Adrianne Bendich

Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D

Background: Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency, but the vitamin D status that fully normalizes absorption is not known for humans. Objective: To quantify calcium absorption at two levels of vitamin D repletion, using pharmacokinetic methods and commercially marketed calcium supplements. Design: Two experiments performed in the spring of the year, one year apart. In the first, in which participants were pretreated with 25-hydroxyvitamin D (25OHD), mean serum 25OHD concentration was 86.5 nmol/L; and in the other, with no pretreatment, mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a standard low calcium breakfast. A low calcium lunch was provided at mid-day. Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter. Methods: Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve (AUC) for the load-induced increment in serum total calcium. Results: AUC9 (± SEM), was 3.63 mg hr/dL ± 0.234 in participants pretreated with 25OHD and 2.20 ± 0.240 in those not pretreated (P < 0.001). In brief, absorption was 65% higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L (both values within the nominal reference range for this analyte). Conclusions: Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges, calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus, individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake. We conclude that the lower end of the current reference range is set too low.

Primary and secondary preventive nutrition

Part I. Introduction Preventive Nutrition: Historic Perspective and Future Economic Outlook J. Michael McGinnis and Nancy D. Ernst Part II. Cancer Vitamin Supplements and Cancer Risk: Epidemiologic Research and Recommendations Ruth E. Patterson, Alan R. Kristal, and Marian L. Neuhouser Soy and Cancer Prevention David B. Fournier, John W. Erdman, Jr., and Gary B. Gordon Micronutrients as Intermediate Biomarkers in Chemotherapy and Enhancement for Certain Cancer Treatments Wolfgang J. Issing Part III. Cardiovascular/Renal Disease, Diabetes, and Obesity Health Effects of Trans Fatty Acids Susanne H. F. Vermunt and Ronald P. Mensink Antioxidant Vitamins and Atherosclerosis Howard N. Hodis, Wendy J. Mack, and Alex Sevanian Oxidative Stress and Antioxidants in Type 2 Diabetes Srivevi Devaraj and Ishwarlal Jialal Hyperhomocysteinemia, Diabetes, and Cardiovascular Disease Ellen K. Hoogeveen and Kenneth J. Rothman Genetic and Environmental Influences on Obesity David B. Allison, Patty E. Matz, Angelo Pietrobelli, Raffaella Zannolli, and Myles S. Faith Obesity and Insulin Resistance in Childhood and Adolescence Erik Bergstrom and Olle Hernell Can Childhood Obesity Be Prevented? Christine L. Williams Obesity and Chronic Disease: Impact of Weight Reduction Henry I. Frier and Harry L. Greene Meal Replacement Products and Fat Substitutes in Weight Control and Maintenance Allan Geliebter, Amy Funkhouser, and Steven B. Heymsfield Part IV. Growth, Immunity, and Infection Role of Long-Chain Polyunstaturated Fatty Acids in Infant Growth and Development Berthold Koletzko and Tamas Decsi Vitamin A-Related Childhood Blindness, Mortality, and Morbidity: Interventions for Prevention Barbara A.Underwood Polyunsaturated Fatty Acids and Autoimmune Diseases Andrea Belluzzi Part V. Bone Diseases Osteoarthritis: Role of Nutrition and Dietary Supplement Interventions Timothy E. McAlindon Calcium Requirements During Treatment of Osteoporosis in Women: Calcium Supplements Alone and in Association with Antiresorptive Drugs in Osteoporosis Claudia A. Pereda and Richard Eastell Part VI. Critical Issues for the 21st Century Preventive Nutrition Issues in Ethnic and Socioeconomic Groups in the United States Shiriki K. Kumanyika and Susan M. Krebs-Smith Micronutrient Deficiencies: First Link in a Chain of Nutritional and Health Events in Economic Crises Martin W. Bloem and Ian Darnton-Hill Alcohol: The Balancing Act William E. M. Lands Health Claims for Foods and Dietary Supplements in the United States and Japan Annette Dickinson Incorporating Preventive Nutrition into Medical School Curricula Claudia S. Plaisted and Steven H. Zeisel Preventive Nutrition Throughout the Life Cycle: A Cost-Effective Approach to Improved Health Adrianne Bendich and Richard J. Deckelbaum Part VII. Nutrition-Related Resources Books Related to Primary and Secondary Preventive Nutrition Websites of Interest

