Summary of Vitamin D
Primary Information, Benefits, Effects, and Important Facts
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.
Things To Know & Note
Also Known As
Cholecalciferol (Vitamin D3), Ergocalciferol (Vitamin D2)
Do Not Confuse With
Calcitriol or 1, 25-Dihydroxyvitamin D (Hormonally active yet not directly supplemented form)
Caution NoticeExamine.com Medical Disclaimer
Vitamin D is usually seen as non-stimulatory
Vitamin D may have enhanced absorption when taken with meals
How to Take Vitamin D
Recommended dosage, active amounts, other details
The recommended daily allowance for Vitamin D is currently set at 400-800IU/day, but this is too low for adults. The safe upper limit in the United States and Canada is 4,000IU/day. Research suggests that the true safe upper limit is 10,000IU/day. For moderate supplementation, a 1,000-2,000IU dose of vitamin D3 is sufficient to meet the needs of most of the population. This is the lowest effective dose range. Higher doses, based on body weight, are in the range of 20-80IU/kg daily.
Vitamin D3 supplementation (cholecalciferol) is recommended over D2 supplementation (ergocalciferol), since D3 is used more effectively in the body.
Vitamin D should be taken daily, with meals or a source of fat, like fish oil.
Frequently Asked Questions about Vitamin D
Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects vitamin d has on your body, and how strong these effects are.
|Grade||Level of Evidence [show legend]|
|Robust research conducted with repeated double-blind clinical trials|
|Multiple studies where at least two are double-blind and placebo controlled|
|Single double-blind study or multiple cohort studies|
|Uncontrolled or observational studies only|
Studies Excluded from Consideration
Used injections of the active hormone
Scientific Research on Vitamin D
Click on any below to expand the corresponding section. Click on to collapse it.
Vitamin D is a compound classified as an essential vitamin that derives its name from simply being discovered shortly after Vitamins A, B (prior to the realization that Vitamin 'B' was not a single molecule), and Vitamin C. It was initially found to be a component of Cod Liver Oil, and credited as the 'anti-rachitic' (against rickets) compound to explain how Cod Liver Oil was effective in treating rickets.
Vitamin D is a term used to refer to a group of related molecules, which collectively increase the body's pool of 25-hydroxyvitamin D (circulating form of Vitamin D) and subsequently 1,25-dihydroxyvitamin D (the active hormone).
Food sources of vitamin D3 include:
Dairy appears to be the best food source for vitamin D3. Cod liver oil effectiveness varies, depending on the processor and the method of analysis.
Previously, the RDA was set at 400IU in 1997 (International Units, approximately equal to 10mcg Vitamin D3) as this dose is sufficient to reduce the risk of rickets in children. Even currently, an intake of 400IU (despite keeping the mother in a clinically 'deficient' state according to current definitions) is sufficient to prevent the occurrence of rickets.
This 400IU target intake, as well as the actual overall intake of Vitamin D3, is commonly seen as deficient in adults as 400IU cannot ideally sustain circulating levels between 50-75nmol/L, which is seen as ideal.
The old recommended daily allowance of vitamin D is currently seen as insufficient for adults, despite being sufficient to prevent rickets in offspring. Higher dietary levels are needed.
Synthesis of vitamin D can occur after contact with the sun, where bodily stores of 7-dehydrocholesterol (a derivative of cholesterol) converts to cholecalciferol (vitamin D3).
In some scenarios, the rate of vitamin D synthesis is reduced; such as:
Latitudes that are further away from the equator tend to reduce synthesis rates due to less exposure to solar radiation. Several studies note that Northern USA (relative to Southern USA) experience less UVB radiation, which appears to be related to cancer risk
A combination of latitude and season, with the Northern Hemisphere (Boston and Edmonton; latitude 42.2-55°N) failing to produce any vitamin D between October and March
Areas with higher ozone breakdown (assessed by Dobson units) appear to have higher UVB radiation
Darker skin has a slower synthesis rate than lighter skin and Black persons are routinely at a higher risk for vitamin D deficiency when compared to lighter skin tones (Asian, Caucasian, Hispanic) when other factors are controlled for.
Several factors listed above influence the rates of vitamin D synthesis from the sun. The two most relevant factors are latitude, since being closer to the equator results in more vitamin D synthesis, and skin tone, with black people having a higher risk of vitamin D deficiency. An outright failure to produce any UVB-induced previtamin D has been noted above latitude 42.2°N (Boston) from November to February (4 months), which is prolonged to 6 months above latitude 55°N (Edmonton). The range of 18-32°N still produces vitamin D during the winter.
Despite some sunscreen potentially being related to reduced cancer risk from the sun (Melanoma), a topic that is somewhat mixed in results, sunscreens appear to significantly attenuate synthesis of vitamin D by interfering with the topical influences of UVB rays. Chronic (not acute) sunscreen usage has been associated with Vitamin D deficiency.
Sunscreen is able to significantly diminish synthesis of vitamin D, and chronic usage may be associated with vitamin D deficiency, if no oral supplementation exists.
The standard supplement is vitamin D3, otherwise known as cholecalciferol; vitamin D3 tends to be better absorbed than other forms of vitamin D. In the liver, cholecalciferol is turned into 25-hydroxycholecalciferol via the enzyme cholecalciferol 25-hydroxylase and then sent out to the kidneys to get hydroxylated into 1,25-dihydroxycalciferol. 1,25-dihydrocalciferol is also known as Calcitriol, and is the active hormone that is the result of vitamin D3 ingestion.
Vitamin D is known to be a steroid precursor, which implies that it is currently not bioactive but can become active in the body after metabolism. There are different pathways for oral supplementation and biological synthesis originating in the skin.
When supplementation is not relevant, bodily stores of 7-dehydrocholecalciferol must be converted to cholecalciferol (Vitamin D3). This initial metabolite is present in the skin and the metabolism is initiated by light (spectrum 280-320 UVB) which breaks a part of the molecule known as the B-ring. The metabolite, called pre-vitamin D3, then isomerizes to Vitamin D3 and can then be subject to metabolism in the liver.
The first stage of bioactivation from the molecule cholecalciferol towards the product 25-hydroxycholecalciferol is mediated by a 25-hydroxylase, both CYP2R1 and CYP27A1 being implicated. This process occurs primarily in the liver and due to the next enzyme (CYP27B1) being primarily expressed in the kidneys a large amount of 25-hydroxycholecalciferol is ejected into serum so it can reach this tissue. Upon being subject to CYP27B1 the product is then converted into 1,25-dihydroxycholecalciferol which is considered the active form of Vitamin D as a hormone.
Vitamin D3 is bioactived into its hormone form in either two stages (if starting from a dietary supplement containing Vitamin D3) or in three stages if starting from skin storages, with the skin mediating the first (nonsupplemental) conversion and the later two metabolic steps being handled in the liver and kidneys respectively
Vitamin D itself is divided into two forms, ergocalciferol (vitamin D2), which is mostly derived from plants, and cholecalciferol (vitamin D3), which is the form produced in mammals and fish and thus is a component of cod liver oil supplementation (alongside vitamin A and fish oil fatty acids). The only difference in these two molecules is a methyl group, as vitamin D3 is 27 carbons in length, while D2 is 28 carbons.
Both vitamin D2 and D3 are seen as prohormone compounds (acting to increase circulating levels of 25-hydroxyvitamin D) although it appears there is controversy over which form is superior in increasing circulating 25-hydroxyvitamin D, with many sources suggesting that vitamin D3 is more effective as the active hormone is 25-hydroxycholecalciferol rather than ergocalciferol (more closely resembling that of D3 than D2 in structure) and that D2 should not be sold as a supplement.
Due to the differences in molecular weight one IU of vitamin D3 is 25ng in weight, while one IU is 25.78ng in weight (the difference being the aforementioned methyl group) meaning that a dose of 400IU for vitamin D3 (10µg) would be 385IU, and this difference was thought to be significant for the prevention of rickets and food fortification.
Vitamin D2 and D3 are two forms of vitamin D supplementation that are capable of increasing circulating levels of the active hormone. Although D3 is more potent than D2 (based on weight), it is (controversially) thought that standardizing the two to an IU value normalizes the difference.
Some studies, such as 11 weeks of supplementation at the winter at 1,000IU (D2 or D3, with a third group given 500IU of each) either as supplementation or orange juice fortification have noted equivalence between the two forms, and elsewhere supplementation of 1,000IU daily in vitamin D deficient persons has noted a difference in circulating hormone levels but no differences in parathyroid hormone.
In a few cases, supplementation of vitamin D2 have increased levels of the molecule 1,25-dihydroxyergocalciferol yet reduced circulating levels of 1,25-dihydroxycholecalciferol.
Other studies using daily dosing of 1,600IU for a year, 4,000IU over 14 days,, and for intermittent doses 50,000IU one monthly for a year or a one time dose as well as acute doses of up to 300,000IU D3 have also been noted to be more effective than D2, and according to a meta-analysis the difference in efficacy between D3 and D2 is more notable with bolus supplementation than with daily supplementation.
When comparing D2 against D3 (on an IU basis), there is mixed evidence for both supplements suggesting either bioequivalence (no significant difference) or a superiority of vitamin D3. As there are no studies suggesting that D2 is more efficient, it would be prudent to choose D3 supplementation.
D2 is synthetically produced (for the purpose of supplementation) from irradiation of ergosterol (from mold ergot) whereas D3 is synthesized from 7-dehydrocholesterol.
D2 and D3 are synthesized (for supplementation) by different means, and there appear to be differences in their stability, with D3 being more stable than D2, in powder form.
Currently, the generally accepted terms to refer to different possible 'states' of Vitamin D status are:
Deficiency (Less than 30nmol/L or 12ng/mL, leading to rickets in children and osteomalacia in adults)
Insufficieny (between 30-50nmol/L, the range of 12-20ng/mL)
Adequate (between 50-125mol/L, or 20-50ng/mL)
High (above 125nmol/L or 50ng/mL)
(where 2.5 nmol/L is approximately equal to 1 ng/mL, and 1 microgram (mcg or µg) of Vitamin D3 is approximately 40IU)
The above are generally accepted guidelines for vitamin D, and will be used as reference for this article. 'Optimal vitamin D levels' is not a legitimate term to refer to one of these four ranges.
A target of 75nmol/L has been considered to as optimal for bone health in older individuals and bone-related conditions such as dental health or reducing the risk of falls and fractures in the elderly. This also appears to be a target for colorectal cancer prevention.
Even in studies that recommend higher oral intakes (5,000IU), the end goal still appears to be around 75-80nmol/L.
Recommended levels of vitamin D are roughly 75nmol/L (30ng/mL) for some conditions.
Vitamin D deficiency appeared to rise from the year 1988 onwards; using 75nmol/L as a cut-off, the percentage of the population below this level increased from 55% to 77% in 2004. It appears to have somewhat stabilized, with 79% below 80nmol/L.
Deficiency rates in the population appear to have increased over the past two decades but they may have stabilized in recent years.
Using other cut-offs, in 2010 29% of the American population was below 50nmol/L (clinical insufficiency) and 3% below 20nmol/L (clinical deficiency). These levels vary by season, and using 50nmol/L as a cut-off again, 11% of people are below this line at the end of summer (testing area of Boston, latitude 42°N), while at the end of winter this number increases to 30%. In a slightly more northern region on the other side of the globe (Britain, latitude 53.1°N) rates of deficiency still increase. When assessing the serum levels of 25, 50, and 75nmol/L the percentage of the population having less than these values increases from 3.2%, 15.4%, and 60.9% at the end of summer to 15.5%, 46.6%, and 87.1% at the end of winter. Estonia (59°N) has the percent of the population scoring below 25nmol/L and 50nmol/L recorded at 8% and 73% at the end of winter, respectively.
Vitamin D deficiency still occurs in locations closer to the equator. One study in Isfahan City, Iran (32°N) had the percent of the population being recorded at below 25,50, and 75nmol/L at 26.9%, 50.8%, and 70.4%, respectively. Cultural and Religious issues may come into play with this study, as the population consisted of both sexes and included women who wear religious clothing in public in this region. Southern Florida (Miami, 25°N) has recorded 38% and 40% of men and women, respectively, at below 50nmol/L.
Despite the above importance on latitude, at least one study has suggested that this may only account for one fifth of the variance seen.
Latitude plays an important role, but deficiency (when defined by serum levels of 25nmol/L or below) and insufficiency (50nmol/L) are prevalent worldwide.
Deficiency is extremely common in medical inpatients, with 22% of patients having serum levels below 20 nmol/L and 57% having levels below 37.5 nmol/L in one study.
