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Vitamin D-3

Response to an adequate dietary intake of vitamin D3 modulates the effect of estrogen therapy on bone density.

Aside from the well-accepted role of vitamin D in skeletal health, epidemiologic and cross-sectional studies have suggested associations between vitamin D status and diabetes,energy metabolism, heart disease,cancer (including colorectal, prostate, and breast), and compromised immune function. However, some clinicians and researchers are suggesting caution regarding widespread measurement of 25-hydroxyvitamin D3 (25OHD3) or recommendation of robust vitamin D repletion in the absence of clear evidence demonstrating a benefit.

Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency

It has long been known that insulin-like growth factor 1 (IGF1) causes an increase in the circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), the hormonally active vitamin D metabolite, by stimulating the expression and activity of the 1α-hydoxylase that produces 1,25(OH)2D in the kidney. Indeed, plasma 1,25(OH)2D is significantly higher in active than controlled acromegaly, with a tendency to hypercalcemia, hyperphosphatemia, and hypercalciuria. On the other hand, more recent data has suggested that vitamin D may contribute to determining IGF1 concentrations. Mice knockout for the vitamin D receptor (VDR) exhibit 30% lower IGF1 levels compared with WT animals and a significant increase in serum IGF1 was noted in response to vitamin D in two small cohorts of children. Furthermore, cross-sectional analyses of community-based cohorts disclosed a positive correlation between the concentrations of 25-hydroxyvitamin D (25(OH)D), the marker of vitamin D status, and IGF1. Here we first conducted an open-label, controlled study of the changes in circulating IGF1 following vitamin D supplementation in adults. Then, we asked whether the influence of vitamin D on IGF1 might be clinically relevant for the management of growth hormone deficiency (GHD), which relies on measurement of IGF1 levels.

Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials

The antifracture benefits of vitamin D have been questioned by several recent trials,1- 4 leading to uncertainty among patients and physicians regarding recommendations for vitamin D supplementation. Two 2007 meta-analyses5,6 included most of these trials and concluded that vitamin D may not reduce fractures significantly or may do so only in combination with calcium and primarily among institutionalized older individuals. A third 2007 meta-analysis7 concluded that calcium with or without vitamin D may reduce total fracture risk by 12%, a result that was questioned by a more recent meta-analysis8 of high-quality trials of calcium supplementation alone in which calcium had a neutral effect on nonvertebral fractures and a possible adverse effect on hip fracture risk. Apart from the mixed data on calcium, the recent meta-analyses with vitamin D did not consider heterogeneity by received dose (incorporating adherence) or achieved level of 25-hydroxyvitamin D. A dose-response relationship between vitamin D and fracture reduction is supported by epidemiologic data showing a significant positive trend between serum 25-hydroxyvitamin D concentrations and hip bone density9 and lower extremity strength.10,11 In addition, greater antifracture efficacy with higher achieved 25-hydroxyvitamin D levels was documented in an earlier meta-analysis of high-quality primary prevention trials with supplemental vitamin D.12 Factors that may obscure a benefit of vitamin D are low adherence to treatment,2 low dose of vitamin D, or the use of less potent ergocalciferol (vitamin D2).13,14 Furthermore, open study design trials1 may bias results toward the null because vitamin D supplementation is available over the counter.

Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads.

In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor α and β were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.

Acid haze air pollution and breast and colon cancer mortality in 20 Canadian cities.

Sulfur dioxide absorbs ultraviolet light in the region of the spectrum which is most active in forming vitamin D on the skin. Sulfate particles reflect light at this wavelength. High concentrations of these pollutants (acid haze) may lead to vitamin D deficiencies in exposed populations. Epidemiologic and laboratory evidence suggests that vitamin D plays a role in reducing risk of colon and breast cancer. We examined the association between sulfur dioxide and ultraviolet-light-blocking aerosols in 20 Canadian cities, and age-adjusted breast and colon cancer mortality rates in the census divisions encompassing these cities. Statistically significant positive associations were found between these two measures of air pollution and age-adjusted mortality rates for colon cancer in women (multiple r = +.74, p = 0.003), and men (multiple r = +.61, p = 0.03), and breast cancer in women (multiple r = +.69, p = 0.007). Mortality rates for all other reported cancer sites were also examined, and no statistically significant positive associations were found consistently in both sexes. The ecological nature of this study is emphasized, and the possibility that an indirect association could explain these findings is discussed.

Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation.

Epidemiologic and laboratory evidence suggests that vitamin D may play a role in reducing breast cancer risk. Lack of exposure to ultraviolet sunlight can increase the prevalence of vitamin D deficiency. This deficiency may place some populations at higher risk for breast cancer. The association between total average annual sunlight energy striking the ground and age-adjusted breast cancer mortality rates in 87 regions of the United States was evaluated. Annual age-adjusted mortality rates for breast cancer varied over a 1.8-fold range, from 17-19 per 100,000 in the South and Southwest United States to 33 per 100,000 in the Northeast; the overall U.S. rate was 27.3 per 100,000. Risk of fatal breast cancer in the major urban areas of the United States was inversely proportional to intensity of local sunlight (r = -0.80, P = 0.0001); multiple regression with stratospheric ozone measurements, r = -0.82, P = 0.0001). Vitamin D from sunlight exposure may be associated with low risk for fatal breast cancer, and differences in ultraviolet light reaching the United States population may account for the striking regional differences in breast cancer mortality. The ecological nature of this study is emphasized, and the possibility that an indirect association with dietary and socioeconomic factors could explain these findings is discussed.

The role of vitamin D in cancer prevention

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

Vitamin D and prevention of breast cancer: pooled analysis

Intake of 2000 IU/day of Vitamin D3, and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.

Vitamin D intake and the risk for pancreatic cancer in two cohort studies.

Ecologic studies suggest that areas with greater sunlight exposure have lower incidence and mortality rates for colon, breast, and prostate cancer, leading investigators to posit a role for vitamin D in cancer prevention by virtue of the greater potential for vitamin D creation in skin by UV irradiation in areas of greater sunlight. Laboratory studies show 1,25 dihydroxyvitamin D3 (calcitriol) receptor expression in pancreatic cancer cell lines; others report that calcitriol and analogues inhibit pancreatic cancer cell proliferation, induce differentiation, and promote apoptosis. However, investigation of the influence of vitamin D intake on the risk for pancreatic cancer is limited to a single prospective study conducted in Finland among male smokers.

Association of high vitamin d status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males

Vitamin D is recognized to be an essential element for bone metabolism and skeletal health; however, its deficiency can cause rickets in children as well as an increased propensity for osteoporosis. In addition, it may also affect extraskeletal health. Indeed, vitamin D deficiency has been identified as a risk factor for diabetes mellitus, cancers, multiple sclerosis and other autoimmune diseases, atherosclerosis, and infectious diseases. Few past studies have reported the impact of vitamin D deficiency on autoimmune thyroid disease and demonstrated inconclusive results. Besides affecting the thyroid gland through immune-mediated processes, vitamin D has been shown to influence rat thyroid follicular cells by directly inhibiting thyrotropin-stimulated iodide uptake in a dose-dependent manner. Recently, a population-based study has reported that high vitamin D status in younger individuals is associated with low circulating thyroid-stimulating hormone (TSH). However, it remains unknown as to why no relationship between vitamin D status and serum TSH levels in middle-aged and elderly individuals was found in this study. Therefore, in the present study, we examined the relationship between vitamin D status and circulating TSH levels in middle-aged and elderly individuals with thyroid autoimmunity, while taking thyroid function into consideration in addition to the relationship between vitamin D insufficiency and thyroid autoimmunity, the presence of thyroid nodule(s) and thyroid volume in a cross-sectional study.

