Vitamin D

Last Updated: September 28 2022

Vitamin D is a fat-soluble vitamin that our skin synthesizes when exposed to the sun. It benefits us in many ways, from bone health to mood.

Vitamin D is most often used for.

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Sources and Structure


Sources and Intake

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.[4] 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.[5]

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:

  • Milk, being the most common source of vitamin D in the USA[6] and has trended downwards in recent decades[7]
  • Cod liver oil at around 2.54-2.78mcg/mL;[8] although labels would be more precise on a product-specific basis as some are lower than this estimate such as 33.5-172.3IU/mL[9][10]

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.[11] 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.[12]

This 400IU target intake, as well as the actual overall intake of Vitamin D3, is commonly seen as deficient in adults[13] as 400IU cannot ideally sustain circulating levels between 50-75nmol/L, which is seen as ideal.[14][15]

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 from the Sun

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).[16]

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[17], which appears to be related to cancer risk[18]
  • Weather patterns or seasons that reduce solar exposure, such as clouds or darkness[19][20]
  • 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[21]
  • Areas with higher ozone breakdown (assessed by Dobson units) appear to have higher UVB radiation[22]
  • 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.[23][24]

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),[25][26] a topic that is somewhat mixed in results,[27] sunscreens appear to significantly attenuate synthesis of vitamin D by interfering with the topical influences of UVB rays.[28][29] Chronic (not acute) sunscreen usage has been associated with Vitamin D deficiency.[30]

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[31]) 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.[31][32]

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.[16] 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.[16]

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


Variants of Supplementation

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).[33][34] The only difference in these two molecules is a methyl group, as vitamin D3 is 27 carbons in length, while D2 is 28 carbons.[35]

Both vitamin D2 and D3 are seen as prohormone compounds (acting to increase circulating levels of 25-hydroxyvitamin D)[33] 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 _ergo_calciferol (more closely resembling that of D3 than D2 in structure) and that D2 should not be sold as a supplement.[36]

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[37] or orange juice fortification[38] 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.[39]

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.[40]

Other studies using daily dosing of 1,600IU for a year,[35] 4,000IU over 14 days,[41], and for intermittent doses 50,000IU one monthly for a year[35] or a one time dose[42] as well as acute doses of up to 300,000IU D3[43] 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.[44]

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.[45]

D2 appears to be less chemically stable than D3 ex vivo (not in an oil base, however)[46][47] leading to some authors suggesting that it may have a poorer shelf-life.[36]

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.


Circulating Vitamin D levels


Target Levels

Currently, the generally accepted terms to refer to different possible 'states' of Vitamin D status are:[48]

  • Deficiency (Less than 30nmol/L or 12ng/mL, leading to rickets in children and osteomalacia in adults)
  • Insufficiency (between 30-50nmol/L, the range of 12-20ng/mL)
  • Adequate (between 50-125nmol/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[49])

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[50] and bone-related conditions such as dental health or reducing the risk of falls and fractures in the elderly.[51] This also appears to be a target for colorectal cancer prevention.[51]

Even in studies that recommend higher oral intakes (5,000IU), the end goal still appears to be around 75-80nmol/L.[13]

Recommended levels of vitamin D are roughly 75nmol/L (30ng/mL) for some conditions.


Deficiency (Predictors)

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.[52] It appears to have somewhat stabilized, with 79% below 80nmol/L.[53]

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).[53] 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%.[54] 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.[55] 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.[56]

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.[57] 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.[58]

Despite the above importance on latitude, at least one study has suggested that this may only account for one fifth of the variance seen.[59]

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.[60]

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[61]) 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.[61] 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,[51] with 1700IU needed for 95% of the population to reach 75nmol/L.[62] Despite these doses, the human body appears to be able to metabolize more than these levels (up to 3000-5000IU in men[63]) 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.[64]

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[65] 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[66] or 225mcg.[67] 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.[65] 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),[65] and similar results have been noted with another review noting that 100IU of Vitamin D3 increases serum Vitamin D by 1-2nmol/L[68] and an increase of 10-25nmol/L with 1,000IU.[69] 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.[70][71][72][73]

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.[65] This study could not assess age or gender due to confounds.[65]

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.[74] 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.[75]

Vitamin D is best absorbed with a meal, preferrably one with a little fat in it.

20,000IU daily has been associated with toxicity,[64], while daily supplementation of 10,000IU does not appear to induce toxicity,[76]

Sometimes acute boluses are used on a weekly or monthly basis, and toxicity has been associated with a bolus of 300,000IU.[64]

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.[77]

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.[65]

Vitamin D3 appears to be a more reliable form of supplemental vitamin D, relative to D2, for increasing serum levels to an adequate range.


Lifespan and Extension



Low vitamin D levels are independently associated with an increase in all-cause mortality in the general population.[61] 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,[78] 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.[79] 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[78] (an increase of 10nmol/L can be obtained by ingestion of approximately 1000IU per day[63]).

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.[78] 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).[61] 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.[80] 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.[80]

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).[81]

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.[82]



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.[83] 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.[83]

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.




Mechanisms (General)

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. [84]

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.[85] 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.[86] 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.[87] 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. [88]

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.


Enzymatic Interactions

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.[89] The hormonally active form of Vitamin D3 appears to be a tissue-specific aromatase modulator, increasing its expression in osteoblasts and fibroblasts in bone,[90] as well as adrenocortical[91] and prostate cancer cells (a beneficial effect),[91][92] and decreasing it in breast cancer cells.[91] Vitamin D3 also appears to induce aromatase activity in placental cells.[93]

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.[94] This may be secondary to disrupting calcium metabolism, since supplementation of calcium to these mice normalized actions of aromatase.[94]

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.[95]

Interestingly, a synthetic analogue of Vitamin D3 (known as EB1089) inhibits aromatase via a currently novel inhibitory pathway.[95] This is an analogue that has also shown efficacy in reducing breast cancer in animal models.[96][97]

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.[98] 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.[99][100] 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.[101] Higher doses (in this study, 50,000IU weekly of Vitamin D2) appear to be more effective in reducing subjective reports of joint pain.[102]

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,[103] with the highest concentrations of this enzyme occuring in the hypothalamus and dopaminergic neurons of the substantia nigra.[104] 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,[104] and is expressed in glial cells of the brain.[104]

Calcium metabolism appears to underlie neuronal cell death via excitotoxicity,[105][106][107][108] and hormonally active vitamin D confers a protective effect in vitro at physiologically relevant concentrations up to 100nM but not above.[109] This mechanism of protection appears to be mediated via a downregulation of L-type voltage-sensitive Ca2+ ion channels,[109] an effect which has also been seen in bone cells.[110][111] These L-type channels have been implicated in excitotoxicity.[112][113]

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.[114]

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).[115] Anxiety and anger ratings were similarily unaffected.[115] 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.[116] Average vitamin D levels were increased from 25 ng/mL (64 nmol/L) to 52 ng/mL (130 nmol/L).[116]



A inverse correlation between vitamin D and depression (lower vitamin D status being related to more depressive symptoms) was first reported in 1979[117] and associations have resurfaced in those at risk for cardiovacular incidents,[118] fibromyalgia,[119] and in women during the winter.[120]

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.[121]

In a randomized, controlled clinical trial high-dose vitamin D supplementation was shown to reduce depressive symptoms in individuals with major depressive disorder (MDD),[122] a condition associated with persistent depressed mood and loss of interest in normally pleasurable activities.[123] 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).[122]

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.[124] 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.[115] A failure to reduce depressive symptoms has been noted elsewhere in post-menopausal women given calcitriol supplementation (an active hormonal form of vitamin D).[125]

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

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.[126][127] A putative connection between multiple sclerosis and vitamin D comes from associations between MS and latitude, which also correlates highly with vitamin D[128][129] and sun exposure during childhood being inversely related to MS risk in adulthood.[130][131] No link between maternal vitamin D levels during gestation and risk of MS in offspring has been found, however.[132] Evidence exists suggesting protective effects from sun exposure,[129][130][131] with one observational study establishing a protective connection between multiple sclerosis and vitamin D serum levels directly.[132]

