December 1992: 463-466
Micronutrient Requirements of the Elderly Robert M. Russell, M.D.
The Question of Decreased Need
The specific requirements for micronutrients in the elderly have not been studied until quite recently. In the 1989 edition of the Recommended Dietary Allowances (RDA),’ only four micronutrients are listed as being different for the age group over 51 years and the age group 23-50 years: thiamin, riboflavin, niacin, and iron. The RDA committee judged that there is a decreased need for these vitamins with advancing age because of decreased caloric and protein intakes, and for iron due to the lack of menstrual periods in elderly females. However, there is mounting evidence that some of these recommended decrements (which are based on theory but have never actually been measured in the elderly) may not be correct. For example, in the case of riboflavin, Boisvert et al. (unpublished data) have recently shown that the requirements for elderly people are exactly the same as for younger people. In young adults (aged 20-40 years), Horwitt et al.’ had shown a very gradual increase in urinary riboflavin excretion with increasing dietary riboflavin, until a dietary level of 1.1 mg/day was reached. Above this level of dietary intake, the slope of the riboflavin urinary excretion curve suddenly became much steeper. The point at which the slopes of the urinary excretion curves on the lower and higher dietary intakes of riboflavin intersect is called the critical intake, which defines the level of tissue saturati,on. Boisvert performed a similar study in elderly people aged 60-85. These persons were maintained on a steady diet comprised of 11% protein, 31% fat, and 57% carbohydrate, which is currently the typical North American diet. The subjects were depleted to begin with, but then were repleted in staged increments of 0.9, 1.1, 1.3, and 1.5 mg. Urinary excretion was measured daily. It was found that the critical intake point, measuring the point of intersection of the two Dr. Russell is Professor of Medicine and Nutrition at the Schools of Medicine and Nutrition and Assistant Director of the USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA. Nutrition Reviews, Vol. 50, No. 12
urinary excretion slopes on lower and higher dietary intakes, was precisely the same as that found by Horwitt’ for young adults-that is, 1. I mg/day. Thus, the assumption made by the RDA committee that riboflavin requirements are lower in elderly people than in younger people due to lower caloric intakes does not seem warranted. Rising Need for Vitamins D, B,, and B,,
There are several micronutrients for which there is strong evidence that requirements are in fact increased in the elderly compared to younger people: vitamin D, vitamin B,, and vitamin B,*. It is known from many studies that levels of the active form of vitamin D, I ,25-dihydroxyvitamin D, are lower in older people than in younger people., Moreover, Francis et al.4 have shown that in elderly people with low or borderline-low levels of plasma 25-hydroxyvitamin D, one can increase plasma levels of 1,25-dihydroxy-D by feeding more substrate, that is, 25-hydroxyvitamin D. The reasons for the low circulating levels of 1,25-dihydroxyvitamin D in the elderly could be due to many factors. First, it could be that elderly people ingest less vitamin D in their diet due to decreased intake of dairy products. However, there is additional evidence for metabolic disturbances in vitamin D metabolism due to age. For example, it has been shown by Webb et al.5that there is a decreased ability to form previtamin D, in skin upon ultraviolet light exposure in elderly people vs. young p e ~ p l e Using .~ the skin of an eightyear-old as showing a 100% response for previtamin D synthesis upon ultraviolet exposure, the skin of an 82-year-old person is able to give a relative response of only 40%. The reason for this decreased conversion appears to be smaller amounts of 7-dehydrocholesterol concentrations in the skin with advancing age.6 Since a large part of the vitamin D requirement is met by skin synthesis, rather than by dietary ingestion of the vitamin, impaired skin synthesis would result in a higher dietary need in the older person in order to meet his or her requirement. 463
