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Vitamin D (Ergocalciferol, Cholecalciferol)

Vitamin D Forms

Vitamin D is a fat-soluble vitamin, a conditionally essential nutrient, which means, it can be produced in your body in sufficient amounts when your skin is exposed to sun light for a certain period of time, but when it is not, you need to get additional amount from food or supplements ^[1].

Vitamin D2 or ergocalciferol in plant foods and vitamin D3 or cholecalciferol in animal foods and human skin are inactive forms of vitamin D. They are converted into calcidiol (25OHD) in your liver and, finally, mainly in your kidneys, into calcitriol (1-25OHD), which is the only active form of vitamin D in the human body ^[1].

Vitamin D Functions

Vitamin D ^[1]:

Promotes absorption of calcium and phosphate in the intestine. When blood calcium levels are low, vitamin D, stimulated by the parathyroid hormone (PTH), promotes the absorption of calcium and phosphate from the small intestine and bones. When blood calcium levels are high, vitamin D stimulates calcium incorporation into the bones and teeth and thus strengthen them. Vitamin D deficiency can result in rickets, osteomalacia or osteoporosis.
Helps to maintain the muscle strength and normal glucose levels
Helps to maintain immunity

Sources of Vitamin D

Skin Exposure to Sun

Ultraviolet (UV-B) rays from the sun convert dehydrocholesterol in the skin into vitamin D3 (cholecalciferol). Exposure of the face, arms, legs or back (without sunscreen) to sun for 5-30 minutes between 10 AM and 3 PM twice a week (less than 42° latitude from March to October, and less than 34° year through) results in the production of sufficient amount of vitamin D in the body in healthy people ^[1,8]. Cloudy weather or being in shade reduces UV exposure to about 50% ^[1]. UV light does not penetrate windows so indoor exposure to sun through windows does not result in vitamin D production in the skin ^[1]. Prolonged exposure to sun, visiting sunbathing saloons or using UV lamps for the purpose of increasing vitamin D is NOT recommended, since they can increase the risk of skin cancer, but it does not lead to vitamin D toxicity [7].

Recommended Daily Intake

According to the Institute of Medicine of the National Academics in the US, the Recommended Dietary Allowance (RDA) for vitamin D for adults between 19-50 years is 15 mcg or 600 IU (International Units)/day, for 71+ years 20 mcg (800 IU)/day and for pregnant and breastfeeding women 15 mcg (600 IU)/day ^[1].

Recommended Intake for Infants

Human breast milk contains about 0.5-1 mcg (25-40 IU) of vitamin D per liter ^[3,7,10], which is much less than the Recommended Dietary Allowance (RDA) for vitamin D for 0-12 old infants is 10 mcg (400 IU)/day, so American Academy of Pediatrics recommends that infants should get 400 IU/day by supplements–available as nonprescription multivitamin drops–from the first days on ^[9]. To increase the concentration of vitamin D in the breast milk to meet the infants needs, mothers would need to take supplements in large doses, but for now this is generally not recommended ^[11,12].

1 liter of vitamin D fortified formula or fortified cow’s milk should provide enough vitamin D to meet the infants’ needs ^[16].

Foods High in Vitamin D

Vitamin D can be mainly found in oily fish and liver and in smaller amounts in meat and dairy. In the US, Canada and some other countries, milk and, often, soy milk, margarine, ready-to-eat cereals, rice and orange juice are fortified with vitamin D (D2 or D3). Plant foods (fruits, vegetables, nuts, legumes, cereals) do not naturally contain vitamin D.

