Vitamin D — Benefits, Sources, Deficiency & Overdose Symptoms

by Arpi Gasparyan | Last updated on March 25, 2024

Medically reviewed by Victoria Mazmanyan

Introduction

Vitamin D, or calciferol, is a fat-soluble vitamin found in a few foods and available as a dietary supplement. It is also produced in the organism when the UV lights from sunlight strike the skin.

Vitamin D comes in two forms: vitamin D2 (ergocalciferol) and D3 (cholecalciferol); chemically, they differ only in their side-chain structures. Most experts choose vitamin D3 over D2 as it is the most “natural” form, binds well and tighter to receptors, circulates longer in the body, and is more stable on the shelf (1, 2).

Absorption & Metabolism

Vitamin D is well absorbed in the small intestine by passive diffusion and a mechanism involving intestinal membrane carrier proteins. The concurrent presence of fat increases vitamin D absorption; however, some vitamin D is absorbed without fat (1).

Ultraviolet B radiation penetrates the sun-exposed skin and converts 7-dehydrocholesterol to pre-vitamin D3, which later becomes vitamin D3 (1).

Season, time and length of day, clouds, skin melanin levels, sunscreen, and other factors affect vitamin D synthesis from sunlight. For example, older people and those with dark skin produce less vitamin D (1).

Vitamin D obtained from sun exposure, foods, and dietary supplements undergoes two hydroxylations in the body to become biologically active. The first hydroxylation occurs in the liver, converting vitamin D to its major circulating form, 25-hydroxyvitamin D (25(OH)D) or calcidiol. The second hydroxylation occurs in the kidney's proximal tubules, forming the physiologically active hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D) or calcitriol (1, 3).

Vitamin D and its metabolites are bound to vitamin D-binding protein (DBP) and albumin in the blood; however, vitamin D enters most tissue cells in its free or unbound form. Vitamin D-binding protein-bound metabolites enter kidney and parathyroid gland cells (3).

Recommended Intake & Serum Concentrations

According to the 2020–2025 Dietary Guidelines for Americans, the recommended daily value for vitamin D is 600 IU (15mcg) (4).

The table below shows the serum concentrations of vitamin D and its health effects (1).

Serum vitamin D levels	Health effect
<12 ng/mL	Leads to bone disease, such as rickets in children and osteomalacia in adults
12 to <20 ng/mL	Considered inadequate for bone and overall health
≥20 ng/mL	Considered adequate for bone and overall health
>50 ng/mL	Can lead to potential adverse effects, particularly at >60 ng/mL

Sun Exposure

A 21-year-old person exposed to summer ultraviolet B light generates 10000 IU or 250 mcg of vitamin D in 15-20 minutes; however, longer exposure to sunlight does not lead to more vitamin production (2).

Sun exposure through a window won’t lead to vitamin D synthesis, as glass blocks the UV light.

Several experts suggest that approximately 5-30 minutes of sun exposure between 10 AM and 4 PM, daily or a minimum twice a week, without sunscreen, may lead to sufficient vitamin D synthesis. However, limiting skin exposure to sunlight is suggested, considering that UV radiation is a carcinogen and may lead to skin cancer (1).

Sunscreens with an SPF of at least 8 block vitamin D-producing UV rays. In practice, many people do not apply enough sunscreen or cover all sun-exposed skin; thus, their skin still synthesizes some vitamin D (1).

Dietary Sources

The primary dietary sources of vitamin D are fatty fish. Red meat, egg yolks, cheese, fortified cereals, juices, milk, and milk alternatives also contain varying amounts of vitamin D.

The table below demonstrates the vitamin D levels of selected foods.

Food	Vitamin D level per 100g serving
Cod liver oil	250 mcg
Maitake mushroom	28.1 mcg
Trout	19 mcg
Salmon, smoked	17.1 mcg
Sardines	4.8 mcg
Caviar, black and red	2.9 mcg
Egg	2.2 mcg
Milk, fortified with vitamin D	1.2 mcg
Soy milk, with added vitamin D	1.1 mcg
Pork chop	1 mcg
Pork liver, Chicken liver	0 mcg

Fruits and vegetables are absent in vitamin D. Mushrooms exposed to sunlight contain varying amounts of vitamin D. Different types of cheese also contain varying vitamin D levels.

Vitamin D Health Benefits & Risks During Deficiency

Most observational studies and clinical trials have shown mixed results regarding blood vitamin D levels and health outcomes. Nonetheless, the only firmly established relationship is between vitamin D and bone health.

Bone Health & Osteoporosis

Vitamin D is required for normal bone development and maintenance, as it increases the absorption of calcium, magnesium, and phosphate. Vitamin D deficiency leads to rickets in children and osteoporosis in adults.

Bones are constantly being remodeled, which involves cells that form bones (osteoblasts) and cells that break down the bones (osteoclasts). As people age, bone breakdown rates become higher than bone formation rates.

