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Healthy older individuals can take several measures to preserve and improve their health. Even if past nutritional and lifestyle practices were not optimal, much can be done to reduce the risk of chronic disease and disability in future years. The first challenge is to recognize and address the profound changes in body composition that occur with aging. Older persons tend to accumulate relatively more body fat and less lean body mass, ie, muscle and bone. With a gain in body weight, which usually occurs, these changes are exaggerated. Because muscle tissue has a much higher metabolic rate than does fat tissue, older individuals generally develop lower metabolic rates. To avoid excess weight gain, older individuals must make major restrictions in caloric intake and increases in energy expenditure. Women experience changes in body composition similar to those in men, with changes becoming more prominent at menopause. Exercise improves body composition among healthy elderly, both by reducing fat mass and by increasing bone and muscle mass, thereby helping to restore higher metabolic rates. In men and women aged >/=65 y and taking calcium and vitamin D supplements for 3 y, the rate of bone loss slowed and the incidence of nonvertebral fractures was reduced. Several population studies of older persons show that following nutritional and lifestyle guidelines for cancer prevention reduces risk by one-third. Improving serum lipid concentrations in adults over 65 y of age with coronary artery disease decreases the risk of future cardiac events by as much as 45%. Furthermore, the greatest benefit from control of hypertension is in older individuals.

Garlic has been used medicinally since antiquity. In virtually every early civilization known, such as ancient India, Egypt, Rome, China, and Japan, garlic was part of the therapeutic regimen for a variety of maladies. Therefore, the ancient medicinal tradition of garlic use would qualify it as a folk medicine or as an alternative or complementary medicine. But is garlic an alternative to established methods of disease prevention or treatment? Scientists from around the world have identified a number of bioactive substances in garlic that are water soluble (e.g., S-allyl methylcysteine), and fat soluble (e.g., diallyldisulfide). Mechanisms of action are being elucidated by modern technology. The validity of ancient medicine is now being evaluated critically in cell-free systems, animal models, and human populations. Preventive and therapeutic trials of garlic are still in early stages. There are many promising lines of research suggesting the potential effects of garlic. The current state of knowledge does not recognize garlic as a true alternative, but it will likely find a place for garlic as a complement to established methods of disease prevention and treatment. Our goal should be to examine garlic together with other agents to evaluate its possible efficacy and toxicity under conditions of actual use in humans.

As early as 1550 B.C., Egyptians realized the benefits of garlic as a remedy for a variety of diseases. Many epidemiological studies support the protective role of garlic and related allium foods against the development of certain human cancers. Natural garlic and garlic cultivated with selenium fertilization have been shown in laboratory animals to have protective roles in cancer prevention. Certain organoselenium compounds and their sulfur analogs have been identified in plants. Organoselenium compounds synthesized in our laboratory were compared with their sulfur analogs for chemopreventive efficacy. Diallyl selenide was at least 300-fold more effective than diallyl sulfide in protecting against 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas in rats. In addition, benzyl selenocyanate inhibited the development of DMBA-induced mammary adenocarcinomas and azoxymethane-induced colon cancer in rats and benzo[a]pyrene-induced forestomach tumors in mice. The sulfur analog, benzyl thiocyanate, had no effect under the same experimental conditions. Furthermore, we showed that 1,4-phenylenebis(methylene)selenocyanate, but not its sulfur analog, significantly inhibited DMBA-DNA adduct formation and suppressed DMBA-induced mammary carcinogenesis. Collectively, these results indicate that structurally distinctive organoselenium compounds are superior to their corresponding sulfur analogs in cancer chemoprevention. Additionally, synthetic aromatic selenocyanates are more effective cancer chemopreventive agents than the naturally occurring selenoamino acids. Because plants are capable of utilizing selenium in a manner similar to that in sulfur assimilation pathways, future studies should aim at determining whether, under appropriate conditions, these potent cancer chemopreventive synthetic selenium compounds can be synthesized by garlic and related allium foods.

There is increasing evidence that allium derivatives from garlic have significant antiproliferative actions on human cancers. Both hormone-responsive and hormone-unresponsive cells lines respond to these derivatives. The effects shown by allium derivatives include induction of apoptosis, regulation of cell cycle progression and modification of pathways of signal transduction. Allium derivatives appear to regulate nuclear factors involved in immune function and inflammation, as well as in cellular proliferation. Our own studies indicate that allium derivatives inhibit proliferation of the human prostate cancer cell line (LNCaP) and the human breast cancer cell line (MCF-7). Further research is required to clarify the mechanisms of inhibition of cellular proliferation by allium derivatives and to explore their potential application to cancer prevention and control.

