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PubMed2004

Maternal micronutrients and fetal outcome.

Maternal micronutrient deficiency has been related to adverse fetal effects. It is believed that micronutrient supplementation during pregnancy may improve fetal and neonatal outcome. Despite biological plausibility, the evidence base for individual micronutrient benefit on neonatal morbidity, mortality, growth and development is patchy and often contradictory, except for the role of folic acid in prevention of neural tube defects. Single micronutrient supplementation interventions have not been shown to consistently affect size at birth or duration of gestation. Sound evidence is generally lacking that micronutrient supplementation can reduce infection-related adverse pregnancy outcomes. However, preliminary data suggests that antenatal zinc supplements may cause reduction in later diarrheal and infectious morbidity in infants. The evidence linking maternal micronutrient deficiency to children's cognitive and motor functioning also lacks a clear consensus except for iodine in endemic areas. There is a pressing need for good quality randomized controlled trials evaluating food based and multiple micronutrient interventions in pregnancy and preconceptually. Future studies should also evaluate the effect on body composition and metabolism along with the functional consequences.

Adolescent↗

PubMed2003

Micronutrient deficiencies. Hohenheim Consensus Conference.

OBJECTIVE: The aim of this study was to consider the risk of micronutrient deficiencies and approaches for intervention, and to summarize existing knowledge and identify areas of ignorance. DESIGN: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic. INTERVENTION: The experts met and discussed the questions and arrived at a consensus. CONCLUSION: Though healthy balanced diet is available for the general European population, a few defined groups are at risk of micronutrient deficiencies. In addition, the intake of specific micronutrients such as iron, folic acid, vitamin D and vitamin B12 are often marginal. To overcome these deficiencies, either selected micronutrients or a mixture of different micronutrients might be recommended. However, to define and detect micronutrient deficiencies, specific biomarkers are only available for a few micronutrients (e. g. vitamin D, folic acid, vitamin C, iron). The definition of a risk group, based on scientific data, might be an appropriate way to justify intervention with supplements.

Aging↗

PubMed2004

[Micronutrients status of Ile-de-France inhabitants. A literature review].

PURPOSE: A review of the literature about micronutrients status of Ile-de-France inhabitants. CURRENT KNOWLEDGE AND KEY POINTS: During the last decades, substantial changes in the French diet had an impact on micronutrients intake. Over this time, several studies conducted in Ile-de-France showed that a large part of its inhabitants is subject to an increased risk of mild to severe deficiency in one or more micronutrient(s). Teenagers and subjects over 70 years-old are groups at risk for vitamin D deficiency. During the 1980s, iron intake was insufficient in a majority of menstruating women and iron deficiency was common during pregnancy. Vitamin C deficiency is constantly present in homeless people and often associated with an insufficient intake in a number of micronutrients. FUTURE PROSPECTS AND PROJECTS: Identification of the groups at risk favours a better adequacy of preventive action on micronutrient deficiencies in this population. However, the efficacy of prevention is to be determined. Controlled trials of micronutrients' supplementation may be useful to value the beneficial effects of micronutrient supplementation on the incidence of cardiovascular diseases and cancer.

Adolescent↗

PubMed2000

Growth and micronutrient needs of adolescents.

OBJECTIVE: This paper focuses on micronutrients in relation to needs throughout adolescence, a period which involved growth and development that occur through a complex interaction of genetic instructions, hormones and environmental influences, many of them of dietary origin. In the context of micronutrient 'needs' it is of special importance to differentiate between the 'nutritional needs' and 'metabolic needs'. Two main questions arise in relation to the micronutrient needs: (1) why are micronutrients necessary? and (2) how are their needs assessed? RESULTS: The 'necessary' amount will differ according to the objectives pursued: (a) to achieve a satisfactory rate of growth and development; and (b) to maintain 'optimal health'. The assessment of micronutrient needs and status has proved to be difficult, but when elucidating and establishing them, it is imperative to arrive at the estimates in the light of their interdependent role in metabolism and functions. The knowledge of micronutrient metabolic needs can be approached through epidemiological observations, bioavailability studies and clinical trials. However, there is a nearly total absence of reports on the particular metabolic and dietary needs of adolescents. CONCLUSION: Thus more studies are required in relation to the effect of features associated with adolescence on 'needs', evaluating their impact on bioavailability and turnover (storage and losses), and the interactions among micronutrients in the assessment of metabolic and nutritional needs. Another aim should be to establish static and functional indexes, reference values and cut-off points in adolescence, to be used in clinical and epidemiological studies. Future studies should focus on needs to determine those required to maintain 'optimal functions' and regarding the potential prevention of chronic adult diseases.

