Vitamin D is a fat-soluble vitamin that is naturally present in very few foods. It helps fight against cancer, improves physical performance, prevents osteoporosis, helps promote brain function and reduces depression. Deficiency of this vitamin may lead to brain disorders like Parkinson’s and Alzheimer’s.

What is Vitamin D?

Vitamin D, also known as the “sunshine vitamin”, is an essential fat-soluble vitamin. 

It can either be obtained in the diet, through food and dietary supplements or synthesized in the skin upon exposure to sunlight [1].

Although classified as a vitamin, it should be considered a prohormone because it is involved in many metabolic processes in the body [2, 3].

Vitamin D plays a role in calcium and phosphorus balance important in bone health, and nerve and muscle activity.

It also regulates blood pressure, immune function, cell production, and insulin secretion [4, 5, 6].

It plays a potential role in the prevention and therapy of cancer and chronic conditions such as autoimmune disorders, cardiovascular disease, and infections [7].

Health Benefits of Vitamin D

It’s important to note that many of the studies regarding vitamin D are association studies, which means that deficiency is correlated with a certain issue, but doesn’t necessarily cause that issue. However, in many of these cases, the reason why people’s health is worse is because they aren’t getting enough sun, rather than being deficient in vitamin D. The sun has a lot of health benefits that are independent of vitamin D. So low vitamin D is often more of a signal that someone isn’t getting enough sun, which is the real cause of the health problem.

1) Crucial to Bone Health

Vitamin D maintains calcium and phosphorus balance in the body [4, 8].

It promotes calcium and phosphorus absorption from the gut, calcium reabsorption in the kidney, and calcium mobilization in bone [9].

It suppresses parathyroid hormone and reduces bone degradation thus indirectly increasing bone mass [10, 11].

Vitamin D is needed for bone growth and formation by bone cells.

It regulates the growth and function of human bone-forming cells (osteoblasts) [12, 13].

Furthermore, higher doses of this vitamin stimulate cells that degrade bone (osteoclast) due to its narrow therapeutic range [11, 14].

2) Prevents Rickets and Osteomalacia

Vitamin D deficiency causes rickets in infants, young children, and adolescents and osteomalacia in adults [15, 3].

Rickets is characterized by a delay in the mineralization of growth cartilage.

Bones soften over time and become deformed, leading to growth retardation, enlargement of the epiphyses of the long bones, and leg deformities [3, 16].

Maternal vitamin deficiency can affect skeletal development of fetuses

In a study of 424 pregnant women, mothers with vitamin D deficiency were more likely to have fetuses with femoral bones that had rachitic features [17].

Osteomalacia is an absence or delay in the mineralization of newly formed bone collagen [16, 18].

Adults with osteomalacia may experience global bone discomfort, and muscle aches and weakness [16].

Osteomalacia and rickets attributable to vitamin deficiency are preventable with adequate nutritional intake of this vitamin.

Varying doses and treatment regimes have been described with the aim is to achieve a blood level between 20 and 50 ng/mL [19].

3) Prevents Osteoporosis and Fractures

Low blood levels of vitamin D are associated with lower bone mineral density, mineralization defects, and an increased risk of bone loss or fracture in both men and women [20, 21, 22, 23].

This vitamin should be considered for the therapy of osteoporosis, alone or in a combination with other therapeutic bone agents [24, 25].

Studies show that in adults aged 50 years or older, vitamin D supplementation in combination with calcium has beneficial effects on bone mineral density, osteoporotic fractures and falls without evidence of harm [26, 27, 28].

In elderly women that were given 1,200 mg of calcium and 800 IU of vitamin D3 daily for 3 years, the risk of hip fracture was reduced by 43%.

The risk of fracture was reduced by 32% [29].

Populations that shield themselves from the sun or who have dark skin, African American and Hispanic men, may be at elevated risk of vitamin deficiency and fractures [30, 23].

However, annual administration of high doses of vitamin D (500,000 IU) resulted in an increased risk of falls and fractures in older community-dwelling women [31].

4) Can Improve Physical Performance

Clinical evidence suggests that vitamin D plays a role in muscle metabolism and function [32].

Hence the function of the muscle is either of an indirect nature or does not involve the known receptor [33].

Supplementation with this vitamin has been shown to improve muscle strength, balance, and physical performance.

It reduces falls in diverse settings including adolescents, the elderly, and chronic kidney disease patients [34, 35, 36].

Supplementation also reduced the risk of falls by more than 20% [37].

Vitamin D may increase muscle strength by improving the atrophy of type II muscle fibers, which may lead to decreased falls and hip fractures [38].

Insufficiency of this vitamin is associated with increased fat infiltration in the muscles of healthy young women [39].

