Written By Dr Senani Wijesena
Vitamin D deficiency is quickly being recognised as an increasing problem in today’s world where multiple factors including sedentary, indoor lives and use of sun protection/hats are part of modern lifestyle. Low Vitamin D levels according to research has also been increasingly identified and linked with multiple health problems and risk of diseases far beyond its role of protection against osteoporosis.
What is Vitamin D?
Vitamin D is a fat soluble vitamin and hormone precursor that is present in 2 forms, Vitamin D2 and Vitamin D3.
Ergocalciferol or Vitamin D2 is present in plants and some fish.
Cholecalciferol or Vitamin D3 is synthesized in the skin by sunlight (UVB rays). Vitamin D3 has been found to be more effective than vitamin D2, with a potency of 3 times greater on the basis of its ability to elevate blood levels of 25 (OH) D concentrations (the marker of vitamin D status).
The natural diets most humans consume contain little vitamin D, unless those diets are rich in wild caught, fatty fish e.g. sardines, salmon or cod liver oil. Fortified foods such as milk, orange juice, and cereals in the US and margarines in Europe contain small amounts of added vitamin D but such sources are usually minor contributors to vitamin D stores compared to sunlight.
The manufacture of vitamin D by skin is extraordinarily rapid and efficient; production after only a few minutes of midday, mid-latitude summer sunlight easily exceeds dietary sources by a large magnitude. For example, when fair-skinned people bathe in the summer (one full body, minimal erythemal dose of UV-B radiation), they produce more than 20,000IU of vitamin D in less than 30minutes. This is 20 times the recommended daily dietary allowance for vitamin D.
It is recommended that to achieve this daily allowance (1,000 IU), 30 minutes of partial skin exposure (e.g. face and arms or legs) before 10am or after 2pm (non-midday sun) or 15 minutes of mid-day sun without sunscreen or clothing/hats is required.
The production of vitamin D in the skin is affected by sunscreen blocks of UVB rays, pigment content in the skin, cloud coverage and time of day and latitude. High latitude (e.g. Northern Europe), cloud coverage and increased skin pigmentation are associated with less UVB ray penetration and less vitamin D synthesis.
Vitamin D normally enters the circulation after UVB rays from sunlight strikes 7-dehydrocholesterol in the skin, converting it through thermal energy to Vitamin D3. The liver then hydroxylates vitamin D3 to 25 OH D, the circulating form of vitamin D and this is then further hydroxylated to the active endocrine form calcitriol 1,25 (OH)2D by the kidneys. It is known that disease of the kidneys and liver can affect the production of this active form.
In the past 15 years it has also been known that the enzyme (cytochrome P450) that hydroxylates 25(OH) D to calcitriol (active vitamin D3) is present in a wide variety of tissues other than the kidney e.g. bone cells, skin, colon, brain and macrophages (immune cells). This may account for its broad range of effects on the body. Unconverted Vitamin D3 (produced in the skin) does not have any known intrinsic biological activity and must be converted to its active form 1,25 OH D3 to function.
1,25 (OH) D3 exerts its effects via acting on a vitamin D receptor (VDR) in various tissues. The VDR has been found to be located in at least 36 tissues in the body including, fat tissue (adipose), adrenal, bone, brain, breast, cancer cells, cartilage, colon, testes, hair follicle, intestine, kidney, lung, immune cells, muscle, heart muscle cells, ovary, pancreas, pituitary, prostate, skin, thyroid and uterus amongst others. The cells of these tissues therefore have the potential to produce biological responses, depending on the availability of active vitamin D3. This also accounts for the wide range of actions and health benefits of vitamin D throughout the body. It is not just limited to maintaining bone density and bone health as previously believed.
Vitamin D and Bones
Vitamin D controls calcium absorption in the small intestine and works with parathyroid hormone to mediate bone mineralisation and maintain calcium balance in the blood stream.
Without vitamin D, the small intestine absorbs no more than 10-15% of dietary calcium.
Low vitamin D levels are a risk factor for the development of osteoporosis and increased risk of fracture due to weaker bone structure.
Although combination calcium and vitamin D supplementation is associated with higher bone mineral density and decreased incidence of hip fractures, the evidence for vitamin D supplementation alone (without calcium) is less clear.
A recent analysis found that vitamin D supplementation at doses of more than 700IU daily (plus calcium) prevented bone loss compared with placebo.
Vitamin D supplementation without calcium, however, can decrease the incidence of non-vertebral (spine) fractures if given at doses >400IU according to a recent meta-analysis of 12 Randomised controlled trials.
Vitamin D deficiency during bone development and growth in children causes the bone deforming disease rickets. It is recommended that infants and children not exposed to sun light in adequate amounts and are solely breastfed be supplemented with oral vitamin D.
