There is growing evidence of the vital role Vitamin D plays in multiple aspects of human physiology and that sub-optimal levels may be widespread, potentially contributing to ill-health in a number of ways. Vitamin D is a generic term for the family of cholesterol-like, fat-soluble substances called secosteroids and essentially functions as a ‘pro-hormone’ within the body. It has the potential to be converted into molecules with hormonal functions that can operate in both endocrine and exocrine pathways.
This technical bit may leave you wanting to poke your eyes out!! But please persevere because if you have at least a better understanding of some of these factors, you’ll take vitamin D much more seriously… and we all should.
Vitamin D requires participation from the skin, bloodstream, liver and kidneys to convert it from its biologically inactive precursor molecules, choleclaciferol (vitamin D3) and ergocalciferol (vitamin D2) into the biologically active form calcitriol. The former is synthesised by humans in the skin upon exposure to ultraviolet-B radiation from sunlight, whilst the latter is derived from plant sources and therefore can be obtained from the diet.
As a fat-soluble nutrient, dietary vitamin D is primarily absorbed in the small intestine by passive diffusion, delivered to the enterocytes in micelles, and then secreted into the lymphatic system as chylomicrons.
From there it enters circulation and is bound to vitamin D binding protein for further transportation to tissues and organs. A large amount of circulating vitamin D is extracted by the liver cells and metabolised to calcidiol. This is the major circulation form of vitamin D.
Calcidiol then must be biologically activated in the kidneys into calcitriol. Calcitriol is the active form of vitamin D utilised by the body for a range of biochemical processes. The status of vitamin D is generally assessed by measuring circulation-calcidiol (calcitriol levels are increased by parathyroid activity and so may mask low calcidiol levels).
Although all initial forms of vitamin D are theoretically metabolised in the same way in the body, according to one small scale study in 2004, vitamin D3 appeared initially to be more effective than D2 at increasing the active (calcitriol) form. However, a more recent study (2007) challenges this view, suggesting that D2 is as effective in sustaining levels of calcidiol and calcitriol as D3.
Risk factors for vitamin D deficiency
• People with dark coloured skin synthesise less vitamin D on exposure to sunlight
• Fat malabsorption syndromes: e.g. cystic fibrosis and cholestatic liver disease impair the absorption of dietary vitamin D
• Infants who are exclusively breast-fed may be at risk of vitamin D deficiency. The American Academy of paediatrics recommends that breast fed infants be given a vitamin D supplement of 200iu/day
• Ageing: The elderly have reduced capacity to synthesise vitamin D in the skin when exposed to UVB radiation
• Inflammatory bowel disease: People with IBD appear to be at increased risk of vitamin D deficiency, especially those who have had small bowel resections
• Obesity: Vitamin D is deposited in body fat stores, making it less bioavailable to people with large stores of body fat
Listed below are some of the main advantages of a diet rich in Vitamin D. Some may be familiar to you whilst others are less well known.
Calcitriol alone increases intestinal absorption of calcium and, via a feedback loop, also reduces parathyroid hormone (PTH) secretion. Without sufficient vitamin D to support calcium utilisation, there is an elevation in PTH secretion by the parathyroid glands resulting in calcium being taken from bones to maintain serum levels. The presence of adequate vitamin D levels normalises the process, resulting in proper maintenance of both serum and bone calcium levels.
The results of most clinical trials since 2003 suggest that vitamin D supplementation can slow bone density losses or decrease the risk of osteoporotic fracture in men and women. For example post-menopausal women taking at least 600ius of vitamin D per day had a risk of osteoporotic hip fracture that was 37% lower than women who consumed less than 140iu/day.
Overall evidence suggests vitamin D at levels of about 800ius per day may be helpful in reducing bone loss and fracture rates in the elderly. For vitamin D supplementation to be effective, adequate calcium is also needed.
The proliferation of cells without healthy differentiation may lead to diseases like cancer. Calcitriol inhibits proliferation and stimulates appropriate differentiation of cells (see the work of Feskanich and Willett, 2004).
Many malignant tumours have been found to contain vitamin D receptors, including breast, lung, skin (melanoma), colon, and bone. Calcitriol has been found to induce cell differentiation and/or inhibit proliferation of a number of cancerous and non-cancerous cell types. The mechanism of action of the anti-carcinogenic activity of vitamin D is not fully understood, but has been found to induce death of cancer cells in vitro (under laboratory conditions) and in vivo (in the living organism). In experiments performed with mice (2000) vitamin D supplementation produced tumours that were less ‘vascularised’.
Further evidence of the link between vitamin D and cancer includes a long term study, in 2002, of more that 88,000 women, which found that higher intakes of vitamin D were associated with significantly lower breast cancer risk in premenopausal women but not postmenopausal women. Studies on the relationship between vitamin D and prostate cancer risk/incidence are inconclusive. There is mixed evidence on the relationship between colorectal cancer and vitamin D status, but a recent meta-analysis suggests a link between tissue levels of vitamin D and reduced incidence at higher levels of supplementation.