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[133] and slow the progression of the disease.[134] Furthermore, synergism may exist between vitamin D and the standard MS therapy, interferon-beta.[135] The benefits of vitamin D may be related to attenuating demyelination from neurons in vitro.[136]

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.[137] Similar to other neurological conditions, Vitamin D in serum appears to be inversely related to AD risk;[138] the risk appears to be a bit lesser than Parkinson's, which have lower serum levels of Vitamin D.[139][140] Vitamin D receptor polymorphisms have been found in AD,[141] and low serum Vitamin D in older individuals has some predictive validity (assessed by subgroup analysis; small sample).[142]

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.[143]



Vitamin D tends to be inversely associated with risk[144][145] and its receptor a candidate for Parkinson's therapy[146] as there appears to be an association with one of its polymorphisms and PD risk.[147] Interestingly, persons with Parkinsons appear to have less circulating Vitamin D than do age-matched counterparts with Alzheimer's[139][140] and appears to exist prior to diagnosis of PD (during early disease pathology)[148] which tends to decline further as the disease progresses.[140][149]

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.[150][151] 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.[152] This is in contrast to previous studies in vitro[153] and in animals[154] where excess levels of Vitamin D3 protected neurons from stressors up to 100ng/mL (higher concentrations associated with toxicity).[153]

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.


Sleep Quality

It has been hypothesized[155] that Vitamin D deficiency is central to a recent 'epidemic' of disturbed sleep patterns[156][157] that roughly correlates with when the majority of humans began to spend most time indoors.[155]

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[158] or are confounded with other nutrients such as Magnolia Officinalis and Soy Isoflavones.[159] 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.


Cardiovascular Health


Disease Risk

Those with insufficient Vitamin D levels are significantly more likely to develop heart disease than those who do not. [160]

At least one systemic review concludes that 1000IU of Vitamin D daily can reduce the risk of cardiovascular disease based on systemic biomarkers,[161]

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.[162] 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.[163]

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.


Blood Pressure

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.[164][165] 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[166] possible secondary to increased serum angiotensin, androsterone, and tissue renin.[167]

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,[168] 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.[167]

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[169] 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.[169]

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.[170]

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).[171] However, another study using 800 IU for 12 weeks in healthy vitamin D-insufficient people found no effect on blood pressure.[163]

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.


Cardiac Tissue

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[172] which is due to an increase in Angiotension II (AGE II) that has been noted in VDR-/- mice[167][173] and is known to induce cardiac hypertrophy.[174][175] Treatment with Captopril, an ACE inhibitor that blocks production of AGE II, reduces cardiac hypertrophy in Vitamin D deficient mice.[172]

Mice lacking the vitamin D receptor appear to have cardiac enlargement due to increased serum angiotension II and increased activity of the RAS system.


Red Blood Cells

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.[163]


Blood Flow

Vitamin D status is associated with arterial stifness and vascular dysfunction in otherwise healthy humans. [176]

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. [177]

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). [178]

Supplementing 3320IU/d of Vitamin D helped improve several health markers of cardiovascular health during weight loss [179]



It has been noted that endoplasmic reticulum (ER) stress (oxidative stress on a certain organelle in a cell) is pivotall for foam cell production[180] via damaging the macrophage secondary to cholesterol accumulation;[181][182] macrophages isolated Vitamin D deficient mice appear to be characterized by higher levels of ER stress[166] normalizing this stress with agents known to reduce ER stress normalized the increased foam cell production seem in Vitamin D deficient mice.[166] This suggests that Vitamin D acts to reduce atherosclerosis by reducing oxidative ER stress in macrophages and subsequently preventing foam cell formation.[166]

These effects are mediated by the Vitamin D receptor,[183] and may be related to a shift of Macrophage phenotype from M2 to M1, which appears to be less atherogenic.[184] 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 atherogenic foam cells[185][186] 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-atherogenic.[187][188][166]

Vitamin D appears to act to suppress atherosclerosis 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.


Interactions with Glucose Metabolism


Insulin Sensitivity

Vitamin D levels have been inversely correlated with insulin resistance in non-diabetic adults [189]

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. [190]

Vitamin D levels have an inverse correlation with insulin resistance in both obese and non-obese children. [191]

Vitamin D levels are associated with insulin sensitivity even in non-diabetic adults. [189]

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. [192]

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. [193]

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).[122] 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).[122]



Decreased serum Vitamin D levels increase risk of the development of Diabetes. [194]

Higher Vitamin D levels prevent the occurence of Type 2 Diabetes. [195]

Low levels of Vitamin D are associated with complications of Type 1 Diabetes. [196]

Vitamin D supplementation improves outcomes of Type 2 Diabetes. [197]


Fat Mass and Obesity



It has been hypothesized that Vitamin D insufficiency is a possible contributor to obesity,[198] 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.[199][200] 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.[201]

Elsewhere, it has been noted that Vitamin D levels are lower in obese persons when compared to controls of similar demographics[202][203][204] including pregnant mothers[205] which exists with an increase in serum parathyroid hormone, which Vitamin D normally suppresses.[206] 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).[207]

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.[208]

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.[209] 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.[210]

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.


Skeletal Muscle and Physical Performance



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[211] such as activation of Protein Kinase C (PKC)[212] which is apparently coupled to a G-protein,[213] Phospholipase D via the same G-protein,[213][214] and Protein Kinase A2.[215] 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[216][217]) 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.[218] Past studies using autoradiography which confirmed the presence of the VDR in intestinal enterocytes, osteoblasts, parathyroid cells, and distal renal tubules[219] has also failed to detect the VDR in skeletal muscle.[220][221]

Thus, the detected receptor in the previous studies 'confirming' its actions[213][214][215] may be a false positive when investigating another receptor.

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)[222][223] as well as 20% smaller muscle diameter.[224]

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.[225]

In vitro evidence suggests that vitamin D may improve muscle recovery after mechanical damage.



A deficiency of Vitamin D is associated with an increase level of fat in skeletal muscle tissue, as assessed by this study in otherwise healthy young women.[226]

In young females, normalizing a Vitamin D deficiency does not appear to confer benefits to hand-grip or pinch-grip strength.[227]



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.[228]

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.[209]

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.[225]


Injury and Illness

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,[229] with a correlation existing between players getting injured having less Vitamin D levels.[230]

Vitamin D deficiency appears to be correlated with increased risk of illness and injury among athletes,[231] especially in regards to stress fractures.[232]


Skeleton and Bone Metabolism



Osteoblasts themselves are capable to expressing CYP27B1 and converting inactivate vitamin D (25-hydroxycalciferol) into the active steroid form (1,25-dihydroxycalciferol).[233]

The vitamin D receptor is expressed in osteoblasts[234] where it is involved in controlling their proliferation.[235] 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.[236]

Vitamin D acting upon its receptor does promote mineralization of bone tissue.[237]



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.[238][232] 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[232] 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[239] 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.[240]

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),[241]


Falls in the Elderly

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;[242] it was suggested that an oral dose of 700-800IU was effective, although one response[243] 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.[244]

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.[245]

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.[246]

Supplementation of vitamin D does not appear to significantly reduce joint pain associated with osteoarthritis.


Inflammation and Immunology



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.[247]


Atopic Dermatitis (AD)

Atopic dermatitis (AD) is a chronic inflammatory disease associated with dry, itchy skin and hypersensitivity to allergens.[248] Although the exact causes of the disease are not completely understood,[249] 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.[250][251]

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.[252]

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.[248] 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.[248] 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.