The objective of this review is to examine briefly the medical uses of garlic throughout the ages and the role that it was considered to play in prevention and treatment of disease. Interest in the potential benefits of garlic has origins in antiquity and is one of the earliest documented examples of plants employed for treatment of disease and maintenance of health. Garlic was in use at the beginning of recorded history and was found in Egyptian pyramids and ancient Greek temples. There are Biblical references to garlic. Ancient medical texts from Egypt, Greece, Rome, China and India each prescribed medical applications for garlic. In many cultures, garlic was administered to provide strength and increase work capacity for laborers. Hippocrates, the revered physician, prescribed garlic for a variety of conditions. Garlic was given to the original Olympic athletes in Greece, as perhaps one of the earliest "performance enhancing" agents. It is of interest that cultures that developed without contact with one another came to similar conclusions about the efficacy of garlic. Modern science is tending to confirm many of the beliefs of ancient cultures regarding garlic, defining mechanisms of action and exploring garlic's potential for disease prevention and treatment.

Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompanied by induction of jun kinase activity and a marked increase in endogenous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhibitory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents.

Background: This study determined the effects of S-allylmercaptocysteine (SAMC), a phytoconstituent from garlic, on the expression of androgen-responsive biomarkers, prostate specific antigen (PSA), and prostate specific membrane antigen (PSMA), in human prostatic carcinoma cells (LNCaP)., Methods: Secretion of PSA was determined as well as the activity of PSMA measured as a function of its ability to hydrolyze poly-gamma-glutamated folate and N-acetylaspartylglutamate (NAAG). Folate hydrolase capacity was also determined in SAMC-treated cells grown in charcoal stripped fetal calf serum (CS-FCS). In addition, testosterone disappearance was measured from culture media of SAMC-treated LNCaP and PC-3 cells as well as from cell free lysates., Results: PSA secretions were significantly decreased compared to control values at 1 day (8.4 +/- 2.6 vs. 18.9 +/- 1.7, P < 0.01), 4 days (18.9 +/- 5.3 vs. 73.8 +/- 4. 4, P < 0.001), and 6 days (35.6 +/- 2.1 vs. 96.5 +/- 17.9 ng/10(5) cells, P < 0.01; mean +/- SD). By contrast, PSMA activity measured as either folate hydrolase or NAAG dipeptidase (NAALADase) activity increased in cells treated with SAMC. PSMA-folate hydrolase activity in SAMC-treated cells grown in CS-FCS increased beyond that observed in cells grown in CS-FCS alone. Pre-exposure of LNCaP cells to SAMC resulted in enhanced rate of testosterone disappearance from culture media at 6 hr (P < 0.01) and at 48 hr (P < 0.001) compared to media from cells not previously exposed to SAMC. Results similar to these were also observed in androgen-independent PC-3 cells treated with SAMC. In lysates of SAMC-treated LNCaP cells, the rate of testosterone catabolism was twice that from phosphate buffered saline (PBS)-treated cells. SAMC-treated LNCaP cells grown in media supplemented with testosterone temporarily exhibited enhanced growth over a 2 day period but cell numbers declined later to levels similar to those of SAMC treatment., Conclusions: These results show that SAMC exhibits differential effects on recognized biomarkers for LNCaP cells similar to those produced by androgen deprivation and strongly suggests that this effect may be mediated, in part, by diminishing the trophic effects of testosterone, likely by converting it to metabolites less reactive toward androgen receptors., (Copyright 2000 Wiley-Liss, Inc.)

The purpose of this investigation was to determine whether there is an effect of age and the presence of predisposing risk factors on the pattern of bone resorption in men with spinal osteoporosis. We present iliac bone histomorphometric data after in vivo double tetracycline labeling in 21 men aged 34-74 with significant spinal osteoporosis as evidenced by compression spinal fracture without significant trauma. Fourteen of the 21 men (67%) had identifiable predisposing risk factors for their osteoporosis, such as ethanol abuse, hypercortisolism, hypogonadism, or underlying medical conditions. The other 7 men (33%) had no such identifiable risk factors. The conclusions of the study were that (1) there was no correlation between age of the patient and degree of bone resorption based on two parameters of resorption and (2) there was no difference in the pattern of bone resorption between the groups with and without known predisposing risk factors for osteoporosis or underlying medical conditions.