A second problem with vitamin D metabolism with age appears to be decreased synthesis of 1,25dihydroxyvitamin D by the kidney following parathyroid hormone ~ t i m u l a t i o n .Upon ~ intravenous infusion of parathyroid hormone, younger people show a marked rise in serum 1,25-dihydroxyvitamin D levels, whereas older osteoporotic individuals show little or no rise. Despite a relative defect in converting 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the aged kidney, the provision of more substrate, at least for those who have borderline vitamin D nutritional status, could result in a higher concentration of 1,25-dihydroxyvitamin D, the most active form of the vitamin. Dawson-Hughes et a1.* have recently studied the effect of vitamin D supplementation on bone mineralization in healthy postmenopausal women. These women were studied in both winter-spring and summer-fall periods. This study was a doubleblind, placebo-controlled trial lasting for one year in which equal numbers of women were randomized to receive either placebo or 400 international units (IU) of vitamin D daily. All were on their usual dietary intakes of vitamin D of 100 IU daily. The authors found a net gain in both spine and wholebody bone mineral density as measured by dual x-ray absorptiometry during the summer-fall period, and a net loss in the winter-spring period. However, there was significantly less spinal loss in the vitamin D-supplemented group than in the placebo-treated group during the winter-spring period. Moreover, over the entire one-year period of study, there was a net increase in the spinal bone mineral density in the vitamin D-supplemented group vs. the placebo-treated group. From this, it is concluded that at latitude 42", healthy postmenopausal women with dietary vitamin D intakes of 100 IU daily can reduce their winter bone loss and improve spinal bone density over a one-year period by supplementing themselves with 400 IU each day. The present RDA for vitamin D in the United States is 200 IU daily for all adults, regardless of age. From the Dawson-Hughes study,8 it appears quite likely that the vitamin D intake necessary to prevent bone mineral loss of the spine exceeds this value. This is particularly true in elderly people who cannot or will not expose themselves to sunlight and in those living in northern latitudes. Vitamin 8, Many elderly populations have been found to be deficient in vitamin B,. In one Dutch study,' in which high-aspartate aminotransferase activity coefficient was used as the indicator of vitamin B, deficiency, 10% of Dutch elderly over the age of 65 were found to be deficient. Using low-plasma pyridoxal phosphate level as the indicator, it was found 464
that 13% of females and 45% of males were deficient. The current RDAs for vitamin B, for young and elderly adults are the same and are based on 0.16-mg vitamin B, per gram of dietary protein. This results in vitamin B, allowances of 2.0 and 1.6 mg/ day for men and women, respectively (based on the upper boundary of acceptable protein intakestwice the RDA for protein). Ribaya-Mercado et al." have recently reported on a vitamin B, depletionrepletion study of normal healthy elderly volunteers studied on a metabolic unit. These individuals were first depleted of vitamin B, and then repleted in staged increments. Urinary xanthurenic acid excretion after a tryptophan load did not return to baseline values until the third repletion period in both males and females, representing dietary intakes of 1.96 mg for elderly men and approximately 1.90 mg for elderly women. Thus, the assumption that the vitamin B, requirement does not change with age appears to be wrong. The current RDAs appear to be insufficient for the elderly and should be reevaluated, since the RDAs are intended to meet the nutrient needs of practically all healthy persons. Vitamin B,, Vitamin B,, requirements may be increased in a large number of elderly people who have atrophic gastritis, an age-related degenerative condition of the stomach that results in less acid and pepsin secretion. This condition can be identified by serum pepsinogen markers, with a pepsinogen 1:II ratio of less than 2.9 defining individuals with the condition." Using this marker, in the United States, 25% of persons aged 60-69 and almost 40% over the age of 80 have atrophic gastritis.', This disorder may cause problems in vitamin B,, absorption by several different mechanisms. In most cases, the stomach continues to put out sufficient amounts of intrinsic factor so that vitamin B,, absorption is not impaired. However, both impaired digestion of cobalamin from food protein due to the lack of acidpepsin digestion as well as to bacterial uptake of vitamin B,, in the proximal small intestine have been shown to be factors in vitamin B,, malabsorption in patients with atrophic gastritis. I3,l4 The lack of acid to kill swallowed bacteria enables large amounts of bacteria to reside in the stomach and small intestine of individuals with atrophic gastritis. King et al." have shown that when vitamin B,, joined to protein is fed to persons with atrophic gastritis, only subnormal amounts of the vitamin are absorbed. Moreover, this vitamin B malabsorption is not improved by giving intrinsic factor. However, when the protein-bound vitamin B,, is given along with acid or acid plus pepsin, absorption returns to normal. Suter et al.I4 have recently shown that treating persons with atrophic gastritis with tetNutrition Reviews, Vol. 50, No. 12
