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For 5 months a year the UK has insufficient sunlight for cutaneous synthesis of vitamin D and winter requirements are met from stores made the previous summer. Although there are few natural dietary sources, dietary intake may help maintain vitamin D status. We investigated the relationship between 25-hydroxyvitamin D (25(OH)D), bone health, overweight, sunlight exposure and dietary vitamin D in 3113 women (age 54.8 [SD 2.3] years) living at latitude 57 degrees N between 1998-2000. Serum 25(OH)D was measured by high performance liquid chromatography (HPLC), dietary intakes (food frequency questionnaire, n=2598), sunlight exposure (questionnaire, n=2402) and bone markers were assessed. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in all women at the sampling visit and 6 years before. Seasonal variation in 25(OH)D was not substantial with a peak in the autumn (23.7 [9.9] ng/ml) and a nadir in spring (19.7 [7.6] ng/ml). Daily intake of vitamin D was 4.2 [2.5] mug from food only and 5.8 [4.0] mug including vitamin D from cod liver oil and multivitamins. The latter was associated with 25(OH)D at each season whereas vitamin D simply from food was associated with 25(OH)D in winter and spring only. Sunlight exposure was associated with 25(OH)D in summer and autumn. 25(OH)D was negatively associated with increased bone resorption and bone loss (P<0.05) remaining significant after adjustment for confounders (age, weight, height, menopausal status/HRT use, physical activity and socio-economic status). Using an insufficiency cut-off of <28 ng/ml 25(OH)D, showed lower concentrations of bone resorption markers in the upper category (fDPD/Cr 5.1 [1.7] nmol/mmol compared to 5.3 [2.1] nmol/mmol, P=0.03) and no difference in BMD or bone loss. 25(OH)D was lower (P<0.01) and parathyroid hormone higher (P<0.01) in the top quintile of body mass index. In conclusion, low vitamin D status is associated with greater bone turnover, bone loss and obesity. Diet appears to attenuate the seasonal variation of vitamin D status in early postmenopausal women at northerly latitude where quality of sunlight for production of vitamin D is diminished.
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PMID:Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D. 1832 55

American men have a lifetime risk of about 18% for prostate cancer diagnosis. Large international variations in prostate cancer risks and increased risks among migrants from low- to high-risk countries indicate important roles for environmental factors. Major known risk factors include age, family history, and country/ethnicity. Type 2 diabetes appears to reduce risk, while high birth weight and adult height are linked to increased risk of aggressive prostate cancer. Limited evidence supports an association with a history of sexually transmitted infections. A previous meta-analysis of eight cohort studies indicated no associations with plasma androgen, estrogen, or sex hormone binding globulin (SHBG) levels. However, there were dose-response relationships with baseline plasma testosterone levels in two studies that adjusted for other serum hormones and obesity. Finasteride (a drug that blocks testosterone activation) reduced prostate cancer risk by 25%. Low-frequency genes linked to familial prostate cancer only explain a small fraction of all cases. Sporadic cases were linked to relatively common polymorphisms of genes involved in (1) androgen synthesis, activation, inactivation and excretion, (2) hormone and vitamin D receptors, (3) carcinogen metabolism, and (4) DNA repair. Epidemiologic evidence supports protective roles for dietary selenium, vitamin E, pulses, tomatoes/lycopene, and soy foods, and high plasma 1,25-dihydroxyvitamin D levels. There is inadequate evidence that vegetables, fruit, carotenoids, and vitamins A and C reduce risk and that animal fat, alpha-linoleic acid, meat, coffee, and tea increase risk. Two major cohort studies found dose-response relationships with dietary calcium intake. Total dietary energy intake may enhance risk. Limited evidence supports a protective role for physical activity and elevated risk for farmers and other men with occupational pesticide exposure, particularly to organochlorine compounds and phenoxy herbicides. There is inadequate evidence for a relationship with alcohol or smoking. Most known or suspected external risk factors may act through hormonal mechanisms, but our review found little supporting evidence, and substantial further research is needed.
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PMID:Role of hormonal and other factors in human prostate cancer. 1836 55

Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.
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PMID:Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity. 1844 61