Finally, some studies that compare quartiles of Vitamin D levels (dividing the population in to quarters based on the amount of Vitamin D that circulates) find that 50.3% of African Americans are in the lowest quartile of Vitamin D levels (in this study, below 17.3ng/mL) and 7.8% in the highest quartile (32.1%); white people had 9.5% in the lowest quartile and 43.5% in the highest quartile, with Mexican-Americans and all others being split approximately 20%/20% on these quartiles. These results suggest the reduced synthesis rates of vitamin D associated with darker skin hold practical relevance.
Approximately 1000IU daily is needed for 50% of the population to reach 75nmol/L, with 1700IU needed for 95% of the population to reach 75nmol/L. Despite these doses, the human body appears to be able to metabolize more than these levels (up to 3000-5000IU in men) and the body tends to stop solar synthesis (when the UV index is greater than 3) of Vitamin D at a level roughly equivalent to 10,000 IU.
Generally, 2,000IU should be sufficient to meet the needs of most individuals completely, with doses between 2,000-10,000IU not necessarily providing more benefit overall, but not being toxic either.
One meta-analysis of 76 trials has been conducted on serum Vitamin D levels (of people over 50 taking either D2 or D3) with variable daily doses of vitamin D of 5-53.5mcg in most trials with two trials using 124-250mcg daily or 225mcg. When dividing trials by how much vitamin D was supplemented, 10mcg was associated with an average increase of 9ng/mL and an interquartile range (IQR; 25th-75th percentile) of 7.2-14.8ng/mL with double the oral dose (20mcg) being associated with an average serum increase of 12.9ng/mL and an IQR of 9.2-20.4ng/mL. This study calculated (based off meta-analysis) that a predicted increase of 0.78ng/mL (1.95nmol/L) per microgram of Vitamin D3 daily supplement is to not exceed 20mcg (in older adults without calcium supplementation), and similar results have been noted with another review noting that 100IU of Vitamin D3 increases serum Vitamin D by 1-2nmol/L and an increase of 10-25nmol/L with 1,000IU. Despite the first meta-analysis only being conducted in people over 50, this general dose-response over a period of time appears to exist for all age groups.
The main predictors of serum vitamin D levels were form used (vitamin D3 outperforming vitamin D2) and the dose of vitamin D used, which were both statistically significant; coingested calcium supplements and baseline serum vitamin D (lower resulting in a greater increase after supplementation) both trended to increase bioavailability but were not statistically significant. This study could not assess age or gender due to confounds.
In regards to dosing, lower oral doses seem more efficient at increasing serum vitamin D levels, with higher doses still increasing serum levels, but not as much (reduced absorption at higher doses), which underlies variability between individuals. At the lower ranges of oral dosing, vitamin D appears to be linearly increased, with each 100IU increasing serum by approximately 1-2nmol/L and 1,000IU being implicated in the range of 10-25nmol/L (and 2,000IU 20-50nmol/L).
Vitamin D was found to be best absorbed with a low-fat (11 g of fat) meal compared with both a high-fat (35 g of fat) meal and no meal. Further research by the same group found that fat is indeed a central macronutrient for increasing absorption of vitamin D; peak vitamin D plasma levels were found to be 32% higher in subjects consuming a meal with 30 g of fat compared to a fat-free meal of otherwise similar protein content. The composition of the fat (polyunsaturated versus monounsaturated) did not affect absorption.
Vitamin D is best absorbed with a meal, preferrably one with a little fat in it.
Sometimes acute boluses are used on a weekly or monthly basis, and toxicity has been associated with a bolus of 300,000IU.
Preloading a large bolus of Vitamin D (in this study, 50,000-100,000IU) prior to a maintenance period does not appear to provide more benefit than simply taking a daily maintaining dose.
Toxicity has been noted at very high daily doses of vitamin D, which are about 10-fold higher than the aforementioned 2,000IU daily dose.
When comparing vitamin D2 against D3, one meta-analysis noted that when they were controlled on a weight basis (micrograms rather than IU) that vitamin D3 was associated with an average serum level increase, which was 4.29ng/mL higher than vitamin D2.
Vitamin D3 appears to be a more reliable form of supplemental vitamin D, relative to D2, for increasing serum levels to an adequate range.
Mortality in research tends to refer to death rates from all causes, and its association is established through survey and epidemiological research, since death is infrequent. Causation is almost never established in these instances. Vitality is a general, and mostly colloquial, term used to refer to physical capacity and well being, and is independent of the actual lifespan. Longevity is sometimes seen as a combination of avoiding mortality while promoting vitality.
Low vitamin D levels are independently associated with an increase in all-cause mortality in the general population. Smaller samples sizes (derived from NHANES survey data) suggest that this association with mortality is not influenced by gender or by race, and is only dependent on circulating levels of vitamin D, although the higher frequency of low serum vitamin D in blacks (due to less skin synthesis rates) has been shown to increase the overall risk of mortality in an elderly cohort. Another analysis of the NHANES data found that a dose-dependent reduction in all-cause mortality of 6-11% per 10nmol/L increase in circulating vitamin D levels, although this association was borderline insignificant once confounders were taken into account (an increase of 10nmol/L can be obtained by ingestion of approximately 1000IU per day).
When comparing the lower circulating levels of vitamin D against the higher circulating levels in cohort studies, a relationship between risk of death and lower circulating levels are seen; one study noted that those with 50nmol/L (20ng/mL) or less had a relative risk (RR) of all-cause mortality of 1.65. Another study noting that their lowest measured quartile of 17.8ng/mL was independently associated with a 26% greater risk of death relative to the highest quartile (whose serum levels were greater than 32.1ng/mL). Furthermore, in the non-institutionalized elderly, frailty was 1.98-fold higher in the lowest quartile when compared to the highest quartile, and was positively associated with mortality; the lowest quartile had a 2.98 greater relative risk of death compared to the highest quartile. This is important to note as it is suspected that the most benefit against mortality from vitamin D supplementation is a reduction in frailty of the elderly.
A major systematic review consisting and meta-analysis of clinical trials (mainly in the elderly) assessing all forms of vitamin D supplementation has confirmed these observational studies findings of vitamin D's effect on all-cause mortality, finding a relative risk (RR) of all-cause mortality with supplementation of 0.97 (95% confidence interval 0.94-0.99); when specific forms of vitamin D were analyzed, it was found that only vitamin D3 conferred a significant risk reduction (RR of 0.94, 95% confidence interval of 0.91-0.98).
Many observational studies have found an inverse correlation between serum vitamin D levels and all-cause mortality. Clinical trials examining the effect of supplementation on mortality seem to confirm a slight reduction in all-cause mortality, especially in the elderly population. Vitamin D3 supplementation seems to be the most effective form of supplementation with regards to reductions in mortality.
In general, supplementation of 1,000 IU vitamin D3 daily (seen as a lower dose estimate) has been estimated to reduce the medical costs of cancer treatment by about $16-$25 billion by exerting a general protective and preventative effect.
One study investigating the offspring of nonagenarians (90 or older) with one living sibling (to assume genetic longevity) noted that, when looking at the vitamin D levels of their offspring, that the levels of vitamin D were not elevated beyond that of control; their marital partners. Specifically, the offspring of nonagenarians had 6% less vitamin D and significantly reduced frequency of the CYP2R1 gene that predisposes persons to higher Vitamin D levels.
It is plausible that vitamin D could be a biomarker for something else that is associated with longevity, although no evidence exists to suggest vitamin D can enhance lifespan, just, indirectly of mortality, reduce the risk of premature death.
Vitamin D3 exerts most of its effects either directly via its receptor (the Vitamin D Receptor, known as VDR) acting in the nucleus and promoting protein synthesis, or by a 'non-genomic' action which may still be through the VDR localized not in the nucleus but in cell membrane caveolae. 
While classically the VDR was thought to exert its action solely in the nucleus by mediating genomic transcription, it was later shown to translocate from the nucleus towards the cytoplasmic membrane when activated by hormonally active Vitamin D3, suggesting that VDR may play a role in both the genomic and non-genomic actions of vitamin D. Additional evidence for the dual role of the VDR comes from another study in spermatids, which noted that activation of the VDR induced changes in the cell that were abolished by VDR inhibitors yet were not genomic in nature. At the same time, it seems that there are additional membrane-bound non-VDR receptors for vitamin D which may also play a role in the non-genomic actions of vitamin D, such as the 1,25(OH)2D3 Membrane-Associated, Rapid-Response Steroid-binding protein (1,25D3-MARRS, also known as Endoplasmic Reticulum stress Protein 57, or ERp57), which has no sequence similarity to the classical VDR. These two proteins can sometimes work together; for instance, both the VDR and 1,25D3-MARRS have been observed to work in tandem in the case of photoprotection. 
Vitamin D exerts its effects secondary to activating its receptors. The classical Vitamin D Receptor can act both genomically and non-genomically, while another receptor known as 1,25D3-MARRS can work non-genomically.
Aromatase is an enzyme that is expressed in multiple tissues; one of its primary functions is to produce estrogen locally, which can have a beneficial effect on bone growth and matainance, but can encourage growth of breast cancer tumors. The hormonally active form of Vitamin D3 appears to be a tissue-specific aromatase modulator, increasing its expression in osteoblasts and fibroblasts in bone, as well as adrenocortical and prostate cancer cells (a beneficial effect), and decreasing it in breast cancer cells. Vitamin D3 also appears to induce aromatase activity in placental cells.
A knockout mutation of vitamin D receptors in mice reduced the actions of the aromatase enzyme (CYP19) to varying degrees; activities in the ovaries, testes, and epididymus were reduced by 24%, 58%, and 35% concomitant with reduced gene expression. This may be secondary to disrupting calcium metabolism, since supplementation of calcium to these mice normalized actions of aromatase.
In MCF-7 cells (a breast cancer cell line), 100nM of active Vitamin D3 can reduce aromatase mRNA to 60% of control and almost abolish cultured cell growth in response to incubation of alcohol, which proliferates MCF-7 cells.
Interestingly, a synthetic analogue of Vitamin D3 (known as EB1089) inhibits aromatase via a currently novel inhibitory pathway. This is an analogue that has also shown efficacy in reducing breast cancer in animal models.
Vitamin D appears to be a tissue-selective aromatase modulator, able to increase or decrease aromatase activity dependent on the tissue in question.
In people using pharmaceutical-grade aromatase inhibitors (usually breast cancer therapy), vitamin D levels may be depleted, which predisposes them to musculoskeletal symptoms. although this does not appear to be the most predictive biomarker, with the intentional depletion of estrogen (as treatment for breast cancer) being most predictive and thought to be causative. However, the incidence of joint pain was significantly reduced (odds ratio 0.12, 95% confidence interval 0.03-0.40) in those who achieved serum levels greater than 40 ng/mL with supplementation of 800IU vitamin D daily followed by 16,000IU twice monthly. Higher doses (in this study, 50,000IU weekly of Vitamin D2) appear to be more effective in reducing subjective reports of joint pain.
Vitamin D may attenuate joint pain induced by potent Aromatase Inhibitors (AIs). This may be secondary to potent AIs depleting vitamin D.
The most plausible reason for joint pain with AI usage remains a depletion of estrogens, where depletion of oestrogen is highly associated with induction of athralgia and joint pain.
Neurons in the brain appear to express the enzyme required to bioactivate vitamin D, with the highest concentrations of this enzyme occuring in the hypothalamus and dopaminergic neurons of the substantia nigra. Most cells express the Vitamin D Receptor (VDR), but it appears to be absent in the nucelar basalis of Meynert and Purkinje cells in the cerebellum, and is expressed in glial cells of the brain.
Calcium metabolism appears to underlie neuronal cell death via excitotoxicity, and hormonally active vitamin D confers a protective effect in vitro at physiologically relevant concentrations up to 100nM but not above. This mechanism of protection appears to be mediated via a downregulation of L-type voltage-sensitive Ca2+ ion channels, an effect which has also been seen in bone cells. These L-type channels have been implicated in excitotoxicity.
One study in rodents have observed such neuroprotective effects in vivo, noting a slower rate of decline in neuronal density in the hippocampus during aging in long-term treatment with vitamin D, indicative of preservation of neuronal cells.
Vitamin D appears to be able to modulate a subset of calcium channels on neurons, and control cell death via excitotoxicity based on in vitro an animal data.