racycline for a period of ten days also can correct abnormal vitamin B,, absorption. Thus, the lack of acid-pepsin digestion and bacterial uptake of the vitamin appears to be a factor. Since intrinsic factor is not lacking in most people with atrophic gastritis, and since their ileums are working normally, it is probable that increasing the level of dietary vitamin BIZ(or giving crystalline vitamin B,, as an oral supplement) may be all that is needed in these persons to ensure B,, adequacy. The issue of vitamin B,, adequacy is an important one, since Lindenbaum et a1.I6 have recently shown that many elderly people with dementia have subtle B,, deficiency not manifested by low serum B,, levels, but, rather, by elevated serum homocysteine or methylmalonate levels and, in most cases, by multilobed polymorphonuclear leukocytes on careful examination of blood smears. Vitamin A Requirement
One vitamin for which there is some evidence of a lower requirement for the elderly than for younger people is vitamin A. It has been known for some time that although only two-thirds of elderly people (65-75 years old) in the United States ingest the RDA for vitamin A, mean and median liver levels of vitamin A do not drop with advancing age.” Hollander and MorganI8 have shown that in rats there is increased absorption of vitamin A from perfused intestinal segments. It has been postulated that this is due to a change in the character of the unstirred water layer, which allows fat-soluble substances to penetrate the cell membrane more easily, increasing their absorption. However, Krasinski et aI.l9 have recently shown that higher blood vitamin A tolerance curves in elderly vs. younger people may not, in fact, be due to increased absorption of the vitamin, but, rather, to its decreased clearance by hepatic and other peripheral tissues. In a series of studies, the investigators’’ first fed a high-vitamin A diet and then performed plasmapheresis to obtain vitamin A-laden chylomicrons and chylomicron remnants. They then reinfused these remnants back into the donors. They found that the rate of vitamin A clearance from blood was twice as fast in younger people as in the elderly. It has also been shown by Krasinski et a1.” that elderly persons taking vitamin A supplements have higher levels of circulating retinyl esters, which are toxic indicators, than do elderly persons not taking vitamin A supplements. For the present, it is prudent not to recommend vitamin A-containing supplements for the elderly until several longitudinal studies are carried out. A few studies have been performed with regard to carotenoid metabolism and aging; so far carotene has been shown to have Nutrition Reviews, Vol. 50, No. 12
no toxic potential in either elderly or younger people. Minerals, Vitamin E, and Vitamin C There is no clear evidence that mineral requirements are different in elderly and young individuals, other than lower iron requirements in postmenopausal females. For example, although zinc absorption from the gastrointestinal tract has been shown to be lower in elderly than in younger adults, overall zinc balance is not different because of decreased net losses in the elderly.2’ Moreover, although it has been shown that the intestines of elderly persons are less able to adapt to low-calcium diets (i.e., by increasing the efficiency of calcium absorption) than are those of younger persons, increasing calcium intakes beyond 800 mg/day (the current RDA for all adults) has not been shown to be of any benefit in terms of preserving bone mass.,, This brings up a philosophical problem in defining vitamin and mineral requirements in the elderly, depending on whether one is trying to prevent deficiency states or trying to guard against disease and chronic degenerative states. For example, Meydani et al.23have shown that supplementation of 800 mg/ day of vitamin E will stimulate various parameters of immune function over a short period. However, whether these effects would be maintained over a longer term and whether physiologic amounts of the vitamin-e.g., what could be obtained in a normal diet-would also stimulate immune function are unknown. Surely, no one would set an RDA for vitamin E at 800 mg, even if it resulted in less infection. The situation is less clear with vitamin C, in that individuals eating less than 125 mg/day have been shown to have a fourfold increase in risk of developing cataracts compared to persons eating over 500 m g / d a ~ . ’The ~ current RDA for vitamin C in the United States is 60 mg, although a 500-mg allowance can easily be met in the diet. Ames et al.25 have recently shown that ascorbate is the most effective antioxidant in human blood and may be important in protecting against oxidant stress-related diseases and degeneration. Thus, maintaining tissue levels at full saturation may be desirable. Data by Jacob et aLZ6have recently shown that about 140 mg/day of vitamin C are necessary to saturate the total body ascorbate pool. In the case of vitamin C, one may not wish to define the RDA in terms of its antiscorbutic effects, but, rather, in terms of its cataract-preventive effects or its antioxidant effects. Furthermore, in the case of vitamin C, it may be desirable t o maintain a high tissue saturation throughout the life span and not just in elderly persons in whom the chronic diseases appear, since the pathogenesis of these diseases may have started years earlier. 465