Safety of Vitamins and Minerals: Controversies and Perspective

Available information suggests that currently over 47% of males and 59% of females use dietary supplements for health benefits, and the number of users is rapidly increasing. However, numerous studies published over more than a decade have linked some supplements (including vitamins E, C, D, A, and B, as well as selenium) to no health benefits or even to adverse health effects. Recent studies with negative results, which drew media attention, include the following: a 2008 study on the ability of vitamin E and selenium to lower the risk of prostate cancer was halted amidst fear of potential harm; vitamin C may do more harm than good as it may protect cancer cells; intake of vitamins E and C by 15,000 male physicians for 10 years had no health benefits. In contrast, there are compelling cause and effect data linking the use of folic acid with consistent and significant reductions in fetal adverse pregnancy outcomes, demonstrating no beneficial effects of calcium and vitamin D supplements in improving bone strength and reducing fractures. These equivocal and conflicting findings on the effects of supplements on health outcomes have left consumers confused about their benefits and wary of the possible adverse effects of vitamin and mineral supplementation. The objectives of this session are to characterize the current state of the science as it relates to the impact of vitamin and mineral supplementation on human health, review the statutory and regulatory perspective of vitamin use from a safety perspective, assess the credibility of meta-analysis in the safety assessment of vitamins, and elicit the mechanisms of these interactions-pro-oxidant versus antioxidant effects and beneficial versus adverse effects.

Micronutrients in women’s health and immune function

Lawrence J. Machlins contributions to elucidating the roles of nutrients in optimizing human health included the support of research in the areas of womens health and immune function. Several essential nutrients have been shown to affect womens health throughout the different life stages. Symptoms of premenstrual syndrome affect the vast majority of menstruating women, and calcium supplementation significantly reduces physical and emotional symptoms. Premenstrual syndrome in fact might be a predictor of osteoporosis induced by low calcium intake. Periconceptional multivitamin supplementation has reduced the risk of serious birth defects, premature delivery, and low birth weight by 50% and improved maternal health during pregnancy. Micronutrients of particular importance for prevention of adverse pregnancy outcomes are folic acid, zinc, and iron. However, if the preterm delivery is caused by preeclampsia, then data suggest that calcium supplementation and high doses of vitamins C and E significantly reduce that risk. Well-controlled studies consistently have shown that calcium supplementation, with or without vitamin D, significantly reduces the risk of hip fracture. Antioxidants such as vitamins C and E have been shown to reduce the risk of fracture in women smokers. As in the rapidly growing embryo, the immune system includes rapidly multiplying cells whose functions are dramatically affected by an individuals micronutrient status. Multivitamins have been shown to enhance many aspects of immune response, and antioxidant micronutrients consistently have been found to enhance lymphocyte-proliferative responses and skin-test responses, especially in the elderly.

Dietary antioxidants: potential effects on oxidative products in cigarette smoke

Cigarette smoking is the most popular form of smoking, and is one of the most prevalent social habits worldwide. It has been estimated that almost 1.1 billion people are classified as smokers of whom over 2 million are expected to die every year. This makes smoking the leading preventable cause of death and disability in the world. In addition to mortality, smoking was shown to deplete the body of its endogenous antioxidants such as vitamins C and E, β-carotene, ubiquinol, glutathione and α-lipoic acid. Antioxidant depletion was shown to increase individual vulnerability to free radicals and other oxidant species produced by cigarette smoking and therefore leads to elevated morbidity, aging, and death. Dietary supplementation with antioxidants can reduce the overall oxidative burden that is increased by cigarette smoking. However, supplementation can not substitute for the greater benefits of smoking cessation.

Effect of UV exposure and β-carotene supplementation on delayed-type hypersensitivity response in healthy older men

OBJECTIVES The aims of this study were to determine if ultraviolet light (UV) is immunosuppressive in healthy older males, if beta-carotene (betaC) supplementation could prevent any observed UV-induced immunosuppression, and to compare these effects with those observed previously in younger men. METHODS The study was a placebo-controlled, randomized trial that employed a 2 x 2 factorial design. Healthy older men (mean age 65.5 years) received 30 mg betaC or placebo daily throughout the 47-day trial, while on a low carotenoid diet. After 28 days, half of each group received 12 suberythemic exposures to UV over a 16-day period. Delayed-type hypersensitivity (DTH) tests and plasma carotenoid assays were performed at baseline, pre-UV and post-UV time points, with DTH testing performed on an area of skin protected from UV exposure. RESULTS UV exposure resulted in significantly suppressed DTH response in the placebo group but not in the betaC-UV group. While there was no significant interaction between betaC supplementation and UV on DTH response, there was a significant inverse relationship between final plasma betaC concentration and extent of UV-induced suppression of DTH response. A similar correlation existed among subjects not exposed to UV. CONCLUSIONS Suberythemic UV exposure was immunosuppressive, as measured by DTH response, in healthy older men as in younger men. Higher plasma betaC was significantly associated with maintenance of DTH response, although the extent of protective effect of betaC appeared less than previously observed in younger subjects. The attenuated effect of betaC in the older UV-exposed subjects may have resulted in part from muted plasma betaC responses to betaC supplementation and/or higher plasma vitamin E levels than those of younger men. The finding that stronger DTH responses were associated with higher plasma betaC concentrations in both UV and non-UV subjects further supports a role for this nutrient in immunomodulation.

