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Evolving Story of Vitamin D

by Michael Sellar(more info)

listed in nutrition, originally published in issue 116 - October 2005

Until 1980 the great thrust of research on vitamin D centred on its role in mineral metabolism and its importance in bone health. But new discoveries have focused research on vitamin Ds other roles. These roles have turned out to be extensive, with profound implications for human health.

Vitamin D isn't really a vitamin at all. It was given this status about a century ago when it was discovered as the anti-rickets factor in cod liver oil. But later it was realized that exposure to the sun could also prevent or cure this childhood bone disorder. It wasn't until the late 1960s when it was postulated that vitamin D had no biological activity but had to be metabolically activated before it could function. This was confirmed with the understanding that vitamin D, whether obtained through the diet or the action of sunlight on the skin, had to be transformed into a different chemical form in the liver. Although this is the major circulating form, it is only made biologically active by the kidney. This active form is called calcitriol. In this form it can function directly on the small intestine, signalling it to absorb calcium and phosphorus and to modulate their activity within the blood and bones. It would be more accurate to call calcitriol a hormone and the inactive vitamin D, a prohormone.

The Vitamin D Receptor

Research into how calcitriol carried out its functions led to another important discovery in 1974, the vitamin D receptor. Calcitriol binds to specific cellular proteins involved with the transfer of genetic information and with switching genes on and off. It is now known that more than 50 genes in tissues throughout the body are regulated by calcitriol, and it can be made in many body tissues. In fact most tissues and cells in the body, including heart, stomach, pancreas, brain, skin and immune cells have vitamin D receptors.[1] Vitamin D, therefore, must have many functions that go beyond mineral metabolism.

It has long been observed that winter and spring births, as well as living at higher latitudes, have associations with particular health problems. These include schizophrenia, bipolar disorder, autism, Alzheimer¡¦s disease, amyotrophic lateral sclerosis, multiple sclerosis, rheumatoid arthritis, type 1 (insulin-dependent) diabetes mellitus, hypertension, many cancers, and obesity.[2]

With the new knowledge that vitamin D receptors are found all over the body, an explanation for these conditions could be found in the level of sunlight exposure. Ultraviolet (UV) B radiation from the sun has to be strong enough for the body to manufacture vitamin D. The amount of UV-B exposure we are subjected to and can utilize will depend on many factors, including latitude, altitude, season of the year, time of day, cloud cover, pollution, skin colour, clothing cover, sunscreen use, ageing, and obesity.

In Britain the UV-B band isn¡¦t strong enough for six months of the year between October and March to promote any vitamin D synthesis at all. Although some vitamin D can be stored within our fatty tissues to be utilized during the winter months, the half-life of vitamin D in the blood is no more than six weeks, so deficiencies are likely to be well established by late winter or early spring. This is especially so because vitamin D is poorly supplied in our diets. Ninety per cent of our intake comes from sunlight exposure. If we don't 'stock up' with the vitamin during the summer months, then we are at great risk of deficiency. Babies born during winter and spring are particularly vulnerable.

Vitamin D, The Nervous System and Schizophrenia

Rodent experiments show that vitamin D deficient mothers give rise to offspring with damaged brains and this leads to persistent changes in the brain of the adult.[3] These studies suggest neurological development in humans could be impaired and give rise to a number of irreversible nervous system disorders.

It has been proposed that low vitamin D during brain development interacts with susceptibility genes giving rise to schizophrenia. Vitamin D is an attractive ¡¥genetic¡¦ candidate because its nuclear hormone receptor regulates gene expression and nervous system development.[4]

The 'vitamin D hypothesis' for schizophrenia is also attractive because it ties in with many of its epidemiological features. It is significantly increased in people born in the winter or spring. This effect is exaggerated the higher the latitude. Years with the least amount of sunlight have the most cases of people born with the condition. Darker skinned people – who can take up to six times as long to make the same amount of vitamin D as those with white skin – have higher levels of schizophrenia.[2] Since these neurological conditions are not reversible it is important to maintain good levels throughout pregnancy and beyond. Yet 76% of mothers who had just given birth were found to be severely vitamin D deficient as well as 81% of their infants.[5] Breast-fed babies are also at risk as breast milk contains little vitamin D.