Conclusion Knowledge of vitamin and mineral requirements in the elderly is evolving. One can state now that not all vitamin and mineral requirements stay static over the adult life span. Each micronutrient must be examined individually and specific recommendations will evolve. In 1992, one can state with some certainty that the requirements for vitamins B, and D are increased in the elderly. Also, for a large proportion of the elderly, the requirements for vitamin B,, are probably elevated. For riboflavin, the requirement stays the same (and does not decrease as previously thought), and there is evidence that the requirement for vitamin A either stays the same or decreases. 1. National Research Council. Recommended dietary allowances, 10th ed. Washington, DC: National Academy Press, 1989 2. Horwitt MK, Harvey CC, Hills OW, Liebert E. Correlation of urinary excretion of riboflavin with dietary intake and symptoms of ariboflavinosis. J Nutr 1950;41:247-64 3. Dandona P, Menon RK, Shenoy R, Houlder S, T h o m a s M , M a l l i n s o n WJW. L o w 1,25d ihyd roxyvitam in D, secondary hyper parat hyroidism, and normal osteocalcin in elderly subjects. J Clin Endocrinol Metab 1986;63:459-62 4. Francis RM, Peacock M, Storer JH, Davies AEJ, Brown WB, Nordin BEC. Calcium malabsorption in the elderly: the effect of treatment with oral 25hydroxyvitamin D., Eur J Clin Inv 1983;13:391-6 5. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D., Exposure to winter sunlight in Boston and Edmonton will not promote vitamin D, synthesis in human skin. J Clin Endocrinol Metab 1988;67:
373-8 6. MacLaughlin JA, Holick MF. Aging decreases the capacity of human skin to produce vitamin D., J CIin Invest 1 985;76: 1 536-8 7. Slovik DM, Adams JS, Neer RM, Holick MF, Potts JT. Deficient production of 1,25dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med
1981 ;305:372-4 8. Dawson-Hughes B, Dallal GE, Krall EA, Harris S , Sokoll LJ, Falconer G. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med
1991 ;115:505-12 9. Tolonen M, Schrijver J, Westermarck T, Halme M, Tuominen SEJ, Frilander A, Keinonen M, Sarna S. Vitamin B, status of Finnish elderly, comparison with Dutch younger adults and elderly. The effect of supplementation. Int J Vitam Nutr Res 1988;58:
73-7 10. Ribaya-Mercado JD, Russell RM, Sahyoun N, Morrow FD, Gershoff SN. Vitamin B, requirement of elderly men and women. J Nutr 1991 ;121:1062-74
466
11. Samloff IM, Varis K, lhamaki T. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. Gastroenterology
1982;83:204 12. Krasinski SD, Russell RM, Samloff IM, et al. Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators. J Am Geriatr SOC1986;34:800-6 13. Doscherholmen A, McMahon BS, Ripley D. Vitamin B, assimilation from chicken meat. Am J Clin Nutr 1978;31:825-30 14. Suter PM, Golner BB, Goldin BR, Morrow FD, Russell RM. Reversal of protein-bound vitamin BIZ malabsorption with antibiotics in atrophic gastritis. Gastroenterology 1991 ;lo1:lo3945 15. King CE, Leibach J, Toskes PP. Clinically significant vitamin B, deficiency secondary to malabsorption of protein-bound vitamin BIZ. Dig Dis Sci
1979;24:397-402 16. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8 17. Hoppner L, Phillips WEJ, Murray TK, Campbell JS. Survey of liver vitamin A stores of Canadians. Can Med Assoc J 1968;99:983-6 18. Hollander D, Morgan D. Aging: its influence on vitamin A intestinal absorption in vivo by the rat. Exp Gerontol 1979;14:301-5 19. Krasinski SD, Cohn JS, Schaefer EJ, Russell RM. Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. J Clin Invest 1990;85:883-92 20. Krasinski SD, Russell RM, Otracdovec CL, et al. Vitamin A and E intake: relationship to fasting plasma retinol, retinol binding protein, retinyl ester, carotene and alpha tocopherol levels in the elderly and young adults. Am J Clin Nutr 1989;49:
1 12-20 21. Turnland J, Costa F, Margen S. Zinc, copper, and iron balance in elderly men. Am J Clin Nutr 1981; 3412641-7 22. Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990;323:878-83 23. Meydani SN, Barklund MP, Liu S, et al. Rocklin R, Blumberg JB. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr 1990;52:557-63 24. Jacques PF, Chylack LT. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. Am J Clin Nutr
1991 ;53:352S-58 25. Balz F, Stocker R, Ames BN. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 1988;85:9748-52 26. Jacob RA, Skala JH, Omaye ST. Biochemical indices of human vitamin C status. Am J Clin Nutr
1987;46:818-26
Nutrition Reviews, Vol. 50, No. 12
Micronutrient Requirements of the Elderly Robert M. Russell, M.D.
