oz cup of milk. Initial H, testing of these 30 subjects demonstrated that nine were not lactose maldigesters, ie, they completely absorbed lactose. Thus, 27% of subjects who considered themselves to be severely lactose intolerant clearly had misdiagnosed their problem. The 30 subjects were enrolled in a double-blind study in which they ingested one 8 oz cup of conventional or one 8 oz cup of lactose-hydrolyzed milk with breakfast for 1 week in a cross-over design. In contrast to the subjects’ prestudy belief that the severity of symptoms during the conventional milk period would cause them to drop out of the study, there were no significant differences in symptoms between the two treatment periods. We concluded that individuals commonly misattribute symptoms to lactose intolerance and that virtually all lactase nonpersistent subjects can ingest one cup of milk per
day without fear of appreciable symptoms. Controlled trials have demonstrated that as the dose of lactose is increased, symptoms become more frequent. Approximately 80% of subjects had symptoms when 50 g of lactose (the quantity in a quart of milk) was taken as a single dose,‘l and another study2” indicated that symptoms were relatively frequent when 20 g (1.5 cups of milk) was ingested as a single dose. Symptoms may have been overestimated in the many studies that have tested tolerance via the feeding of lactose solutions in the absence of other food. Lactose ingested in milk with meals appears to be better tolerated because the presence of other nutrients slows gastric emptying, which in turn slows passage of lactose through the small bowel. This results in increased lactose digestion and slower delivery of the unabsorbed sugar to the colon. Controlled trials will be required to determine the tolerance of lactase nonpersistent subjects to the daily ingestion of several cups of milk when this milk is ingested in physiological fashion, ie, a cup of milk with several different meals.
Treatment of lactose Intolerance It is apparent from the above that one cup of milk taken with breakfast is associated with negligible symptoms and hence no treatment is required. Although not yet tested, it seems likely that two cups of milk daily, one with breakfast and one with dinner, similarly will be welltolerated because the symptomatic periods resulting from these two doses are unlikely to overlap. The use of lactose digestive aids should be reserved primarily for subjects wishing to ingest more than one cup of milk (or the equivalent lactose load) at a single sitting or for 149
BANNAN
& LEVITT
Table 4. Cost Comparisons Between Milk and Low-Lactose Alternatives Product
Cost per 240 mL Milk
Increment in Cost (%)
$0.19 $0.27 $0.37
0 42 95
$0.79 $0.49
158-316
Milk Lactase (liquid) producing 70% LHM Lactase (liquid) producing 100% LHM Lactase caplets Cartons of 12 units Cartons of 100 units Prehydrolyzed milk Plain yogurt Flavored yogurt LHM.
lactose
hydrolyzed
$0.36
$0.49 $0.60
89
158 218
nenbaum S. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990;323: 878-83. 7. Holbrook
8.
milk. 9.
those wishing to drink more than two cups of milk daily, The commercial products available for the treatment of lactose intolerance and their approximate cost is shown in Table 4.23 Relatively lactose-free milk now is becoming widely available. In addition, various lactase preparations can be purchased as over-the-counter products. One of these preparations is added to milk, which is then incubated overnight. In addition, there are lactase tablets that may be taken at the time of ingestion of dairy products. Although not extensively tested, breath H, measurements have shown that these products enhance lactose absorption, and it seems likely that their use will reduce the symptoms that follow ingestion of large doses of lactose. However, these products increase the cost of milk by 33-200%, depending upon the product and the dosage employed (see Table 4). Thus, these products should largely be reserved for subjects who wish to drink more than two cups of milk per day. It is important to note that not all dairy products are created equal with regard to their ability to induce symptoms in lactase nonpersistent subjects. For example, yogurt contains high concentrations of lactase due to the production of this enzyme by the yogurt bacteria. As a result, lactose ingested in yogurt is better tolerated than is an equivalent dose of lactose ingested in milkez4 150
There is a good deal of confusion in both the medical and lay communities with regard to the lactose content of cheese. As shown in Table 1, hard cheeses (cheddar, Swiss, etc.) contain minimal lactose, less than 1 g/serving. In the process of manufacturing hard cheeses, much of the lactose is removed with the whey. Most of the remaining lactose is fermented during the aging or ripening process. Three to four servings of cheese a day provide the RDA for calcium and a total lactose load (<5 g/day) that can be readily tolerated by lactase nonpersistent subjects.