In vitamin D-sufficient young adults (30.64 +/- 7.96 ng/mL or 76.6 +/- 19.9 nmol/L), the addition of 5000 IU vitamin D to the diet for one month failed to influence working memory, response inhibition, or cognitive flexibility despite serum levels of vitamin D being increased to an average 39 ng/mL (98 nmol/L). Anxiety and anger ratings were similarily unaffected. However, an 18-week intervention in healthy adults reported that supplementing 4000 IU of vitamin D significantly improved visual memory but not verbal memory, executive function, or working memory. Average vitamin D levels were increased from 25 ng/mL (64 nmol/L) to 52 ng/mL (130 nmol/L).
A inverse correlation between vitamin D and depression (lower vitamin D status being related to more depressive symptoms) was first reported in 1979 and associations have resurfaced in those at risk for cardiovacular incidents, fibromyalgia, and in women during the winter.
Vitamin D blood levels are inversely correlated with depressive symptoms in some cohorts.
One study noting a correlation between insufficient vitamin D (35-50nmol/L) and depressive symptoms in 54 adolescents also noted an attenuation of symptoms following supplementation of 4000IU for one month and 2000IU for the next two months, where serum vitamin D was increased to 90-91nmol/L (high range of sufficient); a 42% reduction as assessed by WHO-5 rating scale was seen, and improvements seemed universal.
In a randomized, controlled clinical trial high-dose vitamin D supplementation was shown to reduce depressive symptoms in individuals with major depressive disorder (MDD), a condition associated with persistent depressed mood and loss of interest in normally pleasurable activities. In a randomized, double-blinded experimental model, 40 subjects received either a single 50,000 IU vitamin D capsule per week (n=20) or a placebo (n=20) for 8 weeks. Testing with the Beck Depression Inventory (BDI), where a lower score indicates less depressive symptoms, indicated that patients receiving the vitamin D supplement had significantly reduced depressive symptoms at the end of the 8 week trial relative to placebo (-8.0 for vitamin D and -3.3 for placebo, p=0.06).
In contrast, a number of studies have reported that vitamin D fails to alleviate depressive symptoms in various populations. Improvements in depressive symptoms have been noted elsewhere in a small pilot study of women with low (less than 40ng/mL) vitamin D levels and depressive symptoms in the winter months. Conversely, another study noted that with young adults (21.8+/-2.9yrs) with baseline serum levels of 76.6+/-19.9nmol/L (sufficient) given 5,000IU daily for a month, there is no reduction of depression despite an increase of serum vitamin D to 98nmol/L. A failure to reduce depressive symptoms has been noted elsewhere in post-menopausal women given calcitriol supplementation (an active hormonal form of vitamin D).
While some correlational evidences suggests that there may be a link between vitamin D levels and depressive symptoms, the evidence that vitamin D supplementation can help with such symptoms is mixed, and the positive results tend to be in populations with low vitamin D to begin with.
Multiple Sclerosis (MS) is a neurological and proinflammatory condition affecting the myelin sheath of neurons, and is the most common neural inflammatory condition in developed nations. A putative connection between multiple sclerosis and vitamin D comes from associations between MS and latitude, which also correlates highly with vitamin D and sun exposure during childhood being inversely related to MS risk in adulthood. No link between maternal vitamin D levels during gestation and risk of MS in offspring has been found, however. Evidence exists suggesting protective effects from sun exposure, with one observational study establishing a protective connection between multiple sclerosis and vitamin D serum levels directly.
Multiple Sclerosis (MS) prevalence is correlated with latitude and sun exposure, both of which are in turn correlated with vitamin D levels.
In animal models of experimental autoimmune encephalomyelitis (a model of MS), Vitamin D can both reduce the occurrence of and slow the progression of the disease. Furthermore, synergism may exist between vitamin D and the standard MS therapy, interferon-beta. The benefits of vitamin D may be related to attenuating demyelination from neurons in vitro.
Vitamin D appears to exert protective effects in an animal model of multiple sclerosis.
Alzheimer's Disease (AD) is a neurological condition associated with deficient cholinergic signalling and synaptic function; the mechanisms of Vitamin D appear to hold therapeutic promise for Alzheimer's Disease. Similar to other neurological conditions, Vitamin D in serum appears to be inversely related to AD risk; the risk appears to be a bit lesser than Parkinson's, which have lower serum levels of Vitamin D. Vitamin D receptor polymorphisms have been found in AD, and low serum Vitamin D in older individuals has some predictive validity (assessed by subgroup analysis; small sample).
Although weaker than other correlations, there does appear to be some correlation between Alzheimer's disease and vitamin D.
Vitamin D has been found to stimulate immune cells to catabolize amyloid-β protein aggregates in vitro.
Vitamin D tends to be inversely associated with risk and its receptor a candidate for Parkinson's therapy as there appears to be an association with one of its polymorphisms and PD risk. Interestingly, persons with Parkinsons appear to have less circulating Vitamin D than do age-matched counterparts with Alzheimer's and appears to exist prior to diagnosis of PD (during early disease pathology) which tends to decline further as the disease progresses.
Low serum vitamin D is correlated with increased risk of Parkinson's Disease (PD) and further associated with the severity of the disease state.
It has been hypothesized that due to the stabilizing effect of Vitamin D on neurons, that deficiency could predispose neurons to toxic stressors. One study that induced Vitamin D deficiency in mice prior to a toxic insult (seen as a method of inducing PD) did not find an exacerbation of damage during deficiency, however. This is in contrast to previous studies in vitro and in animals where excess levels of Vitamin D3 protected neurons from stressors up to 100ng/mL (higher concentrations associated with toxicity).
Mechanistically, vitamin D may protect neurons from stressors, although a deficiency does not appear to inherently increase the risk of neuronal damage on the cells associated with Parkinson's disease.
Currently, there are no clinical trails assessing people with PD and the pathology of PD (cognitive outcomes). Some studies are assessing hip fracture rates, which are covered in the Bone Health section.
It has been hypothesized that Vitamin D deficiency is central to a recent 'epidemic' of disturbed sleep patterns that roughly correlates with when the majority of humans began to spend most time indoors.
Some studies in humans suggest improved sleep quality with Vitamin D, but are either done in persons with Chronic Pain being normalized to sufficient levels from deficient or are confounded with other nutrients such as Magnolia Officinalis and Soy Isoflavones. Both studies showed promise, but no controlled trials have been conducted with vitamin D in isolation.
It is plausible that a vitamin D deficiency can hinder sleep quality, and normalizing vitamin D status can normalize sleep function to a degree. There is limited evidence for this relationship at this time.
Vitamin D levels above 85nmol/L (34ng/mL), which are above sufficient, have been anecdonately noted to impair sleep quality, as assessed by REM.
Those with insufficient Vitamin D levels are significantly more likely to develop heart disease than those who do not. 
At least one systemic review concludes that 1000IU of Vitamin D daily can reduce the risk of cardiovascular disease based on systemic biomarkers,
However, some individual trials have come up with null results. In one such trial, healthy postmenopausal women given 400IU or 1000IU Vitamin D for a period of 1 year saw no significant benefit to cardiovascular disease risk. In another such trial, people who had vitamin D insufficiency but were otherwise healthy saw no change in several cardiovascular disease markers (blood pressure, LDL-C, HDL-C) when supplemented for 12 weeks with 800 IU vitamin D.
Correlational studies suggest that low vitamin D levels may associated with cardiovascular disease risk. Some, but not all, interventional studies have also found that vitamin D supplementation at moderate to high doses may reduce the risk of cardiovascular disease.
Vitamin D was first sought out in relation to blood pressure when it was noted that UV light was able to reduce blood pressure in the general population. In susbequent studies using VDR-receptor knockout mice (mice lacking the Vitamin D receptor, to see what happens in a model of no Vitamin D receptor activity) the mice appear to display increased blood pressure possible secondary to increased serum angiotensin, androsterone, and tissue renin.
Vitamin D appears to suppress Renin via activation of the Vitamin D receptor. Inducers of Renin production tend to work via cAMP as the Renin promoter in the nucleus has many cAMP sensitive response elements, and it was found that Vitamin D can directly suppress renin gene expression via a vitamin D response element that is present in the renin gene.
Vitamin D appears to be a negative regulator of renin expression and reduces activity of the Renin-Angiotension System (RAS). A deficiency of vitamin D lessens the suppression and increases activity of the RAS system, which subsequently increases blood pressure.
A meta-analysis on the topic of Vitamin D and blood pressure investigating eleven trials of persons with hypertension found that noted a reduction in systolic blood pressure that failed to reach statistical significance (95% CI of -8.0 to 0.7) with a small but statistically significant reduction in diastolic blood pressure (95% CI of -5.5 to -0.6) and noted that Vitamin D failed to exert any blood pressure reducing effects in normotensive persons.
One study using 1mcg of active Vitamin D hormone noted that 4 months of treatment was able to reduce diastolic blood pressure in persons with essential hypertension, but only in those with low-renin hypertension.
800IU of Vitamin D3 (with 1,200mg Calcium) has been noted to decrease systolic blood pressure 9.3% in elderly women over 8 weeks, which was to a greater extent than active control (1,200mg Calcium in isolation). However, another study using 800 IU for 12 weeks in healthy vitamin D-insufficient people found no effect on blood pressure.
The reduction in blood pressure associated with vitamin D supplementation in humans appears to be weak in magnitude and possibly dependent on some alteration in metabolism (which would cause hypertension), but it does appear to reduce blood pressure slightly in some people with hypertension.
The blood pressure lowering effect is most likely not strong nor reliable enough to be considered monotherapy to reduce blood pressure, but might be a good complement to other medications.
In mice lacking the Vitamin D receptor (VDR-/- mice), they appear to have cardiac hypertrophy (up to 22% greater than control mice) as a side-effect which is due to an increase in Angiotension II (AGE II) that has been noted in VDR-/- mice and is known to induce cardiac hypertrophy. Treatment with Captopril, an ACE inhibitor that blocks production of AGE II, reduces cardiac hypertrophy in Vitamin D deficient mice.
Mice lacking the vitamin D receptor appear to have cardiac enlargement due to increased serum angiotension II and increased activity of the RAS system.
Supplementation with 800 IU vitamin D for 12 weeks in people with low vitamin D status but who were otherwise healthy led to small drops in red blood cell count, hemoglobin, and hematocrit when compared to placebo.
Vitamin D status is associated with arterial stifness and vascular dysfunction in otherwise healthy humans. 
Vitamin D levels have been associated with brachial flow-mediated dilation in Type 2 Diabetics. This indicates it plays an important role in heart function, especially in people with disease states. 
Vitamin D status might in part help explain the difference in risk of the development of peripheral arterial disease in darker populations (who are more likely to be Vitamin D deficient). 
Supplementing 3320IU/d of Vitamin D helped improve several health markers of cardiovascular health during weight loss 
It has been noted that endoplasmic reticulum (ER) stress (oxidative stress on a certain organelle in a cell) is pivotall for foam cell production via damaging the macrophage secondary to cholesterol accumulation; macrophages isolated Vitamin D deficient mice appear to be characterized by higher levels of ER stress normalizing this stress with agents known to reduce ER stress normalized the increased foam cell production seem in Vitamin D deficient mice. This suggests that Vitamin D acts to reduce artherosclerosis by reducing oxidative ER stress in macrophages and subsequently preventing foam cell formation.
These effects are mediated by the Vitamin D receptor, and may be related to a shift of Macrophage phenotype from M2 to M1, which appears to be less artherogenic. M2 macrophages (induced by IL-4, IL-10, or immunocomplex) are known to be anti-inflammatory but have a higher potential to accumulate lipids and form artherogenic foam cells while IFN-γ induced M1 cells tend to be proinflammatory and recruits more immune cells but expresses receptors that facilitate macrophage plaque egression and are anti-artherogenic.
Vitamin D appears to act to suppress artherogenesis by reducing oxidation in macrophages (immune cells) at the level of the endoplasmic reticulum (ER). Stress at the ER causes an accumulation of lipids and cholesterol, which turn into macrophages and subsequently into 'foam cells', which then contribute to plaque. Vitamin D attenuates this process.
Vitamin D levels have been inversely correlated with insulin resistance in non-diabetic adults 
Vitamin D levels were inversely associated with serum levels of insulin in adolescents in the United States. People with a serum level of 75nmol/L or more had approximately 24% lower levels of insulin on average than those with lower Vitamin D levels. 
Vitamin D levels have an inverse correlation with insulin resistance in both obese and non-obese children. 
Vitamin D levels are associated with insulin sensitivity even in non-diabetic adults. 