The Question of Decreased Need
The specific requirements for micronutrients in the elderly have not been studied until quite recently. In the 1989 edition of the Recommended Dietary Allowances (RDA),’ only four micronutrients are listed as being different for the age group over 51 years and the age group 23-50 years: thiamin, riboflavin, niacin, and iron. The RDA committee judged that there is a decreased need for these vitamins with advancing age because of decreased caloric and protein intakes, and for iron due to the lack of menstrual periods in elderly females. However, there is mounting evidence that some of these recommended decrements (which are based on theory but have never actually been measured in the elderly) may not be correct. For example, in the case of riboflavin, Boisvert et al. (unpublished data) have recently shown that the requirements for elderly people are exactly the same as for younger people. In young adults (aged 20-40 years), Horwitt et al.’ had shown a very gradual increase in urinary riboflavin excretion with increasing dietary riboflavin, until a dietary level of 1.1 mg/day was reached. Above this level of dietary intake, the slope of the riboflavin urinary excretion curve suddenly became much steeper. The point at which the slopes of the urinary excretion curves on the lower and higher dietary intakes of riboflavin intersect is called the critical intake, which defines the level of tissue saturati,on. Boisvert performed a similar study in elderly people aged 60-85. These persons were maintained on a steady diet comprised of 11% protein, 31% fat, and 57% carbohydrate, which is currently the typical North American diet. The subjects were depleted to begin with, but then were repleted in staged increments of 0.9, 1.1, 1.3, and 1.5 mg. Urinary excretion was measured daily. It was found that the critical intake point, measuring the point of intersection of the two Dr. Russell is Professor of Medicine and Nutrition at the Schools of Medicine and Nutrition and Assistant Director of the USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA. Nutrition Reviews, Vol. 50, No. 12
urinary excretion slopes on lower and higher dietary intakes, was precisely the same as that found by Horwitt’ for young adults-that is, 1. I mg/day. Thus, the assumption made by the RDA committee that riboflavin requirements are lower in elderly people than in younger people due to lower caloric intakes does not seem warranted. Rising Need for Vitamins D, B,, and B,,
There are several micronutrients for which there is strong evidence that requirements are in fact increased in the elderly compared to younger people: vitamin D, vitamin B,, and vitamin B,*. It is known from many studies that levels of the active form of vitamin D, I ,25-dihydroxyvitamin D, are lower in older people than in younger people., Moreover, Francis et al.4 have shown that in elderly people with low or borderline-low levels of plasma 25-hydroxyvitamin D, one can increase plasma levels of 1,25-dihydroxy-D by feeding more substrate, that is, 25-hydroxyvitamin D. The reasons for the low circulating levels of 1,25-dihydroxyvitamin D in the elderly could be due to many factors. First, it could be that elderly people ingest less vitamin D in their diet due to decreased intake of dairy products. However, there is additional evidence for metabolic disturbances in vitamin D metabolism due to age. For example, it has been shown by Webb et al.5that there is a decreased ability to form previtamin D, in skin upon ultraviolet light exposure in elderly people vs. young p e ~ p l e Using .~ the skin of an eightyear-old as showing a 100% response for previtamin D synthesis upon ultraviolet exposure, the skin of an 82-year-old person is able to give a relative response of only 40%. The reason for this decreased conversion appears to be smaller amounts of 7-dehydrocholesterol concentrations in the skin with advancing age.6 Since a large part of the vitamin D requirement is met by skin synthesis, rather than by dietary ingestion of the vitamin, impaired skin synthesis would result in a higher dietary need in the older person in order to meet his or her requirement. 463
A second problem with vitamin D metabolism with age appears to be decreased synthesis of 1,25dihydroxyvitamin D by the kidney following parathyroid hormone ~ t i m u l a t i o n .Upon ~ intravenous infusion of parathyroid hormone, younger people show a marked rise in serum 1,25-dihydroxyvitamin D levels, whereas older osteoporotic individuals show little or no rise. Despite a relative defect in converting 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the aged kidney, the provision of more substrate, at least for those who have borderline vitamin D nutritional status, could result in a higher concentration of 1,25-dihydroxyvitamin D, the most active form of the vitamin. Dawson-Hughes et a1.