References 1. Wardlaw GM. Putting osteoporosis 2.
3. 4.
5.
6.
in perspective. J Am Diet Assoc 1993;93:1000-6. Tolstoli CG, Levin RM. Osteoporosis--the treatment controversy. Nutr Today 1992 July/August;629. Heaney RP. Calcium in the prevention of osteoporosis. J Int Med 1992; 231:169-80. Nordin BEC, Need AG, Chatterton BE, Horowitz M, Morris HA. The relative contributions of age and years since menopause to postmenopausal bone loss. J Clin Endocrinol Metab 1990;70:83-8. Jensen FT, Charles P, Mosekilde L, Hansen HH. Calcium metabolism evaluated by 47calcium-kinetics: a physiological model with correction for faecal lag time and estimation of dermal calcium loss. Clin Physiol 1983;3:187-204. Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoung N, Tan-
10.
11.
12.
13.
14.
15.
TL, Barrett-Connor E, Wingard DL. Dietary calcium and risk of hip fracture: 14-year prospective population study. Lancet 1988; ii:1046-9. Cumming RC. Calcium intake and bone mass: a quantitative review of the evidence. Calcif Tissue Int 1990; 47:194-201. National Institutes of Health. Osteoporosis Consensus Development Conference Statement. JAMA 1984; 252:799-802. Robinson CH, Lawler MR. Mineral elements. In: Normal therapeutic nutrition, 15th ed. New York: Macmillan Publishing Co., 1977:107. Scrimshaw NS, Murray EB. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr 1988;48(Suppl): 1083-159. Bowes A, Church H. Food values of portions commonly used, 16th ed. Philadelphia: JB Lippincott Co., 1994. Gilat T, Russo S, Gelman-Malachi E, Aldor TAM. Lactase in man: a noninducible enzyme in man. Gastroenter01 1972;62:1125-7. Simoons FJ. The geographic hypothesis and lactose malabsorption: a weighing of the evidence. Am J Dig Dis 1978;23:963-80. Levitt MD, Donaldson RM. Use of respiratory hydrogen (H,) excretion to detect carbohydrate malabsorption. J Clin Lab Med 1970;75:937-
45. 16. Hertzler
SR, Huynh B, Savaiano DA. How much lactose is “low lactose.” J Am Diet Assoc. In press. 17. Bond JH, Levitt MD. Fate of soluble carbohydrate in the colon of rats and man. J Clin Invest 1976;57: 1158-64. 18. Levitt MD, Berggren T, Hastings J,
Bond JH. Hydrogen (H,) catabolism in the colon of the rat. J Lab Clin Med 1974;84:163-7. 19. Bayless TM, Rothfeld B, Massa C, Wise L, Paige D, Bedine MS. Lactose and milk intolerance: clinical implications. N Engl J Med 1975;292: 1156-9. 20. Suarez F, Savaiano DA, Levitt MD. A comparison of symptoms with milk or lactose-hydrolyzed milk in people with self-reported severe Prim Care Update
Ob/Gyns
LACTOSE lactose intolerance. N Engl J Med 1995;333:1-4. 21. Haverberg L, Kwon PH, Scrimshaw NS. Comparative tolerance of adolescents of differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks: initial experience with a double-blind procedure. Am J Clin Nutr 1980;33:1721.
Volume
3, Number
4, 19%
22. Unger M, Scrimshaw NS. Comparative tolerance of adults of differing ethnic backgrounds to lactose-free and lactose-containing dairy drinks. Nutr Res 1981;1227-33. 23. Suarez FL, Savaiano DA, Levitt MD. Treatment of lactose intolerance. Alimentary Pharmacol Ther 19%; 9:589-97. 24. Kolars JC, Levitt MD, Mostafa A,
INTOLERANCE
Savaiano DA. Yogurt: an autodigesting source of lactose. N Engl J Med 1984;310:1-3.
Address correspondence and reprint requests to Michael D. Levitt, MD, ACOS Research, Veterans Affairs Medical Center, Minneapolis, MN 55417.