Adolescent↗

PubMed1997

Non-milk extrinsic sugars in the diets of pre-school children: association with intakes of micronutrients, energy, fat and NSP.

Concern has been expressed that high dietary concentrations of non-milk extrinsic sugars (NMES) may potentially compromise nutrient intakes in population groups with low energy intakes (Department of Health, 1991). The objective of the present study was to examine data from the National Diet and Nutrition Survey of Children Aged 1.5 to 4.5 years (Gregory et al. 1995) for evidence of an inverse association between energy from NMES and micronutrient intakes, and if possible to quantify a level of NMES-energy at which micronutrient intakes may, theoretically, be compromised. Energy and nutrient intakes were compared across quintiles of NMES-energy for boys (n 848) and girls (n 827). As the concentration of NMES increased, energy intake rose (in boys only) while percentage energy from fat fell from 40 to 32% across quintiles 1 to 5. Intakes of most micronutrients also fell, while intakes of vitamin C rose. Mean intakes of most micronutrients (Ca, thiamin, riboflavin, niacin, folate and vitamin C) were adequate in comparison with dietary reference values. However, intakes of Fe, Zn and vitamin D were low at all levels of NMES-energy and fell below the estimated average requirement for Fe and Zn for NMES concentrations exceeding 24% of energy. Lower Intakes of milk, meat, bread and vegetables, and higher intakes of fruit juice largely explain the observed trends in micronutrient intake. It is concluded that the inverse association of NMES with micronutrient intakes is of most significance for the 20% of children with diets highest in NMES. However, further work is required to establish whether the associations observed have biological significance with regard to micronutrient status.

Animals↗

PubMed2001

Micronutrient deficiency in children.

Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to humans, the biology of deficiency as well as excess of micronutrients in humans must continue to be investigated with vigour.

Breeding↗

PubMed2005

Acceptability of multiple micronutrient supplements by pregnant and lactating women in Mali.

BACKGROUND: In Mali, an estimated 73% of pregnant women are anaemic largely due to iron deficiency. National policy recommends women to take iron and folic acid supplements daily from first prenatal contact until 3 months postpartum. However, many pregnant women in Mali could benefit from multiple micronutrient supplements. OBJECTIVE: To assess pregnant women's acceptability of and adherence to a daily multiple micronutrient supplementation scheme compared with the current daily iron and folic acid supplementation scheme. DESIGN: Seventy pregnant women were allocated to either the daily multiple micronutrient or daily iron and folic acid supplementation scheme. Women started receiving supplements at the end of the first trimester of pregnancy until delivery and throughout the first 3 months postpartum. RESULTS: No significant differences were observed between comparison groups with respect to women's perceptions about supplement size, colour, taste or flavour. Adherence to the multiple micronutrient supplementation scheme was better (257.5+/-20.9 tablets; average adherence 95.4%) than that to the iron and folic acid supplementation scheme (238.5+/-32.7 tablets; average adherence 92.2%; P=0.008) although both were very good, as were women's perceptions about the benefits of micronutrient supplements to their health and that of their newborns. CONCLUSION: Malian women adhere to prenatal/postpartum micronutrient supplementation - no matter what supplement is chosen - when access to supplements is guaranteed and when they are provided with minimum, consistent and easily understandable information and counselling, indicating that these are key elements to ensure effective programmes. These findings, together with those of the global research agenda on the efficacy of multiple micronutrient supplements for pregnant women, will inform policy development in Mali for the effective control of iron deficiency and iron-deficiency anaemia in pregnant women.

Adolescent↗

PubMed2005

Micronutrient requirements of physically active women: what can we learn from iron?