Interactions with Hormones


Parathyroid Hormone

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. [253]



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.[254] 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.[254] 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.[255]

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.[256]

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.[94] This study in receptor deficient mice noted reduced estrogen levels in serum.[94]


Follicle Stimulating Hormone

Follicle-Stimulating Hormone (FSH) is increased in mice lacking the Vitamin D receptor, and this appears to be independent of calcium metabolism.[94]


Luteinizing Hormone

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.[94]


Interactions with Cancer Metabolism


Breast Cancer

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)[257][258]. Additionally, Vitamin D deficiency appears to be more prevalent in persons with breast cancer (diagnosed)[259][260] and is similarly correlated with severity of breast cancer.[261] This risk appears more prevalent in black women, where one survey suggested 42% of black women (USA) had serum levels below 15ng/mL (deficiency).[262]

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.[263] This study reported a 28% increase in serum Vitamin D from 16.9ng/mL to 21.6ng/mL,[263] 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.[65] Another study has noted that 400IU Vitamin D was insufficient to increase serum levels of Vitamin D3 to adequate,[264] 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, [257] 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.[261]


Colon Cancer

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;[258]

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.[265]



Vitamin D appears to be inversely correlated with Prostate Cancer risk according to a systematic review of survey research, looking at 26 studies.[258]



Doses as low as 600IU/d lower the risk of pancreatic cancer [266]



Vitamin D appears to be inversely related to Ovarian Cancer risk, according to 7 epidemiological studies assessed in this review.[258]

UVB irradiation (which produces Vitamin D) is associated with a decreased risk of developing ovarian cancer in women [267]


Cancer Patients

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. [268]


Interactions with Lungs



In otherwise healthy adults, higher serum Vitamin D appears to be associated with improved lung function as assessed by forced exhalation.[269]



Low levels of Vitamin D are associated with increased corticosteroid use in asthmatic children, [270] while supplementation of 1200IU daily is associated with decreased asthmatic attacks in children previously diagnosed with Asthma.[271]



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.[272] From this study, a protective effect on smoke-induced damage was hypothesized.


Respiratory Sickness

Children taking 1200IU of Vitamin D daily were 40% less likely to get the flu during the winter in this study conducted in Japan,[271] while a Mongolian study on children and 300IU daily noted similar benefits.[273]

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. [274]

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.[275]

Lower Vitamin D levels are associated with an associated with a higher risk of active tuberculosis[276]


Obstructive Sleep Apnea

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.[277]


Interactions with Sexuality


Seminal Parameters

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.[278][279] This suggests direct actions on sex organs rather than indirect via regulating calcium, which also interacts with sexuality.[280] Vitamin D receptors are also expressed on the spermatid itself, during the late stages of spermatogenesis.[279][281] Male mice who lack the VDRs suffer from infertility[282][94] and impaired sperm parameters.[283]

Mechanistically, Vitamin D appears to increase calcium content in spermatids[284] and can act directly on mature sperm cells.[86] 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.[86]

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[284] but that serum levels above 50ng/mL were also associated with less favorable seminal parameters, with an ideal range of 20-50ng/mL.[285] Vitamin D appears to be an independent predictor of seminal parameters in both infertile and fertile men, with more statistical power in infertility.[286]

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.



Pregnancy and Lactation



Vitamin D deficiency rates appear to be higher in pregnant women than age matched non-pregnant women[288][289] with deficiency or insufficiency affecting 97% of African-Americans, 81% of Hispanics, and 67% of Caucasians in one trial[290] and another trial in South Carolina (Latitude 32N) noting 48% deficiency rates and 15% sufficiency rates.[291]

This deficiency state has been linked to lower offspring birth weights, which appears to be of most importance in the first trimester,[292] a higher risk of type 1 diabetes developing in the offspring,[293] and higher asthma/rhinitus risk.[294]

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).[295] 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).[296]

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[297] 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).[298]

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.


Interactions with Various Disease States


Lupus Erythematosus

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.[299]



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.[300]

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.[301]

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).[300] 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).[302]

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[303] and Vitamin D deficiency may contribute to an age-related loss of muscle function in elderly persons[304] 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.[305]

At least one intervention has noted preservation of type II muscle fibers in elderly persons associated with Vitamin D supplementation,[306] and intervention has been associated with improved muscular function in Vitamin D deficiency women.[307]


Nutrient-Nutrient Interactions


Vitamin K

Vitamin D is potentially synergistic with Vitamin K supplementation as the two share many mechanisms of action in the cardiovascular and bone metabolism systems.[308]



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. [309]


Safety and Toxicity



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.[310] The increased risk of kidney stones and the decreased mortality rates were both only seen with vitamin D3 supplementation.[310]


Squamous dysplasia

High serum vitamin D levels have been associated with esophageal Squamous dysplasia,[311] 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.[311]