Picture 1. Examples of foods high in vitamin D

Chart 1. Foods High in Vitamin D
Animal Foods	Vitamin D (IU)
Salmon, swordfish, trout (3 oz, 85 g)	300-730
Fish oil, cod liver (1 tsp, 5 g)	450
Halibut, mackerel, sturgeon (3 oz, 85 g)	200-450
Flatfish, herring, rockfish, sardines, tilapia (3 oz, 85 g)	120-150
Buttermilk, eggnog (1 cup, 237 mL)	130
Anchovies, tuna (3 oz, 85 g)	40-70
Egg (50 g); all vitamin D is in the yolk	40
Cod, haddock, pollock (3 oz, 85 g)	20-40
Pork, veal (3 oz, 85 g)	20-50
Beef liver (3 oz, 85 g)	30-40
Fat: chicken, turkey (1 tbsp, 13 g)	25
Beef, duck, lamb, turkey (3 oz, 85 g)	5-20
Cheese (2 oz, 57 g)	10-15
Lard (1 tbsp, 13 g)	13
Butter (1 tbsp, 15 g)	10
Chicken (3 oz, 85 g)	5
Plant Foods
Tofu (90 g)	40
Mushrooms, shiitake (100 g)	30
Mushrooms, white (100 g)	8
Fortified Foods
Mushrooms, portabella, exposed to UV light (100 g)	525
Fortified beverages (1 cup, 237 mL)	80-325
Milk, plain or chocolate, soymilk (1 cup, 237 mL)	100-130
Formulated bars (80 g)	60-120
Cereals ready-to-eat (30 g dry = 1 cup prepared)	30-100
Yogurt (6 oz, 170 g)	80-90
Margarine (1 tbsp, 15 g)	60
Cheese, American, pasteurized (2 oz, 57 g)	60

References: USDA.gov ^[3]

Vitamin D Absorption

Vitamin D is absorbed in the small intestine. Absorption can occur only in the presence of fats from the food, and bile acids.

Blood Tests, Normal Blood Levels Range

The most commonly measured form of vitamin D in the blood is calcidiol (25OHD), which reflects the recent production of the vitamin in your body and the vitamin intake, but not the body vitamin stores ^[1]. Calcitriol (1-25OHD) levels decrease only in severe deficiency so they are not a good indicator of the body vitamin D status ^[1].

Normal blood levels of vitamin D (calcidiol, 25 OHD) are 50-125 nmol/L (20-50 ng/mL).

Abnormal levels ^[1]:

Levels below 30 nmol/L are associated with rickets in infants and osteomalacia in adults.
Levels 30-50 nmol/L are considered inadequate for bone and general health.
Levels above 125 nmol/L can cause side effects.

Vitamin D Deficiency: Causes, Symptoms

Causes

Low production of vitamin D in the skin, which may be due to a low exposure to sunlight, skin completely covered with clothes, dark skin color, using sunscreen (a sun-protecting factor 8 reduces vitamin D production by 95%), living at altitudes greater than 42°, old age
Low vitamin D intake combined with a low exposure to sunlight in exclusively breastfed infants ^[10] and strict vegetarians
Fat malabsorption in celiac disease, Crohn’s disease, liver cirrhosis, obstruction of the bile duct by gallstones, chronic pancreatitis, cystic fibrosis, gastric bypass (bariatric surgery) ^[4], short bowel syndrome (after surgical removal of a large part of the small intestine) ^[13], small intestinal bacterial overgrowth (SIBO) ^[5]
Obesity–vitamin D is diluted in body fat
Chronic kidney disorders resulting in impaired synthesis of the active form of vitamin D (calcitriol)
Magnesium deficiency ^[8]
Interactions with medications (corticosteroids, orlistat, cholestiramine, phenytoin, phenobarbital)
Reference: ^[1]

Symptoms

Vitamin D deficiency can cause hypocalcemia with numbness and tingling in the fingers, toes and around the mouth (paresthesia), lightheadedness, excessive bleeding, leg cramps or muscle twitching, constipation, seizures or abnormal heart rhythm (arrhythmia). Chronic hypocalcemia can cause dry and itchy skin.

Vitamin D deficiency results in poor mineralization of bones causing rickets in children, and osteomalacia (soft bones) and osteoporosis (when calcium is also deficient) in adults. Symptoms include deformed, fragile bones, teeth defects, muscle pain and weakness and bone pain.