Vitamin D and Cardiovascular health.
Low vitamin D levels have been shown in studies to be positively associated with cardiovascular mortality as well as all-cause mortality and that intake of a vitamin D supplement at normal doses was associated with decreased all-cause mortality rates.
Observational studies have shown a relationship between low vitamin D levels and high blood pressure, coronary artery calcification and existing cardiovascular disease and events. Vitamin D receptors are present in vascular smooth muscle, endothelium and cardiomyocytes (heart muscle cells).
Vitamin D (1,25 Oh D) is effective in down-regulating renin and angiotensin (hormones that control blood vessel diameter and fluid balance in the kidneys) and thereby decreasing blood pressure.
Vitamin D and Diabetes Mellitus
Recent studies in animal models and humans have suggested that vitamin D may also play a role in the homeostasis of glucose metabolism and the development of type 1 and type 2 Diabetes mellitus. Low vitamin D exposure in early life has been linked with the development of Type 1 diabetes mellitus and there is evidence that increased vitamin D intake by infants may reduce the risk of the development of type 1 DM.
VDR’s have strong immune-modulating effects and it is known that type 1 DM has an autoimmune aetiology. In some populations the development of type 1 DM is associated with polymorphisms (variations) in the vitamin D receptor gene.
Vitamin D has recently been associated with several of the contributing factors known to be linked to the development of type 2 DM, including defects in pancreatic B cell function, insulin sensitivity and secretion and systemic inflammation.
Vitamin D and Cancer
Both observational studies in humans and animal models support that vitamin D has a beneficial role in cancer prevention and survival.
The mechanism of action is probably related to its role in the regulation of cell growth and differentiation. In fact it has been shown that a wide variety of normal tissues as well as various cancer cells, including colon cancer, breast cancer, and lung cancer all have the ability to make 1,25 OHD which then regulates cell growth and decreases proliferative activity of that tissue.
In the health professionals follow up study each increment in 25 OH D level of 25mmol/L in the blood was associated with a 17% reduction of total cancer cases.
In the National health and Nutrition Examination Survey, serum 25OH D levels of >80nmol/L conferred a 72% reduction in risk of colorectal cancer compared with a level lower than 50nmol/L.
In a recent meta-analysis of 63 observational studies looking at the relationship between vitamin D levels and cancer incidence and mortality, the majority of the studies showed beneficial effects of increased vitamin D levels in those with colon cancer, breast cancer and prostate cancer. An increased risk of breast and prostate cancer occurs in individuals with serum 25OH D levels <50nmol/L.
Other health benefits
Recent epidemiological studies have observed relationships between low vitamin D levels and multiple disease states, probably caused by its anti-inflammatory and immune-modulating properties and possible effects on cytokine levels (small proteins released by cells that affect activity of other cells).
Several studies have also shown a link between low vitamin D and a variety of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, inflammatory bowel disease and MS (multiple sclerosis) with higher levels being protective. Vitamin D is known to have immune modulating effects and several studies have shown that it affects the growth and differentiation of immune cells such as macrophages, dendritic cells, T cells and B cells.
With regards to Multiple sclerosis, low levels of vitamin D are associated with more severe disability and relapses, and epidemiological studies show a higher incidence of MS in countries of rising latitude in both the northern and southern hemisphere. Migration studies have shown that the risk can be modified at an early age from both high to low and low to high.
Exposure to sun in early childhood is associated with reduced risk of developing MS. A Norwegian case control study found that fish and cod liver oil have a protective effect against the development of MS and several large studies in the US including the Nurses Health Study found that vitamin D supplementation in the form of a multivitamin seemed to lower their MS risk by 40%.
In patients with diagnosed MS, there is a lack of research regarding vitamin D supplementation and control of the disease. However, a small safety study of 12 patients taking 40,000IU of Vitamin D for 28 weeks (with a 25OHD level of 158ng/ml) showed a decline in the number of brain lesions on MRI.
Observational studies have shown that people with Alzheimer’s disease have lower vitamin D levels than do matched controls without dementia. This may be due to Vitamin D’s antioxidant effects and the presence of vitamin D receptors in the hippocampus (area of the brain that controls memory/emotion) which may modulate mitochondrial and brain function.
Vitamin D also influences neuromuscular function, muscle strength and balance and decreases muscle pain.
Vitamin D assessment and causes of deficiency
The best way to assess vitamin D status in the body is to measure circulating serum 25 (OH) vitamin D levels. In recent studies it has been shown that the prevalence of vitamin D deficiency (25(OH) D < 50nmol/l) in healthy adults may be as high as 20-30% particularly in high latitude countries in the winter. A healthy concentration of 25(OH) D, is however, considered to be > 80-100nmol/L.
