Adequate vitamin D nutrition is associated with the prevention of rickets in children and therefore, little thought is given about the consequences of vitamin D deficiency in adults. However, it is now becoming clear that vitamin D plays an important role in maintaining bone health from birth until death. Of equal importance is that vitamin D has a multitude of other biologic functions in the body that may be important for the prevention of common cancers, hypertension, type 1 diabetes, as well as a host of other common maladies that afflict elders.

Unlike most fat soluble and water soluble vitamins that are plentiful in a healthy diet, very few foods naturally contain vitamin D. Consumption of oily fish, such as salmon or makerel, three to four times a week or ingestion of cod liver oil on a daily basis are two natural sources. Some foods such as milk and some breads and cereals are also fortified with vitamin D. However, the vitamin D content that is added to milk in the US has in the past been found to be highly variable and in some cases, absent. (Milk in the UK is not fortified with vitamin D). It is not appreciated that most of our vitamin D requirement, i.e. 80-100%, comes from our exposure to sunlight.

The body has a huge capacity to produce vitamin D₃. A person in a bathing suit exposed to sunlight or ultraviolet B radiation for an amount that would cause a light pinkness to the skin (1 minimal erythemal dose; 1 MED) will raise the blood levels of vitamin D₃ to the same degree as if the individual took between 10,000 and 25,000 IU of vitamin D. Anything that alters the amount of ultraviolet B radiation that penetrates into the skin will have a dramatic influence on the cutaneous production of vitamin D. Increase in skin pigmentation, use of sunscreens, increase in latitude, increase in the Zenith angle of the sun due to seasonal changes, and aging all dramatically influence the cutaneous production of vitamin D₃. The topical application of a sunscreen with an SPF of 8 will reduce the cutaneous production of vitamin D₃ by 97.5%.

Vitamin D deficiency is extremely common in the US and UK adult population. More than 50% of free living and institutionalized elders in the US have been reported to be vitamin D deficient. It has been assumed that young and middle-aged adults are not at risk for vitamin D deficiency. However, the lifestyle of the young and middle-aged adults is such that they are constantly working indoors and when outdoors they wear a sunscreen because of their concern of sun exposure and risk of skin cancer. A study in Boston reported that 32% of medical students and residents aged 18-29 years were vitamin D deficient at the end of the winter. The NHANES III study reported that 41% of African American women of child bearing age (15-49 years) were found to be vitamin D deficient at the end of the winter.

Chronic vitamin D deficiency has subtle and insidious consequences for both bone health and overall health and well-being for all adults and in particular elders. Vitamin D deficiency can precipitate and exacerbate osteoporosis due to the accompanying secondary hyperparathyroidism. Vitamin D deficiency also causes osteomalacia, which is often associated with muscle pain, weakness, and bone pain, weakness and increased risk of fracture.

Vitamin D is biologically inert and is metabolized in the liver to its major circulating form 25-hydroxyvitamin D [25(OH)D]. 25(OH)D is converted in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)₂D] that is responsible for regulating intestinal calcium absorption and stimulating osteoclastogenesis. Vitamin D receptors (VDR) are present in most tissues and immune cells in the body. 1,25(OH)₂D is one of the most potent inhibitors of cellular growth. In addition, 1,25(OH)₂D alters both activated T and B lymphocyte function. VDR is present in the kidney and recently it was demonstrated that 1,25(OH)₂D down regulates the renin/angiotension system.

It is now recognized that the kidney is not the sole source for the production of 1,25(OH)₂D. Many other organ systems, including colon, prostate, breast, and skin have the enzymatic machinery to produce 1,25(OH)₂D locally. This may be the explanation for why chronic vitamin D deficiency, often associated with living at higher latitudes, is associated with increased risk of dying from colon, prostate, breast, and ovarian cancer. Exposure to ultraviolet B radiation was effective in treating moderate hypertension. In animal models 1,25(OH)₂D treatment was effective in preventing multiple sclerosis-like disease and type 1 diabetes. The recent observation that vitamin D supplementation of children resulted in a decreased risk of type 1 diabetes by 80% is noteworthy.

There is a great need to increase our awareness of vitamin D nutritional status and its health implications. The only method to determine vitamin D status is to measure circulating concentrations of 25(OH)D. Recently, the National Academy of Sciences has recommended that vitamin D intakes be increased for elders to 600 IU/day. However, in the absence of exposure to any sunlight, this is probably inadequate. It is now estimated that 1,000 IU of vitamin D a day is required to satisfy the body’s needs and maintain circulating concentrations of 25(OH)D at least 30 ng/ml, which is thought to be important to maximize bone health and cellular health.

High levels of heart disease in Britain may be caused by insufficient vitamin D which is normally obtained by the action of sunlight on skin.

The higher incidence of heart disease in Scotland compared with England, or in England compared with southern European countries such as France, Italy or Spain may be explained by relatively weak sunlight and short summers in the north. In fact the good health associated with the Mediterranean diet may be accounted for as much by the Mediterranean sun as by the regional food.

Dr Armin Zitterman from the Heart and Diabetes Center, Ruhr University Bochum, Germany, argues that insufficient vitamin D causes the calcification of arteries that commonly occurs in people with heart disease. Higher levels of vitamin D produced by supplements or sun exposure prevents heart disease by reducing inflammatory processes and disorganised cell proliferation in blood vessels and in the heart, he believes.

"Protection against chronic disease can be obtained in winter by taking 2000 IUs (50 micrograms) vitamin D per day. In summer, enough vitamin D can be obtained by sunbathing for 10 minutes or so in the middle of the day, exposing the whole body. This will protect against bone disease and is likely to prevent heart disease too," says Dr Zittermann.