* have recently studied the effect of vitamin D supplementation on bone mineralization in healthy postmenopausal women. These women were studied in both winter-spring and summer-fall periods. This study was a doubleblind, placebo-controlled trial lasting for one year in which equal numbers of women were randomized to receive either placebo or 400 international units (IU) of vitamin D daily. All were on their usual dietary intakes of vitamin D of 100 IU daily. The authors found a net gain in both spine and wholebody bone mineral density as measured by dual x-ray absorptiometry during the summer-fall period, and a net loss in the winter-spring period. However, there was significantly less spinal loss in the vitamin D-supplemented group than in the placebo-treated group during the winter-spring period. Moreover, over the entire one-year period of study, there was a net increase in the spinal bone mineral density in the vitamin D-supplemented group vs. the placebo-treated group. From this, it is concluded that at latitude 42", healthy postmenopausal women with dietary vitamin D intakes of 100 IU daily can reduce their winter bone loss and improve spinal bone density over a one-year period by supplementing themselves with 400 IU each day. The present RDA for vitamin D in the United States is 200 IU daily for all adults, regardless of age. From the Dawson-Hughes study,8 it appears quite likely that the vitamin D intake necessary to prevent bone mineral loss of the spine exceeds this value. This is particularly true in elderly people who cannot or will not expose themselves to sunlight and in those living in northern latitudes. Vitamin 8, Many elderly populations have been found to be deficient in vitamin B,. In one Dutch study,' in which high-aspartate aminotransferase activity coefficient was used as the indicator of vitamin B, deficiency, 10% of Dutch elderly over the age of 65 were found to be deficient. Using low-plasma pyridoxal phosphate level as the indicator, it was found 464
that 13% of females and 45% of males were deficient. The current RDAs for vitamin B, for young and elderly adults are the same and are based on 0.16-mg vitamin B, per gram of dietary protein. This results in vitamin B, allowances of 2.0 and 1.6 mg/ day for men and women, respectively (based on the upper boundary of acceptable protein intakestwice the RDA for protein). Ribaya-Mercado et al." have recently reported on a vitamin B, depletionrepletion study of normal healthy elderly volunteers studied on a metabolic unit. These individuals were first depleted of vitamin B, and then repleted in staged increments. Urinary xanthurenic acid excretion after a tryptophan load did not return to baseline values until the third repletion period in both males and females, representing dietary intakes of 1.96 mg for elderly men and approximately 1.90 mg for elderly women. Thus, the assumption that the vitamin B, requirement does not change with age appears to be wrong. The current RDAs appear to be insufficient for the elderly and should be reevaluated, since the RDAs are intended to meet the nutrient needs of practically all healthy persons. Vitamin B,, Vitamin B,, requirements may be increased in a large number of elderly people who have atrophic gastritis, an age-related degenerative condition of the stomach that results in less acid and pepsin secretion. This condition can be identified by serum pepsinogen markers, with a pepsinogen 1:II ratio of less than 2.9 defining individuals with the condition." Using this marker, in the United States, 25% of persons aged 60-69 and almost 40% over the age of 80 have atrophic gastritis.', This disorder may cause problems in vitamin B,, absorption by several different mechanisms. In most cases, the stomach continues to put out sufficient amounts of intrinsic factor so that vitamin B,, absorption is not impaired. However, both impaired digestion of cobalamin from food protein due to the lack of acidpepsin digestion as well as to bacterial uptake of vitamin B,, in the proximal small intestine have been shown to be factors in vitamin B,, malabsorption in patients with atrophic gastritis. I3,l4 The lack of acid to kill swallowed bacteria enables large amounts of bacteria to reside in the stomach and small intestine of individuals with atrophic gastritis. King et al." have shown that when vitamin B,, joined to protein is fed to persons with atrophic gastritis, only subnormal amounts of the vitamin are absorbed. Moreover, this vitamin B malabsorption is not improved by giving intrinsic factor. However, when the protein-bound vitamin B,, is given along with acid or acid plus pepsin, absorption returns to normal. Suter et al.I4 have recently shown that treating persons with atrophic gastritis with tetNutrition Reviews, Vol. 50, No. 12