1.^Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, Dick W, Willett WC, Egli AMonthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical TrialJAMA Intern Med.(2016 Feb)
2.^Lawrence J Appel, Erin D Michos, Christine M Mitchell, Amanda L Blackford, Alice L Sternberg, Edgar R Miller 3rd, Stephen P Juraschek, Jennifer A Schrack, Sarah L Szanton, Jeanne Charleston, Melissa Minotti, Sheriza N Baksh, Robert H Christenson, Josef Coresh, Lea T Drye, Jack M Guralnik, Rita R Kalyani, Timothy B Plante, David M Shade, David L Roth, James Tonascia, STURDY Collaborative Research GroupThe Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults : A Response-Adaptive, Randomized Clinical TrialAnn Intern Med.(2021 Feb)
3.^Lauren A Burt, Emma O Billington, Marianne S Rose, Richard Kremer, David A Hanley, Steven K BoydAdverse Effects of High-Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than MalesJ Bone Miner Res.(2020 Dec)
4.^Wolpowitz D, Gilchrest BAThe vitamin D questions: how much do you need and how should you get itJ Am Acad Dermatol.(2006 Feb)
5.^Zhang R, Naughton DPVitamin D in health and disease: current perspectivesNutr J.(2010 Dec 8)
8.^Bartolucci G, Giocaliere E, Boscaro F, Vannacci A, Gallo E, Pieraccini G, Moneti GVitamin D3 quantification in a cod liver oil-based supplementJ Pharm Biomed Anal.(2011 Apr 28)
9.^Monard AM, Berthels J, Nedelkovitch G, Draguet M, Bouche RDetermination of the total vitamin D3 content of cod-liver oil by high-performance liquid chromatographyPharm Acta Helv.(1986)
10.^Porojnicu AC, Bruland OS, Aksnes L, Grant WB, Moan JSun beds and cod liver oil as vitamin D sourcesJ Photochem Photobiol B.(2008 May 29)
12.^Holick MFResurrection of vitamin D deficiency and ricketsJ Clin Invest.(2006 Aug)
14.^Grant WB, Holick MFBenefits and requirements of vitamin D for optimal health: a reviewAltern Med Rev.(2005 Jun)
16.^Prosser DE, Jones GEnzymes involved in the activation and inactivation of vitamin DTrends Biochem Sci.(2004 Dec)
20.^O'Connor PAClouds, skin color, and ricketsPediatrics.(1980 Aug)
22.^Lubin D, Jensen EH, Gies HPGlobal surface ultraviolet radiation climatology from TOMS and ERBE dataJ Geophys Res-Atmos.(1998 Aug)
23.^Coney P, Demers LM, Dodson WC, Kunselman AR, Ladson G, Legro RSDetermination of vitamin D in relation to body mass index and race in a defined population of black and white womenInt J Gynaecol Obstet.(2012 Jul 17)
25.^Manson JE, Rexrode KM, Garland FC, Garland CF, Weinstock MAThe case for a comprehensive national campaign to prevent melanoma and associated mortalityEpidemiology.(2000 Nov)
26.^Garland CF, Garland FC, Gorham EDCould sunscreens increase melanoma riskAm J Public Health.(1992 Apr)
28.^Matsuoka LY, Wortsman J, Hollis BWUse of topical sunscreen for the evaluation of regional synthesis of vitamin D3J Am Acad Dermatol.(1990 May)
29.^Matsuoka LY, Ide L, Wortsman J, MacLaughlin JA, Holick MFSunscreens suppress cutaneous vitamin D3 synthesisJ Clin Endocrinol Metab.(1987 Jun)
30.^Matsuoka LY, Wortsman J, Hanifan N, Holick MFChronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary studyArch Dermatol.(1988 Dec)
32.^Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts JT Jr, Anderson RR, Blank IH, Parrish JA, Elias PPhotosynthesis of previtamin D3 in human skin and the physiologic consequencesScience.(1980 Oct 10)
35.^Binkley N, Gemar D, Engelke J, Gangnon R, Ramamurthy R, Krueger D, Drezner MKEvaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adultsJ Clin Endocrinol Metab.(2011 Apr)
36.^Houghton LA, Vieth RThe case against ergocalciferol (vitamin D2) as a vitamin supplementAm J Clin Nutr.(2006 Oct)
37.^Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum ADVitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin DJ Clin Endocrinol Metab.(2008 Mar)
38.^Biancuzzo RM, Young A, Bibuld D, Cai MH, Winter MR, Klein EK, Ameri A, Reitz R, Salameh W, Chen TC, Holick MFFortification of orange juice with vitamin D(2) or vitamin D(3) is as effective as an oral supplement in maintaining vitamin D status in adultsAm J Clin Nutr.(2010 Jun)
39.^Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WDSerum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferolBone.(2009 Nov)
41.^Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth REvidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2Am J Clin Nutr.(1998 Oct)
42.^Armas LA, Hollis BW, Heaney RPVitamin D2 is much less effective than vitamin D3 in humansJ Clin Endocrinol Metab.(2004 Nov)
43.^Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D'Erasmo E, Carnevale V, Scillitani A, Minisola SShort and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderlyJ Clin Endocrinol Metab.(2008 Aug)
44.^Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hyppönen E, Berry J, Vieth R, Lanham-New SComparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysisAm J Clin Nutr.(2012 Jun)
50.^Visser M, Deeg DJ, Puts MT, Seidell JC, Lips PLow serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admissionAm J Clin Nutr.(2006 Sep)
51.^Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes BEstimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomesAm J Clin Nutr.(2006 Jul)
52.^Ginde AA, Liu MC, Camargo CA JrDemographic differences and trends of vitamin D insufficiency in the US population, 1988-2004Arch Intern Med.(2009 Mar 23)
53.^Brock K, Huang WY, Fraser DR, Ke L, Tseng M, Stolzenberg-Solomon R, Peters U, Ahn J, Purdue M, Mason RS, McCarty C, Ziegler RG, Graubard BLow 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 womenJ Steroid Biochem Mol Biol.(2010 Jul)
54.^Tangpricha V, Pearce EN, Chen TC, Holick MFVitamin D insufficiency among free-living healthy young adultsAm J Med.(2002 Jun 1)
56.^Kull M Jr, Kallikorm R, Tamm A, Lember MSeasonal variance of 25-(OH) vitamin D in the general population of Estonia, a Northern European countryBMC Public Health.(2009 Jan 19)
57.^Hovsepian S, Amini M, Aminorroaya A, Amini P, Iraj BPrevalence of vitamin D deficiency among adult population of Isfahan City, IranJ Health Popul Nutr.(2011 Apr)
58.^Levis S, Gomez A, Jimenez C, Veras L, Ma F, Lai S, Hollis B, Roos BAVitamin d deficiency and seasonal variation in an adult South Florida populationJ Clin Endocrinol Metab.(2005 Mar)
59.^van der Mei IA, Ponsonby AL, Engelsen O, Pasco JA, McGrath JJ, Eyles DW, Blizzard L, Dwyer T, Lucas R, Jones GThe high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitudeEnviron Health Perspect.(2007 Aug)
60.^Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JSHypovitaminosis D in medical inpatientsN Engl J Med.(1998 Mar 19)
61.^Melamed ML, Michos ED, Post W, Astor B25-hydroxyvitamin D levels and the risk of mortality in the general populationArch Intern Med.(2008 Aug 11)
62.^Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, Holick MF, Hollis BW, Lamberg-Allardt C, McGrath JJ, Norman AW, Scragg R, Whiting SJ, Willett WC, Zittermann AThe urgent need to recommend an intake of vitamin D that is effectiveAm J Clin Nutr.(2007 Mar)
63.^Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJHuman serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferolAm J Clin Nutr.(2003 Jan)
66.^Mastaglia SR, Mautalen CA, Parisi MS, Oliveri BVitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic womenEur J Clin Nutr.(2006 May)
67.^Corless D, Dawson E, Fraser F, Ellis M, Evans SJ, Perry JD, Reisner C, Silver CP, Beer M, Boucher BJ, et alDo vitamin D supplements improve the physical capabilities of elderly hospital patientsAge Ageing.(1985 Mar)
68.^Cranney A, Weiler HA, O'Donnell S, Puil LSummary of evidence-based review on vitamin D efficacy and safety in relation to bone healthAm J Clin Nutr.(2008 Aug)
69.^Grant WB, Schuitemaker GEHealth benefits of higher serum 25-hydroxyvitamin D levels in The NetherlandsJ Steroid Biochem Mol Biol.(2010 Jul)