A Potent Immune System Modulator

Until 1980 no one could imagine vitamin D had any role to play in immunity, but since then vitamin D receptors have been found in most cells within the immune system including activated T and B lymphocytes and activated macrophages. Autoimmune responses, in which the body attacks its own tissues, are mediated by T cells. Calcitriol can modulate T cell responses and thereby diminish autoimmune responses.

Experiments using mice that are prone to the most common autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and type 1 diabetes, found they could be largely prevented if given calcitriol early in life. For instance the risk of diabetes was reduced by 80%.[1]

A Finnish study tested whether this research applied to humans. During the first year of life, children who received 2000 IU of vitamin D for several years had an 80% reduced risk of developing type 1 diabetes. Children who were suspected of having rickets during the first year of life had a fourfold risk of getting type 1 diabetes.[6]

Studies following nearly 200,000 women for up to 20 years found those in the highest 20% of dietary intake had a 33% reduced risk of developing multiple sclerosis compared to those in the lowest 20% of dietary intake. Women who took a vitamin D supplement of 400 IU or more had a 41% reduced risk compared to those who didn't take supplements.[7]

Post-menopausal women with the highest intake of vitamin D had a significantly lower risk of developing rheumatoid arthritis compared to those with the lowest intake at 11 years of follow up.[8] Another study found serum vitamin D levels were frequently very low in rheumatoid arthritis patients, with the lowest values found in those with the highest disease activity.[9]

UV-B Chart

Mortaility Rates Chart

Circulating Vitamin D Chart

Cut Risk of Heart Attack by Half

Northern latitudes have higher levels of hypertension and heart disease and more heart attacks occur in the winter months. British towns with greater sunshine hours have fewer heart disease deaths compared to towns with less sunshine hours.[2]

Heart attack patients were found to have significantly less circulating vitamin D in their blood compared to those who hadn¡¦t had a heart attack. Those with average or better levels had a 57% reduced risk of a heart attack compared with those who had below average levels.[10]

Young adults with vitamin D deficiency were found to be at greater risk of congestive heart failure than their vitamin D sufficient counterparts.[2] Calcitriol reduced C-reactive protein, an inflammatory marker associated with heart disease by 23%.[11] Other research demonstrates that the greater the calcitriol levels, the lower the extent of arterial calcification, a common feature of atherosclerosis.[12]

Calcitriol has been shown to influence a gene that plays a role in the system that controls blood volume and blood pressure. Patients with high blood pressure exposed to UV-B radiation for three months saw their circulating concentrations of calcitriol increase by 180% with a 6 mm Hg drop in their diastolic and systolic blood pressure, a result similar to what one would expect from drug therapy. A similar group exposed to UV-A radiation that doesn't promote vitamin D synthesis, saw no increase in calcitriol levels and no change in blood pressure.[1]

Lose Weight Lying in the Sun?

People who are obese are chronically deficient in vitamin D because it is efficiently deposited in fat stores and is less bioavailable. They can only raise blood levels about half as much as non obese individuals when given supplements or exposed to UV-B. Yet UV-B stimulates the production of alpha-melanocyte stimulating hormone that helps to regulate weight loss and energy production. Low vitamin D levels were found to be an independent predictor of obesity.[2] In theory it might be possible to lose weight by sunbathing, but further research is needed.

Reducing Cancer Risk

Over 60 years ago it was observed that people living at higher latitudes of the USA had a higher risk of dying from the most common cancers compared to those living at lower latitudes. This was confirmed in the late 1980s and early 1990s when several investigators reported increased risks of dying from colon, prostate and breast cancer, in people living at higher latitudes in both the USA and Europe.[1]

More than 25% of breast cancer deaths in Europe have been attributed to low sunlight exposure.[1] In men with certain gene variants, high sun exposure reduced prostate cancer risk by as much as 65%.[13] Lung cancer patients with the highest vitamin D intake who had surgery in the summer had a three-fold better disease-free survival and a four-fold better overall survival than patients who had surgery during winter with the lowest vitamin D intake. At least 17 types of cancer have been linked with reduced exposure to UV-B.[14] An important function of calcitriol, first discovered in 1985, is its ability to down-regulate cells that are dividing too rapidly. By acting as a brake on cell growth, it can prevent uncontrolled cell division as happens in cancer. It has also been found to act in a number of other ways to prevent the initiation and growth of tumours. Laboratory research and trial evidence are confirming the epidemiological observations.

