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Vitamin D deficiency is linked to numerous medical conditions, including Rickets, Osteomalacia, and a slew of other medical and neurological conditions. The information below is a collection of sources scanning the globe for the latest studies on Vitamin D research.

Health Effects

Bone health
One of the most important roles of vitamin D is to “maintain skeletal calcium balance by promoting calcium absorption in the intestines, promoting bone resorption by increasing osteoclast number, maintaining calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels. Vitamin D deficiency can result in lower bone mineral density and an increased risk of bone loss (osteoporosis) or bone fracture because a lack of vitamin D alters mineral metabolism in the body.[99] Vitamin D has been studied as a potential treatment for osteoporosis, but since treatment of vitamin D deficiency is associated with an increase of mineralization of osteoid, it remains unclear whether vitamin D has any effect on osteoporotic bone.[99] In cross-sectional studies there was a positive relationship between vitamin D and bone mineral density in the hip.[100] Lips (2001) reported that bone mineral deficit in osteomalacia was larger than that in milder degrees of vitamin D deficiency.[100]

There is also a relationship between low bone mineral density and sedentary life style. This is evident in frail, elderly subjects because they are often vitamin D deficient and lead an inactive lifestyle. Lips (2001) also reported that mild vitamin D deficiency was not associated with an increased risk for hip fracture. A study done in Norway consisted of 246 patients with hip fractures who were studied for risk factors.[100] Results showed that a vitamin D intake lower than 100 IU/day was associated with an increased risk for hip fracture.[100] Vitamin D supplements may also increase bone mineral density in other parts of the skeleton.[100] A study showed that a supplement of 800 IU per day of vitamin D increased the bone mineral density of the lumbar spine in postmenopausal women in comparison with the control group.[100] Persons over the age of 50 years need higher levels of vitamin D. In a study discussed in LoPiccolo et al. (2010), adults who consumed a daily supplementation with 482–770 IU of vitamin D had reduced fracture rates of 20% for non-vertebral fractures.[101] However, there was no reported reduction in fracture risk for persons who had 400 IU or less of vitamin D daily.[101]

Immune system

Vitamin D receptor ligands have been shown to increase the activity of natural killer cells, and enhance the phagocytic activity of macrophages.[25] Active vitamin D hormone also increases the production of cathelicidin, an antimicrobial peptide that is produced in macrophages triggered by bacteria, viruses, and fungi.[102][103][104] Suggestions of a link between vitamin D deficiency and the onset of multiple sclerosis posited that this is due to the immune-response suppression properties of Vitamin D[105] and that vitamin D is required to activate a histocompatibility gene (HLA-DRB1*1501) necessary for differentiating between self and foreign proteins in a subgroup of individuals genetically predisposed to MS.[106] Whether vitamin D supplements during pregnancy can lessen the likelihood of the child developing MS later in life is not known;[107][108] however, vitamin D fortification has been suggested to have caused a pandemic of allergic disease[109] and an association between vitamin D supplementation in infancy and an increased risk of atopy and allergic rhinitis later in life has been found.[110] Veteran vitamin D researcher Hector DeLuca has cast doubt on whether vitamin D affects MS.[111]

Tuberculosis and HIV

Historically, vitamin D3 was used to treat tuberculosis patients, but has not been adequately investigated in controlled clinical trials.[112] The hormonally active form of vitamin D3, 1,25-dihydroxycholecalciferol (1,25(OH)2D), has been shown to have antimycobacterial activity in vitro, but the applicability of this effect to clinical situations has not been shown.[113][114] Vitamin D3 supplementations has not shown any improvement in treating tuberculosis except in a small subset of patients with the tt genotype of the TaqI vitamin D receptor polymorphism.[112] Several studies have shown an association between low serum levels of 25-hydroxycholecalciferol (25(OH)D) and increased risk for both active tuberculosis disease progression and susceptibility. More prospective studies will be required to ascertain the potential role of vitamin D supplementation in treating patients with tuberculosis.[115]

Vitamin D3 has also shown some anti-HIV-1 effects in vitro, including the induction of autophagy.[116] The potential effect in humans has not been investigated. Lower levels of 1,25(OH)2D in HIV infected patients are correlated with significantly lower CD4+ T cell counts and higher tumor necrosis factor levels,[117] which normally decrease in number with progression to AIDS, although no causative association has been shown. In an epidemiological study of HIV positive women in Tanzania, there appeared to be a correlation between reduced levels of Vitamin D and speed of HIV disease progression. These results will need to be confirmed in a blinded clinical trial before dietary recommendations can be made.[118]

Influenza

Lack of vitamin D synthesis is a possible explanation for high rates of influenza infection during winter;[119] however, see flu season for the factors apart from vitamin D that are also hypothesized to influence rates of infection during winter.[120] For viral infections, other implicated factors include low relative humidities produced by indoor heating and cold temperatures that favor virus spread during winter.[121]

Cancer

The molecular basis for thinking that vitamin D has the potential to prevent cancer lies in its role in a wide range of cellular mechanisms central to the development of cancer.[122] These effects may be mediated through vitamin D receptors expressed in cancer cells.[25] Polymorphisms of the vitamin D receptor (VDR) gene have been associated with an increased risk of breast cancer.[123] Women with mutations in the VDR gene had an increased risk of breast cancer.[124]