racycline for a period of ten days also can correct abnormal vitamin B,, absorption. Thus, the lack of acid-pepsin digestion and bacterial uptake of the vitamin appears to be a factor. Since intrinsic factor is not lacking in most people with atrophic gastritis, and since their ileums are working normally, it is probable that increasing the level of dietary vitamin BIZ(or giving crystalline vitamin B,, as an oral supplement) may be all that is needed in these persons to ensure B,, adequacy. The issue of vitamin B,, adequacy is an important one, since Lindenbaum et a1.I6 have recently shown that many elderly people with dementia have subtle B,, deficiency not manifested by low serum B,, levels, but, rather, by elevated serum homocysteine or methylmalonate levels and, in most cases, by multilobed polymorphonuclear leukocytes on careful examination of blood smears. Vitamin A Requirement
One vitamin for which there is some evidence of a lower requirement for the elderly than for younger people is vitamin A. It has been known for some time that although only two-thirds of elderly people (65-75 years old) in the United States ingest the RDA for vitamin A, mean and median liver levels of vitamin A do not drop with advancing age.” Hollander and MorganI8 have shown that in rats there is increased absorption of vitamin A from perfused intestinal segments. It has been postulated that this is due to a change in the character of the unstirred water layer, which allows fat-soluble substances to penetrate the cell membrane more easily, increasing their absorption. However, Krasinski et aI.l9 have recently shown that higher blood vitamin A tolerance curves in elderly vs. younger people may not, in fact, be due to increased absorption of the vitamin, but, rather, to its decreased clearance by hepatic and other peripheral tissues. In a series of studies, the investigators’’ first fed a high-vitamin A diet and then performed plasmapheresis to obtain vitamin A-laden chylomicrons and chylomicron remnants. They then reinfused these remnants back into the donors. They found that the rate of vitamin A clearance from blood was twice as fast in younger people as in the elderly. It has also been shown by Krasinski et a1.” that elderly persons taking vitamin A supplements have higher levels of circulating retinyl esters, which are toxic indicators, than do elderly persons not taking vitamin A supplements. For the present, it is prudent not to recommend vitamin A-containing supplements for the elderly until several longitudinal studies are carried out. A few studies have been performed with regard to carotenoid metabolism and aging; so far carotene has been shown to have Nutrition Reviews, Vol. 50, No. 12
no toxic potential in either elderly or younger people. Minerals, Vitamin E, and Vitamin C There is no clear evidence that mineral requirements are different in elderly and young individuals, other than lower iron requirements in postmenopausal females. For example, although zinc absorption from the gastrointestinal tract has been shown to be lower in elderly than in younger adults, overall zinc balance is not different because of decreased net losses in the elderly.2’ Moreover, although it has been shown that the intestines of elderly persons are less able to adapt to low-calcium diets (i.e., by increasing the efficiency of calcium absorption) than are those of younger persons, increasing calcium intakes beyond 800 mg/day (the current RDA for all adults) has not been shown to be of any benefit in terms of preserving bone mass.,, This brings up a philosophical problem in defining vitamin and mineral requirements in the elderly, depending on whether one is trying to prevent deficiency states or trying to guard against disease and chronic degenerative states. For example, Meydani et al.23have shown that supplementation of 800 mg/ day of vitamin E will stimulate various parameters of immune function over a short period. However, whether these effects would be maintained over a longer term and whether physiologic amounts of the vitamin-e.g., what could be obtained in a normal diet-would also stimulate immune function are unknown. Surely, no one would set an RDA for vitamin E at 800 mg, even if it resulted in less infection. The situation is less clear with vitamin C, in that individuals eating less than 125 mg/day have been shown to have a fourfold increase in risk of developing cataracts compared to persons eating over 500 m g / d a ~ . ’The ~ current RDA for vitamin C in the United States is 60 mg, although a 500-mg allowance can easily be met in the diet. Ames et al.25 have recently shown that ascorbate is the most effective antioxidant in human blood and may be important in protecting against oxidant stress-related diseases and degeneration. Thus, maintaining tissue levels at full saturation may be desirable. Data by Jacob et aLZ6have recently shown that about 140 mg/day of vitamin C are necessary to saturate the total body ascorbate pool. In the case of vitamin C, one may not wish to define the RDA in terms of its antiscorbutic effects, but, rather, in terms of its cataract-preventive effects or its antioxidant effects. Furthermore, in the case of vitamin C, it may be desirable t o maintain a high tissue saturation throughout the life span and not just in elderly persons in whom the chronic diseases appear, since the pathogenesis of these diseases may have started years earlier. 465