During a glucose tolerance test, subjects who were considered to have insufficient levels of Vitamin D (50nmol/L or less) were more likely to be insulin resistant and have beta cell dysfunction than those who had higher levels of serum Vitamin D. 
Supplementation of Vitamin D has been found to improve insulin sensitivity in people who were found to be deficient in Vitamin D, and improve their tolerance to a glucose tolerance test. 
In a randomized, controlled clinical trial high-dose vitamin D supplementation was shown to improve markers for glucose homeostasis in individuals with major depressive disorder (MDD). In a randomized, double-blinded experimental model, 40 subjects received either a single 50,000 IU vitamin D capsule per week (n=20) or a placebo (n=20) for 8 weeks. Subjects receiving the vitamin D supplement had significantly reduced serum insulin levels (-3.6 μIU/ml, compared to + 2.9 μIU/ml for placebo, P = 0.06), decreased insulin resistance as estimated by the homeostasis model assessment (HOMA, -1.0 compared to +0.6 for placebo, P= 0.02), and improved beta cell function as estimated by HOMA (-13.9 compared with +10.3 for placebo, P= 0.03).
Decreased serum Vitamin D levels increase risk of the development of Diabetes. 
Higher Vitamin D levels prevent the occurence of Type 2 Diabetes. 
Low levels of Vitamin D are associated with complications of Type 1 Diabetes. 
Vitamin D supplementation improves outcomes of Type 2 Diabetes. 
It has been hypothesized that Vitamin D insufficiency is a possible contributor to obesity, based on the assumption that serum Vitamin D acts as a sunlight sensor and seasonal and its decline encourages consumption of energy; this consumption of energy to then increase body mass and decrease relative body surface area to confer a thermic advantage in cold environments according to Bergmann's Law. This study attempted to sum up evolutionary theory with the possible mechanism of activating the AgRP/NPY neural circuit while suppressing the POMC/CART circuit of energy intake (although did not provide evidence) with one comment in support of this hypothesis.
Elsewhere, it has been noted that Vitamin D levels are lower in obese persons when compared to controls of similar demographics including pregnant mothers which exists with an increase in serum parathyroid hormone, which Vitamin D normally suppresses. For every 1kg/m2 increase in BMI, it appears that serum Vitamin D is reduced 1.15% (and a 10% increase being related to 4.2% less Vitamin D).
There is a theory that states a deficiency state of vitamin D contributes to the obesity epidemic, but the reasoning is somewhat strained and dependent on caloric overconsumption. An association between lower vitamin D status and obesity has been noted in numerous trials.
One study in mice with 10 IU Vitamin D3 per kilogram of feed (relative to control with 1IU/kg) which increased serum vitamin D from around 175 to 425pg/mL noted that fat mass increased independent of overall body weight gain associated with increased PPARγ expression (122% increase), TNF-α secretion (208% increase) and a suppression of UCP2.
In humans, supplementation of 4000IU of Vitamin D3 daily in conjunction with resistance training and a post workout beverage (same in both groups) there was a trend to increase fat mass accrual over the experimental period but this failed to reach significance. Elsewhere, a trial in overweight/obese women given 1,000 IU of Vitamin D daily for 12 weeks resulted in a significant reduction in fat mass (2.7+/-2.1kg lost with Vitamin D, 0.47+/-2.7kg lost in placebo) independent of body weight changes.
There is either no significant effect on fat mass overall or a possible pro-obesogenic effect associated with vitamin D supplementation at high doses. The amount of literature investigating this is admittedly small.
The Vitamin D receptor (VDR) was thought to be expressed on the nuclear membrane which mediates genomic actions and there appears to be a cytoplasmic membrane receptor which can mediate nongenomic actions such as activation of Protein Kinase C (PKC) which is apparently coupled to a G-protein, Phospholipase D via the same G-protein, and Protein Kinase A2. However, these previous trials appeared to use general (rather than specific) immunostaining (chick monoclonal antibody 9A7 and rabbit polyclonal antibody C-20 both detecting receptors beyond the VDR) to find receptors and a more recent trial using precise VDR immunostaining failed to find any evidence for the expression of this receptor in skeletal muscle. Past studies using autoradiography which confirmed the presence of the VDR in intestinal enterocytes, osteoblasts, parathyroid cells, and distal renal tubules has also failed to detect the VDR in skeletal muscle.
There may not be any detectable vitamin D receptors on skeletal muscle tissue, despite a series of studies that suggest this. These appear to be research artifacts caused by inprecise immunostaining techniques.
The nuclear membrane and the actions of Vitamin D appear to be critical for functioning of muscle cells, as otherwise healthy mice who lack this receptor (VDR knockout mice) induces poor swimming ability and induce postural problems which are indicative of poor muscular performance (although these results also implicate the central nervous system and nerve health) as well as 20% smaller muscle diameter.
Despite the lack of vitamin D receptor expression directly on skeletal muscle cells, there appear to be impairments to physical function and reduced skeletal muscle hypertrophy associated with VDR knockout mice.
Skeletal muscle damaged through mechanical scraping showed improved migration when incubated with 10 or 100 nmol 1α,25(OH)2D3 but only the 10 nmol treatment lead to improved myotube number. Creatine kinase activity was also elevated in the 10 nmol treatment condition, above both 100 nmol and vehicle. These data together suggest that vitamin D may play a role in improved muscle recovery after damage, a finding that was tested in vivo in the same study and which is described below.
In vitro evidence suggests that vitamin D may improve muscle recovery after mechanical damage.
Supplementation of Vitamin D to correct a deficiency may improve Athletic performance in athletes. A serum Vitamin D level of 50ng/ml (125nmol/L) may be required to do so.
One intervention on sedentary overweight/obese adults given 4000IU of vitamin D daily in conjunction with a resistance training program noted that Vitamin D was assocaited with an increase in power output while placebo was not.
Another intervention on healthy young men found that 4000 IU of vitamin D daily for 6 weeks led to improved muscle recovery after damage induced by eccentric exercise of the quadriceps. The supplemented group was able to generate more torque at a speed of 60 degrees per second at 48 hours and 7 days after the exercise compared to placebo. However, there was no differences between the groups when measuring torque at a higher rate of 180 degrees per second.
When assuming an optimal level of 75nmol/L, one study in NFL players noted that up to 64% of athletes had deficient Vitamin D levels, with a correlation existing between players getting injured having less Vitamin D levels.
Osteoblasts themselves are capable to expressing CYP27B1 and converting inactivate vitamin D (25-hydroxycalciferol) into the active steroid form (1,25-dihydroxycalciferol).
The vitamin D receptor is expressed in osteoblasts where it is involved in controlling their proliferation. In particular, exposure of an osteoblast to vitamin D is known to suppress proliferation of osteoblasts associated with increasing the expression of osteocalcin, bone sialoprotein-1, and RANKL.
Vitamin D acting upon its receptor does promote mineralization of bone tissue.
In relatively young and otherwise healthy adults (18-44 years), vitamin D levels in serum are inversely related to fracture risk (military recruits of both genders) with no relation to with BMI nor smoking. When looking at levels of serum intake, there is progressively less risk associated with increasing vitamin D concentrations in the range of 20-50ng/mL ultimately reaching an odds ratio of 0.51 (half the risk at any point in time).
A literature review on the effects of calcium and vitamin D in youth noted that only one prospective study assessed vitamin D, and in this study 800IU vitamin D and 2,000mg calcium was supplemented to female Navy recruits over eight weeks which resulting in a reduction of stress fractures by 21% relative to placebo.
When examining stress fractures in youth, vitamin D is correlated with less risk for fractures. Interventions of vitamin D supplementation appear to further protect individuals from stress fractures.
Trials in elderly indivudals measuring fracture rates have noted a decreased rate in persons with Parkinson's Disease with injections of active vitamin D hormone (reduction of eight fractures over 18 months to one),
Supplemental Vitamin D, in elderly cohorts, has been noted to reduce the risk of falls by greater than 20% relative to placebo in at least one meta-analysis on the topic; it was suggested that an oral dose of 700-800IU was effective, although one response noted that this dose was not shown to be optimal. Another meta-analysis noted that this risk reduction for falls holds true for persons with low serum Vitamin D, but when including persons with normal serum Vitamin D levels the protective effect dose not appear to be significant.
Supplementation of vitamin D appears to reduce the risk of falls in the elderly, but may only work in people with lower serum vitamin D levels at baseline.
Vitamin D levels in serum appear to predict sensitivity of a joint to heat pain, although they are not related to subjective measures of pain in osteoarthritis.
Serum vitamin D does not appear to correlate with osteoarthritic symptom presence or symptom severity.
In persons with knee osteoarthritis, supplementation of vitamin D3 at 2,000IU daily (dose escalation allowed to assure plasma levels above 36ng/mL) failed to reduce cartilage volume losses and pain symptoms of osteoarthritis (assessed by NSAID usage and WOMAC) relative to placebo.
Supplementation of vitamin D does not appear to significantly reduce joint pain associated with osteoarthritis.
Vitamin D at concentrations above 30ng/mL appears to be associated with less endoplasmic reticulum stress in monocytes, the stress which results in pro-oxidative events that induce adhesion of monocytes to the arterial wall.
Atopic dermatitis (AD) is a chronic inflammatory disease associated with dry, itchy skin and hypersensitivity to allergens. Although the exact causes of the disease are not completely understood, the disorder is associated with improper skin barrier function and over-activity of the immune system, affecting up to 20% of children and 3% of adults.
Given the current lack of understanding of the underlying causes of disease, treatments have been elusive. An emerging body of evidence has implicated low vitamin D levels in a number of cases, however, suggesting that vitamin D deficiency may be a factor.
Atopic Dermatitis, an inflammatory disease associated with dry, itchy skin, has been linked to vitamin D deficiency.
As is the case with many nutritional intervention studies, controlled trials examining the efficacy of vitamin D supplementation for AD have reported mixed results. To examine whether vitamin D supplements may help reduce the symptoms of AD, a systematic review and meta-analysis of the published literature was undertaken by Kim and Bae. Their initial search yielded 266 citations, of which 9 studies met selection criteria for the meta-analysis. The results of the meta-analysis indicated that patients supplementing with vitamin D (dosage range 800-4000 IU, depending on the study) showed a strong trend for reduced severity of AD symptoms. (As assessed in the study by a higher mean difference in the severity of AD symptoms compared to placebo (mean difference = -5.81, 95% CI: -9.03 to -2.59, P= 0.0004)). Although the meta-analysis indicated a strong trend toward reduction in symptoms with vitamin D supplementation, in no case did vitamin D cure the disease. This suggests that although low vitamin D is a factor linked to severity of symptoms, it is not the underlying cause of the disease.
Vitamin D supplementation showed a significant trend toward reduced atopic dermatitis (AD) symptoms across several different trials, suggesting that it may be particularly useful for reducing AD symptoms. Although safe and effective for alleviating AD symptoms, vitamin D is not a cure. More research is needed to uncover, and hopefully cure the underlying cause of disease.
Serum parathyroid hormone levels are inversely associated with Vitamin D until Vitamin D levels reach between 75 and 100 nmol/L, meaning serum levels below 75 nmol/L might indicate deficient levels of Vitamin D. 
In a cross-sectional study assessing correlations between androgens and Vitamin D, it was noted that (n=2299) Vitamin D was positively associated with androgen status (higher testosterone and lower SHBG) even after BMI, smoking, alcohol, beta-blockers and diabetes were controlled for. Additionally, significant correlations were found between androgen status and time of the year, when the sun exposure correlated with higher Vitamin D status, with the peaks (March, August) having 16-18% variation in testosterone levels, but these did not extend to SHBG. Additionally, when investigating serum levels of testosterone and their relationship to falls in the elderly, persons who take Vitamin D/Calcium supplements have significantly less risk additive to testosterone.
In a study on nondiabetics (n=165) where the men were analyzed as a specific subset (n=54), supplementation of 3332IU of Vitamin D daily for a year that was able to normalize serum Vitamin D (increase above 50nmol/L) noted improvements in testosterone (+25.2%), bioactive test (+19%), and free test (+20.2%) in men that were at the low-end of normal for testosterone previously; there was no change in placebo over this time period.
Vitamin D in serum appears to be positively correlated with overall androgen status, with sufficient levels of vitamin D acting to normalize testosterone. There is currently no evidence to suggest supraphysiological levels of vitamin D further enhances testosterone.
Vitamin D appears to regulate estrogen secondary to the aromatase enzyme (converting androgens into estrogens) where deletion of the Vitamin D receptor in mice reduces aromatase activity; calcium supplementation alleviates this suppression, suggesting that Vitamin D regulates aromatase activity via calcium metabolism. This study in receptor deficient mice noted reduced estrogen levels in serum.