It may improve athletic performance in vitamin D-deficient athletes.

This vitamin deficiency appears to be correlated with increased risk of illness and injury among athletes, especially in regards to stress fractures [40, 41, 42].

5) May Protect Against Cancer

The majority of studies found that sufficient vitamin D protects against cancer and the risk of dying [43].

Vitamin D and its byproducts inhibit the spreading of cancer and cancer cell growth. It also induces cancer cell death.

As a result, it reduces the potential for the cancerous cell to survive [44, 45, 46, 47].

Breast Cancer

Women with a high dietary intake of this vitamin and regular exposure to sunlight had a significantly lower incidence, recurrence, and risk of dying from breast cancer [48, 49].

Intake of 2,000 IU/day of Vitamin D is associated with a reduction by 50% in the incidence of breast cancer [50].

Low vitamin levels were also associated with faster progression of metastatic breast cancer [50, 51, 52, 53, 54, 55].

In breast cancer cells, estrogen production and aromatase enzyme activity decreased, while the production of androgens (testosterone, DHT) increased [56].

Breast cancer patients must maintain adequate levels of this vitamin to minimize medical complications associated with its deficiency including bone loss, falls, fractures, and infection [57, 58, 59].

Some studies did not show an association between higher vitamin D intakes and lower breast cancer risk in postmenopausal women.

Daily supplementation with 1,000 mg of calcium combined with 400 IU of vitamin D3 had no effect on breast cancer incidence [60, 61].

Colon Cancer

Epidemiological studies reported that higher blood levels of vitamin D are associated with a lower risk of colorectal cancer [43, 62, 63].

Daily intake of 1,000 – 2,000 IU/day of this vitamin could reduce the incidence of colorectal cancer by 50% [64].

Prostate Cancer

Risk of dying from prostate cancer goes down in people who get more UVB, the principal source of Vitamin D [65, 66].

Deficiency of this vitamin may increase the risk of initiation and progression of prostate cancer [67, 68].

In prostate cancer cells, vitamin D deficiency increases the production of androgens (testosterone and dihydrotestosterone) [69], which increases the growth of prostate cancer.

Pancreatic Cancer

Higher intakes of vitamin D were associated with lower risks for pancreatic cancer.

Doses of 600 IU/d or more of this vitamin lowered the risk of pancreatic cancer by 41% [70].

Ovarian Cancer

It has been shown that low vitamin D levels are present in ovarian cancer patients, and are associated with lower overall survival rate [71].

Ultraviolet B (UVB) radiation is associated with a lower risk of ovarian cancer [72].

6) Beneficial for Brain Development and Function

Vitamin D is considered a hormone active in the brain (neurosteroid) [73, 74].

The vitamin D receptor (VDR) and the enzyme responsible for the synthesis of the active form of this vitamin are present in the brain [75, 76, 77].

Studies indicate that this vitamin is important for brain development.

And its deficiency is associated with a wide range of psychiatric and neurological diseases [73, 78, 79, 80].

It may protect brain cells through detoxification pathways (production of the antioxidant glutathione, inhibition of nitric oxide). 

Furthermore, it also helps the synthesis of proteins necessary for the survival of brain cells in aging and neurological diseases (neurotrophins) [81, 82, 83].

Epidemiological studies show that low concentrations of vitamin D are associated with:

  • impairments in cognitive functions such as memory and orientation [84, 85, 86].
  • diagnosis of dementia and Alzheimer’s disease [87].
  • higher rates of psychotic experiences and schizophrenia [88, 89, 90].
  • depressive symptoms [91, 92, 93].

7) Improves Cognitive Functions

Studies suggest that low levels of blood vitamin D are associated with low mood, impaired cognitive functions, and dementia [86, 85, 94, 84].

While other studies suggest that blood levels of this vitamin do not influence cognitive or emotional functioning.

Supplementation of 5,000 IU/daily of this vitamin for 6 weeks did not have beneficial effects on memory, depression, anxiety or anger [95, 96].

8) Reduces Depression

Deficiency of vitamin D was associated with an 8 14% increase in the prevalence of depression.

And a 50% increase in suicide rates [97, 98].

Supplementation may reduce depressive symptoms, and improve physical functioning in patients with depression [99, 100].

Also, some studies showed that supplementation of this vitamin neither worsened nor improved depressive symptoms.

In elderly postmenopausal women, there was no effect of hormone therapy and vitamin D either individually or in combination on depression [101].

9) Reduces the Risk of Parkinson’s Disease

Vitamin D deficiency may contribute to the development of Parkinson’s disease.

It is present early in the disease, and vitamin levels tend to decline further as the disease progresses [102, 103, 104].