Youth, 9-18 years (n = 202), living in homeless shelters in Minneapolis, Minnesota, were assessed for height, weight, dietary intake, and perceptions of food insecurity. Perceptions of food security were measured by asking youth to respond to the statements (1) "There are times when we do not have enough food in the house," (2) "I go to bed hungry at night," (3) "I do not get enough to eat at home," and (4) "Have you ever had to miss a meal (or not been able to eat) because there was no food at home?" Additionally, questions evaluated coping mechanisms used by children to ward off hunger. Fifty-five percent of the children reported not enough food in the house and 25% reported going to bed hungry. Youth had inadequate intakes of vitamin D, calcium, and potassium and the majority consumed less than the estimated average requirements (EAR) for vitamins A, C, and E, phosphorus, folate, and zinc. Fruits, vegetables, and dairy were also consumed below recommended levels. Forty-five percent of boys and 50% of girls were at risk-for-overweight or were overweight. Overeating, eating anything, eating disliked foods, and eating at the homes of family and friends were identified as strategies to cope with food insecurity. Overeating when food is available may explain why we see a hunger-obesity paradigm to the magnitude that we do among the poorest Americans. These strategies protect children from the immediate negative associations of poverty and hunger, but they may contribute to long-term weight problems currently found in the US.
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PMID:Dietary intake, overweight status, and perceptions of food insecurity among homeless Minnesotan youth. 1849 7

Natural products have potential for inducing apoptosis, inhibiting adipogenesis and stimulating lipolysis in adipocytes. The objective of this review is to discuss the adipocyte life cycle and various dietary bioactives that target different stages of adipocyte life cycle. Different stages of adipocyte development include preadipocytes, maturing preadipocytes and mature adipocytes. Various dietary bioactives like genistein, conjugated linoleic acid (CLA), docosahexaenoic acid, epigallocatechin gallate, quercetin, resveratrol and ajoene affect adipocytes during specific stages of development, resulting in either inhibition of adipogenesis or induction of apoptosis. Although numerous molecular targets that can be used for both treatment and prevention of obesity have been identified, targeted monotherapy has resulted in lack of success. Thus, targeting several signal transduction pathways simultaneously with multiple natural products to achieve additive or synergistic effects might be an appropriate approach to address obesity. We have previously reported two such combinations, namely, ajoene+CLA and vitamin D+genistein. CLA enhanced ajoene-induced apoptosis in mature 3T3-L1 adipocytes by synergistically increasing the expression of several proapoptotic factors. Similarly, genistein potentiated vitamin D's inhibition of adipogenesis and induction of apoptosis in maturing preadipocytes by an enhanced expression of VDR (vitamin D receptor) protein. These two examples indicate that combination therapy employing compounds that target different stages of the adipocyte life cycle might prove beneficial for decreasing adipose tissue volume by inducing apoptosis or by inhibiting adipogenesis or both.
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PMID:Phytochemicals and regulation of the adipocyte life cycle. 1849 57

African Americans have lower serum 25-hydroxyvitamin D concentrations and a lower risk of fragility fractures than do other populations. I review the evidence on factors other than vitamin D that might explain this paradox and the calcium economy in different life stages. Researchers are actively trying to explain this genetically programmed advantage. Factors that could protect African Americans against fracture include their higher peak bone mass, increased obesity rates, greater muscle mass, lower bone turnover rates, and advantageous femur geometry. In addition, bone histomorphometry in young adults shows longer periods of bone formation. Although African Americans fall as frequently as do whites, the direction of their falls and their manner of breaking falls could protect them from fractures. African American girls accrue more calcium than do white girls during adolescence as the result of increased calcium absorption and superior renal calcium conservation. In adulthood, higher parathyroid hormone concentrations do not result in increased bone loss in African Americans because of their skeletal resistance to parathyroid hormone, and their superior renal conservation of calcium persists. These advantages diminish in the elderly, in whom further increases in parathyroid hormone result in increased bone turnover and bone loss. Ultimately, I explain the paradox by multiple factors associated with fracture risk and calcium economy in African Americans. Despite African Americans' reduced risk of osteoporotic fractures, such fractures remain an important public health problem for this population that vitamin D intervention studies have not addressed.
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PMID:African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. 1868 99