Osteoporosis is caused by long-term calcium and vitamin D insufficiency. It is characterized by low bone mass or density, bone fragility, and increased risk of bone fractures, mainly in women of menopausal and postmenopausal age (1, 6).

Rickets cause pain, poor growth, and soft, weakened bones and prevent children from reaching their genetically determined height (5). Fortifying milk with vitamin D and calcium has decreased the incidence of rickets worldwide.

Bone health also depends on support from surrounding muscles, and vitamin D is required for the normal development and growth of muscle fibers (1).

Neurological & Mental Health

Depression

Vitamin D has a neuroprotective role in the brain; it is involved in various brain processes and has receptors on neurons and glia.

Fourteen observational studies have found an association between low levels of vitamin D and depression. However, clinical trials have found no improvement in symptoms and vitamin D intake (1).

Multiple Sclerosis

Multiple sclerosis is an autoimmune disease affecting the CNS (central nervous system), hindering or blocking messages between the brain and body, causing vision and sensory loss, weakness, spasticity, tremor, and cognitive impairment.

Many epidemiological and genetic studies have found an association between the disease and low vitamin D levels. Observational studies suggest that adequate vitamin D levels may reduce the risk of contracting multiple sclerosis and, once present, decrease the risk of relapse and slow the progression. However, there are currently no high-quality clinical trials to confirm the role of vitamin D in disease outcomes (1).

Alzheimer’s disease

Vitamin D modulates the inflammatory response, intracellular oxidative stress, and mitochondrial respiratory function in people with Alzheimer’s. Vitamin D enhances the amyloid plaque’s phagocytosis and clearance by the immune cells.

Studies have found an association between low serum vitamin D levels and Alzheimer’s development. However, most studies found no effect between increased vitamin D intake or supplementation in those with Alzheimer’s disease; moreover, several results show the worsening effect of vitamin D on disease progression. Still, a few studies showed promising results regarding vitamin D intake and Alzheimer’s (7).

Parkinson’s disease

Vitamin D intake may positively affect people with Parkinson’s disease by reducing neuronal damage and limiting neuroinflammation. However, no definitive and confirming results are available, and the conclusions regarding vitamin D intake and the risk of developing Parkinson’s disease are controversial.

One of the most consistent findings is the inverse association between vitamin D levels and motor symptom severity (7).

Migraine

Several observational, cross-sectional, and case-control studies have found an association between low vitamin D serum levels and migraine and other types of headaches.

Vitamin D levels are lower in people with migraine and tension-type headaches. Still, it is hard to say whether vitamin D deficiency or headaches appear first.

In clinical trials, increased vitamin D intake and supplementation have significantly reduced headache attack frequency and numbers, but the effects on pain intensity were less evident (7).

Cancer

According to laboratory and animal studies, vitamin D may inhibit carcinogenesis (cancer formation) and slow cancer progression via several mechanisms. Vitamin D also has anti-inflammatory, immunomodulatory, proapoptotic, and antiangiogenic effects, decreasing the risk of cancer formation. However, the evidence is mixed on whether vitamin D intake or its concentration in the organism affects cancer incidence and progression.

Several studies have concluded that higher blood vitamin D concentrations may decrease the risk of cancer development and cancer mortality rates, while others have found no associations. Several other studies have suggested that vitamin D supplementation does not decrease cancer development risks, but it decreases mortality rates.

According to several studies, vitamin D may decrease breast cancer risk, and high levels may increase pancreatic and prostate cancer risks. Interestingly, several other studies found that high vitamin D levels may decrease mortality rates in prostate cancer patients.

However, the evidence is insufficient to conclude whether vitamin D benefits or harms, but the data suggests vitamin D intake may reduce cancer mortality rates (1).

Heart Disease

Vitamin D is linked to cardiovascular health and may decrease the risk of heart disease.

Vitamin D regulates the RAAS (renin-angiotensin-aldosterone system), regulating blood pressure; it also participates in vascular cell growth, inflammation, and fibrosis. Thus, vitamin D deficiency may lead to vascular dysfunction, arterial stiffening, left ventricular hypertrophy, and increased blood lipids. According to studies, low vitamin D concentrations may be linked to increased myocardial infarction, atrial fibrillation, ischemic heart disease, heart failure, stroke, and mortality risks. Several studies suggest increased blood vitamin D may benefit heart health, whereas others have found no associations between vitamin D levels and heart disease risks and outcomes (1, 8).

Type-2 Diabetes

Vitamin D participates in glucose metabolism by stimulating insulin secretion and reducing peripheral insulin resistance. Considering these effects, it is suggested that vitamin D may be involved in the pathophysiology of type 2 diabetes. However, clinical trials have shown that vitamin D intake does not improve type 2 diabetes measurements or decrease the risk of progression from prediabetes to diabetes (1).

Seasonal Flu

Vitamin D intake may reduce the risk of respiratory tract infections, such as seasonal influenza and COVID-19, due to its impact on innate and adaptive immune responses (9).