The health benefits of physical activity are well established and there is increasing recognition of the importance of fitness as a key modulator of chronic disease. The impact of physical activity on micronutrient requirements is a topic of tremendous interest to the lay public, but the interest is in sharp contrast to data from well-designed studies. Research in this area is poorly controlled for nutritional status of the participants, standardized exercise protocols, markers and cutoff points for measurement of micronutrient status, and variability in subject characteristics. The micronutrient status of women in the general population is of concern, but it is not clear that physical activity increases the requirement of most micronutrients. When dietary intake is adequate, the results of most studies are either equivocal or show no benefit to performance of supplementation. In the few instances where exercise does appear to increase an individual's requirement, the increase can be obtained within the additional calories required for energy balance. In the absence of consistent data, micronutrient supplementation is often indiscriminate without regard to nutrient status. Because iron is such a key nutrient for physical activity, and the status in women is often compromised, it serves as a useful example of how current research limits the ability to make recommendations regarding the impact of exercise on micronutrients requirements in women. With the recent recognition of the importance of physical activity to the prevention and treatment of chronic diseases through the life span, more attention should be focused on the impact of exercise on micronutrient requirements, especially in the context of weight loss regimens.

Diet↗

PubMed2005

Micronutrient deficiencies in early pregnancy are common, concurrent, and vary by season among rural Nepali pregnant women.

Pregnant women in developing countries are vulnerable to multiple micronutrient deficiencies. We investigated their prevalence and seasonal variation as part of a baseline assessment in a population-based, maternal micronutrient supplementation trial conducted in the rural Southeastern plains of Nepal. Serum concentrations of 11 micronutrients were assessed in 1165 pregnant women in the 1st trimester before supplementation. Using defined cutoff values, the prevalence of deficiencies of vitamins A, E, and D were 7, 25, and 14%, respectively. Nearly 33% of the women were deficient in riboflavin, and 40 and 28% had serum vitamin B-6 and B-12 deficiencies, respectively. Only 12% of the women were folate deficient, but 61% were zinc deficient. The prevalence of low serum iron concentration was 40%, and 33% were anemic (hemoglobin < 110 g/L). Multiple micronutrient deficiencies were common among pregnant women. Over 10% of the pregnant women were both anemic and deficient in B-complex vitamins, whereas 22% of women were both anemic and zinc deficient. Only 4% of women had no deficiency, whereas approximately 20% of the women had 2, 3, or 4 deficiencies. Almost 18% of women had >/=5 deficiencies. Micronutrient status varied by season; it was generally best during the winter months, except for serum vitamin D concentration, which peaked during the hot summer and monsoon months. Women in rural South Asia are likely to begin a pregnancy with multiple micronutrient deficiencies that may vary with seasonality in micronutrient-rich food availability.

Adolescent↗

PubMed2006

Toxicology of micronutrients: adverse effects and uncertainty.

The establishment of safe upper intake levels for micronutrients must consider the intake-response relations for both deficiency and toxicity. Limited data are available on the toxicities of most micronutrients, and few studies that meet the criteria considered essential for the risk assessment of other chemicals in food, such as pesticides and food additives, have been performed. In some cases, the application of large uncertainty factors, which are used to establish the amount of a chemical that would be safe for daily intake throughout life, could result in nutritionally inadequate intakes of micronutrients. As a consequence, lower than normal uncertainty factors have been applied to determine safe or tolerable intakes of many micronutrients. There is no clear scientific rationale, on the basis of the metabolism and elimination of micronutrients or the nature of the adverse effects reported for high intakes, for the use of reduced uncertainty factors for micronutrient toxicity. A review of recent evaluations of selected vitamins and minerals shows little consistency in the application of uncertainty factors by different advisory groups, such as the Institute of Medicine in the United States and the Scientific Committee on Foods in the European Union. It is apparent that, in some cases, the uncertainty factor applied was selected largely to give a result that is compatible with nutritional requirements; therefore, the uncertainty factor represented part of risk management rather than hazard characterization. The usual risk assessment procedures for chemicals in food should be revised for micronutrients, so that the risks associated with intakes that are too low and too high are considered equally as part of a risk-benefit analysis.

Animals↗

PubMed1996

Prospective study of serum micronutrients and ovarian cancer.