Animal studies suggest that calcitriol plays a role in insulin secretion where there is high insulin demand. Limited data (2003 – Borissova, Tankova et al) in humans suggests that insufficient vitamin D levels may have an adverse effect on insulin secretion and glucose tolerance in type 2 diabetes. According to one correlational study in 2004, higher vitamin D status correlated with a 60% improvement in insulin sensitivity. In a clinical trial by Borissova and others, using 1,332 ius/day for only 30 days in 10 women with type 2 diabetes, vitamin D supplementation was shown to improve insulin sensitivity by 21%.
Finally a cohort study in 2001, of children born in 1966 and followed up for thirty years found that those who received vitamin D in the first year of life had a significantly lower risk of developing type 1 diabetes.
Blood Pressure Control
Epidemiological studies since 1997 suggest that conditions that decrease vitamin D synthesis in the skin, such as having dark skin and living in temperate latitudes, are associated with increased prevalence of high blood pressure. At present, results from controlled clinical trials utilising vitamin D are mixed, but predominantly positive. Higher levels of parathyroid hormone, resulting from low levels of vitamin D, are also linked with hypertension, as well as infarction and stroke (see the work of Kamycheva and Sundsfjord).
Vitamin D as calcitriol is a potent immune system modulator. The vitamin D receptor is expressed by most cells of the immune system – including T cells and antigen-presenting cells. Vitamin D appears to both enhance innate immunity and inhibit the development of autoimmunity (see the work of Griffin, Xing and Kumar, 2003).
Vitamin D may positively affect autoimmune function by suppressing the activity of dendritic cells (or Langerhan’s cells in the skin), which regulate immune activity by secreting nitric acid. Calcitriol has also been found to modulate T cell responses, such that autoimmune responses are diminished.
Epidemiological studies have found the prevalence of insulin dependent diabetes, multiple sclerosis, and rheumatoid arthritis increases as latitude increases, suggesting vitamin D synthesis may play a role in these autoimmune diseases. In fact calcitriol has been effective in the treatment of psoriasis when applied topically in some double-blind, placebo-controlled trials. This may be due to anti-proliferative effect on the skin keratinocytes.
There is the potential for oral vitamin D to also support appropriate immune function in those with psoriasis as with other autoimmune conditions such as multiple sclerosis.
Vitamin D supplement use was associated with a significant reduction in the risk of developing MS in two large cohorts of women followed for at least ten years (Munger, Zhang and O’Reilly, 2004). Research conducted in 2003, gave 39 MS patients 800mg calcium and 1,000 ius of vitamin D per day for six months and noted a modest/moderate anti-inflammatory effect. More recent data has suggested very high doses offer what many consider ‘miraculous’ results. See: The Vitamin D3 Miracle by Jeff T. Bowles.
In terms of rheumatoid arthritis, a study in 2004, noted that postmenopausal women with the highest total vitamin D intakes were at significantly lower risk of developing the condition after eleven years of follow up than those with the lowest levels.
Calcium’s role in maintenance of vascular tone may be useful in cases of migraine. Two cases have been reported of a reduction in menstrual migraine attacks following supplementation with calcium and up to 1,600 iu of vitamin D in women with vitamin D deficiency.
There is growing evidence of the vital role Vitamin D plays in multiple aspects of human physiology and that sub-optimal levels may be widespread, potentially contributing to ill health in a number of ways. Vitamin D is a generic term for the family of cholesterol-like, fat soluble substances called secosteroids and essentially functions as a ‘pro-hormone’ within the body i.e. it has the potential to be converted into molecules with hormonal functions that can operate in both endocrine and exocrine pathways.
Mood and Depression
Recent research has shown that vitamin D can also have a positive effect on mood. The incidence of depression has increased over the last century which has been largely due to our changes in lifestyle, including reducing our exposure to sunlight through changing work practices i.e. working indoors, our use of cars and our use of sun block. In turn this has contributed to reduced vitamin D levels in the blood. According to Klerman and Weissman’s 2003 research, major depression increases when vitamin D in the blood dips below normal levels.
Vitamin D, in two human studies, was found to significantly enhance positive effect and possibly reduce negative affect. In 1999, a study found that 10,000 iu of vitamin D administered in one oral dose improved depression more significantly than light therapy in a group of patients suffering from seasonal affective disorder (SAD).
The mechanism of the possible mood-modulating effect of vitamin D is unclear. It is speculated that it may influence brain serotonin levels. Research on vitamin D, exposure to sunlight and the effect it can play on mood is an area of great potential and one, which can contribute significantly to our understanding
of depression – and much is being done in this area.
Skeletal muscles have receptors for calcitriol. Aching bones and muscles may be due to vitamin D deficiency. In a cross-sectional study (2003) of 150 consecutive patients referred to a clinic in Minnesota for the evaluation of persistent, non-specific musculoskeletal pain, 93% had serum calcidiol levels indicative of vitamin D deficiency. Overall low vitamin D levels may be a factor in a range of non-specific joint and muscle disorders and conditions such as fibromyalgia.
Vitamin D has a very wide range of functions in many aspects of physiology. There are ongoing developments in research showing its vital and central role for general health as well as some of the more serious chronic diseases. There is also increasing evidence of epidemiological levels of deficiency or sub-optimal intake of vitamin D especially in northern European countries like the U.K.
In future, supplementation of vitamin D is likely to become more and more important in the conventional management of health and disease.