Follicle-Stimulating Hormone (FSH) is increased in mice lacking the Vitamin D receptor, and this appears to be independent of calcium metabolism.
Vitamin D appears to be involved with Luteinizing Hormone (LH), as mice lacking the Vitamin D receptor (abolishing the effects of Vitamin D) appear to have elevated levels of LH; this is not helped with calcium supplementation, suggesting that these effects are independent of calcium metabolism.
When looking at observational studies, Vitamin D in serum appears to be inversely related to breast cancer risk (higher serum levels being associated with lower risk). Additionally, Vitamin D deficiency appears to be more prevalent in persons with breast cancer (diagnosed) and is similarly correlated with severity of breast cancer. This risk appears more prevalent in black women, where one survey suggested 42% of black women (USA) had serum levels below 15ng/mL (deficiency).
Breast cancer risk is inversely correlated with serum vitamin D levels, which suggests a link between the two.
One large intervention in postmenopausal women (n=36,282) where a smaller cohort had serum parameters of Vitamin D measured (n=1092) following ingestion of 400IU Vitamin D and 1000mcg Calcium daily for 7 years failed to find a significantly reduced risk or breast cancer associated with supplementation. This study reported a 28% increase in serum Vitamin D from 16.9ng/mL to 21.6ng/mL, an increase lower than expected according to a separate meta-analysis where 10mcg Vitamin D3 (400IU) should have increased serum levels to 25.5ng/mL. Another study has noted that 400IU Vitamin D was insufficient to increase serum levels of Vitamin D3 to adequate, suggesting this large study may have used a subactive dose (in addition to compliance issues, if the aforementioned meta-analysis is accurate in its assumptions).
Supplemental ingestion of 400-800IU daily appears to be inadequate to decrease the risk of breast cancer.
Women supplementing with 2000IU/d of Vitamin D may see up to a 50% reduction in the incidence of breast cancer,  and another study that noted while 1000IU daily was somewhat effective in improving Vitamin D status that weekly administration of 50,000IU was more effective.
According to one systematic review of epidemiological (survey) research (n=30), Vitamin D appears to be inversely correlated with risk of colon and colorectal cancers;
For colorectal cancer outcomes, people with serum levels of 82.5 nmol/L or greater had a 50% lower risk of developing cancer than those with a serum level below 30 nmol/L, and this risk reduction was observed with 2000IU supplemental Vitamin D.
Vitamin D appears to be inversely correlated with Prostate Cancer risk according to a systematic review of survey research, looking at 26 studies.
Doses as low as 600IU/d lower the risk of pancreatic cancer 
Vitamin D levels have been inversely associated with BMI in cancer patients. This might be an indicator that nutritional requirements of Vitamin D may be increased for larger individuals. 
In otherwise healthy adults, higher serum Vitamin D appears to be associated with improved lung function as assessed by forced exhalation.
A retrospective analysis of survey data between 1984 and 2003 in 626 adult men noted that those without Vitamin D deficiency (serum levels above 20ng/mL) and those who smoked had lower lung function than Vitamin D sufficient smokers, with no relation being found for non-smoking men. From this study, a protective effect on smoke-induced damage was hypothesized.
Children taking 1200IU of Vitamin D daily were 40% less likely to get the flu during the winter in this study conducted in Japan, while a Mongolian study on children and 300IU daily noted similar benefits.
Post menopausal African women taking 800 IU daily for 3 years were 3x less likely to get the flu than those who didn't. Those taking 800 IU daily for the first 2 years and then 2000 IU daily for the next year were 26x less likely to get the flu. This means supplementing with Vitamin D helps prevent the flu. 
One intervention using monthly injections of Vitamin D in otherwise healthy adults (200,000IU for the first two months, 100,000IU for 16 months) failed to find a significant reduction in the frequency of Upper Respiratory Tract Infections in the Vitamin D group among these 322 adults.
Lower Vitamin D levels are associated with an associated with a higher risk of active tuberculosis
In correlative research, Vitamin D appears to be correlated with sleep quality. In 190 persons with Obstructive Sleep Apnea (OSA), it was found that patients suffering from OSA had lower vitamin D levels than did the control group and that the lowest levels in the OSA group tended to have the most severe symptoms.
Vitamin D receptors (VDRs) as well as their regulatory enzymes, are expressed in the male reproductive tract; specifically the testes, epididymus and its glandular epithelium, seminal vesicles, and the prostate. This suggests direct actions on sex organs rather than indirect via regulating calcium, which also interacts with sexuality. Vitamin D receptors are also expressed on the spermatid itself, during the late stages of spermatogenesis. Male mice who lack the VDRs suffer from infertility and impaired sperm parameters.
Mechanistically, Vitamin D appears to increase calcium content in spermatids and can act directly on mature sperm cells. Incubation of a sperm cell with hormonally active Vitamin D3 increases calcium influx into the cell secondary to the VDR (due to being abolished by inhibiting the receptor), but not via genomic means and instead via Phospholipase C.
Mechanistically, vitamin D appears to act on the sperm itself (mature spermatid) and improve its motility while enhancing cell survival.
Vitamin D appears to positively correlated with sperm motility, with an assessment of 300 men indicating that those with lower Vitamin D in serum had significantly less seminal motility but that serum levels above 50ng/mL were also associated with less favorable seminal parameters, with an ideal range of 20-50ng/mL. Vitamin D appears to be an independent predictor of seminal parameters in both infertile and fertile men, with more statistical power in infertility.
25-50ng/mL (62.4-124.8nmol/L) appears to be an adequate range to preserve optimal seminal properties in otherwise healthy men, with both lower and higher serum ranges being associated with infertility.
Vitamin D deficiency rates appear to be higher in pregnant women than age matched non-pregnant women with deficiency or insufficiency affecting 97% of African-Americans, 81% of Hispanics, and 67% of Caucasians in one trial and another trial in South Carolina (Latitude 32N) noting 48% deficiency rates and 15% sufficiency rates.
This deficiency state has been linked to lower offspring birth weights, which appears to be of most importance in the first trimester, a higher risk of type 1 diabetes developing in the offspring, and higher asthma/rhinitus risk.
In regards to the mother, Vitamin D concentrations below 37.5nmol/L have been associated with an increased need for caesarean section rather than vaginal birth (about 4-fold increased odds). During the first trimester, lower Vitamin D (below 20nmol/L) appears to be associated with greater risk for bacterial vaginosis (57% of women below 20nmol/L; 23% of women above 80nmol/L).
There appears to be lower serum vitamin D in pregnant women, relative to non-pregnant women, with these lower concentrations of Vitamin D being associated with adverse effects for both mother and child. The deficiency appears to be more critical during the first trimester, and thus supplementing vitamin D in response to pregnancy notification (rather than as a daily preventative) may not be prudent and miss time-sensitive periods.
A one time dose of 200,000IU or a daily dose of 800IU during pregnancy has been noted to be insufficient to reach desired serum levels of Vitamin D in pregnant women with dose-dependent increases being noted with daily usage of 2,000-4,000IU (with an author conclusion that the latter is the recommended dosage).
A slightly higher intake of vitamin D may be required to reach sufficiency in pregnant women, relative to nonpregnant women and men, with intakes of up to 4,000IU being advised.
One study lasting 7 months in length using pharmaceutical levels of Vitamin D (100k IU weekly for a month, reduced to once monthly 100k IU for 6 months) noted that, in 20 persons with both Lupus and Vitamin D deficiency, that normalization of serum Vitamin D to 41.5+/-10.1ng/mL was associated with increased naive and regulatory T cell count and reduced memory B cells; possibly beneficial to Systemic Lupus Erythematosus.
One study noted that there was no significant association between Muscle Pain and Vitamin D deficiency when compared to control, but used a control of persons with osterarthritis.
In a cohort of Vitamin D deficient immigrants with complaints of non-specific musculoskeletal pain, once weekly doses of 150k IU Vitamin D3 (19.7mmol/L at baseline, 63.5 nmol/L at 6 weeks and 40nmol/L at 12) reported more reductions of symptoms of muscle pain then placebo (34.9%) and more persons reported an improved abiliy to walk stairs (21.0%), indicative of better muscle function.
Other studies on non-specific musculoskeletal pain note that 50,000IU of Vitamin D2 in 50 persons with diffuse skeletal muscle pain and serum levels belo 20nmol/L failed to significantly improve self-reported ratings of muscle pain (assessed by VAS), although the placebo appeared to elevate their serum Vitamin D levels (thought to have been from sunlight). This same dose was replicated with Vitamin D3 instead of D2, and noted greater improvements than placebo in a Fibromyalgia rating scale; no significant benefit was noted in severely deficient individuals however, and the Firbomyalgia subset was the only one showing improvement (with other subscales not showing significant improvement).
Vitamin D may aid fibromyalgic symptoms (pain and lack of function), but further study is needed.
Expression of the Vitamin D Receptor (VDR) in muscle cells decreases with age and Vitamin D deficiency may contribute to an age-related loss of muscle function in elderly persons as well as stand as an independent predictor of muscle strength and mass, with lower serum Vitamin D levels being associated with higher risk of Sarcopenia.
At least one intervention has noted preservation of type II muscle fibers in elderly persons associated with Vitamin D supplementation, and intervention has been associated with improved muscular function in Vitamin D deficiency women.
Vitamin D is potentially synergistic with Vitamin K supplementation as the two share many mechanisms of action in the cardiovascular and bone metabolism systems.
People with mean serum levels of 86.5 nmol/L had 65% better absorption of calcium than people with mean serum levels of 50 nmol/L. 
One Meta-Analysis that examined the link between Vitamin D and mortality (of which a decrease was seen mostly in elderly women) found that there was a higher risk for nephrolithiasis (Kidney Stones) when Vitamin D was paired with Calcium supplementation, with a RR of 1.17 and a CI of 1.02 to 1.34 from a sample size of 74,789. The increased risk of kidney stones and the decreased mortality rates were both only seen with vitamin D3 supplementation.
High serum vitamin D levels have been associated with esophageal Squamous dysplasia, as one study taking a cross-sectional study of 720 participants in China noted that subjects with Dysplasia had circulating vitamin D levels of 36.5nmol/L while those without dysplasia had 31.5nmol/L and the highest quartile had a relative risk of 1.86 compared to the lowest quartile.
- Sato Y, et al. Amelioration of osteopenia and hypovitaminosis D by 1alpha-hydroxyvitamin D3 in elderly patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. (1999)
- Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it. J Am Acad Dermatol. (2006)
- Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J. (2010)
- Calvo MS, Whiting SJ. Prevalence of vitamin D insufficiency in Canada and the United States: importance to health status and efficacy of current food fortification and dietary supplement use. Nutr Rev. (2003)
- Bowman SA. Beverage choices of young females: changes and impact on nutrient intakes. J Am Diet Assoc. (2002)
- Bartolucci G, et al. Vitamin D3 quantification in a cod liver oil-based supplement. J Pharm Biomed Anal. (2011)
- Monard AM, et al. Determination of the total vitamin D3 content of cod-liver oil by high-performance liquid chromatography. Pharm Acta Helv. (1986)
- Porojnicu AC, et al. Sun beds and cod liver oil as vitamin D sources. J Photochem Photobiol B. (2008)
- DRI DIETARY REFERENCE INTAKES FOR Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride.
- Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. (2006)
- Whiting SJ, Green TJ, Calvo MS. Vitamin D intakes in North America and Asia-Pacific countries are not sufficient to prevent vitamin D insufficiency. J Steroid Biochem Mol Biol. (2007)
- Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev. (2005)
- Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. (2005)
- Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci. (2004)
- Frederick JE, Lubin D. The budget of biologically active ultraviolet radiation in the Earth-atmosphere system. J Geophys Res-Atmos. (1988)
- Ainsleigh HG. Beneficial effects of sun exposure on cancer mortality. Prev Med. (1993)
- Engelsen O, et al. Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem Photobiol. (2005)
- O'Connor PA. Clouds, skin color, and rickets. Pediatrics. (1980)
- Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. (1988)
- Lubin D, Jensen EH, Gies HP. Global surface ultraviolet radiation climatology from TOMS and ERBE data. J Geophys Res-Atmos. (1998)
- Coney P, et al. Determination of vitamin D in relation to body mass index and race in a defined population of black and white women. Int J Gynaecol Obstet. (2012)
- Fiscella K, Franks P. Vitamin D, race, and cardiovascular mortality: findings from a national US sample. Ann Fam Med. (2010)
- Manson JE, et al. The case for a comprehensive national campaign to prevent melanoma and associated mortality. Epidemiology. (2000)
- Garland CF, Garland FC, Gorham ED. Could sunscreens increase melanoma risk. Am J Public Health. (1992)
- Diffey BL. Sunscreens as a preventative measure in melanoma: an evidence-based approach or the precautionary principle. Br J Dermatol. (2009)
- Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3. J Am Acad Dermatol. (1990)
- Matsuoka LY, et al. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab. (1987)
- Matsuoka LY, et al. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary study. Arch Dermatol. (1988)
- Vitamin D Metabolism, Mechanism of Action, and Clinical Applications.