70.^Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MFVitamin D and its major metabolites: serum levels after graded oral dosing in healthy menOsteoporos Int.(1998)
73.^Pepper KJ, Judd SE, Nanes MS, Tangpricha VEvaluation of vitamin D repletion regimens to correct vitamin D status in adultsEndocr Pract.(2009 Mar)
74.^Dawson-Hughes B, Harris SS, Palermo NJ, Ceglia L, Rasmussen HMeal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementationJ Bone Miner Res.(2013 Aug)
75.^Dawson-Hughes B, Harris SS, Lichtenstein AH, Dolnikowski G, Palermo NJ, Rasmussen HDietary fat increases vitamin D-3 absorptionJ Acad Nutr Diet.(2015 Feb)
77.^Papaioannou A, Kennedy CC, Giangregorio L, Ioannidis G, Pritchard J, Hanley DA, Farrauto L, DeBeer J, Adachi JDA randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses over daily supplementationBMC Musculoskelet Disord.(2011 Jun 20)
79.^Kritchevsky SB1, Tooze JA, Neiberg RH, Schwartz GG, Hausman DB, Johnson MA, Bauer DC, Cauley JA, Shea MK, Cawthon PM, Harris TB, Rubin SM, Tylavsky FA, Houston DK; Health ABC Study25-Hydroxyvitamin D, parathyroid hormone, and mortality in black and white older adults: the health ABC studyJ Clin Endocrinol Metab.(2012 Nov)
80.^Smit E, Crespo CJ, Michael Y, Ramirez-Marrero FA, Brodowicz GR, Bartlett S, Andersen REThe effect of vitamin D and frailty on mortality among non-institutionalized US older adultsEur J Clin Nutr.(2012 Jun 13)
81.^Bjelakovic G1, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud CVitamin D supplementation for prevention of mortality in adultsCochrane Database Syst Rev.(2014 Jan 10)
83.^Noordam R, de Craen AJ, Pedram P, Maier AB, Mooijaart SP, van Pelt J, Feskens EJ, Streppel MT, Slagboom PE, Westendorp RG, Beekman M, van Heemst DLevels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity StudyCMAJ.(2012 Dec 11)
86.^Blomberg Jensen M, Dissing SNon-genomic effects of vitamin D in human spermatozoaSteroids.(2012 Aug)
87.^Nemere I1, Farach-Carson MC, Rohe B, Sterling TM, Norman AW, Boyan BD, Safford SERibozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cellsProc Natl Acad Sci U S A.(2004 May 11)
88.^Sequeira VB1, Rybchyn MS, Tongkao-On W, Gordon-Thomson C, Malloy PJ, Nemere I, Norman AW, Reeve VE, Halliday GM, Feldman D, Mason RSThe role of the vitamin D receptor and ERp57 in photoprotection by 1α,25-dihydroxyvitamin D3Mol Endocrinol.(2012 Apr)
89.^Simpson ER1, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, Speed C, Jones MAromatase--a brief overviewAnnu Rev Physiol.(2002)
90.^Yanase T1, Suzuki S, Goto K, Nomura M, Okabe T, Takayanagi R, Nawata HAromatase in bone: roles of Vitamin D3 and androgensJ Steroid Biochem Mol Biol.(2003 Sep)
91.^Krishnan AV, Swami S, Peng L, Wang J, Moreno J, Feldman DTissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapyEndocrinology.(2010 Jan)
93.^Barrera D, Avila E, Hernández G, Halhali A, Biruete B, Larrea F, Díaz LEstradiol and progesterone synthesis in human placenta is stimulated by calcitriolJ Steroid Biochem Mol Biol.(2007 Mar)
94.^Kinuta K, Tanaka H, Moriwake T, Aya K, Kato S, Seino YVitamin D is an important factor in estrogen biosynthesis of both female and male gonadsEndocrinology.(2000 Apr)
98.^Waltman NL, Ott CD, Twiss JJ, Gross GJ, Lindsey AMVitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapyCancer Nurs.(2009 Mar-Apr)
101.^Prieto-Alhambra D, Javaid MK, Servitja S, Arden NK, Martinez-García M, Diez-Perez A, Albanell J, Tusquets I, Nogues XVitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort studyBreast Cancer Res Treat.(2011 Feb)
102.^Rastelli AL, Taylor ME, Gao F, Armamento-Villareal R, Jamalabadi-Majidi S, Napoli N, Ellis MJVitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trialBreast Cancer Res Treat.(2011 Aug)
103.^Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, Hewison MExtrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylaseJ Clin Endocrinol Metab.(2001 Feb)
104.^Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJDistribution of the vitamin D receptor and 1 alpha-hydroxylase in human brainJ Chem Neuroanat.(2005 Jan)
105.^Rothman SM, Olney JWExcitotoxity and the NMDA receptorTrends Neurosci.(1987 Jul)
107.^Choi DWExcitotoxic cell deathJ Neurobiol.(1992 Nov)
108.^Nicotera P, Orrenius SThe role of calcium in apoptosisCell Calcium.(1998 Feb-Mar)
109.^Brewer LD, Thibault V, Chen KC, Langub MC, Landfield PW, Porter NMVitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neuronsJ Neurosci.(2001 Jan 1)
112.^Weiss JH1, Hartley DM, Koh J, Choi DWThe calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicityScience.(1990 Mar 23)
113.^Uematsu D1, Araki N, Greenberg JH, Sladky J, Reivich MCombined therapy with MK-801 and nimodipine for protection of ischemic brain damageNeurology.(1991 Jan)
115.^Dean AJ, Bellgrove MA, Hall T, Phan WM, Eyles DW, Kvaskoff D, McGrath JJEffects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trialPLoS One.(2011)
118.^May HT, Bair TL, Lappé DL, Anderson JL, Horne BD, Carlquist JF, Muhlestein JBAssociation of vitamin D levels with incident depression among a general cardiovascular populationAm Heart J.(2010 Jun)
119.^Armstrong DJ, Meenagh GK, Bickle I, Lee AS, Curran ES, Finch MBVitamin D deficiency is associated with anxiety and depression in fibromyalgiaClin Rheumatol.(2007 Apr)
120.^Shipowick CD, Moore CB, Corbett C, Bindler RVitamin D and depressive symptoms in women during the winter: a pilot studyAppl Nurs Res.(2009 Aug)
121.^Högberg G, Gustafsson SA, Hällström T, Gustafsson T, Klawitter B, Petersson MDepressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementationActa Paediatr.(2012 Jul)
123.^van Loo HM, de Jonge P, Romeijn JW, Kessler RC, Schoevers RAData-driven subtypes of major depressive disorder: a systematic reviewBMC Med.(2012 Dec 4)
124.^Shipowick CD, Moore CB, Corbett C, Bindler RVitamin D and depressive symptoms in women during the winter: a pilot studyAppl Nurs Res.(2009 Aug)
126.^Ascherio A, Munger KL, Simon KCVitamin D and multiple sclerosisLancet Neurol.(2010 Jun)
127.^Compston A, Coles AMultiple sclerosisLancet.(2008 Oct 25)
129.^Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor BLatitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysisJ Neurol Neurosurg Psychiatry.(2011 Oct)
130.^Islam T, Gauderman WJ, Cozen W, Mack TMChildhood sun exposure influences risk of multiple sclerosis in monozygotic twinsNeurology.(2007 Jul 24)
131.^Dalmay F, Bhalla D, Nicoletti A, Cabrera-Gomez JA, Cabre P, Ruiz F, Druet-Cabanac M, Dumas M, Preux PMMultiple sclerosis and solar exposure before the age of 15 years: case-control study in Cuba, Martinique and SicilyMult Scler.(2010 Aug)
132.^Salzer J1, Hallmans G, Nyström M, Stenlund H, Wadell G, Sundström PVitamin D as a protective factor in multiple sclerosisNeurology.(2012 Nov 20)
135.^van Etten E, Gysemans C, Branisteanu DD, Verstuyf A, Bouillon R, Overbergh L, Mathieu CNovel insights in the immune function of the vitamin D system: synergism with interferon-betaJ Steroid Biochem Mol Biol.(2007 Mar)
136.^Wergeland S, Torkildsen Ø, Myhr KM, Aksnes L, Mørk SJ, Bø LDietary vitamin D3 supplements reduce demyelination in the cuprizone modelPLoS One.(2011)
137.^Lu'o'ng KV, Nguyên LTThe beneficial role of vitamin D in Alzheimer's diseaseAm J Alzheimers Dis Other Demen.(2011 Nov)
138.^Annweiler C, Llewellyn DJ, Beauchet OLow Serum Vitamin D Concentrations in Alzheimer's Disease: A Systematic Review and Meta-AnalysisJ Alzheimers Dis.(2012 Oct 5)
139.^Evatt ML, Delong MR, Khazai N, Rosen A, Triche S, Tangpricha VPrevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer diseaseArch Neurol.(2008 Oct)
141.^Gezen-Ak D, Dursun E, Bilgiç B, Hanagasi H, Ertan T, Gürvit H, Emre M, Eker E, Ulutin T, Uysal O, Yilmazer SVitamin d receptor gene haplotype is associated with late-onset Alzheimer's diseaseTohoku J Exp Med.(2012)