Association of Hypogonadism with Vitamin D Status: The European Male Ageing Study

The classical role played by vitamin D and parathyroid hormone (PTH) in maintaining bone health and controlling calcium metabolism is well documented  Whether synthesised in the skin or derived from dietary sources, vitamin D is first hydroxylated in the liver to produce 25-hydroxyvitamin D (25(OH)D), which is in turn further hydroxylated (primarily in the kidneys) to yield the active molecule, 1,25(OH)2D. Serum levels of 25(OH)D, the major circulating form of the vitamin, are typically measured to determine an individual's vitamin D status. An increasing body of observational data has linked low serum levels of vitamin D to a variety of chronic diseases related to ageing, including diabetes and cardiovascular disease. However, the nature of these associations is poorly defined and our understanding of the pathophysiological role(s) of vitamin D other than in calcium homeostasis remains rudimentary. Age-related declines in testosterone (T) and other anabolic hormones have been well documented in men from the age of 40 years onwards (6, 7, 8), with low T levels suggested to be a risk factor for diabetes and cardiovascular disease. However, the degree to which these changes in hypothalamic–pituitary–testicular (HPT) axis function directly or indirectly influence age-related declines in physical (frailty), cardiovascular (atherosclerosis, erectile dysfunction) and psychological health (cognitive function) remains contentious. Recently, Wehr et al. observed a positive, cross-sectional association between T and 25(OH)D together with a concordant pattern of seasonal variation for both hormones. The authors hypothesise that serum vitamin D levels may impact directly on gonadal functioning, with biological plausibility stemming from the presence of vitamin D receptor (VDR) in the testis, hypothalamus and pituitary gland. Previous work in our group has shown that multilevel functional alterations in the HPT axis are linked to distinct risk factors, such as obesity and comorbidity that interact with age to contribute to declining T levels. Since serum concentrations of vitamin D have also been linked to a number of other adverse health and lifestyle factors, it is important to investigate in more detail how 25(OH)D and also seasonality are associated with hormones of the HPT axis in men. Using baseline data from the European Male Ageing Study (EMAS), we aimed to determine whether 25(OH)D levels were associated with the key hormonal components of the HPT axis, to evaluate the influence of season on vitamin D and individual HPT axis hormone levels, and to investigate whether biochemical hypogonadism, based on combined T/LH levels, was associated with low vitamin D status.

Association between Plasma 25-OH Vitamin D and Testosterone Levels in Men.

A small randomized controlled trial suggested that vitamin D might increase the production of testosterone in men, which is supported by experimental studies in animals and a cross-sectional study showing positive associations between plasma 25-hydroxyvitamin D [25(OH)D] and testosterone and concordant seasonal variation of both biomarkers.

Association of vitamin D status with serum androgen levels in men.

Men with sufficient 25(OH)D levels (≥30 μg/l) had significantly higher levels of testosterone and FAI and significantly lower levels of SHBG when compared to 25(OH)D insufficient (20–29·9 μg/l) and 25(OH)D-deficient (<20 μg/l) men (P < 0·05 for all). In linear regression analyses adjusted for possible confounders, we found significant associations of 25(OH)D levels with testosterone, FAI and SHBG levels (P < 0·05 for all). 25(OH)D, testosterone and FAI levels followed a similar seasonal pattern with a nadir in March (12·2 μg/l, 15·9 nmol/l and 40·8, respectively) and peak levels in August (23·4 μg/l, 18·7 nmol/l and 49·7, respectively) (P < 0·05 for all).

Vitamin D is an Essential Vitamin or Mineral known as the sunlight vitamin, since it is synthesized in the skin when exposed to the sun's radiation. It provides benefits for bone structure support...

Vitamin D is a fat-soluble nutrient. It is one of the 24 micronutrients critical for human survival. The sun is the major natural source of the nutrient, but vitamin D is also found naturally in fish and eggs. It is also added to dairy products. Supplemental vitamin D is associated with a wide range of benefits, including increased Cognition, immune health, bone health and well-being. Supplementation can also reduce the risks of cancer, heart disease, diabetes and multiple sclerosis. People deficient in vitamin D may also experience increased Testosterone levels after supplementation. The body produces vitamin D from cholesterol, provided there is an adequate amount of UV light from sun exposure. There is only a sufficient amount of UV light coming from the sun when the UV index is 3 or higher, which only occurs year-round near the equator, between the 37th parallels. Most people are not deficient in vitamin D, but they do not have an optimal level of vitamin D either. Due to the many health benefits of vitamin D, supplementation is encouraged if optimal levels are not present in the body.