151
A high calcium intake reduces the severity of osteoporosis. Although dairy products are rich and inexpensive sources of calcium, these products contain large quantities of lactose, a sugar that is digested with di$cuIty by an appreciable fraction of the population. The resultant malabsorption of lactose may produce abdominal symptoms, a condition known as lactose intolerance. To prevent these symptoms, many individuals mistakenly believe they must either avoid all dairy products or use commercial digestive aids. This article reviews the role of calcium and dairy products in osteoporosis with particular emphasis on the importance of lactose intolerance as a deterrent to ingestion of dairy products. We conclude that problems resulting from lactose intolerance have been overemphasized, and virtually all subjects can ingest atleast I cup of milkper day with breakfast without recognizable symptoms. Thus, lactose digestive aids should be reserved for higher doses of milk. Alternatively, lactose intolerant subjects who wish to ingest large quantities of dairy products can eat yogurt (which contains bacterial lactase) or hard cheeses (which contain minimal amounts of lactose). (Prim Care Update
Ob/Gyns
1996;
3:146-151)
From Washington, Veteran’s Affairs Minnesota.
146
DC, and the *Department of Medical Center, Minneapolis,
0 1996 Elsevier
Science
D. Levitt, MD*
ELSEVIER
Bone fractures represent a common and serious health problem in the elderly. Although many factors contribute to the high frequency of these fractures, decreased bone mass secondary to osteoporosis is of major importance in postmenopausal women. Osteoporosis affects 20-25 million Americans over the age of 45,* and osteoporosis is the rule for elderly white women who suffer about 1.3 million fractures per year.’ The development of osteoporosis is, in part, related to inadequate calcium intake, and a high calcium intake may slow the decrement in bone mass observed in postmenopausal women. The simplest and most readily accepted way to ingest calcium is via normal dietary constituents. Although milk and milk products are the single richest dietary source of calcium, these products also contain lactose, a disaccharide that is poorly digested by a large fraction of the population. The symptoms that result from maldigestion of this sugar (lactose intolerance) have received enormous publicity both in lay and medical publications. As a result, the public is extremely knowledgeable concerning lactose-induced symptoms, and real or imagined problems following lactose ingestion have caused many individuals to avoid dairy products. A diet devoid of milk and milk products seldom contains the quantity of calcium recommended to minimize osteoporosis. In this report we briefly review the pathophysiology of osteoporosis and the role of dietary calcium in Inc., all rights
reserved.
1066-607X/96/$15.00
l
this condition and then discuss the importance of ingestion of dairy products with particular emphasis on the problem of lactose intolerance.
Pathophysiology of Osteoporosis Bone mass increases rapidly during childhood and adolescence followed by a more gradual increase until about age 30.~ An obligatory bone loss begins in the mid 30s, and this loss is enhanced by the superimposition of estrogen deficiency in the postmenopausal state.4 A fraction of the body’s calcium is lost via the digestive tract, urine, and skin (sweat and desquamated cells).5 This excretion cannot be prevented or regulated. In addition, the gut and kidneys excrete additional calcium in response to a high-calcium intake. When losses exceed absorption from the diet, extracellular calcium tends to fall. Extracellular ionized calcium concentration is defended at the expense of bone via mobilization of calcium from bone. It follows that maintenance of normal serum calcium levels from ingested calcium minimizes the “borrowing” of bone calcium and maximizes bone mass.
Relationship of Calcium Intake and Osteoporosis Maximal bone mass is determined in part by genetic factors, eg, African American females have a much
PII SlO68-607X(96)00022-8
Prim Care Update
Ob/Gyns
greater maximal bone density than do Caucasians. In addition, the consumption of adequate calcium during childhood, adolescence, and young adulthood is thought to result in a greater maximal bone mass. There also is evidence that subsequent high calcium intake can slow the progression of osteoporosis and the incidence of fractures in postmenopausal women. For example, a controlled study of 300 postmenopausal women showed that increasing calcium intake from 400 to 900 mglday reduced the bone loss otherwise observed in elderly women.6 Another study found that elderly individuals consuming >800 mg/day of calcium had 60% fewer fractures than did subjects ingesting ~400 mg/daye7 A metaanalysis’ of published studies concluded that there was a clear-cut relationship between calcium intake and bone strength.