142.^Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Beauchet OSerum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal studyDement Geriatr Cogn Disord.(2011)
143.^Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB1α,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-β phagocytosis and inflammation in Alzheimer's disease patientsJ Alzheimers Dis.(2013 Jan 1)
144.^Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel JEpidemiology and etiology of Parkinson's disease: a review of the evidenceEur J Epidemiol.(2011 Jun)
145.^Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara MSerum vitamin D and the risk of Parkinson diseaseArch Neurol.(2010 Jul)
146.^Butler MW, Burt A, Edwards TL, Zuchner S, Scott WK, Martin ER, Vance JM, Wang LVitamin D receptor gene as a candidate gene for Parkinson diseaseAnn Hum Genet.(2011 Mar)
147.^Kim JS, Kim YI, Song C, Yoon I, Park JW, Choi YB, Kim HT, Lee KSAssociation of vitamin D receptor gene polymorphism and Parkinson's disease in KoreansJ Korean Med Sci.(2005 Jun)
148.^Evatt ML, DeLong MR, Kumari M, Auinger P, McDermott MP, Tangpricha V; Parkinson Study Group DATATOP InvestigatorsHigh prevalence of hypovitaminosis D status in patients with early Parkinson diseaseArch Neurol.(2011 Mar)
149.^Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh KAbnormal bone and calcium metabolism in immobilized Parkinson's disease patientsMov Disord.(2005 Dec)
151.^Newmark HL, Newmark JVitamin D and Parkinson's disease--a hypothesisMov Disord.(2007 Mar 15)
152.^Dean ED, Mexas LM, Cápiro NL, McKeon JE, DeLong MR, Pennell KD, Doorn JA, Tangpricha V, Miller GW, Evatt ML25-Hydroxyvitamin D depletion does not exacerbate MPTP-induced dopamine neuron damage in micePLoS One.(2012)
154.^Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, Wang YVitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in ratsBrain Res.(2001 Jun 15)
155.^Gominak SC, Stumpf WEThe world epidemic of sleep disorders is linked to vitamin D deficiencyMed Hypotheses.(2012 Aug)
156.^Bonnet MH, Arand DLWe are chronically sleep deprivedSleep.(1995 Dec)
157.^Van Cauter E, Spiegel K, Tasali E, Leproult RMetabolic consequences of sleep and sleep lossSleep Med.(2008 Sep)
158.^Huang W, Shah S, Long Q, Crankshaw AK, Tangpricha VImprovement of Pain, Sleep, and Quality of Life in Chronic Pain Patients With Vitamin D SupplementationClin J Pain.(2012 Jun 13)
159.^Mucci M, Carraro C, Mancino P, Monti M, Papadia LS, Volpini G, Benvenuti CSoy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopauseMinerva Ginecol.(2006 Aug)
160.^Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RSVitamin D deficiency and risk of cardiovascular diseaseCirculation.(2008 Jan 29)
161.^Wang L, Manson JE, Song Y, Sesso HDSystematic review: Vitamin D and calcium supplementation in prevention of cardiovascular eventsAnn Intern Med.(2010 Mar 2)
162.^Wood AD1, Secombes KR, Thies F, Aucott L, Black AJ, Mavroeidi A, Simpson WG, Fraser WD, Reid DM, Macdonald HMVitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCTJ Clin Endocrinol Metab.(2012 Oct)
163.^Seibert E, Lehmann U, Riedel A, Ulrich C, Hirche F, Brandsch C, Dierkes J, Girndt M, Stangl GIVitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D statusEur J Nutr.(2015 Nov 30)
165.^Krause R, Bühring M, Hopfenmüller W, Holick MF, Sharma AMUltraviolet B and blood pressureLancet.(1998 Aug 29)
166.^Weng S, Sprague JE, Oh J, Riek AE, Chin K, Garcia M, Bernal-Mizrachi CVitamin d deficiency induces high blood pressure and accelerates atherosclerosis in micePLoS One.(2013)
167.^Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin systemJ Clin Invest.(2002 Jul)
168.^Ritthaler T, Scholz H, Ackermann M, Riegger G, Kurtz A, Krämer BKEffects of endothelins on renin secretion from isolated mouse renal juxtaglomerular cellsAm J Physiol.(1995 Jan)
169.^Witham MD, Nadir MA, Struthers ADEffect of vitamin D on blood pressure: a systematic review and meta-analysisJ Hypertens.(2009 Oct)
171.^Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen CEffects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly womenJ Clin Endocrinol Metab.(2001 Apr)
172.^Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YCCardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systemsAm J Physiol Endocrinol Metab.(2005 Jan)
173.^Kong J1, Li YCEffect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null miceAm J Physiol Regul Integr Comp Physiol.(2003 Jul)
176.^Al Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L, Kavtaradze N, Uphoff I, Hooper C, Tangpricha V, Alexander RW, Brigham K, Quyyumi AAVitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humansJ Am Coll Cardiol.(2011 Jul 5)
177.^Yiu YF, Chan YH, Yiu KH, Siu CW, Li SW, Wong LY, Lee SW, Tam S, Wong EW, Cheung BM, Tse HFVitamin D deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetesJ Clin Endocrinol Metab.(2011 May)
178.^Reis JP, Michos ED, von Mühlen D, Miller ER 3rdDifferences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial diseaseAm J Clin Nutr.(2008 Dec)
179.^Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, Stehle P, Koertke H, Koerfer RVitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markersAm J Clin Nutr.(2009 May)
181.^Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, Tabas IThe endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophagesNat Cell Biol.(2003 Sep)
182.^Devries-Seimon T, Li Y, Yao PM, Stone E, Wang Y, Davis RJ, Flavell R, Tabas ICholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptorJ Cell Biol.(2005 Oct 10)
183.^Szeto FL, Reardon CA, Yoon D, Wang Y, Wong KE, Chen Y, Kong J, Liu SQ, Thadhani R, Getz GS, Li YCVitamin D receptor signaling inhibits atherosclerosis in miceMol Endocrinol.(2012 Jul)
184.^Oh J, Riek AE, Weng S, Petty M, Kim D, Colonna M, Cella M, Bernal-Mizrachi CEndoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formationJ Biol Chem.(2012 Apr 6)
186.^Bouhlel MA, Derudas B, Rigamonti E, Dièvart R, Brozek J, Haulon S, Zawadzki C, Jude B, Torpier G, Marx N, Staels B, Chinetti-Gbaguidi GPPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory propertiesCell Metab.(2007 Aug)
187.^Feig JE, Pineda-Torra I, Sanson M, Bradley MN, Vengrenyuk Y, Bogunovic D, Gautier EL, Rubinstein D, Hong C, Liu J, Wu C, van Rooijen N, Bhardwaj N, Garabedian M, Tontonoz P, Fisher EALXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regressionJ Clin Invest.(2010 Dec)
188.^Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AMM-1/M-2 macrophages and the Th1/Th2 paradigmJ Immunol.(2000 Jun 15)
189.^Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PFPlasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adultsJ Nutr.(2009 Feb)
191.^Kelly A, Brooks LJ, Dougherty S, Carlow DC, Zemel BSA cross-sectional study of vitamin D and insulin resistance in childrenArch Dis Child.(2011 May)
192.^Chiu KC, Chu A, Go VL, Saad MFHypovitaminosis D is associated with insulin resistance and beta cell dysfunctionAm J Clin Nutr.(2004 May)
193.^Nazarian S, St Peter JV, Boston RC, Jones SA, Mariash CNVitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucoseTransl Res.(2011 Nov)
194.^Choi HS, Kim KA, Lim CY, Rhee SY, Hwang YC, Kim KM, Kim KJ, Rhee Y, Lim SKLow serum vitamin D is associated with high risk of diabetes in Korean adultsJ Nutr.(2011 Aug)
195.^Knekt P, Laaksonen M, Mattila C, Härkänen T, Marniemi J, Heliövaara M, Rissanen H, Montonen J, Reunanen ASerum vitamin D and subsequent occurrence of type 2 diabetesEpidemiology.(2008 Sep)
198.^Foss YJVitamin D deficiency is the cause of common obesityMed Hypotheses.(2009 Mar)
200.^Hunt G1, Roy KClimate change, body size evolution, and Cope's Rule in deep-sea ostracodesProc Natl Acad Sci U S A.(2006 Jan 31)