Chronically inadequate intake of this vitamin leads to a loss of dopaminergic neurons in the substantia nigra, the region of the brain affected most by Parkinson’s disease [104, 105, 106].

Higher vitamin D blood levels are associated with reduced risk of developing Parkinson’s disease.

Individuals with a blood vitamin concentration of at least 50 nmol/l had a 65% lower risk than those with values under 25 nmol/l [105].

Patients with Parkinson’s disease are more likely to have an insufficiency of this vitamin compared to age-matched patients with Alzheimer’s disease [102, 103].

10) Plays a Role in Alzheimer’s Disease

Vitamin D deficiency is prevalent in Alzheimer’s disease and dementia patients.

Alzheimer’s disease patients have lower blood concentrations of this vitamin compared to age-matched healthy individuals [107, 108].

Blood levels of this vitamin less than 50 nmol/L were associated with a higher risk of Alzheimer’s disease and dementia [109].

Vitamin D stimulates immune cells to break down the buildup of amyloid-β protein in the brain, playing a role in causing Alzheimer’s disease [110, 111].

11) Beneficial in Multiple Sclerosis

Higher vitamin D blood levels protect from developing multiple sclerosis.

In women, each 10 nmol/L increase in blood vitamin levels was associated with a 20% decreased the risk of multiple sclerosis [112, 113, 114].

Also, higher vitamin D levels were associated with a reduced worsening and recurrence of multiple sclerosis symptoms.

Each 10 nmol/l increase resulted in up to a 12% reduction in recurrence [115, 116].

Optimal blood concentrations of this vitamin may decrease disease-related complications, including increased bone degradation, fractures, and muscle weakness [117].

Increased sun exposure during ages 6 – 15 years is associated with a decreased risk of multiple sclerosis.

In addition, outdoor activities are associated with a reduced multiple sclerosis risk [118, 119].

Multiple sclerosis occurs less often if this vitamin is abundant, as in sunny climates, high altitudes, and areas with a diet rich in fish oils [120].

Vitamin D has an anti-inflammatory action in multiple sclerosis.

It decreases secretion of inflammatory cytokines and results in a shift from a Th1 to a Th2 phenotype [121, 122].

12) Improves Sleep Quality

Vitamin D could be important for sleep disorders [123].

Higher concentrations of this vitamin were associated with better maintenance of sleep [124].

In the National Health and Nutrition Examination Survey (NHANES) study, lower vitamin levels were associated with shorter sleep duration [123].

Some studies suggest improved sleep quality with vitamin D supplementation.

It has been hypothesized that its deficiency is central to a recent ‘epidemic’ of disturbed sleep patterns [125125].

Studies have reported a high prevalence of this vitamin deficiency in obstructive sleep apnea syndrome.

This is a widespread disorder characterized by episodes of breathing cessation due to upper airway tract obstruction during sleep [126].

Its deficiency is more pronounced in severe sleep apnea and associated with abnormal glucose production [127, 128].

More studies are needed to prove this relationship between sleep quality and vitamin D supplementation.

13) Reduces the Risk of Cardiovascular Disease

Vitamin D deficiency is associated with increased risk of cardiovascular disease, including hypertension, heart attack, peripheral arterial disease, and stroke [129, 130, 131].

Vitamin D receptor and 1α-hydroxylase are present heart and blood vessels, suggesting a potential role in cardiovascular disease [132, 133, 134].

A study showed that this vitamin supplementation or UVB irradiation may lower blood pressure, improve blood pressure control, and regress heart enlargement.

Its deficiency causes atherosclerosis and blood vessel dysfunction, predisposing individuals to the development of cardiovascular disease [135, 136, 137].

Low levels of vitamin D and decreased exposure to sunlight are associated with an increased risk of heart disease [138, 139, 140].

However, some studies show the opposite findings.

Daily supplementation with 800 IU vitamin D for 12 weeks did not impact blood pressure, renin and fat concentrations, markers of cardiovascular disease [141].

Study of healthy postmenopausal women, given 400 IU/day or 1,000 IU/day vitamin D for a period of 1 year, showed no significant benefit to heart disease risk [142].

14) Reduces Blood Pressure

Skin exposure to UVB radiation is associated with lower blood pressure [143].

Blood pressure is affected by variations in skin color, geographic region and season [143].

Blood pressure was significantly decreased after 6 weeks of therapy in individuals receiving UVB therapy [144].

This vitamin decreases the activity of the renin-angiotensin system.

In vitamin D-sufficient hypertensive rats, oral administration of vitamin D decreased blood pressure by suppression of the renin-angiotensin system [135, 145].

In vitamin D deficient elderly women, there was a 9% decrease in systolic blood pressure (by 13 mmHg) with supplemental vitamin D and calcium compared with calcium alone [146].