Rahitis; vitamin D Deficiency

Picture 1. Rahitis: X-Ray: deformed leg bones in a child
(source: Wikipedia)

Diagnosis. Vitamin D deficiency is estimated from the level of calcidiol (25OHD) in the blood. Calcitriol (1-25OHD) levels are lowered only in severe cases. Treatment is by vitamin D supplements.

Vitamin D Supplements

Without prescription (over-the-counter):

Vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) in usual doses (400 IU) are considered equally effective, but in large doses, vitamin D3 is more effective ^[1].
Vitamin D is included in some multivitamin and calcium supplements and in prenatal vitamins.
Available forms: tablets, chewables, capsules, liquid (drops), powder, sublingual tablets, cream ^[17]

By prescription:

Intravenous injection of calcitriol–the active form of vitamin D–for example, to prevent hypocalcemia in individuals undergoing hemodialysis ^[14]
Intramuscular injection of cholecalciferol (vitamin D3) in megadoses, for example 600,000 IU after bariatric surgery for weigh loss (biliopancreatic diversion)

Possible Vitamin D Benefits

Vitamin D is EFFECTIVE in ^[2,19]:

Treatment of vitamin D deficiency, osteomalacia, rickets
Correction of low blood phosphate levels in familial hypophosphatemia and Fanconi syndrome
Correction of low blood calcium levels due to low parathyroid hormone (PTH) levels (hypoparathyroidism)
Reduction of bone loss during treatment with corticosteroids

Vitamin D is POSSIBLY EFFECTIVE in:

Prevention of hip fractures due to osteoporosis (800 IU in combination with calcium supplements) ^[7,19]
Treatment of renal osteodystrophy – a bone disorder caused by kidney failure ^[18]

Vitamin D is POSSIBLY INEFFECTIVE in prevention of breast cancer, high blood pressure, improving muscle strength in older adults, preventing bone loss after kidney transplantation ^[2].

There is INSUFFICIENT EVIDENCE about vitamin D effectiveness in prevention or treatment of asthma, bronchitis, cancer (breast, colon), chronic obstructive pulmonary disease, depression, diabetes type 1 or 2, fibromyalgia, flu, gum disease, high blood pressure, HIV/AIDS, inflammatory bowel disease (Crohn’s disease) ^[8], chronic kidney disease, low birth weight in infants, metabolic syndrome, mood disorders, multiple sclerosis, muscle weakness, muscle pain caused by statins, myelodysplastic syndrome, osteoarthritis, premenstrual syndrome (PMS), proximal myopathy or warts, rheumatoid arthritis, seasonal affective disorder (SAD), stroke, tooth loss in old people or in promoting immunity, vitiligo, weight gain or loss ^[2,19].

Vitamin D is POSSIBLY INEFFECTIVE in prevention or treatment of eczema, heart disease or high cholesterol ^[19].

Vitamin D Supplements Safety: Side Effects, Toxicity

Institute Of Medicine in the US has set the Tolerable Upper Intake Level (UL)–the amount of oral vitamin D supplements that should not be toxic–at 100 mcg (4,000 IU) per day for adults, but even doses up to 250 mcg (10,000 IU)/day for up to 5 months are not known to cause any toxicity ^[7,8]. According to Mayo Clinic, intramuscular injections of vitamin D in doses up to 300,000 IU 3 times a year are probably safe ^[18].

During Pregnancy

Vitamin D supplements may increase the risk of high blood pressure during pregnancy (preeclampsia) ^[18].

Vitamin D in doses greater than Recommended Dietary Allowance (15 mcg or 600 IU/day) is a pregnancy category C drug, which means harmful effects in fetuses have not been observed so far but cannot be excluded because insufficient studies have been done ^[6]. Intramuscular injections in doses up to 60,000 IU monthly for 3 months are probably safe ^[18]. If you intend to use vitamin D supplements during pregnancy or breastfeeding, speak with your doctor.

Side Effects

Allergic reactions to vitamin D are possible ^[18].