Vitamin D's Many Other Benefits

Vitamin D has been shown to benefit or reduce the incidence of many disorders, including muscle weakness and musculoskeletal pain, falls and fractures, osteoporosis, depression, premenstrual syndrome, seasonal affective disorder, polycystic ovarian syndrome, gum disease, and tuberculosis.

Vitamin D Status in the UK

Dr Zitterman[15] states that blood levels of vitamin D are sufficient above 100 nmol/L. Yet British children average only 52 in winter and 80 in summer. Dark skin children have levels throughout the year ranging from 36-42. Teenagers and young adults are believed to fare even worse than children. The elderly average 23 and 35 in the winter and summer respectively. Vitamin D status in the UK is poor. It is hardly surprising, therefore, that rickets is re-appearing. Unfortunately, because of the assumption that vitamin D status is adequate, or the wrong measurements to determine vitamin D status are performed, deficiency often goes undiagnosed or is misdiagnosed as fibromyalgia.

Vitamin D is found in a restricted number of foods. Oily fish is the best source, but this is not widely eaten. We rely on the sun to provide us with our needs. Just five to ten minutes exposure on hands, face and arms two to three times a week during the summer months would be sufficient for those with white skin. Thirty minutes to an hour for those with dark skin. But exhortations to keep out of the sun or to cover up with sunscreen for fear of skin cancer are restricting our exposure, as well as lifestyle factors. According to Reinhold Vieth who has spent over three decades studying the vitamin, the current recommended daily amount of 200 IU a day is ¡¥woefully inadequate¡¦. He believes this should be quadrupled.[16]

Conclusion

The last 35 years has seen a huge increase in our understanding of vitamin D. With the discovery of its biologically active form and its many functions throughout the body, the epidemiological observations linking certain health conditions with sunlight exposure begins to make sense. This new knowledge makes it imperative to maintain adequate levels of vitamin D in our blood. Yet people in Britain suffer from chronic vitamin D deficiency. Improving vitamin D status in the population with sensible sun exposure during the summer and vitamin D supplements from October to March is likely to see a reduction in the incidence of many chronic health problems.

References

1. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. American Journal of Clinical Nutrition. 79: 362-371. 2004.
2. Gillie O. Sunlight Robbery. Health Research Forum Occasional Reports: No.1. 2004.
3. Feron F et al. Developmental Vitamin D3 deficiency alters the adult rat brain. Brain Res Bull. 65: 141-148. 2005.
4. Mackay-Sim A et al. Schizophrenia, vitamin D, and brain development. Int Rev Neurobiol. 59: 351-380. 2004.
5. Adams M. The Healing Power of Sunlight & Vitamin D. Truth Publishing International. 2005.
6. Hypponen E et al. Intake of vitamin D and risk of type 1 diabetes:a birth-cohort study. Lancet. 358: 1500-1503. 2001.
7. Munger KL et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 62: 60-65. 2004.
8. Merlino LA et al. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women¡¦s Health Study. Arthritis Rheum. 50: 72-77. 2004.
9. Kroger H et al. Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheumatol. 22: 172-177. 1993.
10. Scragg R et al. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol. 19: 559-63. 1990.
11. Timms PM et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? Q J Med. 95: 787-796. 2002.
12. Watson KE et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. 96: 1755-1760. 1997.
13. John EM et al. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res. 65: 5470-5479. 2005.
14. Press Release. Surgery Season and Vitamin D Intake May Predict Successful Lung Cancer Surgery. American Association for Cancer Research. April 18, 2005.
15. Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 89: 552-572. 2003.
16. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition. 69: 842-856. 1999.

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About Michael Sellar

Michael Sellar is the editor of Enzyme Digest, a quarterly newsletter on nutrition and complementary medicine for health professionals. For subscriptions Tel: 0845 1300 776. He is also the proprietor of www.N16health.com a complementary health resource for the residents of Stoke Newington in north London and interested people worldwide. He can be contacted by email at: sellar@blueyonder.co.uk

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