Vitamin D deficiency is prevalent in infants who are solely breastfed and who do not receive vitamin D supplementation and increased risk in adults of all ages who have greater skin pigmentation or who always wear sun protection or limit their outdoor activities.
A heightened awareness of the role that excessive exposure to sunlight plays in increasing the risk of non-melanoma skin cancer and wrinkles led to the widespread use of topical sunscreens.
Sunscreens efficiently absorb UVB radiation and thus markedly diminishes the total number of UVB photons that reach the 7-dehydrocholesterol in the skin’s cells e.g. a sunscreen with a sun protection factor (SPF) of 8 reduces cutaneous production of pre-vitamin D3 by >95% when used on the whole body one time.
Melanin (skin pigment) is a natural sunscreen and it competes quite well with 7-dehydrocholesterol for UVB photons. A person with darker skin requires 10-50 times the exposure to sunlight to produce the same amount of vitamin D3 in their skin as a fair skin person.
Latitude and time of day also affects vitamin D3 synthesis. The ozone layer is efficient at absorbing UVB radiation. When the angle of the sunlight reaching the Earth’s surface is very oblique (i.e. early morning, late afternoon and winter), sunlight must pass through more ozone, hence very few, if any UVB photons reach the earth’s surface. Also at higher latitudes (> 35 degree e.g. northern Europe, Canada, Boston), the angle of the sun is so oblique during the winter months that most, if not all the UVB photons are absorbed by the ozone layer, thereby reducing or completely preventing the production of pre-vitamin D3.
Obesity is often associated with vitamin D deficiency, as once formed in the body, Vitamin D being a fat-soluble vitamin, deposits in adipose tissue and is not bio-available.
It is remarkable that lifeguards and sunworshippers have never suffered from vitamin D intoxication due to excessive exposure to the sun. The reason for this is that pre-vitamin D3 and vitamin D3 efficiently absorb sunlight and are converted to a multitude of other phytoproducts, including lumisterol, tachysterol, suprasterols and toxisterols. Thus because of this unique solar regulation, the skin can never generate quantities of vitamin D3 excessive enough to cause vitamin D3 intoxication.
Vitamin D is included in most multivitamins, usually in strengths from 50-100IU. It can be found as soft gels, capsules, tablets and liquids.
People who are obtaining sun exposure but not at recommended levels, should take at least 600IU/day of vitamin D3 as supplements if <70 years old and 800IU/day if >70 years old. When sun exposure is minimal, the RDA for Vitamin D from both dietary sources and supplements is 1000-2000 IU/day in Australia. These are the recommended daily allowances to maintain normal serum 25 (OH) D levels. Greater amounts can be taken in individuals who have deficiencies. In those with moderate to severe deficiencies (< 50nmol/l), 3000-5000 IU/day for 6-12 weeks is recommended to raise the level of vitamin D quickly, followed by a maintenance dose of 1000-2000 IU per day. The recommended form of vitamin D to be taken is Vitamin D3 (which is the active form) and not Vitamin D2. It is recommended that supplemental doses and monitoring of serum levels occur with a health practitioner prior to commencement of treatment.
The main concerns with excessive vitamin D levels are high calcium levels (hypercalciuria and hypercalcaemia) which can occur with excessive supplementation. Hypercalcaemia is not seen until serum 25 (OH) D levels reach 220 nmol/L and is generally not reported until levels reach 500 nmol/L.
There is no evidence of toxicity based on calcium concentrations at vitamin D doses up to 5000IU per day or 50,000IU per month on an ongoing basis. In individuals with mal-absorption problems, intramuscular administration of Vitamin D (100,000 or 150,000 IU) every few months may be given.
Cod liver oil, which can be used for vitamin D supplementation should be used cautiously as it contains Vitamin A, which can be toxic at high doses and is contra-indicated in pregnant women.
- Caryl A Nowson et al. Vitamin D and health in adults in Australia and New Zealand: a Position statement. Med J Australia 2012; 196 (11) 686-687
- Osteoporosis Australia Medical and scientific Advisory committee, 2015
- Teresa Kulie et al. Vitamin D: An evidence based review. Journal of American board of Family Medicine 2009;22:698-706
- Michael Holick. Vitamin D:importance in the prevention of cancers, type 1 diabetes, heart disease and osteoporosis. American Journal of Clinical Nutrition. 2004; 79:362-71
- Anthony Norman. From Vitamin D to hormone D: Fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 2008:88 (suppl):491S-9S
- John J Cannell, William Grant. What is the role of vitamin D in Autism. Dermato-Endocrinology 5:1; 199-204; Jan/Feb/March 2013
- Pizzorno and Murray. Textbook of Natural Medicine. 2006
- Maurice Shils et all. Modern Nutrition in health and disease. 2006
© 2016, Dr Senani Wijesena (Vitamin D and its health benefits).