BACKGROUND: Antioxidant micronutrients, such as alpha-tocopherol (vitamin E), the carotenoids, and selenium, may protect against the development of cancer by preventing free radical damage at the cellular level. PURPOSE: A nested case--control study was conducted among donors to a serum bank to examine the association between levels of serum micronutrients and/or cholesterol and the development of ovarian cancer. METHODS: In 1974, sera were collected from 20,305 residents of Washington County, MD, over a 4-month period and stored at -70 degrees C. Serum micronutrient concentrations of women who developed ovarian cancer (case subjects, n = 35) were compared with those of women who remained free of cancer and who were matched to case subjects on age and menopausal status (control subjects, n = 67). Serum levels of retinol (vitamin A), alpha- and beta-carotene (the major provitamin A), lycopene (a carotenoid), and alpha- and gamma-tocopherol were measured using high-performance liquid chromatography. Serum selenium was measured by neutron activation analysis. Cholesterol was measured by enzymatic assay. The data were categorized into thirds and conditional logistic regression analyses were performed to determine the association between prediagnostic serum cholesterol and micronutrient levels and the development of ovarian cancer; matched odds ratios (ORs) were determined from these regression analyses. P values for trend and for interaction were calculated with the use of two-sided likelihood ratio tests. RESULTS: Higher serum alpha-tocopherol levels were associated with an increased risk of ovarian cancer (P for trend = .04); however, this association diminished after adjustment for cholesterol. Women with higher serum cholesterol levels had an increased risk of ovarian cancer compared with women in the lowest third of cholesterol levels (OR = 3.2; 95% confidence interval = 0.9-11.3). The association between serum cholesterol levels and the risk of ovarian cancer was examined, stratifying by micronutrient level. The general pattern observed was an increased risk of ovarian cancer associated with cholesterol levels greater than 200 mg/dL, regardless of the micronutrient level. Serum selenium was associated with a decreased risk of ovarian cancer only among case participants diagnosed 4 or more years after blood collections (P for trend = .02). Concentrations of carotenoids and retinol were not associated with the development of ovarian cancer. CONCLUSIONS: Selenium may have a protective role against the development of ovarian cancer. Higher serum cholesterol levels were associated with an increased risk of developing ovarian cancer; an association that persisted regardless of serum micronutrient level. IMPLICATIONS: Given the small size of this study and the inconsistency of results among the few prospective studies of ovarian cancer conducted to test these associations, replications of these findings are highly desirable.

Carotenoids↗

PubMed1999

[Micronutrients in cancer prevention].

Micronutrients are able to influence the process of carcinogenesis by chemoprotection. With regard to preventive medicine, the possible anticarcinogenic effects in the early stages of tumor development, the initiation and promotion stages, require the greatest interest. It is, however, an essential fact that the possible interactions between micronutrients and carcinogenesis are a complex problem that cannot be considered by a simple cause-effect relationship. The basis of our knowledge on a possible protective effect of micronutrients in carcinogenesis are results of in vitro studies and of animal experiments with doses of micronutrients never appearing in the normal nutrition of men. It therefore seems somewhat difficult to transfer the results of those studies to the real-life situation of men. Investigations in humans, mainly epidemiological studies, show controversial results. There has also to be considered that the chemopreventive effect may be different with regard to the single micronutrient. More extensive studies have been performed for beta-carotin or the vitamins A, C, and E as well as for the trace elements selenium and zinc and for calcium. Possible influences of these micronutrients seem to exist mainly in cancers of the breast, lung, gastro-intestinal tract, and prostate. However, chemoprevention may also be produced by various non-nutritive substances, present mainly in food of vegetable origin. Finally it has to be considered that a carcinoprotective effect may not only be induced by enhancing the amount of special micronutrients in the nutrition, but also by avoiding of possible carcinogenic nutrients. The difference between carcinoprotective and carcinogenic is, however, not only a question of quality but not seldom dependent on quantity.

Anticarcinogenic Agents↗

PubMed2002

Growth and micronutrient disturbances in stable, HIV-infected children in Cape Town.

This prospective study of 60 stable, HIV-infected children in an economically deprived setting was designed to document anthropometric and micronutrient disturbances. Investigations included CD4+ counts, anthropometry and plasma levels of albumin, transthyretin, retinol-binding protein (RBP), vitamins A, B6, E and B12, and folate, zinc and copper. The median age was 25 months. Thirty-two per cent had mild, 48% moderate and 20% severe clinical features, and 80% were moderately or severely immunosuppressed. Twenty-eight per cent had a weight Z-score <-2.0 and 58% a height Z-score <-2.0. Many children had micronutrient deficiencies: albumin (70%), transthyretin (100%), RBP (85%), vitamins A (80%), B6 (37%), E (37%) and B12 (5%), zinc (20%) and copper (25%). Sixty-two per cent had two or more trace element or vitamin deficiencies. There was a weak association between micronutrient status and disease status. Micronutrient concentrations did not correlate with chronological age, height-for-age or weight-for-age. CRP was elevated in 53% but did not correlate with any of the micronutrient concentrations. Micronutrient deficiencies were more common and micronutrient concentrations lower in children over 24 months of age.