One of the mechanisms includes the induction of cathelicidins and defensins, lowering viral replication rates, reducing pro-inflammatory cytokines, and increasing anti-inflammatory cytokines concentrations (9, 10).

Vitamin D Deficiency Risk Groups and Causes

Most vitamin D deficiency risk factors and causes are described below (2, 6, 11, 12).

Inadequate amounts of vitamin D in human breast milk.
Inadequate exposure to sunlight. Healthy adults are at a greater risk of vitamin D deficiency at the end of winter.
Aging. Vitamin D production rates are decreased in older people, regardless of sun exposure time.
Obesity or belly fat. Obesity may lead to vitamin D absorption by the fatty tissue and decrease blood vitamin D levels.
Skin pigmentation. People with darker skin contain more melanin, which blocks the UV light and, thus, decreases vitamin D production.
Fully covered skin.
Higher SPF of sunscreen.
Malabsorption. Malabsorption may be caused by small intestinal resection, celiac disease, inflammatory bowel disease, chronic pancreatitis, cystic fibrosis, short bowel syndrome, gastric bypass, and gastrectomy.
Decreased synthesis in the body due to liver disease, chronic kidney disease, hyperparathyroidism, and 1-alpha hydroxylase deficiency.
Medications.
Genetic disorders (i.e., hereditary vitamin D-resistant rickets, vitamin D-dependent rickets type IA).

In clinical practice, gastroenterologists often encounter vitamin D deficiency in elderly individuals and patients with malabsorption or maldigestion syndromes.

We often observe vitamin D deficiency in patients with celiac disease, Crohn's disease, ulcerative colitis, and chronic pancreatitis, and we prescribe vitamin D supplements along with disease treatment. Some of our patients with acid reflux, abdominal pain, and bloating may decrease their food intake to prevent the worsening of symptoms, thus increasing the risk of vitamin D deficiency.

Interactions with Medications

Lipase inhibitors (orlistat) bind lipase in the GI tract and block fat absorption, reducing the absorption of fat-soluble vitamin D. Bile acid sequestrants (colestipol, cholestyramine) bind to bile acids and fat-soluble vitamins, preventing their reabsorption. As vitamin D metabolites are also present in the bile, increased bile acid excretion may reduce the vitamin D stores (1, 13).

Statins (atorvastatin, lovastatin, simvastatin) reduce cholesterol synthesis and may also affect vitamin D synthesis (1, 13).

Glucocorticoids (i.e., prednisone, hydrocortisone) may reduce calcium absorption and alter vitamin D metabolism (1, 13).

Combining thiazide diuretics with vitamin D supplements may lead to hypercalcemia among older adults and people with chronic kidney disease or hyperparathyroidism (1).

Several medications can induce liver p450 enzymes to activate vitamin D degradation. Some of those medications include antiepileptic drugs (phenobarbital, phenytoin (Dilantin), carbamazepine), antimicrobial drugs (rifampin, isoniazid), immunosuppressive agents (cyclosporine, tacrolimus), chemotherapeutic agents, theophylline, nifedipine, spironolactone, clotrimazole (13).

Vitamin D Oversode Symptoms

Vitamin D toxicity is rare. The skin destroys excess vitamin D if exposed to the sun for longer periods, preventing vitamin D intoxication.

Vitamin D toxicity is possible only if the vitamin is ingested in high doses for a prolonged time. Serum concentrations of vitamin D of over 150 ng/mL may cause intoxication and hypercalcemia, as well as pancreatitis, vomiting and dehydration, abdominal pain, constipation, polydipsia, polyuria, confusion, apathy, and dizziness (14, 15).

Vitamin D overdose may also cause changes in ECG: shortened QT interval, ST segment elevation, and bradyarrhythmias with first-degree heart block (15).

Contraindications

Vitamin D supplementation and foods with high vitamin D levels are best avoided and discussed with a physician for people with hypervitaminosis D (high levels of vitamin D), hypercalcemia and hypercalciuria (high calcium levels in the organism and urine), calcium oxalate kidney stones, allergic reaction to vitamin D, and sarcoidosis (16).

Summary

Vitamin D, or calciferol, is a fat-soluble vitamin found mainly in fatty fish and available as a dietary supplement. It is also produced in the skin from sun exposure.

Vitamin D undergoes two hydroxylations in the body to form its physiologically active hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D) or calcitriol.

Vitamin D is required for normal bone formation and maintenance; low levels of vitamin D cause rickets in children and osteoporosis in adults. Vitamin D plays a role in neurological and mental health, cardiovascular health, glucose metabolism, insulin sensitivity, and cancer.

Aging, obesity, darker skin, malabsorption disorders, liver and kidney disease, several genetic disorders, and medications (i.e., orlistat, statins, steroids, thiazide diuretics, antiepileptic drugs) increase the risk of vitamin D deficiency.

References

Author name: Arpi Gasparyan

Education: General Medicine at YSMU

Last updated: March 25, 2024

Medically reviewed by Victoria Mazmanyan