Health Economics of Preventive Nutrition

Health economics examines both the costs of care (economic burden) as well as the potential costs savings of disease/treatment avoidance. The objectives of this chapter are to first examine the current epidemiological data that describe the health status of adults and the economic burden of disease; second, to review the potential for disease/adverse event prevention associated with consumption of healthy diets/nutritional interventions in both developed and developing nations, and finally, to look at the cost-effectiveness of preventive nutrition strategies in relevant populations. The major diseases/conditions examined in this chapter include obesity, nutritionally related adverse pregnancy outcomes, cardiovascular and cerebrovascular diseases, cancer, age-related blindness, and osteoporosis. Our goal is to document the totality and the consistency of the data and then attempt to quantify the savings that could be seen once preventive nutrition strategies are put in place.

Drug-Nutrient Interactions and Immune Function

The overall objectives of this chapter are to provide a brief overview of the immune system, the numbers of individuals affected by immune-related diseases and infections, examine the classes of drugs used to treat the most prevalent diseases of the immune system, and review the data on certain nutrients that have been shown to enhance immune responses in clinical studies.

Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women: reply

We have two serious concerns about the publication of the biomarker data from Kenny et al. [1]. First, while Kenny et al. reconfirm our findings of equivalent bioavailability of calcium from Os-Cal and Citracal [2,3] and also reconfirm our findings of the physiological response to supplementation with calcium carbonate and vitamin D in Os-Cal, i.e. a significant decrease in PTH following supplementation, we can find no biologically plausible explanation for the biomarker data reported in the calcium carbonate arm of this study. Since the decrease in PTH is required for the reduction in resorption markers, and several published studies cited by Kenny et al. have shown that calcium carbonate does reduce resorption biomarkers, we have serious concerns with the Kenny et al. paper. It must be noted that this same group has reported that calcium carbonate reduces biomarkers of bone resorption [4]. In fact, as an example of just one of many studies that have shown that Os-Cal has positive effects on bone biomarkers as well as bone mineral density, Bell et al. [5] have shown that this same OsCal 250+D supplement that was used in the Kenny et al. study decreased urinary N telopeptide by 6.7% over a 2-year intervention and at the same time significantly reduced bone specific alkaline phosphatase by 13.6%. In this study, bone mineral densities in both vertebral and non-vertebral bones remained non-significantly different for over 1 year in the Os-Cal 250+D supplemented group compared with the alendronate plus Os-Cal 250+D group. Thus, we, as Kenny et al., can find no reasonable, biologically plausible explanation for their aberrant findings. Our second concern is that, despite the authors’ assertion otherwise, the study does not use currently available commercial products. In fact, this formulation of Os-Cal with only 125 IU of vitamin D per pill was removed from the marketplace more than 2 years ago and replaced with one containing more calcium and vitamin D. Thus, it would be impossible for any other clinical group to replicate this study. Moreover, as we have shown successfully in a National Advertising Division hearing of the Better Business Bureau, Citracal 250+D was not marketed concurrently with Os-Cal 250+D. Thus, we are uncertain that the investigators actually independently purchased the two ‘‘commercially available’’ supplements and tested these at the same time. No data are presented indicating that the levels of calcium and vitamin D in these supplements were verified before the study was undertaken. Moreover, if the blood and urine samples were taken a long time ago and the bone turnover markers were measured more recently, there may be changes in the marker levels during storage that may mask any biological effects.

Gastric Acid Secretions, Treatments, and Nutritional Consequences

The objectives of this chapter are to provide an overview of the roles of gastric acid in health and disease, the use of acid-suppressive therapies to mitigate prevalent excess acid symptoms and/or diseases, and to review potential detrimental consequences related to their use. Particular emphasis is placed on the nutritional consequences of gastric acid imbalance as it is related to vitamin and mineral status. Finally, reduced gastric acid is also associated with disturbance in the natural bacterial balance throughout the gastrointestinal tract and the resulting gastrointestinal bacterial overgrowth is reviewed.