Anthropometry↗

PubMed2001

Micronutrient interactions: effects on absorption and bioavailability.

A potential risk of interactions between micronutrients affecting absorption and bioavailability has to be considered in any supplementation or fortification strategy. At levels of essential micronutrients present in foods, most micronutrients appear to utilise specific absorptive mechanisms and not be vulnerable to interactions. In aqueous solutions and at higher intake levels competition between elements with similar chemical characteristics and uptake by non-regulated processes can take place. These interactions have clearly been demonstrated in experimental absorption studies and to some extent have been confirmed in supplementation studies. Negative effects of iron supplementation on indices of zinc and copper status and of zinc supplementation on iron and copper status have been reported. In contrast, the negative effect of calcium on iron absorption has not been confirmed in long-term supplementation studies. Ascorbic acid has a strong iron absorption promoting potential and in iron deficient populations ascorbic acid supplementation improves iron status. Thus, ascorbic acid supplements or an increased intake of ascorbic acid rich foods could have important public health implications, especially in populations subsisting on a mainly plant food based diet. The effect of poor status of a given micronutrient on absorption and utilisation of other micronutrients should also be considered while developing strategies to improve micronutrient status in a population. Awareness of these interactions, combined with a balanced evaluation of the dietary intake of the population with regard to absorption promoting and inhibiting substances and the risk for multiple deficiencies, could lead to more effective strategies to improve micronutrient status.

Ascorbic Acid↗

PubMedDate not supplied

[Role of micronutrients in medicine].

Adequate micronutrient intake throughout life course is essential for the maintenance of health. Micronutrients are necessary for the maintenance of intermediary metabolism, play a crucial role as co-factors or co-enzymes in the activity of virtually all enzymes, and have important functions to neutralise the deleterious effects of oxidant species. Claims have been made for the benefits of micronutrient supplementation. Clinical benefit of a supplementation is obvious in those individuals who are severely depleted and at risk of complications. More recently, the concept of subclinical deficit has been developed, which essentially relies upon biochemical abnormalities the interpretation of which remains doubtful in most instances. Symptomatology related to such subclinical deficit is non specific and the potential advantages of micronutrient supplements remain marginal and largely not well-established. In contrast, provision of excess supplements to individuals who do not need them may be harmful. In the general population, a well-balanced diet supplies an adequate intake of micronutrient. Further research is needed to identify the best markers of micronutrient and antioxidant status, so that at risk patients can be identified and appropriate supplementation provided accordingly. New large-scale trials of different doses of micronutrients, based on precise outcome markers, are required to optimise intakes in different groups of patients as well as in the general population.

Dietary Supplements↗

PubMed1996

Micronutrients as chemopreventive agents.

The concept of chemoprevention of cancer by micronutrients is based upon evidence from human epidemiology and from studies of animal carcinogenesis models for cancer-inhibiting potential of certain minerals and vitamins. These micronutrients are diverse with respect to chemical structures and physiological effects, and include calcium, selenium, carotenoids, and vitamins A, C, D and E. The dietary intake of various micronutrients has been observed to alter significantly the incidence and mortality of a variety of human cancers including those of the oesophagus, stomach, colon, breast and cervix. Studies of laboratory animal models have also provided relevant mechanistic and efficacy data on the role of specific micronutrients as well as minor non-nutrients of dietary origin in the carcinogenic process. Micronutrients and such minor non-nutrients have been found to modulate the formation and bioactivation of carcinogens, modify the promotion and progression of carcinogenesis, alter cellular and host defences, and affect cellular differentiation-ultimately leading to variations in tumour incidences. Our understanding of biochemical and biological mechanisms of carcinogenesis and of inhibition of initiation, promotion and progression by particular micronutrients-both naturally occurring forms and their synthetic analogues-has made it possible to develop strategies for clinical intervention by these agents. It is possible that intervention with individual micronutrients and minor non-nutrients, and/or with a combination of such compounds with different modes of action, will prevent, delay or reverse the process of carcinogenesis and thus reduce the incidence of and mortality due to human cancers. A number of Phase II clinical trials have been initiated with the objective of identifying and evaluating intermediate biomarkers that will be used as surrogate end points for cancer. Several surrogate end points have been standardized and validated for their specificity. The results are very encouraging.