A comprehensive and critical review of the evidence relating magnesium (Mg) deficiency to alcohol consumption reveals several important types of interactions. First, alcohol acts acutely as a Mg diuretic, causing a prompt, vigorous increase in the urinary excretion of this metal along with that of certain other electrolytes. Second, with chronic intake of alcohol and development of alcoholism, the body stores of Mg become depleted. During the late stages of alcoholism, the urinary excretion of Mg may become diminished as a physiological response to reduced intake and reduction of body stores. A number of aspects of the clinical syndrome of alcoholism contribute to and intensify that already existing reduction in body Mg stores. Third, a number of manifestations of alcoholism are believed due to effects of Mg deficiency, and some therapeutic benefit has been suggested from treatment of alcoholic patients with Mg. Finally, relatively little attention has been paid to the possible value of Mg administration as a preventive measure to forestall or minimize the deleterious effects of chronic use of alcohol or to prevent the development of cancer than can occur in this setting.

This study investigated whether the growth of transplanted mammary tumors is altered in rats by treatment with the antimalarial drugs chloroquine (CQ) and quinacrine (QN). Female inbred F344 rats were divided into three experimental groups. Animals were injected i.p. with either CQ, QN or normal saline for 5 days a week throughout the entire experimental period (25 days). After 7 days of drug treatment each rat received subcutaneously one 2-mm2 aliquot of R3230AC mammary adenocarcinoma in the mid-thoracic region. Eighteen days after implantation, all rats were sacrificed and tumors were excised, weighed and measured. The results indicate that weights and volumes of tumors as well as tumor-to-body weight ratios were significantly higher in CQ and QN-treated animals than those in saline-treated animals. The final body weights of rats treated with QN were significantly lower than those treated with saline. The prostaglandin E2 content of tumors was significantly reduced by CQ treatment. Erythrocyte glutathione reductase activity coefficient and reduced glutathione concentrations remained unaffected by both treatments. These results suggest that CQ and QN have significant stimulatory effects on the growth of mammary adenocarcinoma in rats.

Taste preferences for saccharin in concentrations ranging from 0.16 mM to 50 mM were determined in rats made hypothyroid with radioactive iodine and in their littermate controls. Hypothyroid rats demonstrated taste preferences for saccharin which were similar to those of controls only at very low (0.016 mM) or very high (49.0 mM) saccharin concentrations. At these concentrations of tastant, the preferences for tastant and water were similar to one another. At a concentration of 5.1 mM, preferences were also very similar in both groups but were very high. At intermediate saccharin concentrations of 1.1 and 3.0 mM, hypothyroid animals showed significantly lower percent preferences for the sweet tastant than did controls, mean +/- SEM (62.48 +/- 5.97 vs. 82.92 +/- 4.60, p = 0.0002) for the 1.1 mM concentration and (74.98 +/- 5.12 vs. 89.40 +/- 2.54, p = 0.0029) for the 3.0 mM concentration. These changes in taste preference for saccharin in hypothyroid rats were similar in direction and magnitude to those previously published by this laboratory using sucrose as the tastant. Thus, hypothyroid rats demonstrate abnormalities in taste preference for both the nonnutritive sweetener, sodium saccharin, as well as for the nutritive sweetener, sucrose.

The anticancer drug Adriamycin has photosensitizing properties which potentially may be detrimental to lens tissue. Since reduced glutathione (GSH) serves to protect lens from photo-oxidative stress and dietary riboflavin is required by glutathione reductase to regenerate GSH, we investigated whether Adriamycin intensifies the depletion of GSH levels in rat lens during dietary riboflavin deficiency. Three-week-old rats were divided into two groups. One group was fed a diet deficient in riboflavin (less than 1 ppm) and the other group was pair-fed a control diet containing adequate riboflavin (8.5 ppm). After 6-12 weeks of dietary treatment, half the animals in each dietary group received Adriamycin (8 mg/kg/day) intraperitoneally for 3 days. After killing the rats, lenses were removed, and GSH content and glutathione reductase activity were measured in freshly prepared homogenates. To determine the extent of systemic oxidative stress and the degree of riboflavin deficiency, glucose-6-phosphate dehydrogenase and glutathione reductase activities, respectively, were measured in erythrocytes. In lens of rats fed the riboflavin-sufficient diet, treatment with Adriamycin did not diminish GSH content or alter glutathione reductase activity. In confirmation of reports by others, lenses of animals fed the riboflavin-deficient diet had diminished GSH levels, lower basal glutathione reductase activity, and elevated glutathione reductase activity coefficients compared to those of animals pair-fed the control diet. The present study shows that in riboflavin-deficient rats, Adriamycin exacerbated the depletion of GSH but did not reduce further glutathione reductase activity. The implications of these findings are that nutritional deficiencies, in particular riboflavin deprivation, may pose a potential risk to lenticular tissue following Adriamycin treatment.