Studies including more than 1,800 patients found an increased risk of high blood pressure in those with vitamin D level <50 nmol/L compared to those >75 nmol/L.

However, studies conducted in women and elderly demonstrated no effect of vitamin D supplementation on blood pressure [147, 148, 147].

15) May Decrease the Risk of Type 1 and Type 2 Diabetes

Vitamin D plays a role in insulin production and secretion from pancreatic cells [149].

Its deficiency leads to impaired glucose and insulin secretion, and increased risk of type 1 and type 2 diabetes mellitus [150, 151, 152, 153, 154, 155, 156].

Studies show that supplementation with this vitamin restored insulin secretion [157, 153, 158, 159].

Vitamin D deficiency in early life predisposes to the later development of type 1 diabetes and its complications [160, 161].

A study found that an intake of 2,000 IU of this vitamin during the first year of life diminished the risk of developing type 1 diabetes (162).

The Diabetes Autoimmunity Study in the Young (DAISY) reported an increased presence of antibodies against pancreatic cells in newborns of mothers with low intake of this vitamin during pregnancy [163].

Studies have demonstrated that blood vitamin concentrations are lower in patients with type 2 diabetes [164, 165, 166].

In the Women’s Health Study, an intake of 511 IU/day of vitamin D or more was associated with a lower risk of type 2 diabetes [167].

It may have a role in delaying the progression to diabetes in adults at high risk of type 2 diabetes.

Supplementation was associated with an improved function of pancreatic cells [168].

It also had an effect on the rise of Hb A1C (shows average blood sugar levels over a period of weeks/months) that occurs over time [168].

16) Prevents Obesity and Metabolic Syndrome

Being overweight or obese is associated with decreased blood concentrations of vitamin D [169, 170].

There is genetic evidence that a higher body mass index (BMI) leads to lower vitamin D status [171].

Lower blood concentrations are associated with higher waist circumference, and percentage of total body fat in children, adolescents, and adults [172, 173, 174, 175, 176].

Obese individuals need higher vitamin doses than lean individuals to achieve the same vitamin D concentrations in the blood [177, 178, 179].

12-week supplementation with 25 μg of vitamin D in overweight and obese women decreased body fat mass by 7% but did not affect body weight and waist circumference [180].

Obese African Americans are at particularly high risk for this vitamin deficiency.

Physicians should consider routine supplementation or screening of these patients for low vitamin D levels [181].

Deficiency of this vitamin may be a risk factor for metabolic syndrome [182, 183, 184].

Higher blood levels of vitamin D were associated with a decrease in the prevalence of the components of metabolic syndrome (elevated blood pressure, elevated triglycerides, and reduced high-density lipoprotein cholesterol) in postmenopausal women [185].

17) Anti-Inflammatory

Studies have shown potent effects of vitamin D on both innate and adaptive immunity.

It has the potential to influence a wide range of immune disorders, particularly infectious and autoimmune diseases [186, 187].

Cells involved in innate and adaptive immune responses (macrophages, dendritic cells, T cells and B cells) express the vitamin D receptor and synthesize the active vitamin D byproduct [188, 189].

Effects of vitamin D on the immune system include:

  • Inhibits B cell production, and antibody secretion [190, 191]
  • Decreases T cell growth, inhibits T cell activation and IL-2 production [192, 193]
  • Results in a shift from a Th1 to a Th2 phenotype [194, 188]
  • Regulates the activity of monocytes/macrophages [195, 196]
  • Inhibits dendritic cells production and growth [195, 196]
  • Decreases the secretion of inflammatory cytokines IL-1, IL-2, IL-6, IL-8, IL-17, TNF-α, IFN-γ, and IL-12 [197, 193, 198, 199]
  • Increases cytokines IL-10 and IL-4 [200, 198, 201, 202]
  • Inhibits production of IgE by B cells and enhances the production of IL-10 by dendritic cells and T cells, playing an important role in allergic immune responses [198, 201]
  • Reduces the expression of MHC class II, CD40, CD80, and CD86 [193, 198]
  • Decreases TGF-beta (contributes to tissue repair by promoting tissue fibrosis) (203, 204, 205, 206)
  • Crucial for T Cell activation [207]
  • Regulates differentiation of CD4+ T cells (decreases Th1 and Th17 cell production, and increases Th2 and Treg cell production) [202, 194]
  • Increases CD8+ T  Cells, important in controlling viruses, intracellular bacteria, and cancer [208, 209]
  • Increases Natural Killer T Cells [210]
  • Releases antimicrobials in response to an infection such as cathelicidin and beta-defensin 4 [211, 212]

18) May Be Beneficial For Inflammatory Bowel Disease and Celiac Disease

Inflammatory bowel disease (IBD) is a chronic inflammation of the gut and includes Crohn’s disease and ulcerative colitis.