- Holick MF, et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science. (1980)
- Vieth R. Why "Vitamin D" is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids. J Steroid Biochem Mol Biol. (2004)
- Holick MF. The use and interpretation of assays for vitamin D and its metabolites. J Nutr. (1990)
- Binkley N, et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. (2011)
- Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. (2006)
- Holick MF, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. (2008)
- Biancuzzo RM, et al. Fortification of orange juice with vitamin D(2) or vitamin D(3) is as effective as an oral supplement in maintaining vitamin D status in adults. Am J Clin Nutr. (2010)
- Glendenning P, et al. Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone. (2009)
- Tjellesen L, et al. Serum concentration of vitamin D metabolites during treatment with vitamin D2 and D3 in normal premenopausal women. Bone Miner. (1986)
- Trang HM, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. (1998)
- Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. (2004)
- Romagnoli E, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. (2008)
- Tripkovic L, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. (2012)
- DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. (2004)
- Huber W, Barlow OW. CHEMICAL AND BIOLOGICAL STABILITY OF CRYSTALLINE VITAMINS D2 AND D3 AND THEIR DERIVATIVES. J Biol Chem. (1943)
- Grady LT, Thakker KD. Stability of solid drugs: degradation of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) at high humidities and elevated temperatures. J Pharm Sci. (1980)
- Dietary Reference Intakes for Calcium and Vitamin D..
- Vitamin D Fact Sheet for Health Professionals.
- Visser M, et al. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr. (2006)
- Bischoff-Ferrari HA, et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. (2006)
- Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. (2009)
- Brock K, et al. Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women. J Steroid Biochem Mol Biol. (2010)
- Tangpricha V, et al. Vitamin D insufficiency among free-living healthy young adults. Am J Med. (2002)
- Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. (2007)
- Kull M Jr, et al. Seasonal variance of 25-(OH) vitamin D in the general population of Estonia, a Northern European country. BMC Public Health. (2009)
- Hovsepian S, et al. Prevalence of vitamin D deficiency among adult population of Isfahan City, Iran. J Health Popul Nutr. (2011)
- Levis S, et al. Vitamin d deficiency and seasonal variation in an adult South Florida population. J Clin Endocrinol Metab. (2005)
- van der Mei IA, et al. The high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitude. Environ Health Perspect. (2007)
- Thomas MK, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. (1998)
- Melamed ML, et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. (2008)
- Vieth R, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. (2007)
- Heaney RP, et al. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. (2003)
- Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. (1999)
- Autier P, Gandini S, Mullie P. A systematic review: influence of vitamin D supplementation on serum 25-hydroxyvitamin D concentration. J Clin Endocrinol Metab. (2012)
- Mastaglia SR, et al. Vitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic women. Eur J Clin Nutr. (2006)
- Corless D, et al. Do vitamin D supplements improve the physical capabilities of elderly hospital patients. Age Ageing. (1985)
- Cranney A, et al. Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr. (2008)
- Grant WB, Schuitemaker GE. Health benefits of higher serum 25-hydroxyvitamin D levels in The Netherlands. J Steroid Biochem Mol Biol. (2010)
- Barger-Lux MJ, et al. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int. (1998)
- Gertner JM, Domenech M. 25-Hydroxyvitamin D levels in patients treated with high-dosage ergo- and cholecalciferol. J Clin Pathol. (1977)
- Harris SS, Dawson-Hughes B. Plasma vitamin D and 25OHD responses of young and old men to supplementation with vitamin D3. J Am Coll Nutr. (2002)
- Pepper KJ, et al. Evaluation of vitamin D repletion regimens to correct vitamin D status in adults. Endocr Pract. (2009)
- Dawson-Hughes B, et al. Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation. J Bone Miner Res. (2013)
- Dawson-Hughes B, et al. Dietary fat increases vitamin D-3 absorption. J Acad Nutr Diet. (2015)
- Glade MJ. A 21st century evaluation of the safety of oral vitamin D. Nutrition. (2012)
- Papaioannou A, et al. A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses over daily supplementation. BMC Musculoskelet Disord. (2011)
- Ford ES, et al. Vitamin D and all-cause mortality among adults in USA: findings from the National Health and Nutrition Examination Survey Linked Mortality Study. Int J Epidemiol. (2011)
- Kritchevsky SB1, et al. 25-Hydroxyvitamin D, parathyroid hormone, and mortality in black and white older adults: the health ABC study. J Clin Endocrinol Metab. (2012)
- Smit E, et al. The effect of vitamin D and frailty on mortality among non-institutionalized US older adults. Eur J Clin Nutr. (2012)
- Bjelakovic G1, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. (2014)
- Grant WB, Garland CF, Gorham ED. An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day. Recent Results Cancer Res. (2007)
- Noordam R, et al. Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study. CMAJ. (2012)
- Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. (2014)
- Capiati D, Benassati S, Boland RL. 1,25(OH)2-vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells. J Cell Biochem. (2002)
- Blomberg Jensen M, Dissing S. Non-genomic effects of vitamin D in human spermatozoa. Steroids. (2012)
- Nemere I1, et al. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells. Proc Natl Acad Sci U S A. (2004)
- Sequeira VB1, et al. The role of the vitamin D receptor and ERp57 in photoprotection by 1α,25-dihydroxyvitamin D3. Mol Endocrinol. (2012)
- Simpson ER1, et al. Aromatase--a brief overview. Annu Rev Physiol. (2002)
- Yanase T1, et al. Aromatase in bone: roles of Vitamin D3 and androgens. J Steroid Biochem Mol Biol. (2003)
- Krishnan AV, et al. Tissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapy. Endocrinology. (2010)
- Lou YR1, Murtola T, Tuohimaa P. Regulation of aromatase and 5alpha-reductase by 25-hydroxyvitamin D(3), 1alpha,25-dihydroxyvitamin D(3), dexamethasone and progesterone in prostate cancer cells. J Steroid Biochem Mol Biol. (2005)
- Barrera D, et al. Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. J Steroid Biochem Mol Biol. (2007)
- Kinuta K, et al. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology. (2000)
- Lundqvist J, Hansen SK, Lykkesfeldt AE. Vitamin D analog EB1089 inhibits aromatase expression by dissociation of comodulator WSTF from the CYP19A1 promoter-a new regulatory pathway for aromatase. Biochim Biophys Acta. (2012)
- Christensen GL, et al. Sequential versus combined treatment of human breast cancer cells with antiestrogens and the vitamin D analogue EB1089 and evaluation of predictive markers for vitamin D treatment. Breast Cancer Res Treat. (2004)
- Larsen SS, Heiberg I, Lykkesfeldt AE. Anti-oestrogen resistant human breast cancer cell lines are more sensitive towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells. Br J Cancer. (2001)
- Waltman NL, et al. Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. Cancer Nurs. (2009)
- Cella D, Fallowfield LJ. Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat. (2008)
- Singh S, et al. Effect of baseline serum vitamin D levels on aromatase inhibitors induced musculoskeletal symptoms: results from the IBIS-II, chemoprevention study using anastrozole. Breast Cancer Res Treat. (2012)
- Prieto-Alhambra D, et al. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat. (2011)
- Rastelli AL, et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Res Treat. (2011)
- Zehnder D, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. (2001)
- Eyles DW, et al. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. (2005)
- Rothman SM, Olney JW. Excitotoxity and the NMDA receptor. Trends Neurosci. (1987)
- Choi DW. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. (1988)
- Choi DW. Excitotoxic cell death. J Neurobiol. (1992)
- Nicotera P, Orrenius S. The role of calcium in apoptosis. Cell Calcium. (1998)
- Brewer LD, et al. Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. J Neurosci. (2001)
- Meszaros JG1, et al. Down-regulation of L-type Ca2+ channel transcript levels by 1,25-dihyroxyvitamin D3. Osteoblastic cells express L-type alpha1C Ca2+ channel isoforms. J Biol Chem. (1996)
- Caffrey JM1, Farach-Carson MC. Vitamin D3 metabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. J Biol Chem. (1989)
- Weiss JH1, et al. The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity. Science. (1990)
- Uematsu D1, et al. Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage. Neurology. (1991)
- Landfield PW, Cadwallader-Neal L. Long-term treatment with calcitriol (1,25(OH)2 vit D3) retards a biomarker of hippocampal aging in rats. Neurobiol Aging. (1998)
- Dean AJ, et al. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trial. PLoS One. (2011)
- Pettersen JA. Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults. Exp Gerontol. (2017)
- Bech P, Hey H. Depression or asthenia related to metabolic disturbances in obese patients after intestinal bypass surgery. Acta Psychiatr Scand. (1979)
- May HT, et al. Association of vitamin D levels with incident depression among a general cardiovascular population. Am Heart J. (2010)
- Armstrong DJ, et al. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol. (2007)
- Shipowick CD, et al. Vitamin D and depressive symptoms in women during the winter: a pilot study. Appl Nurs Res. (2009)
- Högberg G, et al. Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation. Acta Paediatr. (2012)
- Sepehrmanesh Z, et al. Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial. J Nutr. (2016)
- van Loo HM, et al. Data-driven subtypes of major depressive disorder: a systematic review. BMC Med. (2012)
- Yalamanchili V, Gallagher JC. Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms. Menopause. (2012)
- Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. (2010)
- Compston A, Coles A. Multiple sclerosis. Lancet. (2008)
- Kurtzke JF, Beebe GW, Norman JE Jr. Epidemiology of multiple sclerosis in U.S. veterans: 1. Race, sex, and geographic distribution. Neurology. (1979)
- Simpson S Jr, et al. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry. (2011)
- Islam T, et al. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology. (2007)
- Dalmay F, et al. Multiple sclerosis and solar exposure before the age of 15 years: case-control study in Cuba, Martinique and Sicily. Mult Scler. (2010)
- Salzer J1, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology. (2012)
- Lemire JM, Archer DC. 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest. (1991)
- Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci U S A. (1996)
- van Etten E, et al. Novel insights in the immune function of the vitamin D system: synergism with interferon-beta. J Steroid Biochem Mol Biol. (2007)
- Wergeland S, et al. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS One. (2011)
- Lu'o'ng KV, Nguyên LT. The beneficial role of vitamin D in Alzheimer's disease. Am J Alzheimers Dis Other Demen. (2011)
- Annweiler C, Llewellyn DJ, Beauchet O. Low Serum Vitamin D Concentrations in Alzheimer's Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. (2012)
- Evatt ML, et al. Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol. (2008)
- Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson's disease. Neurology. (1997)
- Gezen-Ak D, et al. Vitamin d receptor gene haplotype is associated with late-onset Alzheimer's disease. Tohoku J Exp Med. (2012)
- Annweiler C, et al. Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study. Dement Geriatr Cogn Disord. (2011)
- Mizwicki MT, et al. 1α,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-β phagocytosis and inflammation in Alzheimer's disease patients. J Alzheimers Dis. (2013)
- Wirdefeldt K, et al. Epidemiology and etiology of Parkinson's disease: a review of the evidence. Eur J Epidemiol. (2011)
- Knekt P, et al. Serum vitamin D and the risk of Parkinson disease. Arch Neurol. (2010)
- Butler MW, et al. Vitamin D receptor gene as a candidate gene for Parkinson disease. Ann Hum Genet. (2011)
- Kim JS, et al. Association of vitamin D receptor gene polymorphism and Parkinson's disease in Koreans. J Korean Med Sci. (2005)
- Evatt ML, et al. High prevalence of hypovitaminosis D status in patients with early Parkinson disease. Arch Neurol. (2011)
- Sato Y, et al. Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients. Mov Disord. (2005)
- Evatt ML. Beyond vitamin status: is there a role for vitamin d in Parkinson disease. Arch Neurol. (2010)
- Newmark HL, Newmark J. Vitamin D and Parkinson's disease--a hypothesis. Mov Disord. (2007)
- Dean ED, et al. 25-Hydroxyvitamin D depletion does not exacerbate MPTP-induced dopamine neuron damage in mice. PLoS One. (2012)
- Shinpo K, et al. Effect of 1,25-dihydroxyvitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine. J Neurosci Res. (2000)
- Wang JY, et al. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. (2001)
- Gominak SC, Stumpf WE. The world epidemic of sleep disorders is linked to vitamin D deficiency. Med Hypotheses. (2012)
- Bonnet MH, Arand DL. We are chronically sleep deprived. Sleep. (1995)
- Van Cauter E, et al. Metabolic consequences of sleep and sleep loss. Sleep Med. (2008)
- Huang W, et al. Improvement of Pain, Sleep, and Quality of Life in Chronic Pain Patients With Vitamin D Supplementation. Clin J Pain. (2012)