201.^Zhang Z, Zhang ZComment on "Vitamin D deficiency is the cause of common obesity"Med Hypotheses.(2009 Jul)
202.^Zamboni G, Soffiati M, Giavarina D, Tató LMineral metabolism in obese childrenActa Paediatr Scand.(1988 Sep)
203.^Yanoff LB, Parikh SJ, Spitalnik A, Denkinger B, Sebring NG, Slaughter P, McHugh T, Remaley AT, Yanovski JAThe prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese Black AmericansClin Endocrinol (Oxf).(2006 May)
204.^Sutherland ER, Goleva E, Jackson LP, Stevens AD, Leung DYVitamin D levels, lung function, and steroid response in adult asthmaAm J Respir Crit Care Med.(2010 Apr 1)
205.^Josefson JL, Feinglass J, Rademaker AW, Metzger BE, Zeiss DM, Price HE, Langman CBMaternal obesity and vitamin D sufficiency are associated with cord blood vitamin D insufficiencyJ Clin Endocrinol Metab.(2013 Jan)
206.^Bell NH, Epstein S, Greene A, Shary J, Oexmann MJ, Shaw SEvidence for alteration of the vitamin D-endocrine system in obese subjectsJ Clin Invest.(1985 Jul)
207.^Vimaleswaran KS1, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, Salomaa V, Campbell H, Dunlop M, Mitchell BD, Herzig KH, Pouta A, Hartikainen AL; Genetic Investigation of Anthropometric Traits-GIANT Consortium, Streeten EA, Theodoratou E, Jula A, Wareham NJ, Ohlsson C, Frayling TM, Kritchevsky SB, Spector TD, Richards JB, Lehtimäki T, Ouwehand WH, Kraft P, Cooper C, März W, Power C, Loos RJ, Wang TJ, Järvelin MR, Whittaker JC, Hingorani AD, Hyppönen ECausal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohortsPLoS Med.(2013)
210.^Salehpour A1, Hosseinpanah F, Shidfar F, Vafa M, Razaghi M, Dehghani S, Hoshiarrad A, Gohari MA 12-week double-blind randomized clinical trial of vitamin D₃ supplementation on body fat mass in healthy overweight and obese womenNutr J.(2012 Sep 22)
211.^Norman AWReceptors for 1alpha,25(OH)2D3: past, present, and futureJ Bone Miner Res.(1998 Sep)
212.^Nemere I, Schwartz Z, Pedrozo H, Sylvia VL, Dean DD, Boyan BDIdentification of a membrane receptor for 1,25-dihydroxyvitamin D3 which mediates rapid activation of protein kinase CJ Bone Miner Res.(1998 Sep)
215.^de Boland AR, Boland RL1,25-Dihydroxyvitamin D-3 induces arachidonate mobilization in embryonic chick myoblastsBiochim Biophys Acta.(1993 Oct 7)
216.^Li YC, Pirro AE, Amling M, Delling G, Baron R, Bronson R, Demay MBTargeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopeciaProc Natl Acad Sci U S A.(1997 Sep 2)
217.^Wang Y, Becklund BR, DeLuca HFIdentification of a highly specific and versatile vitamin D receptor antibodyArch Biochem Biophys.(2010 Feb 15)
222.^Minasyan A, Keisala T, Zou J, Zhang Y, Toppila E, Syvälä H, Lou YR, Kalueff AV, Pyykkö I, Tuohimaa PVestibular dysfunction in vitamin D receptor mutant miceJ Steroid Biochem Mol Biol.(2009 Apr)
223.^Kalueff AV, Lou YR, Laaksi I, Tuohimaa PImpaired motor performance in mice lacking neurosteroid vitamin D receptorsBrain Res Bull.(2004 Jul 30)
224.^Endo I, Inoue D, Mitsui T, Umaki Y, Akaike M, Yoshizawa T, Kato S, Matsumoto TDeletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factorsEndocrinology.(2003 Dec)
225.^Owens DJ, Sharples AP, Polydorou I, Alwan N, Donovan T, Tang J, Fraser WD, Cooper RG, Morton JP, Stewart C, Close GLA systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophyAm J Physiol Endocrinol Metab.(2015 Dec 15)
226.^Gilsanz V, Kremer A, Mo AO, Wren TA, Kremer RVitamin D status and its relation to muscle mass and muscle fat in young womenJ Clin Endocrinol Metab.(2010 Apr)
227.^Goswami R, Vatsa M, Sreenivas V, Singh U, Gupta N, Lakshmy R, Aggarwal S, Ganapathy A, Joshi P, Bhatia HSkeletal muscle strength in young Asian Indian females after vitamin D and calcium supplementation: a double-blind randomized controlled clinical trialJ Clin Endocrinol Metab.(2012 Dec)
228.^Cannell JJ, Hollis BW, Sorenson MB, Taft TN, Anderson JJAthletic performance and vitamin DMed Sci Sports Exerc.(2009 May)
229.^Galan F, Ribas J, Sánchez-Martinez PM, Calero T, Sánchez AB, Muñoz ASerum 25-hydroxyvitamin D in early autumn to ensure vitamin D sufficiency in mid-winter in professional football playersClin Nutr.(2012 Feb)
230.^Shindle MK, Voos J, Gulotta L, Weiss L, Rodeo S, Kelly B, Lyman S, Lane J, Barnes R, Warren RVitamin D Status in a Professional American Football Team: 2008: Board #203 June 2 9:00 AM - 10:30 AMMed Sci Sports Exerc.(2011 May)
231.^Halliday TM, Peterson NJ, Thomas JJ, Kleppinger K, Hollis BW, Larson-Meyer DEVitamin D status relative to diet, lifestyle, injury, and illness in college athletesMed Sci Sports Exerc.(2011 Feb)
232.^Burgi AA, Gorham ED, Garland CF, Mohr SB, Garland FC, Zeng K, Thompson K, Lappe JMHigh serum 25-hydroxyvitamin D is associated with a low incidence of stress fracturesJ Bone Miner Res.(2011 Oct)
233.^Atkins GJ, Anderson PH, Findlay DM, Welldon KJ, Vincent C, Zannettino AC, O'Loughlin PD, Morris HAMetabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha,25-dihydroxyvitamin D3Bone.(2007 Jun)
234.^van Leeuwen JP, van Driel M, van den Bemd GJ, Pols HAVitamin D control of osteoblast function and bone extracellular matrix mineralizationCrit Rev Eukaryot Gene Expr.(2001)
235.^van Driel M, Pols HA, van Leeuwen JPOsteoblast differentiation and control by vitamin D and vitamin D metabolitesCurr Pharm Des.(2004)
236.^Atkins GJ, Kostakis P, Pan B, Farrugia A, Gronthos S, Evdokiou A, Harrison K, Findlay DM, Zannettino ACRANKL expression is related to the differentiation state of human osteoblastsJ Bone Miner Res.(2003 Jun)
237.^Matsumoto T, Igarashi C, Takeuchi Y, Harada S, Kikuchi T, Yamato H, Ogata EStimulation by 1,25-dihydroxyvitamin D3 of in vitro mineralization induced by osteoblast-like MC3T3-E1 cellsBone.(1991)
238.^Ruohola JP, Laaksi I, Ylikomi T, Haataja R, Mattila VM, Sahi T, Tuohimaa P, Pihlajamäki HAssociation between serum 25(OH)D concentrations and bone stress fractures in Finnish young menJ Bone Miner Res.(2006 Sep)
240.^Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson KCalcium and vitamin d supplementation decreases incidence of stress fractures in female navy recruitsJ Bone Miner Res.(2008 May)
242.^Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JBEffect of Vitamin D on falls: a meta-analysisJAMA.(2004 Apr 28)
244.^Gillespie LD, Robertson MC, Gillespie WJ, Sherrington C, Gates S, Clemson LM, Lamb SEInterventions for preventing falls in older people living in the communityCochrane Database Syst Rev.(2012 Sep 12)
245.^Glover TL1, Goodin BR, Horgas AL, Kindler LL, King CD, Sibille KT, Peloquin CA, Riley JL 3rd, Staud R, Bradley LA, Fillingim RBVitamin D, race, and experimental pain sensitivity in older adults with knee osteoarthritisArthritis Rheum.(2012 Dec)
247.^Riek AE1, Oh J, Sprague JE, Timpson A, de las Fuentes L, Bernal-Mizrachi L, Schechtman KB, Bernal-Mizrachi CVitamin D suppression of endoplasmic reticulum stress promotes an antiatherogenic monocyte/macrophage phenotype in type 2 diabetic patientsJ Biol Chem.(2012 Nov 9)
249.^Barton M, Sidbury RAdvances in understanding and managing atopic dermatitisF1000Res.(2015 Nov 19)
251.^Williams H, Robertson C, Stewart A, Aït-Khaled N, Anabwani G, Anderson R, Asher I, Beasley R, Björkstén B, Burr M, Clayton T, Crane J, Ellwood P, Keil U, Lai C, Mallol J, Martinez F, Mitchell E, Montefort S, Pearce N, Shah J, Sibbald B, Strachan D, von Mutius E, Weiland SKWorldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in ChildhoodJ Allergy Clin Immunol.(1999 Jan)
252.^Amestejani M, Salehi BS, Vasigh M, Sobhkhiz A, Karami M, Alinia H, Kamrava SK, Shamspour N, Ghalehbaghi B, Behzadi AHVitamin D supplementation in the treatment of atopic dermatitis: a clinical trial studyJ Drugs Dermatol.(2012 Mar)
253.^Holick MFVitamin D deficiencyN Engl J Med.(2007 Jul 19)