Vitamin D supplementation may have a beneficial role in IBD [213, 214].

Studies in mice indicate that this vitamin plays a crucial role in this disease [215].

Vitamin D has an anti-inflammatory effect in patients with IBD.

Oral supplementation increased blood vitamin D levels and reduced blood TNF-α levels (protein playing a main role in the gut inflammation) [216, 214].

A study showed a 32% decrease in CRP (C-reactive protein) levels and a 46% decrease in ESR (erythrocyte sedimentation rate) in patients receiving vitamin D [217].

1200 IU/d vitamin D supplementation reduced recurrence of Crohn’s disease from 29% to 13% [217].

Low vitamin D level is associated with a higher risk of polyps and adenomas in the colon, common complications of ulcerous colitis [218].

Almost 60% of patients with celiac disease were found to be vitamin D deficient or insufficient [219].

19) Plays a Role in Cystic Fibrosis

Low blood vitamin D levels are commonly found in patients with cystic fibrosis (CF).

Its deficiency occurs in 25 – 33% of patients with late-stage CF [220].

Absorption of this vitamin is reduced in patients with CF due to insufficient pancreatic enzymes [221].

Also, CF patients have increased oxidant and P450 activity, which could lead to faster degradation of vitamin D [221].

95% of cystic fibrosis patients required 1,800 IU/day of vitamin D to achieve blood concentration above 25 ng/ml [222].

20) Beneficial in Atopic Dermatitis

Atopic dermatitis affects up to 20% of children and up to 3% of adults [223].

Vitamin D deficiency could be associated with the prevalence of atopic dermatitis [224].

Vitamin supplementation may improve disease symptoms and severity.

It can also be considered as a safe and tolerable therapy [225, 226].

Vitamin D increases the production of cathelicidin, an antimicrobial deficient in atopic dermatitis [227, 228].

21) Effective Therapy for Psoriasis Patients

Vitamin D levels are significantly lower in patients with psoriasis [229, 230].

It regulates the production of keratinocytes and immune cells [231, 232].

A daily dose of 35,000 IU of this vitamin is a safe and effective therapy for psoriasis patients [233].

Topical vitamins calcipotriol and/or tacalcitol are considered as first-line treatment for mild-to-moderate psoriasis.

It can also be taken in combination with other systemic therapies in more severe cases of the disease [234, 235].

22) May Benefit Thyroid Dysfunction

Vitamin D deficiency is associated with autoimmune thyroid disease [236, 237].

Its deficiency is common in patients with Graves’ disease and is associated with an increased size of the thyroid gland [238, 239].

Deficiency may exacerbate the onset and/or development of Graves’ disease

Correction of the deficiency may be able to reverse it [236].

Vitamin insufficiency is associated with Hashimoto’s thyroiditis [240, 241].

Vitamin D deficiency severity was associated with duration of the disease, thyroid gland size, and antibody levels [242].

23) Reduces the Severity of Asthma

Vitamin D deficiency is associated with increased asthma symptoms and severity [243, 244].

Its deficiency causes decreased lung function [245, 246, 247].

Lower vitamin levels are associated with increased markers of allergy and asthma severity [244].

Studies showed that higher vitamin D intake by pregnant mothers reduces the risk of asthma by 40% in children 3 to 5 years old [243, 244, 248].

Vitamin D enhances the anti-inflammatory effects of corticosteroid therapy in asthma [249, 250].

24) Affects Chronic Obstructive Pulmonary Disease

Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD) and correlates with the severity of the disease [251, 252].

Lower blood vitamin levels were associated with a higher risk of COPD [253].

Its deficiency is associated with increased risk of lung infections, causing worsening of COPD (254).

Vitamin D regulates airway contraction and inflammation [255].

It is also associated with bone mineral density and exercise performance in patients with COPD [256, 257].

However, some studies showed no benefit of vitamin D supplementation on COPD symptoms and severity [258, 259].

25) Reduces Risk of Tuberculosis

Patients with low vitamin D levels have a higher risk of active tuberculosis [260, 261, 262].

Extreme vitamin D deficiency is associated with a 5-fold increased risk for progression to tuberculosis among healthy individuals who come in contact with tuberculosis [263, 264].

Blood levels of this vitamin are lower in tuberculosis patients comparing to healthy individuals [265].

Vitamin D supplementation may prevent tuberculosis, reduce infectivity and shorten the duration of disease and treatment [262, 266].

Vitamin D supplementation enhances immunity to mycobacteria [267, 268].