- Mucci M, et al. Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopause. Minerva Ginecol. (2006)
- Wang TJ, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. (2008)
- Wang L, et al. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. (2010)
- Wood AD1, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab. (2012)
- Seibert E, et al. Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status. Eur J Nutr. (2015)
- Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension. (1997)
- Krause R, et al. Ultraviolet B and blood pressure. Lancet. (1998)
- Weng S, et al. Vitamin d deficiency induces high blood pressure and accelerates atherosclerosis in mice. PLoS One. (2013)
- Li YC, et al. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. (2002)
- Ritthaler T, et al. Effects of endothelins on renin secretion from isolated mouse renal juxtaglomerular cells. Am J Physiol. (1995)
- Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens. (2009)
- Lind L, et al. Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study. Am J Hypertens. (1989)
- Pfeifer M, et al. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. (2001)
- Xiang W, et al. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab. (2005)
- Kong J1, Li YC. Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice. Am J Physiol Regul Integr Comp Physiol. (2003)
- Dostal DE, Baker KM. Angiotensin II stimulation of left ventricular hypertrophy in adult rat heart. Mediation by the AT1 receptor. Am J Hypertens. (1992)
- Baker KM, Booz GW, Dostal DE. Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol. (1992)
- Al Mheid I, et al. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. (2011)
- Yiu YF, et al. Vitamin D deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetes. J Clin Endocrinol Metab. (2011)
- Reis JP, et al. Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease. Am J Clin Nutr. (2008)
- Zittermann A, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. (2009)
- Tabas I. The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res. (2010)
- Feng B, et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol. (2003)
- Devries-Seimon T, et al. Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor. J Cell Biol. (2005)
- Szeto FL, et al. Vitamin D receptor signaling inhibits atherosclerosis in mice. Mol Endocrinol. (2012)
- Oh J, et al. Endoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formation. J Biol Chem. (2012)
- Martinez FO, et al. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. (2006)
- Bouhlel MA, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. (2007)
- Feig JE, et al. LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression. J Clin Invest. (2010)
- Mills CD, et al. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. (2000)
- Liu E, et al. Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr. (2009)
- Ford ES, et al. Associations between concentrations of vitamin D and concentrations of insulin, glucose, and HbA1c among adolescents in the United States. Diabetes Care. (2011)
- Kelly A, et al. A cross-sectional study of vitamin D and insulin resistance in children. Arch Dis Child. (2011)
- Chiu KC, et al. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. (2004)
- Nazarian S, et al. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose. Transl Res. (2011)
- Choi HS, et al. Low serum vitamin D is associated with high risk of diabetes in Korean adults. J Nutr. (2011)
- Knekt P, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. (2008)
- Devaraj S, et al. Low vitamin D levels correlate with the proinflammatory state in type 1 diabetic subjects with and without microvascular complications. Am J Clin Pathol. (2011)
- Mitri J, et al. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr. (2011)
- Foss YJ. Vitamin D deficiency is the cause of common obesity. Med Hypotheses. (2009)
- Ruff CB. Climatic adaptation and hominid evolution: The thermoregulatory imperative. Evol Anthropol. (1993)
- Hunt G1, Roy K. Climate change, body size evolution, and Cope's Rule in deep-sea ostracodes. Proc Natl Acad Sci U S A. (2006)
- Zhang Z, Zhang Z. Comment on "Vitamin D deficiency is the cause of common obesity". Med Hypotheses. (2009)
- Zamboni G, et al. Mineral metabolism in obese children. Acta Paediatr Scand. (1988)
- Yanoff LB, et al. The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese Black Americans. Clin Endocrinol (Oxf). (2006)
- Sutherland ER, et al. Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med. (2010)
- Josefson JL, et al. Maternal obesity and vitamin D sufficiency are associated with cord blood vitamin D insufficiency. J Clin Endocrinol Metab. (2013)
- Bell NH, et al. Evidence for alteration of the vitamin D-endocrine system in obese subjects. J Clin Invest. (1985)
- Vimaleswaran KS1, et al. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. (2013)
- Choi H, Myung K. Vitamin D3 regulation of body fat, cytokines, and calpain gene expression. J Sci Food Agr. (2012)
- Carrillo AE, et al. Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults. Clin Nutr. (2012)
- Salehpour A1, et al. A 12-week double-blind randomized clinical trial of vitamin D₃ supplementation on body fat mass in healthy overweight and obese women. Nutr J. (2012)
- Norman AW. Receptors for 1alpha,25(OH)2D3: past, present, and future. J Bone Miner Res. (1998)
- Nemere I, et al. Identification of a membrane receptor for 1,25-dihydroxyvitamin D3 which mediates rapid activation of protein kinase C. J Bone Miner Res. (1998)
- Morelli S, Boland R, de Boland AR. 1,25(OH)2-vitamin D3 stimulation of phospholipases C and D in muscle cells involves extracellular calcium and a pertussis-sensitive G protein. Mol Cell Endocrinol. (1996)
- de Boland AR, Morelli S, Boland R. 1,25(OH)2-vitamin D3 signal transduction in chick myoblasts involves phosphatidylcholine hydrolysis. J Biol Chem. (1994)
- de Boland AR, Boland RL. 1,25-Dihydroxyvitamin D-3 induces arachidonate mobilization in embryonic chick myoblasts. Biochim Biophys Acta. (1993)
- Li YC, et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci U S A. (1997)
- Wang Y, Becklund BR, DeLuca HF. Identification of a highly specific and versatile vitamin D receptor antibody. Arch Biochem Biophys. (2010)
- Is the Vitamin D Receptor Found in Muscle?.
- Stumpf WE, et al. Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science. (1979)
- Pike JW, Goozé LL, Haussler MR. Biochemical evidence for 1,25-dihydroxyvitamin D receptor macromolecules in parathyroid, pancreatic, pituitary, and placental tissues. Life Sci. (1980)
- Narbaitz R, et al. Autoradiographic demonstration of target cells for 1,25-dihydroxycholecalciferol in the chick embryo chorioallantoic membrane, duodenum, and parathyroid glands. Gen Comp Endocrinol. (1980)
- Minasyan A, et al. Vestibular dysfunction in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. (2009)
- Kalueff AV, et al. Impaired motor performance in mice lacking neurosteroid vitamin D receptors. Brain Res Bull. (2004)
- Endo I, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. (2003)
- Owens DJ, et al. A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy. Am J Physiol Endocrinol Metab. (2015)
- Gilsanz V, et al. Vitamin D status and its relation to muscle mass and muscle fat in young women. J Clin Endocrinol Metab. (2010)
- Goswami R, et al. Skeletal muscle strength in young Asian Indian females after vitamin D and calcium supplementation: a double-blind randomized controlled clinical trial. J Clin Endocrinol Metab. (2012)
- Cannell JJ, et al. Athletic performance and vitamin D. Med Sci Sports Exerc. (2009)
- Galan F, et al. Serum 25-hydroxyvitamin D in early autumn to ensure vitamin D sufficiency in mid-winter in professional football players. Clin Nutr. (2012)
- Shindle MK, et al. Vitamin D Status in a Professional American Football Team: 2008: Board #203 June 2 9:00 AM - 10:30 AM. Med Sci Sports Exerc. (2011)
- Halliday TM, et al. Vitamin D status relative to diet, lifestyle, injury, and illness in college athletes. Med Sci Sports Exerc. (2011)
- Burgi AA, et al. High serum 25-hydroxyvitamin D is associated with a low incidence of stress fractures. J Bone Miner Res. (2011)
- Atkins GJ, et al. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha,25-dihydroxyvitamin D3. Bone. (2007)
- van Leeuwen JP, et al. Vitamin D control of osteoblast function and bone extracellular matrix mineralization. Crit Rev Eukaryot Gene Expr. (2001)
- van Driel M, Pols HA, van Leeuwen JP. Osteoblast differentiation and control by vitamin D and vitamin D metabolites. Curr Pharm Des. (2004)
- Atkins GJ, et al. RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res. (2003)
- Matsumoto T, et al. Stimulation by 1,25-dihydroxyvitamin D3 of in vitro mineralization induced by osteoblast-like MC3T3-E1 cells. Bone. (1991)
- Ruohola JP, et al. Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men. J Bone Miner Res. (2006)
- Tenforde AS, et al. Evaluating the relationship of calcium and vitamin D in the prevention of stress fracture injuries in the young athlete: a review of the literature. PM R. (2010)
- Lappe J, et al. Calcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruits. J Bone Miner Res. (2008)
- Bischoff-Ferrari HA, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA. (2004)
- Monaghan H. Review: prophylactic use of vitamin D reduces falls in older people. Evid Based Nurs. (2004)
- Gillespie LD, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. (2012)
- Glover TL1, et al. Vitamin D, race, and experimental pain sensitivity in older adults with knee osteoarthritis. Arthritis Rheum. (2012)
- McAlindon T, et al. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA. (2013)
- Riek AE1, et al. Vitamin D suppression of endoplasmic reticulum stress promotes an antiatherogenic monocyte/macrophage phenotype in type 2 diabetic patients. J Biol Chem. (2012)
- Kim G, Bae JH. Vitamin D and atopic dermatitis: A systematic review and meta-analysis. Nutrition. (2016)
- Barton M, Sidbury R. Advances in understanding and managing atopic dermatitis. F1000Res. (2015)
- Boguniewicz M, Leung DY. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol. (2010)
- Williams H, et al. Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood. J Allergy Clin Immunol. (1999)
- Amestejani M, et al. Vitamin D supplementation in the treatment of atopic dermatitis: a clinical trial study. J Drugs Dermatol. (2012)
- Holick MF. Vitamin D deficiency. N Engl J Med. (2007)
- Wehr E, et al. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf). (2010)
- Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Additive benefit of higher testosterone levels and vitamin D plus calcium supplementation in regard to fall risk reduction among older men and women. Osteoporos Int. (2008)
- Pilz S, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. (2011)
- Garland CF, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. (2007)
- Garland CF, et al. The role of vitamin D in cancer prevention. Am J Public Health. (2006)
- Garland FC, et al. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med. (1990)
- Gorham ED, Garland CF, Garland FC. Acid haze air pollution and breast and colon cancer mortality in 20 Canadian cities. Can J Public Health. (1989)
- Peppone LJ, et al. The effect of various vitamin D supplementation regimens in breast cancer patients. Breast Cancer Res Treat. (2011)
- Nesby-O'Dell S, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. (2002)
- Chlebowski RT, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. (2008)
- Crew KD, et al. High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. (2009)
- Gorham ED, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. (2007)
- Skinner HG, et al. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev. (2006)
- Garland CF, et al. Role of ultraviolet B irradiance and vitamin D in prevention of ovarian cancer. Am J Prev Med. (2006)
- Vashi PG, et al. Serum 25-hydroxyvitamin D is inversely associated with body mass index in cancer. Nutr J. (2011)
- Choi CJ, et al. Relationship Between Serum 25-Hydroxyvitamin D and Lung Function Among Korean Adults in Korea National Health and Nutrition Examination Survey (KNHANES), 2008-2010. J Clin Endocrinol Metab. (2013)
- Searing DA, et al. Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. J Allergy Clin Immunol. (2010)
- Urashima M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. (2010)
- Lange NE1, et al. Vitamin D deficiency, smoking, and lung function in the Normative Aging Study. Am J Respir Crit Care Med. (2012)
- Camargo CA Jr1, et al. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics. (2012)
- Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiol Infect. (2007)
- Murdoch DR1, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. (2012)
- Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. (2008)
- Bozkurt NC, et al. The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities. Endocrine. (2012)
- Stumpf WE. Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting. Histochem Cell Biol. (1995)
- Blomberg Jensen M, et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod. (2010)
- Yoshida M, Kawano N, Yoshida K. Control of sperm motility and fertility: diverse factors and common mechanisms. Cell Mol Life Sci. (2008)
- Nangia AK, et al. Testicular maturation arrest to testis cancer: spectrum of expression of the vitamin D receptor and vitamin D treatment in vitro. J Urol. (2007)
- Bouillon R, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. (2008)
- Kwiecinski GG, Petrie GI, DeLuca HF. Vitamin D is necessary for reproductive functions of the male rat. J Nutr. (1989)
- Blomberg Jensen M, et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod. (2011)
- Hammoud AO, et al. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J Androl. (2012)