This review summarizes three controversial areas of clinical practice that were discussed in many articles that appeared in the American Journal of Clinical Nutrition during the author's tenure as editor in chief. Controversy 1-obesity and high-fructose corn syrup. The increased frequency of obesity in the US is paralleled by increasing annual consumption of high-fructose corn syrup, an extracted sweetener that is routinely added to soft drinks and to many processed foods in the US diet. Metabolic studies implicate increased fructose consumption in increased body fat and obesity and with increased circulating triglyceride levels and hypercholesterolaemia in children. Controversy 2-folic acid fortification and supplements. Together with widespread use of supplemental multivitamins, fortification of the US diet with folic acid has resulted in high serum folate levels in much of the population, which may be associated with increased risk of cognitive decline in ageing people with low vitamin B12 status, decreased natural killer T-cell immune function and increased risk of recurrent advanced precancerous colorectal adenomas and breast cancer. Controversy 3-recommended intakes of vitamin D. Levels of serum 25(OH)D sufficient for fracture prevention are at least 75 nmol/l (30 ng/ml) but cannot be achieved by the current recommended dietary intakes in the US. A recent fracture risk prevention trial showed that the 4-year incidence of all cancers was reduced in US women who received high supplemental doses of both calcium and vitamin D.
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PMID:Perspectives on obesity and sweeteners, folic acid fortification and vitamin D requirements. 1882 93

Interest in all aspects of vitamin D seems to be surging due to perhaps the increased number of diverse positive studies suggesting it could prevent a variety of chronic diseases. However, before patients and health care professionals are educated on the preventive aspects of this vitamin that acts more like a hormone, a basic rapid review of vitamin D is needed. There are multiple reasons for the high rate of vitamin D deficiency around the world, including an aging population, obesity, protective skin care measures, skin pigmentation, increased awareness, more utilized diagnostic assays, and perhaps even the lack of natural and fortified food and beverage sources. Various benefits and limitations of vitamin D2 and vitamin D3 supplementation are discussed. The proper use of the vitamin D blood test, also known as "25-OH vitamin D," is important, and changing the normal range of this test may allow for a slightly higher cutoff value based on parathyroid hormone reductions and experience from clinical trials of osteoporosis prevention. The vitamin D doses needed to adequately increase blood levels are provided. Finally, increasing the recommended daily allowance of this vitamin to 800 to 1,000 IU per day may be beneficial for most age groups.
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PMID:Vitamin D: a rapid review. 1928 58

Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.
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PMID:Age-related bone loss in the LOU/c rat model of healthy ageing. 1899 16

Common obesity is associated with the metabolic syndrome and can be distinguished from secondary obesity and from rare forms of monogenic and polygenic obesity. The prevalence of common obesity has become a public health concern in many countries as phenomenological approaches to the understanding of obesity have failed to achieve any long term effect on prevention or treatment. There is evidence for a central control mechanism which maintains body-weight to a set-point by the regulation of energy intake and energy expenditure through homeostatic pathways. It is suggested in this paper that common obesity occurs when the set-point is raised and that accumulation of fat mass functions to increase body size. Larger body size confers a survival advantage in the cold ambient temperatures and food scarcity of the winter climate by reducing surface area to volume ratio and by providing an energy store in the form of fat mass. In addition, it is suggested that the phenotypic metabolic and physiological changes observed as the metabolic syndrome, including hypertension and insulin resistance, could result from a winter metabolism which increases thermogenic capacity. Common obesity and the metabolic syndrome may therefore result from an anomalous adaptive winter response. The stimulus for the winter response is proposed to be a fall in vitamin D. The synthesis of vitamin D is dependent upon the absorption of radiation in the ultraviolet-B range of sunlight. At ground level at mid-latitudes, UV-B radiation falls in the autumn and becomes negligible in winter. It has previously been proposed that vitamin D evolved in primitive organisms as a UV-B sensitive photoreceptor with the function of signaling changes in sunlight intensity. It is here proposed that a fall in vitamin D in the form of circulating calcidiol is the stimulus for the winter response, which consists of an accumulation of fat mass (obesity) and the induction of a winter metabolism (the metabolic syndrome). Vitamin D deficiency can account for the secular trends in the prevalence of obesity and for individual differences in its onset and severity. It may be possible to reverse the increasing prevalence of obesity by improving vitamin D status.
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PMID:Vitamin D deficiency is the cause of common obesity. 1928 11


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