The Agricultural Revolution was almost certainly associated with a substantial decrease in human calcium intake. Calcium intakes typical of contemporary humans may well be inadequate for many individuals. Various slowly developing chronic disorders such as osteoporosis, hypertension, hyperlipidemia, and colon cancer may be induced or exaggerated by the current low level of dietary calcium intake in Western societies. We propose two hypotheses relating calcium intake to diverse diseases: first, the adaptation required to adjust to low intakes is inadequate to maintain critical components of cellular calcium regulation; second, the constant, forced adaptive response to low intake itself produces untoward consequences.

The present study was undertaken to determine whether treatment with chlorpromazine accelerates the depletion of tissue stores of flavin adenine dinucleotide during dietary riboflavin deficiency. These investigations derived their impetus from earlier findings that low doses of chlorpromazine in rats fed abundant riboflavin increase urinary riboflavin excretion and reduce hepatic flavin stores. From 6 to 10 days after beginning to feed on a riboflavin-deficient diet, rats treated with chlorpromazine, 2 mg/kg body weight twice daily, had approximately twice the urinary riboflavin excretion of that of pair-fed saline-treated controls. When the riboflavin-deficient diets and chlorpromazine treatments were extended for 3 weeks and the animals killed, FAD levels in liver, kidney, and heart were markedly lower in drug-treated than in saline-treated animals. When studies were extended for 7 weeks, tissue FAD levels in saline-treated animals declined further and were equal to those of chlorpromazine-treated rats after only 3 weeks of dietary deficiency. Thus, chlorpromazine treatment accelerated urinary riboflavin loss and accelerated tissue depletion of FAD levels during dietary riboflavin deficiency. Brain levels of FAD by contrast were relatively resistant to both dietary riboflavin withdrawal and treatment with chlorpromazine. Subsequent studies showed that urinary riboflavin excretion began to increase within 6 hr of treatment with chlorpromazine. It is concluded that significant riboflavin depletion occurs following treatment with low doses of chlorpromazine, both in animals fed a normal diet and in animals fed a riboflavin-deficient diet, particularly during the early stages of deficiency.

In livers of adult rats that have been treated with thyroxine, the rate of incorporation of radiolabeled riboflavin into both flavin adenine dinucleotide (FAD) and FAD covalently attached to specific apoflavoenzymes was enhanced markedly. By contrast, thyroxine diminished riboflavin incorporation into FAD in cerebrum and cerebellum but continued to enhance incorporation into the covalently bound fraction of FAD. Diminished net incorporation of riboflavin into FAD in brains of adult rats may reflect increased utilization of this fraction for covalent attachment into specific apoflavoenzymes rather than down regulation of the FAD biosynthetic enzymes, flavokinase and FAD pyrophosphorylase, inasmuch as covalent attachment of FAD occurs subsequent to the formation of FAD. The psychotropic drug, chlorpromazine, over a wide dose range, exerted an inhibitory effect on both incorporation of riboflavin into FAD and the utilization of FAD for incorporation into covalently bound flavoenzymes in liver, cerebrum, and cerebellum. Thus, chlorpromazine inhibition of FAD metabolism occurred regardless of the direction of the thyroxine effect and was compatible with an observed inhibitory effect by this drug upon the flavin biosynthetic enzymes.