Recommended Dietary Allowances (RDA) of Calcium In childhood, the retention of calcium for bone growth is about 100 mglday and obligatory excretory losses are 100-150 mg/day; thus, about 250 mg/day of calcium is required for optimal bone formation3 Because only about 40% of ingested calcium is absorbed, children should ingest about 800 mg of calcium per day to ensure adequate calcium absorption, Similar calculations for adolescents and young adults indicate that calcium intakes should be about 1,000 mglday and 800 mg/day, respectively.” For postmenopausal women, an National Institutes of Health Consensus Conference recommended an intake of 1,0oo-I ,500 mg/day.g Data from phase one of the third National Health and Nutrition Examination Survey indicated that Volume
3. Number
4. lsofi
Table
1. Calcium Content of Average Servings of Various Foeds’O Usual Serving
Food
Milk, fresh Cheese, American process Salmon, pink, canned Turnip greens, cooked Clams or oysters Mustard greens, cooked Shrimp Ice cream Cottage cheese, uncreamed Kale, cooked Soybeans, mature, cooked Broccoli, cooked Orange, whole Sweet potato, boiled Molasses, light Egg, whole Carrots, cooked Cabbage, raw, shredded Bread, 4% nonfat dry milk * Assuming
recommended
dietary
lc 1 oz 3 oz
%c %c %c 3 oz
V8 q 3 oz
%c l/2 c v2 c 1 medium 1 medium 1 tbsp 1 medium l/z c ‘h c 1 slice allowance
of calcium
teenage girls consume an average of only 68% of the RDA for calcium, and adult women roughly 85% of the RDA.’
Sources of Dietary Calcium The preferred source of calcium is calcium-rich foods, particularly dairy foods. In addition to calcium, dairy products provide nutrients, such as zinc and protein, that are important for bone metabolism. As demonstrated in Table 1, it is extremely difficult to ingest the recommended daily requirement of calcium (800 to 1,500 mg) solely via conventional (unfortified) foods if dairy products are excluded from the diet. Calcium-fortified foods and calcium supplements are other means by which optimal calcium intake can be reached in those who cannot meet this need via conventional foods. Fortified orange juice or cereals contain lo-20% of the RDA per serving. Calcium contain-
Calcium (mgl 288 198 167 126 113 97 98 87 77 74 73 66 54 47 33 27 24 22 21
% of Adult Daily Allowance* 36 25 21 16 14 12 12 11 10 9 9 8 7 6 4 3 3 3 3
of 800 mg.
ing tablets provide RDA per tablet.
about 50% of the
Pathophysiology of lactase Deficiency Lactose is an unusual sugar that is found naturally in high concentrations only in milk and milk products (see Table 2). Cow’s milk contains about 11 g per cup (8 oz); human’s milk about 17 g per cup. Hard cheeses contain minimal lactose (cl g/ounce). Lactose is a disaccharide consisting of glucose bound to galactose. Absorption requires hydrolysis to the component monosaccharides, a reaction catalyzed by the intestinal enzyme lactase. Mammals are born with abundant lactase, a necessity for survival given the enormous exposure to lactose that occurs in the newborn. Following weaning, all nonhuman mammals are genetically programmed to reduce lactase synthesis. Lactase levels of adult animals are only about l/10 that of 147
BANNAN & LEVITT 2. Lactose and Calcium Content of Average Servings of Various Dairy Products
Table
Dairy
Product
Milk Human
Lactose’l (g)
Serving
Calcium’z (mg)
lc
17
80
lc
11 11 10 6
290 300 285 80
9
90
2 5
52 300-400 1
cow
Whole Low fat Buttermilk Ice cream Ice milk Sherbet, orange Yogurt, low fat Butter Cheese Swiss American Cheddar, sharp Parmesan Blue
lc IC
l/2 c 1%c %c lc 1 tsp
Trace
oz oz oz oz oz
1 2 o-1 1 1
1 1 1 1 1
infancy, and neither exposure to milk nor lactose prevents the development of this low lactase state. Since weaned animals never encounter milk (unless fed to them by humans), this reduction in lactase has no significance in nature.