Animals↗

PubMed2006

Monitoring micronutrients in cigarette smokers.

Smoking is associated with oxidative stress and increased risks of many chronic diseases that both shorten life and impair its quality. Low concentrations of several micronutrients, especially the antioxidants vitamin C and beta-carotene, are also associated with smoking, and there has been much interest in determining whether deficiencies in micronutrients are involved etiologically in smoking-related diseases. The objective of this review was to bring together reports on dietary intakes, biochemical indicators of micronutrient status, and results of some intervention studies on micronutrients where authors had compared outcomes in smokers and non-smokers. The micronutrients discussed are vitamins A, E, and C; the carotenoids; some of the B-vitamin group; and the minerals selenium, zinc, copper, and iron. The data were then examined to determine whether effects on the biochemical markers of micronutrient status were due to differences in dietary intakes between smokers and non-smokers or to the consequences of inflammatory changes caused by the oxidative stress of smoking. It was concluded that although smoking is associated with reduced dietary intake of vitamin C and carotenoid-containing foods, inflammatory changes increase turnover of these micronutrients so that blood concentrations are still lower in smokers than non-smokers even when there is control for dietary differences. In the case of vitamin E, there is some evidence for increased turnover of this nutrient in smokers, but this has little to no influence on blood concentrations, and there are no differences in dietary intake of vitamin E between smokers and non-smokers. Serum concentrations of vitamin A, folate, and vitamin B12 and B6 markers do not appear to be influenced by smoking, although there is some influence of dietary intake on concentrations of these nutrients in the body. In the case of the minerals examined, the main effects on biochemical markers of mineral status were attributed to inflammation and were therefore greater in heavy or long-term smokers. Serum concentrations of selenium and erythrocyte GPx activity were lower in smokers. Erythrocyte CuZn-SOD activity and serum ceruloplasmin concentrations were elevated, while serum zinc concentrations were depressed only in heavy smokers. Lastly, smoking appears to affect iron homeostasis mainly by changing hemoglobin concentrations, which were in general increased. Serum iron, TfR, and ferritin were mostly unaffected by smoking, except in pregnancy where there is evidence of increased erythropoiesis causing lower saturation of plasma transferrin and some evidence of lowering of iron stores.

Antioxidants↗

PubMed1998

Micronutrients prevent cancer and delay aging.

Approximately 40 micronutrients are required in the human diet. Deficiency of vitamins B12, folic acid, B6, niacin, C, or E, or iron, or zinc, appears to mimic radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both. The percentage of the US population that has a low intake (< 50% of the RDA) for each of these eight micronutrients ranges from 2% to > or = 20%; half of the population may be deficient in at least one of these micronutrients. Folate deficiency occurs in approximately 10% of the US population, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased cancer risk, and perhaps the cognitive defects associated with low folate intake. Some evidence, and mechanistic considerations, suggest that vitamin B12 and B6 deficiencies also cause high uracil and chromosome breaks. Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has approximately double the cancer rate for most types of cancer when compared to the quarter with the highest intake. Eighty percent of American children and adolescents and 68% of adults do not eat five portions a day. Common micronutrient deficiencies are likely to damage DNA by the same mechanism as radiation and many chemicals, appear to be orders of magnitude more important, and should be compared for perspective. Remedying micronutrient deficiencies is likely to lead to a major improvement in health and an increase in longevity at low cost. Aging appears to be due, in good part, to the oxidants produced by mitochondria as by-products of normal metabolism. In old rats mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O2 consumption are lower than in young rats, and the level of oxidants (per unit O2) is higher. The level of mutagenic aldehydes from lipid peroxidation is also increased. Ambulatory activity declines markedly in old rats. Feeding old rats the normal mitochondrial metabolites acetyl carnitine and lipoic acid for a few weeks, restores mitochondrial function, lowers oxidants to the level of a young rat, and increases ambulatory activity. Thus, these two metabolites can be considered necessary for health in old age and are therefore conditional micronutrients. This restoration suggests a plausible mechanism: with age-increased oxidative damage to proteins and lipid membranes causes a deformation of structure of key enzymes, with a consequent lessening of affinity (Km) for the enzyme substrate; an increased level of the substrate restores the velocity of the reaction, and thus restores function.

Aging↗