Nutrition and cancer interact at several levels. Both dietary deficiencies and dietary excesses have been linked with changes in prevalence of certain human cancers. With respect to one particular nutrient, riboflavin, a dietary deficiency may decrease the development of spontaneous tumors in experimental animals but increase carcinogenesis due to certain agents. Cancer itself has profound effects upon nutritional status, and neoplastic tissue appears in general to resist dietary deficiency more effectively than normal tissues. Nutrition has a major role in therapy of cancer, but as an adjunct to the treatment plan rather than as an alternative. Parenteral nutrition, either peripheral or total, can provide support that is critically needed when patients cannot eat or swallow, have obstruction or malabsorption, or are otherwise unable to utilize dietary nutrients in adequate amounts. The advent of home parenteral nutrition now provides a means for long-term rehabilitation of cancer patients.

Nutrition and cancer interact in a number of important ways and nutritional factors are increasingly recognized as relevant to both the prevention and treatment of cancer. The role of several nutrients in cancer development is considered briefly here. Deficiency of riboflavin (Vitamin B2) prolongs the survival of tumor-bearing animals, but may accelerate carcinogenesis caused by certain agents, as flavin cofactors are involved in drug and carcinogen metabolism. Deficiency of Vitamin A may enhance the development of tumors of epithelial origin, particularly lung. Evidence is accumulating that Vitamin A and/or its precursors, the B-carotenes, may possibly have an effect in chemoprevention of certain of these epithelial cancers both in animals and in man. The consumption of dietary fat among various nations is correlated closely with increased development of cancers of the breast, colon, and prostate, and possibly of other organs. Studies of migrant populations from Japan to the United States show changes in prevalence of stomach and colon cancer in the direction of the native United States population. Sources of nitrites are of concern because of their potential conversion to carcinogenic nitrosamines. Limitation of the delivery of nitrites may be difficult to accomplish so investigators are exploring the blockade of conversion of nitrites to nitrosamines. Nutrition should not be viewed as the sole means of cancer prevention and treatment but rather as a vital component of any treatment plan.

Riboflavin deficiency diminishes the rate of growth of spontaneous tumors in experimental animals but enhances the carcinogenicity of specific drugs such as the azo dyes, which are degraded by a microsomal hydroxylase system requiring riboflavin. Human esophageal cancer has been epidemiologically associated with riboflavin deficiency, but the precise role of riboflavin in this tumor remains to be defined. Riboflavin nutriture influences epithelial integrity, tissue flavin concentrations, rates of prostaglandin biosynthesis, and glutathione metabolism, each of which may have implications for carcinogenesis.

The effects of riboflavin deficiency on the activity in vitro of prostaglandin synthetase were determined in rat kidney homogenates. For a period of two to five months, weaning rats were fed either a diet deficient in riboflavin or equal amounts of a diet identical in composition except for the addition of riboflavin at four times the RDA for this vitamin. In further experiments, each group of rats was treated for 10 days with either an inhibitor of cyclooxygenase (flurbiprofen) or buffer. Following sacrifice, prostaglandin biosynthesis in vitro was measured both in the absence and presence of reduced glutathione, and subsequently in the presence of reduced glutathione with and without flurbiprofen. Reaction products were extracted from supernatant solutions with diethylether, and the PGE2 and PGF2 alpha formed were measured by radioimmunoassay. Dietary riboflavin deficiency increased biosynthesis rates in vitro of both PGE2 and PGF2 alpha in rat renal medulla and papilla. When both control and riboflavin deficient rats were treated with flurbiprofen for a 10 day period, PGE2 biosynthesis in vitro was markedly inhibited. This inhibition of PGE2 biosynthesis was partially overcome by the addition of reduced glutathione in vitro. The addition of flurbiprofen in vitro to samples containing reduced glutathione prevented the restoration of PGE2 biosynthesis by the latter. The rate of prostaglandin biosynthesis in kidney homogenates from riboflavin deficient rats remained higher than that of controls with each experimental manipulation. These data in their entirety suggest a possible role for riboflavin in the regulation of renal prostaglandin biosynthesis in the rat.