Prevalence of lactase Deficiency The majority of humans follow the animal pattern and are genetically programmed to lose the ability to synthesize lactase.13 However, a mutation in some population groups allows the infantile level of lactase to persist throughout adulthood. Such subjects are said to be lactase persistent, whereas their counterparts who lose the ability to produce lactase are termed lactase nonpersistent (lactase deficient in older terminology). Table 3 shows the percentage of adults of various ethnic origin who are lactase persistent.14 In general, only individuals of northern or middle European extraction, or about 75% of the adult U.S. population, are likely to be lactase persistent. The remaining 25% tend to be lactase nonpersis148
272 124 204
69 150
tant and maldigest and malabsorb lactose. Roughly 75% of the world’s population is lactase nonpersistent; thus, the inability to digest lactose in adulthood is the norm rather than the exception. Familiarity with the relationship between national origin and intestinal lactase levels has clinical utility for the physician. For example, an adult of Asian, Mediterranean, or African origin is very
3. Ethnic Background and Prevalence of Lactase Nonpersistence
Table
Ethnic
Group
Northern European Scandinavians Middle European Native English Native German Mediterranean Northern Italians Southern Italians Most Africans Masai Asians Latinos Semites (Jews) United States African-Americans Alaska Innuits Asian-Americans Native Americans Caucasians
% Lactose Nonpersistent l-5 3 10-20 11
5 60-90 11
85 80-100 <5
>90 64
90 20-25 70-100 80 80-100
>90 12
likely to have low lactase levels and testing ordinarily is not required to confirm the existence of lactose maldigestion.
Diagnosis of lactose Malabsorption The ability to digest lactose usually is assessed via breath hydrogen (H,) testing. Malabsorbed lactose is fermented to H, by the colonic bacteria. This H, is absorbed, transported by the blood to the lungs and then excreted in expired air. Thus, an increase in breath H, after ingestion of lactose provides a simple, noninvasive indicator that lactose was incompletely absorbed.‘” This technique has shown that even small quantities of lactose (for example 6 g, or the quantity in I/Z cup of milk) are incompletely absorbed by lactase nonpersistent individuals.”
Symptoms Resulting from lactose Malabsorption Malabsorbed lactose holds water in the lumen via its osmotic activity, and diarrhea will result if lactose reaches the rectum. Although lactose, per se, cannot be absorbed from the colon, this sugar is rapidly fermented to organic acids such as acetate and butyrate by the colonic bacteria, and these products are efficiently absorbed and/or metabolized by the colonic mucosa.17 Diarrhea is prevented if most of the osmotic activity of lactose is removed via this mechanism. There are limits, however, to the ability of the colonic bacteria to ferment lactose and the colonic mucosa to remove the fermentation products. Ingestion of large, unphysiological lactose loads may cause diarrhea. Large quantities of gas (CO,, H,, and CH,) are produced during lactose fermentation, and the accumulation of these gases may produce bloatPrim
Care Update
ObiGyns
ing, abdominal discomfort and flatulence. However, these gases are consumed by other bacteria and absorbed across the mucosa.18 Symptoms occur only when these removal mechanisms are exceeded. Thus, it is important to recognize that lactose malabsorption and lactose intolerance are not necessarily synonymous. While all lactose nonpersistent subjects malabsorb lactose, with limited doses this malabsorption may not cause perceptible symptoms, ie, there is no lactose intolerance.
When Is Treatment of lactose Intolerance Indicated? There is controversy about the dosage of lactose that can be tolerated by lactase nonpersistent individuals and the need for lactose digestive aids. This topic has major commercial as well as health implications. For example, if each of the roughly XI million lactase nonpersistent Americans used lactase tablets just once per day, annual sales would be about $3 billion. Initial unblinded studies in which subjects were asked if they had symptoms following milk ingestion suggested that the quantity of lactose in one 8 oz cup of milk (12 g) induced appreciable symptoms in the majority of lactase nonpersistent subjects.lg However, the symptoms of lactose intolerance (mild bloating and gas) are notoriously susceptible to suggestion and readily modified by the placebo effect. Determination of the true ability of lactose to induce symptoms requires rigorous double-blind testing in which symptoms are compared following administration of a lactose containing food verses an identical placebo. There is a taste difference between conventional (lactose Volume
3. Number
4, ISDF,