26) Has a Negative Effect on Sarcoidosis

Vitamin D is produced by macrophages in sarcoid granulomas causing increased blood calcium levels [269, 270, 271].

Increased level of this vitamin is associated with disease activity [272].

Elevated vitamin levels require chronic immunosuppressive therapy in patients with sarcoidosis [273].

Patients with sarcoidosis do not benefit from vitamin D supplementation [274].

27) Decreases the Risk of Respiratory Tract Infections

Lower levels of vitamin D are related to increased risk of respiratory infections [275].

Studies showed a decrease in respiratory tract infections in children taking 600 to 700 IU/d vitamin D supplementation [276].

Supplementation with 1,200 IU/day prevents against influenza A in schoolchildren between December and March [277].

Supplementation with this vitamin (at 300 IU daily) significantly reduced the risk of acute respiratory infections by 50% among Mongolian children with vitamin D deficiency in winter [278].

However, a monthly dose of 100 000 IU of vitamin D in healthy adults did not significantly reduce the incidence or severity of upper respiratory tract infections [279].

28) Plays a Role in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) activity is associated with lower vitamin D blood levels [280].

Approximately 65% of the patients with SLE had vitamin D blood levels < 30 ng/mL [281, 282].

Vitamin D supplementation has an effect on the immune system in patients with SLE.

It decreases memory B cells, effector Th1 and Th17 cells, and increases Tregs [283].

29) Beneficial in Rheumatoid Arthritis

Vitamin D supplementation suppresses Th17 cell cytokines and has the effect potential to treat patients with RA [199].

Vitamin D deficiency is present in 30-63% of people with rheumatoid arthritis [284].

Greater intake of vitamin D may be associated with a lower risk of rheumatoid arthritis in older women [285].

Low blood levels are associated with rheumatoid arthritis symptoms and severity.

Vitamin D supplementation is beneficial for this disease [284, 286].

Supplementation of 500 IU/day to patients with early rheumatoid arthritis along with anti-rheumatic therapy results in higher pain relief [287].

30) Protects Kidney Function

Chronic kidney disease patients have a higher prevalence of vitamin D deficiency compared to the general population [288].

Supplementation decreases elevated calcium level in chronic kidney disease patients thus preventing multiple organ dysfunction [289, 290].

Vitamin D deficiency or insufficiency is frequent after renal transplantation [291].

The VITALE study (VITamin D supplementation in renal transplant recipients) showed that high doses of vitamin D prevent posttransplant bone loss without causing adverse events [292].

Vitamin D prevents kidney damage in sepsis-induced acute kidney injury [293, 294].

It can protect the kidneys from injury in patients with diabetic kidney disease [295].

31) Beneficial in HIV Disease

Vitamin D deficiency is common among individuals infected with human immunodeficiency virus (HIV).

It is associated with an increased risk of HIV disease severity and death [296, 297, 298].

HIV-infected patients with abnormally low vitamin D levels had shorter survival than other HIV-infected subjects [299].

100,000 IU of vitamin D supplementation every 2 months is safe and improves vitamin D status [297, 300].

This vitamin improves HIV-associated immunity.

High doses of vitamin D supplementation decreases virus production and increases white blood cells [301].

32) Affects Male Fertility

Studies on mice show beneficial effects of vitamin D on the male reproductive system [1].

Male mice who lack vitamin D receptors suffer from infertility.

Decreased sperm count and motility, and structural abnormality of the testis were observed [4, 302, 303, 304].

Vitamin D is important for sperm production, growth, and survival [305].

The vitamin D receptor and the vitamin D metabolizing enzyme are present in the male reproductive tract including the testes, sperm, ejaculatory tract, and prostate [306, 307, 308, 309].

Blood levels of this vitamin are associated with sperm motility.

Men with vitamin D deficiency (blood levels <20 ng/mL) had less motile sperm compared with men with high levels.

Also, blood levels above 50 ng/mL were associated with decreased sperm production and quality.

20-50 ng/mL of vitamin D is an ideal range for the proper functioning of the male reproductive system [310, 311].

33) Beneficial in Pregnancy and Lactation

Vitamin D deficiency was high in a diverse group of women during pregnancy, affecting 97% of African Americans, 81% of Hispanics, and 67% of Caucasians.

Mothers with dark skin or wearing concealing clothes are at great risk of vitamin D deficiency [312, 313, 314].

Its deficiency in pregnant women may affect both women and newborns.

The deficiency could lead to a high bone loss and osteomalacia in the mother [315, 316].

It could cause impaired growth, bone and enamel formation, type 1 diabetes, asthma, and schizophrenia in newborns [317, 318, 319].

Vitamin D sufficiency may protect from spontaneous preterm birth risk [320].