The incorporation of a subcutaneous injection of [14C]riboflavin (2.5 muCi/100 g body wt) into flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and flavins bound covalently to proteins was determined at 1, 6, and 18 h in liver, cerebrum, and cerebellum from progeny of normal and maternally riboflavin-deficient Holtzman rats. Radioactivity remaining as riboflavin was also determined under these circumstances. Experiments were initiated within 24 h of birth. In both groups of newborn rats, the incorporation of radioactive riboflavin into covalently bound flavins in liver and brain proceeded more slowly than into the other flavin fractions. In addition, radioactivity incorporated into covalently bound flavins comprised a relatively smaller proportion of the total amount incorporated in brain than in liver. In progeny of riboflavin-deficient dams, an increased rate of incorporation of riboflavin into all three flavin derivatives, particularly FAD, was observed in liver and brain, compared to results in normal progeny. These data provide evidence that maternal riboflavin deficiency enhances the incorporation of riboflavin into tissue flavins in liver, cerebrum, and cerebellum from newborn rats.

The incorporation of radiolabeled riboflavin into flavin mononucleotide, flavin adenine dinucleotide, and flavin covalently bound to protein was determined in Novikoff hepatoma grown in both riboflavin-deficient and normal chow-fed rats. In Novikoff hepatoma, the incorporation of [14C]riboflavin into covalently bound flavins relative to that into FAD was substantially greater than that in host liver, and the turnover rate of riboflavin was also accelerated in tumor compared with the liver. The magnitude of incorporation of [14C]riboflavin into each of the various flavin fractions was substantially greater in tumors from riboflavin-deficient animals than in tumors from control animals. These data support the hypothesis that in conditions of riboflavin deprivation, Novikoff hepatoma maintains the levels of the physiologically important flavin coenzymes at the expense of the free riboflavin fraction. The incorporation of riboflavin into covalently bound flavins relative to that into FAD is substantially greater in Novikoff hepatoma than in liver. Accordingly, covalently bound flavins are either present in greater amounts or regulated differently in tumor than in normal tissue. Because the flavin moiety cannot be reutilized, the covalently bound flavin fraction in Novikoff hepatoma theoretically should be able to sequester riboflavin and thereby deplete the body reserves of this vitamin when dietary intake is marginal.

Nutrition has important potential for the prevention and treatment of osteoporosis. Ensuring the adequacy of calcium intake is central to any program of osteoporosis control, but it must be considered in the context of the many factors, including other nutrients, diseases, and drugs, which influence calcium absorption, utilization, and excretion. The dietary consumption of calcium by large segments of the U.S. population remains inadequate. More attention must be paid not only to increasing calcium intake, but also to maximizing its availability from food sources and its retention by the body. As individuals age, it becomes increasingly difficult to maintain adequate calcium balance; dietary selection must be made with special care for older persons to ensure that all of the nutrients are consumed in sufficient quantities and that neither excessive weight loss nor weight gain occurs.

Enhanced urinary excretion of vitamins induced by drugs is a major factor in development of vitamin deficiencies. In addition to increasing urinary excretion, drugs can induce vitamin deficiencies by altering their intestinal absorption, transport, storage, and/or metabolic conversions. Aside from drugs, other factors known to influence urinary excretion of vitamins include the level of the vitamin in the diet, the degree of tissue saturation of the vitamin, and the extent of protein binding of the vitamin. Alterations in various aspects of flavin metabolism have been observed following administration of certain drugs, namely, antimalarial, antimicrobial, anticancer, and some tricyclic antidepressant and antipsychotic agents. Of these drugs, boric acid and its derivatives as well as the antipsychotic agent, chlorpromazine, have been shown to promote riboflavinuria in both animals and man. Boric acid complexes with the polyhydroxyl ribitol side chain of riboflavin and greatly increases its water solubility. Individuals who have accidentally consumed boric acid or one of its derivatives excrete high levels of riboflavin within the first 24 to 48 hours following ingestion. The phenothiazine ring of chlorpromazine and the isoalloxazine ring of riboflavin have a number of structural features in common and have been shown to form a molecular complex in vitro. In animals treated for a 3- and 7-week period with chlorpromazine, urinary levels of riboflavin are twice that of pair-fed, saline-treated animals. Recent studies have extended these findings to humans. The administration of certain agents, either therapeutic or toxic, which enhance urinary riboflavin excretion may be of particular concern for high-risk patients who are already nutritionally compromised because of illness or disease.