Conclusion Knowledge of vitamin and mineral requirements in the elderly is evolving. One can state now that not all vitamin and mineral requirements stay static over the adult life span. Each micronutrient must be examined individually and specific recommendations will evolve. In 1992, one can state with some certainty that the requirements for vitamins B, and D are increased in the elderly. Also, for a large proportion of the elderly, the requirements for vitamin B,, are probably elevated. For riboflavin, the requirement stays the same (and does not decrease as previously thought), and there is evidence that the requirement for vitamin A either stays the same or decreases. 1. National Research Council. Recommended dietary allowances, 10th ed. Washington, DC: National Academy Press, 1989 2. Horwitt MK, Harvey CC, Hills OW, Liebert E. Correlation of urinary excretion of riboflavin with dietary intake and symptoms of ariboflavinosis. J Nutr 1950;41:247-64 3. Dandona P, Menon RK, Shenoy R, Houlder S, T h o m a s M , M a l l i n s o n WJW. L o w 1,25d ihyd roxyvitam in D, secondary hyper parat hyroidism, and normal osteocalcin in elderly subjects. J Clin Endocrinol Metab 1986;63:459-62 4. Francis RM, Peacock M, Storer JH, Davies AEJ, Brown WB, Nordin BEC. Calcium malabsorption in the elderly: the effect of treatment with oral 25hydroxyvitamin D., Eur J Clin Inv 1983;13:391-6 5. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D., Exposure to winter sunlight in Boston and Edmonton will not promote vitamin D, synthesis in human skin. J Clin Endocrinol Metab 1988;67:
373-8 6. MacLaughlin JA, Holick MF. Aging decreases the capacity of human skin to produce vitamin D., J CIin Invest 1 985;76: 1 536-8 7. Slovik DM, Adams JS, Neer RM, Holick MF, Potts JT. Deficient production of 1,25dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med
1981 ;305:372-4 8. Dawson-Hughes B, Dallal GE, Krall EA, Harris S , Sokoll LJ, Falconer G. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med
1991 ;115:505-12 9. Tolonen M, Schrijver J, Westermarck T, Halme M, Tuominen SEJ, Frilander A, Keinonen M, Sarna S. Vitamin B, status of Finnish elderly, comparison with Dutch younger adults and elderly. The effect of supplementation. Int J Vitam Nutr Res 1988;58:
73-7 10. Ribaya-Mercado JD, Russell RM, Sahyoun N, Morrow FD, Gershoff SN. Vitamin B, requirement of elderly men and women. J Nutr 1991 ;121:1062-74
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11. Samloff IM, Varis K, lhamaki T. Relationships among serum pepsinogen I, serum pepsinogen II, and gastric mucosal histology. Gastroenterology
1982;83:204 12. Krasinski SD, Russell RM, Samloff IM, et al. Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators. J Am Geriatr SOC1986;34:800-6 13. Doscherholmen A, McMahon BS, Ripley D. Vitamin B, assimilation from chicken meat. Am J Clin Nutr 1978;31:825-30 14. Suter PM, Golner BB, Goldin BR, Morrow FD, Russell RM. Reversal of protein-bound vitamin BIZ malabsorption with antibiotics in atrophic gastritis. Gastroenterology 1991 ;lo1:lo3945 15. King CE, Leibach J, Toskes PP. Clinically significant vitamin B, deficiency secondary to malabsorption of protein-bound vitamin BIZ. Dig Dis Sci
1979;24:397-402 16. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8 17. Hoppner L, Phillips WEJ, Murray TK, Campbell JS. Survey of liver vitamin A stores of Canadians. Can Med Assoc J 1968;99:983-6 18. Hollander D, Morgan D. Aging: its influence on vitamin A intestinal absorption in vivo by the rat. Exp Gerontol 1979;14:301-5 19. Krasinski SD, Cohn JS, Schaefer EJ, Russell RM. Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. J Clin Invest 1990;85:883-92 20. Krasinski SD, Russell RM, Otracdovec CL, et al. Vitamin A and E intake: relationship to fasting plasma retinol, retinol binding protein, retinyl ester, carotene and alpha tocopherol levels in the elderly and young adults. Am J Clin Nutr 1989;49:
1 12-20 21. Turnland J, Costa F, Margen S. Zinc, copper, and iron balance in elderly men. Am J Clin Nutr 1981; 3412641-7 22. Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990;323:878-83 23. Meydani SN, Barklund MP, Liu S, et al. Rocklin R, Blumberg JB. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr 1990;52:557-63 24. Jacques PF, Chylack LT. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. Am J Clin Nutr
1991 ;53:352S-58 25. Balz F, Stocker R, Ames BN. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 1988;85:9748-52 26. Jacob RA, Skala JH, Omaye ST. Biochemical indices of human vitamin C status. Am J Clin Nutr
1987;46:818-26
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