A 2006 study using data on over 4 million cancer patients from 13 different countries showed a marked increase in some cancer risks in countries with less sun and another metastudy found correlations between vitamin D levels and cancer. The authors suggested that intake of an additional 1,000 international units (IU) (or 25 micrograms) of vitamin D daily reduced an individual’s colon cancer risk by 50%, and breast and ovarian cancer risks by 30%.[125][126][127][128] Low levels of vitamin D in serum have been correlated with breast cancer disease progression and bone metastases.[123] However, the vitamin D levels of a population do not depend on the solar irradiance to which they are exposed.[129][130][131][132] Moreover, there are genetic factors involved with cancer incidence and mortality which are more common in northern latitudes.[133][134]

A 2006 study found that taking the U.S. RDA of vitamin D (400 IU per day) cut the risk of pancreatic cancer by 43% in a sample of more than 120,000 people from two long-term health surveys.[135][136] However, in male smokers a 3-fold increased risk for pancreatic cancer in the highest compared to lowest quintile of serum 25-hydroxyvitamin D concentration has been found.[137]

A randomized intervention study involving 1,200 women, published in June 2007, reports that vitamin D supplementation (1,100 international units (IU)/day) resulted in a 60% reduction in cancer incidence, during a four-year clinical trial, rising to a 77% reduction for cancers diagnosed after the first year (and therefore excluding those cancers more likely to have originated prior to the vitamin D intervention).[138][139] The study was criticized on several grounds[140] including lack of reported data, use of statistical techniques and comparison with a self-selected (i.e. non-randomized) observational study that found long term convergence of breast cancer incidence (i.e. the cancer occurrence had merely been delayed) [141] The author’s response provided the requested data, explained their statistical usage and commented that even if the vitamin D merely delayed the appearance of cancer (which they did not believe, based on other studies), that this was still a considerable benefit.[140]

In 2007, the Canadian Cancer Society recommended that adults living in Canada should consider taking vitamin D supplementation of 1,000 international units (IU) a day during the fall and winter.[142][143] A US National Cancer Institute study analyzed data from the third national Health and Nutrition Examination Survey to examine the relationship between levels of circulating vitamin D in the blood and cancer mortality in a group of 16,818 participants aged 17 and older. It found no support for an association between 25(OH)D and total cancer mortality. However, the study did find that “[c]olorectal cancer mortality was inversely related to serum 25(OH)D level, with levels 80 nmol/L or higher associated with a 72% risk reduction (95% confidence interval = 32% to 89%) compared with lower than 50 nmol/L, Ptrend = .02.”[84] Unlike other studies, this one was carried out prospectively — meaning that participants were followed looking forward — and the researchers used actual blood tests to measure the amount of vitamin D in blood, rather than trying to infer vitamin D levels from potentially inaccurate predictive models.[132][144]

A meta-study published in the International Journal of Cancer in May 2010 analyzed 35 independent studies of vitamin D and cancer. The researchers determined that a 10 nanogram/milliliter increase in serum vitamin D is associated with a 15% lower risk of colon cancer. The analysis also found an 11% lower risk for breast cancer, although the authors report that due to case study methodology that this finding is ultimately insignificant. [145]

A 2011 study done at the University of Rochester Medical Center found that low vitamin D levels among women with breast cancer correlate with more aggressive tumors and poorer prognosis. The study associated sub-optimal vitamin D levels with poor scores on every major biological marker that helps physicians predict a patient’s breast cancer outcome. The lead researcher stated, “Based on these results, doctors should strongly consider monitoring vitamin D levels among breast cancer patients and correcting them as needed.”[146]

Cardiovascular disease

A report from the National Health and Nutrition Examination Survey (NHANES) involving nearly 5,000 participants found that low levels of vitamin D were associated with an increased risk of peripheral artery disease (PAD). The incidence of PAD was 80% higher in participants with the lowest vitamin D levels (<17.8 ng/mL).[63] Cholesterol levels were found to be reduced in gardeners in the UK during the summer months.[147] Low levels of vitamin D are associated with an increase in high blood pressure and cardiovascular risk. Numerous observational studies show this link, but of two systemic reviews one found only weak evidence of benefit from supplements and the other found no evidence of a beneficial effect whatsoever.[65][75][148]

There is a certain amount of evidence to suggest that dietary vitamin D may be carried by lipoprotein particles[97] into cells of the artery wall and atherosclerotic plaque, where it may be converted to active form by monocyte-macrophages.[98] These findings raise questions regarding the effects of vitamin D intake on atherosclerotic calcification and cardiovascular risk. Calcifediol (25-hydroxy-vitamin D) is implicated in the etiology of atherosclerosis, especially in non-Caucasians.[90][92][149][150] Freedman et al. (2010) found that serum vitamin D correlates with calcified atheroscleratic plaque (CP) in African Americans, but not in Euro-Americans, “Higher levels of 25-hydroxyvitamin D seem to be positively associated with aorta and carotid CP in African Americans but not with coronary CP. These results contradict what is observed in individuals of European descent.”[150] One study found an elevated risk of ischaemic heart disease in Southern India in individuals whose vitamin D levels were above 89 ng/mL.[149] A review of vitamin D status in India concluded that studies uniformly point to low 25(OH)D levels in Indians despite abundant sunshine, and suggested a public health need to fortify Indian foods with vitamin D might exist.[93] The levels found in India are consistent with many other studies of tropical populations which have found that even an extreme amount of sun exposure, such as incurred by rural Indians,[151] does not raise 25(OH)D levels to the levels typically found in Europeans.[129][94][38]

References