containing) milk and lactose prehydrolyzed milk because the hydrolysis products, glucose and galactose, are sweeter than lactose. However, this difference can be disguised by sweetening conventional milk with aspartame.” Well-controlled studies carried out prior to 1995 generally concluded that symptoms with one 8 oz cup of conventional milk were no greater than those with one 8 oz cup of lactose-hydrolyzed milk.21.22 However, this conclusion is contrary to the belief of an enormous group of individuals who are certain that trivial quantities of milk, such as that used with cereal and coffee, cause symptoms. It seemed possible to us that there might be a subset of extremely lactose intolerant individuals who had not been adequately represented in previous investigations. Therefore, we” recently studied 30 subjects who considered themselves to be extremely lactose intolerant, ie, they routinely developed symptoms after ingestion of less than an 8 oz cup of milk. Initial H, testing of these 30 subjects demonstrated that nine were not lactose maldigesters, ie, they completely absorbed lactose. Thus, 27% of subjects who considered themselves to be severely lactose intolerant clearly had misdiagnosed their problem. The 30 subjects were enrolled in a double-blind study in which they ingested one 8 oz cup of conventional or one 8 oz cup of lactose-hydrolyzed milk with breakfast for 1 week in a cross-over design. In contrast to the subjects’ prestudy belief that the severity of symptoms during the conventional milk period would cause them to drop out of the study, there were no significant differences in symptoms between the two treatment periods. We concluded that individuals commonly misattribute symptoms to lactose intolerance and that virtually all lactase nonpersistent subjects can ingest one cup of milk per
day without fear of appreciable symptoms. Controlled trials have demonstrated that as the dose of lactose is increased, symptoms become more frequent. Approximately 80% of subjects had symptoms when 50 g of lactose (the quantity in a quart of milk) was taken as a single dose,‘l and another study2” indicated that symptoms were relatively frequent when 20 g (1.5 cups of milk) was ingested as a single dose. Symptoms may have been overestimated in the many studies that have tested tolerance via the feeding of lactose solutions in the absence of other food. Lactose ingested in milk with meals appears to be better tolerated because the presence of other nutrients slows gastric emptying, which in turn slows passage of lactose through the small bowel. This results in increased lactose digestion and slower delivery of the unabsorbed sugar to the colon. Controlled trials will be required to determine the tolerance of lactase nonpersistent subjects to the daily ingestion of several cups of milk when this milk is ingested in physiological fashion, ie, a cup of milk with several different meals.
Treatment of lactose Intolerance It is apparent from the above that one cup of milk taken with breakfast is associated with negligible symptoms and hence no treatment is required. Although not yet tested, it seems likely that two cups of milk daily, one with breakfast and one with dinner, similarly will be welltolerated because the symptomatic periods resulting from these two doses are unlikely to overlap. The use of lactose digestive aids should be reserved primarily for subjects wishing to ingest more than one cup of milk (or the equivalent lactose load) at a single sitting or for 149
BANNAN
& LEVITT
Table 4. Cost Comparisons Between Milk and Low-Lactose Alternatives Product
Cost per 240 mL Milk
Increment in Cost (%)
$0.19 $0.27 $0.37
0 42 95
$0.79 $0.49
158-316
Milk Lactase (liquid) producing 70% LHM Lactase (liquid) producing 100% LHM Lactase caplets Cartons of 12 units Cartons of 100 units Prehydrolyzed milk Plain yogurt Flavored yogurt LHM.
lactose
hydrolyzed
$0.36
$0.49 $0.60
89
158 218
nenbaum S. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990;323: 878-83. 7. Holbrook
8.
milk. 9.
those wishing to drink more than two cups of milk daily, The commercial products available for the treatment of lactose intolerance and their approximate cost is shown in Table 4.23 Relatively lactose-free milk now is becoming widely available. In addition, various lactase preparations can be purchased as over-the-counter products. One of these preparations is added to milk, which is then incubated overnight. In addition, there are lactase tablets that may be taken at the time of ingestion of dairy products. Although not extensively tested, breath H, measurements have shown that these products enhance lactose absorption, and it seems likely that their use will reduce the symptoms that follow ingestion of large doses of lactose. However, these products increase the cost of milk by 33-200%, depending upon the product and the dosage employed (see Table 4). Thus, these products should largely be reserved for subjects who wish to drink more than two cups of milk per day. It is important to note that not all dairy products are created equal with regard to their ability to induce symptoms in lactase nonpersistent subjects. For example, yogurt contains high concentrations of lactase due to the production of this enzyme by the yogurt bacteria. As a result, lactose ingested in yogurt is better tolerated than is an equivalent dose of lactose ingested in milkez4 150
There is a good deal of confusion in both the medical and lay communities with regard to the lactose content of cheese. As shown in Table 1, hard cheeses (cheddar, Swiss, etc.) contain minimal lactose, less than 1 g/serving. In the process of manufacturing hard cheeses, much of the lactose is removed with the whey. Most of the remaining lactose is fermented during the aging or ripening process. Three to four servings of cheese a day provide the RDA for calcium and a total lactose load (<5 g/day) that can be readily tolerated by lactase nonpersistent subjects.