254.^Wehr E, Pilz S, Boehm BO, März W, Obermayer-Pietsch BAssociation of vitamin D status with serum androgen levels in menClin Endocrinol (Oxf).(2010 Aug)
256.^Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann AEffect of vitamin D supplementation on testosterone levels in menHorm Metab Res.(2011 Mar)
257.^Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FCVitamin D and prevention of breast cancer: pooled analysisJ Steroid Biochem Mol Biol.(2007 Mar)
258.^Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MFThe role of vitamin D in cancer preventionAm J Public Health.(2006 Feb)
260.^Gorham ED, Garland CF, Garland FCAcid haze air pollution and breast and colon cancer mortality in 20 Canadian citiesCan J Public Health.(1989 Mar-Apr)
261.^Peppone LJ, Huston AJ, Reid ME, Rosier RN, Zakharia Y, Trump DL, Mustian KM, Janelsins MC, Purnell JQ, Morrow GRThe effect of various vitamin D supplementation regimens in breast cancer patientsBreast Cancer Res Treat.(2011 May)
262.^Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BAHypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994Am J Clin Nutr.(2002 Jul)
263.^Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O'Sullivan MJ, Yasmeen S, Hiatt RA, Shikany JM, Vitolins M, Khandekar J, Hubbell FA; Women's Health Initiative InvestigatorsCalcium plus vitamin D supplementation and the risk of breast cancerJ Natl Cancer Inst.(2008 Nov 19)
265.^Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MFOptimal vitamin D status for colorectal cancer prevention: a quantitative meta analysisAm J Prev Med.(2007 Mar)
266.^Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CSVitamin D intake and the risk for pancreatic cancer in two cohort studiesCancer Epidemiol Biomarkers Prev.(2006 Sep)
267.^Garland CF, Mohr SB, Gorham ED, Grant WB, Garland FCRole of ultraviolet B irradiance and vitamin D in prevention of ovarian cancerAm J Prev Med.(2006 Dec)
268.^Vashi PG, Lammersfeld CA, Braun DP, Gupta DSerum 25-hydroxyvitamin D is inversely associated with body mass index in cancerNutr J.(2011 May 16)
270.^Searing DA, Zhang Y, Murphy JR, Hauk PJ, Goleva E, Leung DYDecreased serum vitamin D levels in children with asthma are associated with increased corticosteroid useJ Allergy Clin Immunol.(2010 May)
271.^Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida HRandomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildrenAm J Clin Nutr.(2010 May)
272.^Lange NE1, Sparrow D, Vokonas P, Litonjua AAVitamin D deficiency, smoking, and lung function in the Normative Aging StudyAm J Respir Crit Care Med.(2012 Oct 1)
273.^Camargo CA Jr1, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman K, Sumberzul N, Rich-Edwards JWRandomized trial of vitamin D supplementation and risk of acute respiratory infection in MongoliaPediatrics.(2012 Sep)
274.^Aloia JF, Li-Ng MRe: epidemic influenza and vitamin DEpidemiol Infect.(2007 Oct)
275.^Murdoch DR1, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC, Florkowski CM, Livesey JH, Camargo CA, Scragg REffect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trialJAMA.(2012 Oct 3)
279.^Blomberg Jensen M, Nielsen JE, Jørgensen A, Rajpert-De Meyts E, Kristensen DM, Jørgensen N, Skakkebaek NE, Juul A, Leffers HVitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tractHum Reprod.(2010 May)
280.^Yoshida M, Kawano N, Yoshida KControl of sperm motility and fertility: diverse factors and common mechanismsCell Mol Life Sci.(2008 Nov)
282.^Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay MVitamin D and human health: lessons from vitamin D receptor null miceEndocr Rev.(2008 Oct)
283.^Kwiecinski GG, Petrie GI, DeLuca HFVitamin D is necessary for reproductive functions of the male ratJ Nutr.(1989 May)
284.^Blomberg Jensen M, Bjerrum PJ, Jessen TE, Nielsen JE, Joensen UN, Olesen IA, Petersen JH, Juul A, Dissing S, Jørgensen NVitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoaHum Reprod.(2011 Jun)
285.^Hammoud AO, Wayne Meikle A, Matthew Peterson C, Stanford J, Gibson M, Carrell DTAssociation of 25-hydroxy-vitamin D levels with semen and hormonal parametersAsian J Androl.(2012 Nov)
286.^Yang B, Sun H, Wan Y, Wang H, Qin W, Yang L, Zhao H, Yuan J, Yao BAssociations between testosterone, bone mineral density, vitamin D and semen quality in fertile and infertile Chinese menInt J Androl.(2012 Jun 19)
288.^van der Meer IM, Karamali NS, Boeke AJ, Lips P, Middelkoop BJ, Verhoeven I, Wuister JDHigh prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, NetherlandsAm J Clin Nutr.(2006 Aug)
289.^Haliloglu B, Ilter E, Aksungar FB, Celik A, Coksuer H, Gunduz T, Yucel E, Ozekici UBone turnover and maternal 25(OH) vitamin D3 levels during pregnancy and the postpartum period: should routine vitamin D supplementation be increased in pregnant womenEur J Obstet Gynecol Reprod Biol.(2011 Sep)
290.^Johnson DD, Wagner CL, Hulsey TC, McNeil RB, Ebeling M, Hollis BWVitamin D deficiency and insufficiency is common during pregnancyAm J Perinatol.(2011 Jan)
291.^Hamilton SA, McNeil R, Hollis BW, Davis DJ, Winkler J, Cook C, Warner G, Bivens B, McShane P, Wagner CLProfound Vitamin D Deficiency in a Diverse Group of Women during Pregnancy Living in a Sun-Rich Environment at Latitude 32°NInt J Endocrinol.(2010)
292.^Gernand AD, Simhan HN, Klebanoff MA, Bodnar LMMaternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort studyJ Clin Endocrinol Metab.(2013 Jan)
293.^Sørensen IM, Joner G, Jenum PA, Eskild A, Torjesen PA, Stene LCMaternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspringDiabetes.(2012 Jan)
294.^Erkkola M, Kaila M, Nwaru BI, Kronberg-Kippilä C, Ahonen S, Nevalainen J, Veijola R, Pekkanen J, Ilonen J, Simell O, Knip M, Virtanen SMMaternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old childrenClin Exp Allergy.(2009 Jun)
295.^Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MFAssociation between vitamin D deficiency and primary cesarean sectionJ Clin Endocrinol Metab.(2009 Mar)
297.^Yu CK, Sykes L, Sethi M, Teoh TG, Robinson SVitamin D deficiency and supplementation during pregnancyClin Endocrinol (Oxf).(2009 May)
299.^Terrier B, Derian N, Schoindre Y, Chaara W, Geri G, Zahr N, Mariampillai K, Rosenzwajg M, Carpentier W, Musset L, Piette JC, Six A, Klatzmann D, Saadoun D, Cacoub P, Costedoat-Chalumeau NRestoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementationArthritis Res Ther.(2012 Oct 17)
302.^Arvold DS, Odean MJ, Dornfeld MP, Regal RR, Arvold JG, Karwoski GC, Mast DJ, Sanford PB, Sjoberg RJCorrelation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trialEndocr Pract.(2009 Apr)
303.^Bischoff-Ferrari HA, Borchers M, Gudat F, Dürmüller U, Stähelin HB, Dick WVitamin D receptor expression in human muscle tissue decreases with ageJ Bone Miner Res.(2004 Feb)
304.^Bischoff HA, Stahelin HB, Urscheler N, Ehrsam R, Vonthein R, Perrig-Chiello P, Tyndall A, Theiler RMuscle strength in the elderly: its relation to vitamin D metabolitesArch Phys Med Rehabil.(1999 Jan)
307.^Verhaar HJ, Samson MM, Jansen PA, de Vreede PL, Manten JW, Duursma SAMuscle strength, functional mobility and vitamin D in older womenAging (Milano).(2000 Dec)
309.^Heaney RP, Dowell MS, Hale CA, Bendich ACalcium absorption varies within the reference range for serum 25-hydroxyvitamin DJ Am Coll Nutr.(2003 Apr)
310.^Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud CVitamin D supplementation for prevention of mortality in adultsCochrane Database Syst Rev.(2011 Jul 6)
311.^Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YLSerum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasiaCancer Epidemiol Biomarkers Prev.(2007 Sep)
312.^Khajehei M, Abdali K, Parsanezhad ME, Tabatabaee HREffect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndromeInt J Gynaecol Obstet.(2009 May)