Long-term side effects (complications) of vitamin D in high doses can include kidney stones, bone loss, accumulation of calcium in the arteries (arteriosclerosis), heart, kidneys and other organs and increase the risk of urinary tract infections, respiratory infections ^[1,18,22].

Overdose (Hypervitaminosis D)

Large oral doses of vitamin D–over 10,000 IU, but probably only over 50,000 IU for several months–may cause hypercalcemia with weakness, fatigue, sleepiness, headache, dry mouth, metallic taste, excessive thirst, loss of appetite, nausea, vomiting, abdominal cramps, constipation, diarrhea, excessive urination and weight loss ^[7,20,21]. High amounts of vitamin D from foods, or sun exposure do not cause hypervitaminosis D ^[21].

Who may need to use vitamin D supplements with caution?

In individuals with tuberculosis, sarcoidosis, primary hyperparathyroidism, histoplasmosis and lymphoma, even usual doses of vitamin D supplements increase the risk of hypercalcemia ^[1,22].

Vitamin D Supplements Interactions With Drugs

Drugs that can decrease vitamin D (25OHD) blood levels: phenytoin, fosphenytoin, phenobarbital, carbamazepine, rifampin, steroids, chemotherapeutics and antiretrovirals (for HIV/AIDS)
Drugs that can affect vitamin D absorption when taken together with vitamin D
Vitamin D increases the absorption of aluminum from aluminum antacids, possibly resulting in excessive aluminum levels in the body, especially in people with kidney disease.
When taken together, vitamin D may decrease the effectiveness of atorvastatin, clarithromycin, cyclosporine, diltiazem, lovastatin, estrogens, indinavir, triazolam, verapamil, or increase side effects of calcipotriene, digoxin.
Vitamin D taken along with diuretics (chlorothiazide, hydrochlorothiazide, indapamide, metolazone, chlorthalidone) may cause hypercalcemia.
Vitamin D can raise the level of magnesium in people who have low magnesium and low vitamin D levels.
References: ^[8,23]

Vitamin D National Institutes of Health, Office of Dietary Supplements
Vitamin D, evidence Mayo Clinic
List of foods high in vitamin D US Department of Agriculture
Shah M et al, 2013, Long-Term Impact of Bariatric Surgery on Body Weight, Comorbidities, and Nutritional Status Endocrine Society
Sachdev AH et al, 2013, Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance PubMed Central
Ergocalciferol pregnancy and breastfeeding warnings Drugs.com
Holick MF, 2007, Vitamin D Deficiency The New England Journal of Medicine
Vitamin D Linus Pauling Institute
2010, Vitamin D supplementation for infants American Academy of Pediatrics
Hatun S et al, 2005, Vitamin D Deficiency in Early Infancy The Journal of Nutrition
Wagner CL et al, 2006, High-dose vitamin D3 supplementation in a cohort of breastfeeding mothers and their infants: a 6-month follow-up pilot study PubMed
Balasubramanian S, 2011, Vitamin D deficiency in breastfed infants & the need for routine vitamin D supplementation PubMed Central
Braga CB et al, 2011, Serum vitamins in adult patients with short bowel syndrome receiving intermittent parenteral nutrition PubMed
Calcitriol injection, 1 mcg/mL Drugs.com
Einarsdóttir K et al, 2010, Effect of a single ‘megadose’ intramuscular vitamin D (600,000 IU) injection on vitamin D concentrations and bone mineral density following biliopancreatic diversion surgery PubMed
Vitamin D supplementation Centers of Disease Control and Prevention
Sadat-Ali Mir et al, 2014, Topical Delivery of Vitamin D3: A Randomized Controlled Pilot Study PubMed Central
Vitamin D Safety Mayo Clinic
Vitamin D Evidence Mayo Clinic
Hypervitaminosis D MedlinePlus
Zeratsky K, What is vitamin D toxicity, and should I worry about it since I take supplements? Mayo Clinic
Vitamin D safety Mayo Clinic
Vitamin D interactions Mayo Clinic