- Yang B, et al. Associations between testosterone, bone mineral density, vitamin D and semen quality in fertile and infertile Chinese men. Int J Androl. (2012)
- Blomberg Jensen M. Vitamin D metabolism, sex hormones, and male reproductive function. Reproduction. (2012)
- van der Meer IM, et al. High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands. Am J Clin Nutr. (2006)
- Haliloglu B, et al. Bone turnover and maternal 25(OH) vitamin D3 levels during pregnancy and the postpartum period: should routine vitamin D supplementation be increased in pregnant women. Eur J Obstet Gynecol Reprod Biol. (2011)
- Johnson DD, et al. Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatol. (2011)
- Hamilton SA, et al. Profound Vitamin D Deficiency in a Diverse Group of Women during Pregnancy Living in a Sun-Rich Environment at Latitude 32°N. Int J Endocrinol. (2010)
- Gernand AD, et al. Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort study. J Clin Endocrinol Metab. (2013)
- Sørensen IM, et al. Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes. (2012)
- Erkkola M, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy. (2009)
- Merewood A, et al. Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab. (2009)
- Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. (2009)
- Yu CK, et al. Vitamin D deficiency and supplementation during pregnancy. Clin Endocrinol (Oxf). (2009)
- Hollis BW, Wagner CL. Assessment of dietary vitamin D requirements during pregnancy and lactation. Am J Clin Nutr. (2004)
- Terrier B, et al. Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation. Arthritis Res Ther. (2012)
- Warner AE, Arnspiger SA. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol. (2008)
- Schreuder F, Bernsen RM, van der Wouden JC. Vitamin d supplementation for nonspecific musculoskeletal pain in non-Western immigrants: a randomized controlled trial. Ann Fam Med. (2012)
- Arvold DS, et al. Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Endocr Pract. (2009)
- Bischoff-Ferrari HA, et al. Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res. (2004)
- Bischoff HA, et al. Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil. (1999)
- Visser M, Deeg DJ, Lips P; Longitudinal Aging Study Amsterdam. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. (2003)
- Sato Y, et al. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis. (2005)
- Verhaar HJ, et al. Muscle strength, functional mobility and vitamin D in older women. Aging (Milano). (2000)
- Kidd PM. Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern Med Rev. (2010)
- Heaney RP, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. (2003)
- Bjelakovic G, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. (2011)
- Abnet CC, et al. Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Cancer Epidemiol Biomarkers Prev. (2007)
- Dobnig H, et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. (2008)
- Pfeifer M, et al. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int. (2009)
- Barker T, et al. Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults. Nutr Metab (Lond). (2012)
- Ganmaa D, et al. Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial. Am J Clin Nutr. (2012)
- Khan QJ, et al. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat. (2010)
- Borissova AM, et al. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract. (2003)
- Jørgensen SP, et al. Clinical trial: vitamin D3 treatment in Crohn's disease - a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. (2010)
- Broe KE, et al. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. (2007)
- Parker J, et al. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. (2010)
- Munger KL, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. (2004)
- Bischoff-Ferrari HA, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. (2009)
- Li-Ng M, et al. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Epidemiol Infect. (2009)
- Abrams SA, Hawthorne KM, Chen Z. Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: a double-blind randomized controlled trial. Am J Clin Nutr. (2013)
- Gepner AD, et al. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. (2012)
- Sato Y, Honda Y, Iwamoto J. Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease. Neurology. (2007)
- Bogh MK, et al. Narrowband ultraviolet B three times per week is more effective in treating vitamin D deficiency than 1600 IU oral vitamin D₃ per day: a randomized clinical trial. Br J Dermatol. (2012)
- Harris SS, Pittas AG, Palermo NJ. A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans. Diabetes Obes Metab. (2012)
- Abou-Raya A, Abou-Raya S, Helmii M. The Effect of Vitamin D Supplementation on Inflammatory and Hemostatic Markers and Disease Activity in Patients with Systemic Lupus Erythematosus: A Randomized Placebo-controlled Trial. J Rheumatol. (2012)
- McAlindon TE, et al. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med. (1996)
- Pierrot-Deseilligny C, et al. Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation. Ther Adv Neurol Disord. (2012)
- Mohr SB, et al. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia. (2008)
- Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens. (2007)
- Kositsawat J, et al. Association of A1C levels with vitamin D status in U.S. adults: data from the National Health and Nutrition Examination Survey. Diabetes Care. (2010)
- Lappe JM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. (2007)
- Bischoff-Ferrari HA, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. (2009)
- Pfeifer M, et al. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res. (2000)
- Jorde R, et al. Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials. Scand J Infect Dis. (2012)
- Crew KD, et al. Association between plasma 25-hydroxyvitamin D and breast cancer risk. Cancer Prev Res (Phila). (2009)
- Travison TG, et al. The relationship between libido and testosterone levels in aging men. J Clin Endocrinol Metab. (2006)
- Chrysohoou C, et al. Low total testosterone levels are associated with the metabolic syndrome in elderly men: the role of body weight, lipids, insulin resistance, and inflammation; the Ikaria study. Rev Diabet Stud. (2013)
- Westley CJ, Amdur RL, Irwig MS. High Rates of Depression and Depressive Symptoms among Men Referred for Borderline Testosterone Levels. J Sex Med. (2015)
- Giltay EJ, et al. Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study. J Psychosom Res. (2012)
- Feldman HA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. (2002)
- Wu FC, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. (2008)
- Handelsman DJ, et al. Age-specific population centiles for androgen status in men. Eur J Endocrinol. (2015)
- Cote KA, et al. Sleep deprivation lowers reactive aggression and testosterone in men. Biol Psychol. (2013)
- Leproult R, Van Cauter E. Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA. (2011)
- Penev PD. Association between sleep and morning testosterone levels in older men. Sleep. (2007)
- González-Santos MR, et al. Sleep deprivation and adaptive hormonal responses of healthy men. Arch Androl. (1989)
- Cortés-Gallegos V, et al. Sleep deprivation reduces circulating androgens in healthy men. Arch Androl. (1983)
- Nedeltcheva AV, et al. Insufficient sleep undermines dietary efforts to reduce adiposity. Ann Intern Med. (2010)
- O'Leary CB, Hackney AC. Acute and chronic effects of resistance exercise on the testosterone and cortisol responses in obese males: a systematic review. Physiol Res. (2014)
- Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med. (2005)
- Daly W, et al. Relationship between stress hormones and testosterone with prolonged endurance exercise. Eur J Appl Physiol. (2005)
- Hackney AC, Aggon E. Chronic Low Testosterone Levels in Endurance Trained Men: The Exercise- Hypogonadal Male Condition. J Biochem Physiol. (2018)
- Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. J Clin Endocrinol Metab. (2011)
- Tajar A, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. (2010)
- Hall SA, et al. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab. (2008)
- Grossmann M, Matsumoto AM. A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management. J Clin Endocrinol Metab. (2017)
- Corona G, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. (2013)
- Camacho EM, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. (2013)
- . Dietary Reference Intakes for Calcium and Vitamin D. . ()
- Heaney R, et al. Letter to Veugelers, P.J. and Ekwaru, J.P., A statistical error in the estimation of the recommended dietary allowance for vitamin D. Nutrients 2014, 6, 4472-4475; doi:10.3390/nu6104472. Nutrients. (2015)
- Veugelers PJ, Ekwaru JP. A statistical error in the estimation of the recommended dietary allowance for vitamin D. Nutrients. (2014)
- Netter A, Hartoma R, Nahoul K. Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Arch Androl. (1981)
- Chang CS, et al. Correlation between serum testosterone level and concentrations of copper and zinc in hair tissue. Biol Trace Elem Res. (2011)
- Tang YM, et al. Relationships between micronutrient losses in sweat and blood pressure among heat-exposed steelworkers. Ind Health. (2016)
- . Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. . ()
- Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. (2011)
- Valentiner-Branth P, et al. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal. Am J Clin Nutr. (2010)
- Willis MS, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol. (2005)
- Afrin LB. Fatal copper deficiency from excessive use of zinc-based denture adhesive. Am J Med Sci. (2010)
- Maggio M, et al. The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men. Int J Endocrinol. (2014)
- Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. J Am Osteopath Assoc. (2018)
- Costello RB, Moser-Veillon PB. A review of magnesium intake in the elderly. A cause for concern?. Magnes Res. (1992)
- Nielsen FH, Lukaski HC. Update on the relationship between magnesium and exercise. Magnes Res. (2006)
- Institute of Medicine (US) Committee on Military Nutrition Research; Marriott BM, editor. Washington (DC). Nutritional Needs in Hot Environments, “Influence of Exercise and Heat on Magnesium Metabolism”. National Academies Press (US). (1993)
- Consolazio CF, et al. Excretion of sodium, potassium, magnesium and iron in human sweat and the relation of each to balance and requirements. J Nutr. (1963)
- Yoshimura Y, et al. Pharmacokinetic Studies of Orally Administered Magnesium Oxide in Rats. Yakugaku Zasshi. (2017)
- Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnes Res. (2001)
- Gonzales-Arimborgo C, et al. Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study. Pharmaceuticals (Basel). (2016)
- Zenico T, et al. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial. Andrologia. (2009)
- Gonzales GF, et al. Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men. Andrologia. (2002)
- Dording CM, et al. A double-blind placebo-controlled trial of maca root as treatment for antidepressant-induced sexual dysfunction in women. Evid Based Complement Alternat Med. (2015)
- G. D’Aniello, et al. D-asparate, a key element for the improvement of sperm quality. Advances in Sexual Medicine. (2012)
- Topo E, et al. The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reprod Biol Endocrinol. (2009)
- Melville GW, Siegler JC, Marshall PW. Three and six grams supplementation of d-aspartic acid in resistance trained men. J Int Soc Sports Nutr. (2015)
- Willoughby DS, Leutholtz B. D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men. Nutr Res. (2013)
- Nair R, Maseeh A. Vitamin D: The "sunshine" vitamin. J Pharmacol Pharmacother. (2012)
- Parker GB, Brotchie H, Graham RK. Vitamin D and depression. J Affect Disord. (2017)
- Allan GM, et al. Vitamin D: A Narrative Review Examining the Evidence for Ten Beliefs. J Gen Intern Med. (2016)
- Gowda U, et al. Vitamin D supplementation to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition. (2015)
- Spedding S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients. (2014)
- Vellekkatt F, Menon V. Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials. J Postgrad Med. (2018)
- Vaziri F, et al. A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers. BMC Pregnancy Childbirth. (2016)
- Laurent MR, et al. Hypervitaminosis D Associated With Tanning Bed Use: A Case Report. Ann Intern Med. (2017)
- Rodgers S, et al. Serum testosterone levels and symptom-based depression subtypes in men. Front Psychiatry. (2015)
- Johnson JM, Nachtigall LB, Stern TA. The effect of testosterone levels on mood in men: a review. Psychosomatics. (2013)
- Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. (2009)
- Zarrouf FA, et al. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. (2009)
- Davis SR, Wahlin-Jacobsen S. Testosterone in women--the clinical significance. Lancet Diabetes Endocrinol. (2015)
- Sharma A, Madaan V, Petty FD. Exercise for mental health. Prim Care Companion J Clin Psychiatry. (2006)
- Melrose S. Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches. Depress Res Treat. (2015)
- O'Hare C, et al. Seasonal and meteorological associations with depressive symptoms in older adults: A geo-epidemiological study. J Affect Disord. (2016)
- Golden RN, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. (2005)
- Lam RW, et al. The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Am J Psychiatry. (2006)
- Kerr DC, et al. Associations between vitamin D levels and depressive symptoms in healthy young adult women. Psychiatry Res. (2015)
- Frandsen TB, et al. Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: a double-blind randomised placebo-controlled trial. BMC Res Notes. (2014)
- Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. (2011)
- Haq A, et al. Vitamin D deficiency: A single centre analysis of patients from 136 countries. J Steroid Biochem Mol Biol. (2016)