Vitamin D deficiency during pregnancy is associated with:

  • An increased risk of preeclampsia, the leading cause of maternal and neonatal morbidity and mortality [321, 322].
  • Almost 4 times the odds of primary cesarean section [323].
  • Bacterial vaginosis, a highly prevalent vaginal infection that is associated with adverse pregnancy outcomes [324].

Vitamin D supplementation of 4,000 IU/day for pregnant women is safe. It is effective in achieving sufficiency in all women and their newborns and associated with fewer adverse events of pregnancy [325].

It was thought for decades that breast milk was ‘naturally’ low in vitamin D.

Since vitamin D is transferred into the milk, the mother needs a daily source of vitamin D in order to provide her infant with enough substrate to avoid deficiency [326].

An intake of 6400 IU/day of vitamin D provides enough vitamin D to a breastfeeding infant [327].

34) Improves Clinical Manifestations of Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) have low vitamin D blood levels

Supplementation improves various clinical manifestations of PCOS (206, 328).

Vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women [329, 330, 331].

PCOS is accompanied by a high risk of cardiovascular diseases.

Low-dose vitamin D is used as an additional therapy for PCOS and cardiovascular diseases [332].

35) Influences Hair Loss

Studies show an important role of vitamin D receptor in hair loss [333].

The function of the vitamin D receptor is essential for the maintenance of normal hair cycle.

Defective vitamin D receptor function leads to defective growth and loss of hair follicle [334, 335].

Hair loss in both men and women is associated with decreased blood levels of vitamin D [336, 337].

Low blood levels of this vitamin increase the disease severity [338, 337].

Screening patients with hair loss for vitamin D deficiencies seems to be of value for the possibility of supplementing these patients with vitamin D.

Supplementation may be useful to grow hair in case of its deficiency [337].

Active vs Inactive Forms

There are two forms of vitamin D: vitamin D2 and vitamin D3.

Vitamin D2 (ergocalciferol) is produced in plants, fungi, and yeasts.

Vitamin D3 (cholecalciferol) is synthesized in the skin and consumed in animal-based foods [339].

Both forms of vitamin D are biologically inactive and must be activated in the body.

In the liver, vitamin D is converted to calcidiol (25-hydroxyvitamin D [25(OH)D]), the major circulating form of vitamin D, and the indicator of vitamin D status [340].

In the kidneys, calcidiol is converted to calcitriol (1,25-dihydroxy vitamin D [1,25(OH)2D]), the active form of vitamin D [339].

In order to regulate bodily functions, calcitriol binds to vitamin D receptor (VDR) in the cytoplasm of target cells, and goes to the nucleus and binds with the retinoic acid X receptor (RXR).

This complex regulates the expression of vitamin D regulated genes [341].


Vitamin D levels can be increased by getting more natural sunlight, in food or supplements. Sun is the best method for increasing vitamin D.


Most of the vitamin D3 in humans is derived from the synthesis in the skin.

7-dehydrocholesterol, a precursor for vitamin D3, after irradiation with UVB light is converted to vitamin D3 [342, 343].

Factors affecting UV radiation exposure and vitamin D synthesis include the season of the year, latitude, clouds, smog, aging, skin color, use of sunscreen, clothing, and amount of skin exposed [343, 344].


Very few foods in nature contain vitamin D.

Major food sources are fatty fish (salmon, tuna, mackerel), cod liver oil, beef liver, egg yolks, cheese, and mushrooms (shiitake, portabella) [343].

Some foods are fortified with vitamin D. These include milk, soy milk, yogurt, margarine, orange juice, and cereals [343].

Both the United States and Canada mandate the fortification of infant formula with vitamin D: 40 – 100 IU/100 kcal in the United States and 40 – 80 IU/100 kcal in Canada [345].


In supplements, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol) [343].

Vitamin D3 is approximately 87% more effective in raising and maintaining the vitamin D levels in the body than vitamin D2.

Vitamin D3 should be used for supplementation and fortification [346, 347, 348].

Most multivitamins contain 400 IU of vitamin D, and single ingredient vitamin D supplements are available for additional supplementation.

Intake of ordinary doses of vitamin D3 supplements seems to be associated with decreases in the overall risk of dying [349].


Vitamin D taken orally is absorbed in the gut with the aid of bile salts.

It is transported to the blood by chylomicrons and taken up by the liver or storage tissues (fat tissue and muscles) [350].

There are many factors that affect vitamin D absorption resulting in large differences in the bioavailability of vitamin D supplements in some populations [351].

In patients with celiac disease, cystic fibrosis, biliary obstruction, and chronic pancreatitis, the absorption of vitamin D is decreased [221, 350, 352].

Also, individuals taking medications that bind bile acid (such as cholestyramine) will also have impaired vitamin D absorption [353].