References 1. Wardlaw GM. Putting osteoporosis 2.
3. 4.
5.
6.
in perspective. J Am Diet Assoc 1993;93:1000-6. Tolstoli CG, Levin RM. Osteoporosis--the treatment controversy. Nutr Today 1992 July/August;629. Heaney RP. Calcium in the prevention of osteoporosis. J Int Med 1992; 231:169-80. Nordin BEC, Need AG, Chatterton BE, Horowitz M, Morris HA. The relative contributions of age and years since menopause to postmenopausal bone loss. J Clin Endocrinol Metab 1990;70:83-8. Jensen FT, Charles P, Mosekilde L, Hansen HH. Calcium metabolism evaluated by 47calcium-kinetics: a physiological model with correction for faecal lag time and estimation of dermal calcium loss. Clin Physiol 1983;3:187-204. Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoung N, Tan-
10.
11.
12.
13.
14.
15.
TL, Barrett-Connor E, Wingard DL. Dietary calcium and risk of hip fracture: 14-year prospective population study. Lancet 1988; ii:1046-9. Cumming RC. Calcium intake and bone mass: a quantitative review of the evidence. Calcif Tissue Int 1990; 47:194-201. National Institutes of Health. Osteoporosis Consensus Development Conference Statement. JAMA 1984; 252:799-802. Robinson CH, Lawler MR. Mineral elements. In: Normal therapeutic nutrition, 15th ed. New York: Macmillan Publishing Co., 1977:107. Scrimshaw NS, Murray EB. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr 1988;48(Suppl): 1083-159. Bowes A, Church H. Food values of portions commonly used, 16th ed. Philadelphia: JB Lippincott Co., 1994. Gilat T, Russo S, Gelman-Malachi E, Aldor TAM. Lactase in man: a noninducible enzyme in man. Gastroenter01 1972;62:1125-7. Simoons FJ. The geographic hypothesis and lactose malabsorption: a weighing of the evidence. Am J Dig Dis 1978;23:963-80. Levitt MD, Donaldson RM. Use of respiratory hydrogen (H,) excretion to detect carbohydrate malabsorption. J Clin Lab Med 1970;75:937-
45. 16. Hertzler
SR, Huynh B, Savaiano DA. How much lactose is “low lactose.” J Am Diet Assoc. In press. 17. Bond JH, Levitt MD. Fate of soluble carbohydrate in the colon of rats and man. J Clin Invest 1976;57: 1158-64. 18. Levitt MD, Berggren T, Hastings J,
Bond JH. Hydrogen (H,) catabolism in the colon of the rat. J Lab Clin Med 1974;84:163-7. 19. Bayless TM, Rothfeld B, Massa C, Wise L, Paige D, Bedine MS. Lactose and milk intolerance: clinical implications. N Engl J Med 1975;292: 1156-9. 20. Suarez F, Savaiano DA, Levitt MD. A comparison of symptoms with milk or lactose-hydrolyzed milk in people with self-reported severe Prim Care Update
Ob/Gyns
LACTOSE lactose intolerance. N Engl J Med 1995;333:1-4. 21. Haverberg L, Kwon PH, Scrimshaw NS. Comparative tolerance of adolescents of differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks: initial experience with a double-blind procedure. Am J Clin Nutr 1980;33:1721.
Volume
3, Number
4, 19%
22. Unger M, Scrimshaw NS. Comparative tolerance of adults of differing ethnic backgrounds to lactose-free and lactose-containing dairy drinks. Nutr Res 1981;1227-33. 23. Suarez FL, Savaiano DA, Levitt MD. Treatment of lactose intolerance. Alimentary Pharmacol Ther 19%; 9:589-97. 24. Kolars JC, Levitt MD, Mostafa A,
INTOLERANCE
Savaiano DA. Yogurt: an autodigesting source of lactose. N Engl J Med 1984;310:1-3.
Address correspondence and reprint requests to Michael D. Levitt, MD, ACOS Research, Veterans Affairs Medical Center, Minneapolis, MN 55417.
151