The status of riboflavin nutriture was evaluated in 24 healthy elderly female residents of a private, nonprofit facility for the care of ambulatory elderly. Riboflavin intake by history was greater than or equal to the recommended dietary allowances (RDA) for this nutrient in all but three subjects, and the average intake in the group as a whole was 50% greater than the RDA. Confirmatory of the findings by history, the status of riboflavin nutriture was excellent in nearly all subjects as evaluated by urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient. By contrast, calcium intake was greater than or equal to the RDA in ony four of the 24 subjects. The adequacy of calcium intake was found to depend upon a sufficiently high percentage of the total dietary intake of riboflavin being derived from milk and dairy products. It was observed that individual calcium intakes were less than 80% of the RDA unless 40% or more of the total intake of riboflavin was derived from milk and dairy products rather than from other food sources. In those subjects taking daily supplementation with a single multivitamin tablet containing low levels of riboflavin, the total intake of riboflavin and its urinary excretion were increased similarly, suggesting that even small amounts of riboflavin are not retained by elderly subjects consuming a diet adequate in riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS)

The present investigation was undertaken to determine whether administration of ethanol by intragastric intubation to rats modifies the binding of radioactive zinc to its binding proteins in the jejunal mucosa. These studies were prompted by the frequent observation of abnormalities in serum and urine zinc concentrations in alcoholic patients and the necessity to determine whether alcohol diminishes intestinal protein binding of zinc, the first step in zinc absorption. Adult female rats received intragastric ethanol by intubation, either daily for 10 days, or only 1 hour prior to death. After death by decapitation, the small intestinal was removed, and mucosal cell extracts prepared by homogenization and centrifugation. These extracts were incubated with 65ZnCl2, and gel filtration chromatography was performed with Sephadex G-100. A major difference in the chromatographic profiles between control and alcohol-treated animals was observed: binding of zinc to high molecular weight proteins was reduced and that to low molecular weight proteins was increased. These differences occurred both 10 days and 1 hour after ethanol. The finding of diminished binding of zinc to high molecular weight jejunal proteins may represent the first step leading to diminished intestinal absorption of zinc in alcoholism.

Riboflavin deficiency suppresses parasitic growth in malaria. Three possible mechanisms have been proposed previously to explain the survival advantage of riboflavin-deficient hosts: a) enhanced fragility of red blood cells (RBC), b) decreased formation of reticulocytes and/or c) decreased concentrations of reduced glutathione (GSH) and ATP. The validity of these proposed mechanisms was tested by investigating whether riboflavin deficiency alters the hemolytic response to three stimuli: hydrogen peroxide (H2O2), a hypotonic medium or ferriprotoporphyrin IX (FP). Reticulocyte counts and concentrations of ATP and GSH were also determined. The percentage of hemolysis induced by H2O2 or FP was significantly less in riboflavin-deficient than in control animals. By contrast, hemolytic response to a hypotonic medium was enhanced during riboflavin deficiency. Despite diminished activity of glutathione reductase and normal glutathione peroxidase activity during riboflavin deficiency, the erythrocyte concentration of GSH was increased over that in control animals. Concentrations of ATP and hemoglobin in erythrocytes as well as the reticulocyte count were unaltered during riboflavin deficiency. Thus, diminished malarial parasitemia in riboflavin-deficient animals occurs despite greater resistance of RBC to either H2O2- or FP-induced hemolysis, and in the presence of a normal reticulocyte count and erythrocytes ATP concentration. Results of this study raise the possibility that Plasmodium parasites have greater requirements for flavin coenzymes, GSH or ATP than those of host erythrocytes, which may explain the apparent protection of the riboflavin-deficient host from malaria.

Chronic alcoholism is associated with a high prevalence of riboflavin deficiency. Experiments were designed in an animal model to determine whether ethanol alters selectively the absorption of riboflavin and flavin adenine dinucleotide (FAD), the predominant dietary form of the vitamin. Rats received by gavage a liver homogenate to which either [14C]riboflavin or [14C]FAD was added with either ethanol or isocaloric sucrose solutions. Ethanol markedly diminished the bioavailability of [14C]FAD to a greater degree than that of [14C]riboflavin. Corroboration of an ethanol-impaired intraluminal hydrolysis of FAD was provided by using everted jejunal segments and measuring mucosal uptake of [14C]riboflavin together with nonradiolabeled FAD. In subsequent studies with mucosal cell extracts, ethanol markedly inhibited activities of FAD pyrophosphatase and flavin mononucleotide (FMN) phosphatase. These findings suggest that dietary sources of riboflavin (FMN and FAD) are not absorbed as well in the presence of ethanol than are vitamin preparations containing riboflavin, which is utilized more readily.