Obesity is also associated with decreased vitamin D levels [354].

Vitamin D is most efficiently absorbed when consumed with food containing fat.

Taking vitamin D with the largest meal improves absorption, and results in a 50% increase in blood levels of vitamin D [355].


Infants and children aged 0-1 yr should have a daily intake of at least 400 IU of vitamin D [344].

Children 1 yrs and older and adolescents should have a daily intake of 600 IU of vitamin D.

Adults aged 19 – 70 and over 70 yr require at least 600 and 800 IU/d, respectively, of vitamin D to maximize bone health and muscle function, and prevent falls and fractures.

Pregnant and lactating women require at least 600 IU/d of vitamin D.

Many health professionals recommend 2,000 IU or more a day.

Obese and children and adults on anticonvulsant medications, glucocorticoids, antifungals, and medications for AIDS should be given at least two to three times more vitamin D for their age group to satisfy their body’s vitamin D requirement.


Vitamin D deficiency is the most common nutritional deficiency worldwide in both children and adults.

It had been estimated that 20% to 80% of people in the United States, Canada, Mexico, Europe, Middle East, and Asia have a vitamin D deficiency [356357, 358].

The blood level of 25(OH)D is the best method to determine vitamin D status [7].

Vitamin D deficiency is defined as a 25(OH)D level of 20 ng/mL or less, and vitamin D insufficiency as 21 – 29 ng/mL [359, 360, 344].

Studies suggest that blood 25(OH)D levels between 30 ng/mL and 60 ng/mL are associated with lower risks of adverse health outcomes, including cardiovascular disease, cancers and autoimmune diseases [7].

Causes of vitamin D deficiency:

Vitamin D deficiency can come from:

  • Inadequate sun exposure
  • Geographical locations (latitude and altitudes), atmospheric conditions (air pollution, the presence of clouds), and seasonal changes influence the intensity of UVB radiation and thus vitamin D production in the skin [361].
  • People with dark skin, African Americans and Hispanic Americans. Higher skin melanin content reduces the skin’s ability to make vitamin D [362, 363].
  • Wearing protective clothing and hats, and applying sunscreens, reduce skin exposure to sunlight [343, 344, 364].
  • Women in the Middle East and North Africa who wear a headscarf or cover all skin. 96% had blood vitamin D levels less than 20 ng/mL, and 60% had vitamin D levels below 12 ng/mL [365, 366].
  • Malabsorption of vitamin D
  • Patients with gut disease including Crohn’s disease, ulcerous colitis, celiac disease, cystic fibrosis [221, 350, 352].
  • Cholestatic and non-cholestatic liver disease [350].
  • Low vitamin D intake
  • Low vitamin D diet without fortified food or supplements (367).
  • A strict vegan diet [368].
  • Chronic kidney disease leads to reduced synthesis of 1,25-dihydroxy-vitamin D and an increased loss of 25-hydroxyvitamin D in urine [369].
  • Obesity [370].
  • The elderly have a reduced capacity to synthesize vitamin D in the skin and are more likely to stay indoors or use sunscreen [344, 371].
  • Pregnant women [372].
  • Infants who are exclusively breastfed and do not receive vitamin D supplementation [19].
  • Medication: glucocorticoids, antiepileptic drugs, rifampin, antiretroviral therapy [373].

People who are vitamin D deficient may not have any symptoms at all or symptoms may be vague.

Vitamin D deficiency manifests as fatigue, symmetric low back pain, throbbing bone pain, muscle weakness and aches, sweating, digestive problems, obesity, mood swings, and impaired immunity.

These symptoms are often misdiagnosed as fibromyalgia, chronic fatigue, age-related weakness, or even depression [374, 375, 376].

Severe vitamin D deficiency leads to rickets in children and osteomalacia in adults [19, 18].


Vitamin D toxicity is an extremely rare but potentially serious condition.

It occurs from high intakes of supplements (>50,000 IU/d) for a long period of time.

Toxicity does not occur from dietary intake or prolonged sun exposure [377].

Vitamin D is a fat-soluble vitamin, and it is stored in fat tissues. Therefore, toxic effects may last for months after stopping supplementation [378].

High vitamin D levels lead to tissue calcification, and kidney and cardiovascular damage [377, 378, 379].

Symptoms and signs of vitamin D intoxication are headaches, metallic taste, poor appetite, nausea, vomiting, dehydration, constipation, pancreatitis, and kidney stones [377, 378, 380, 381].


Vitamin D supplementation must be considered carefully in patients with granulomatous diseases such as sarcoidosis and Crohn’s disease (active phase), metastatic bone disease, and Williams syndrome (infantile hypercalcemia) [382, 383, 384, 385].

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