But government advice in the UK is seriously out of date and misleads the public into thinking that adults obtain sufficient vitamin D from casual exposure of hands and face to the sun. In fact very little vitamin D is obtained from casual exposure to the sun in the UK. Many people in the UK also get little vitamin D from food, especially if they do not eat margarine or oily fish and choose a wholemeal breakfast cereal such as muesli that contains no vitamin D.

"Current dietary guidelines for vitamin D in the UK are incorrect in stating that adults below age fifty require no vitamin D and specify too little for older people," said Reinhold Vieth, professor of nutritional sciences in Toronto. "Sun avoidance advice makes the vitamin D problem even worse in the UK. The result is an unacceptably high occurrence of what should be regarded as toxic vitamin D deficiency."

This toxic deficiency of D is associated with higher incidence of many chronic diseases. Not only heart disease but several types of cancer including cancer of the breast, prostate and bowel.

Inappropriate exposure to ultraviolet radiation (UVR) in sunlight is critical in development of the common skin cancers. Public Health agencies have emphasized the dangers of inappropriate exposure. By contrast, many studies show relative vitamin D deficiency throughout the world. Vitamin D is not common in nature and humans generally acquire the chemical through the actions of sunlight on skin. Biologically active vitamin D (1,25-dihydroxy vitamin D) exerts key effects on biochemical pathways and maintaining adequate vitamin D is important in determining the efficiency of tissues and risk of various diseases. The range of vitamin D-dependent diseases is potentially large as the chemical exerts effects in many cells including prostatic, colonic and breast and appears to have a key role in mediating insulin sensitivity as well as blood pressure and acute myocardial infarction risk.

There is a therefore a dilemma; the incidence of skin cancer is increasing in many Caucasian populations where many individuals have low vitamin D. We hypothesised that a relative deficiency of vitamin D will increase risk of prostate cancer because of the effects of 1,25-dihydroxy vitamin D in inhibiting the growth of tumour cells as well as maintaining their differentiation.

Several workers have proposed an inverse relationship between UVR and prostate cancer risk. Whilst such data are interesting they have been criticised because associations may result from unrecognised confounding factors. Data for prostate cancer shows that the mortality rate in the colder northern states of the United States is approximately twice that of the warmer southern states.

We have examined the hypothesis that low UVR exposure leads to increased prostate cancer risk. We proposed that the impact of exposure is mediated by characteristics including inherited variations in the DNA sequence of key genes. We focused on genes that determine skin pigmentation, a characteristic that mediates the effects of UVR on skin. Thus, lightly pigmented skin is at relatively high skin cancer risk but is efficient in synthesising vitamin D. We hypothesise that Caucasians with lightly pigmented skin (skin type 1) are at lowest risk of prostate cancer. We propose that this association was mediated by genetic factors particularly those that determine skin pigmentation.

In our first studies we recruited 210 prostate cancer cases and as controls, 155 men with benign prostatic hypertrophy. We asked the men to record aspects of their lifetime UVR exposure. The proportion of cancer cases with very low levels of exposure was markedly higher than the proportion of men with benign prostatic hypertrophy. Other exposure parameters including sunbathing, regular holidays in a hot climate and sun burning were all associated with reduced risk of the cancer. Because this initial study comprised a relatively small number of men we recruited further cancer cases and men with benign prostatic hypertrophy, repeated the initial investigation and obtained virtually identical results. This shows that in northern European men, low levels of UVR exposure are linked with increased prostate cancer risk. As predicted, skin type 1 conferred reduced prostate cancer risk particularly in men with low exposure. Further, inherited variation in genes that mediate pigmentation such as MC1R and TYR are linked with cancer risk. Whilst these findings do not prove the hypothesis they are supporting. Genes linked with the handling of vitamin D are also strong candidates for risk. Thus, the vitamin D receptor, the gene that mediates the biological actions of 1,25-dihydroxy vitamin D demonstrates many inherited variants in its gene sequence and some are linked with prostate cancer risk.

The hypothesis that prostrate cancer risk is mediated by exposure to sunlight is compatible with the known influences of vitamin D on key biological processes. There are data showing associations between exposure, skin type, relevant genes and disease risk. However, caution is required in using these data to derive public health advice. Encouraging people to increase exposure maybe inappropriate if we are not yet sure what levels of exposure are most significant in increasing skin cancer risk. Indeed, advice may need to be tailored to individual characteristics such as level of pigmentation or ability to initiate a pigmentary response to sunlight. It is reasonable to state that these data are interesting and worthy of investigation since the potential public health benefits are huge.

There are powerful environmental factors operating in the determination of MS risk, first quantified after the First War. US veterans with MS were proportionately more from the north. Recent studies allow greater focus. In Australia, a 6-fold difference in risk is present between Tasmania and Queensland.

A geographical gradient occurs in the context of several lines of evidence demonstrating that familial micro-environment appears to play no role in MS risk. These come from studies of adoptees, twins, half-sibling, conjugal pairs, step-siblings and consanguineous matings. In all of these studies, risk is attributable to biological rather than environmental relatedness. The inescapable conclusion is that the environmental factors must act at a broad population level, leaving climate and diet as two obvious candidates. Since diet tends to be familial, some direct or indirect effect of climate is much favoured.

National studies in MS capable of evaluating the question have found latitude to be the most important environmental associate of risk. Four decades ago it was first suggested that MS risk was related to sunlight exposure. This remains increasingly viable based upon the serial exclusion of other proposed mechanisms. Sunlight could influence a variety of biological processes. Timing of effect is uncertain.

Four specific features seem to point to a role for environment in early development. These include an increased risk for dyzygotic twins compared to siblings, a month of birth effect in MS and a maternal effect which appears to be environmental and gestational and is derived from the study of halfsibs. There may be reduced risk for dyzygotic twins again pointing to shared uterine environment.

Its plausibility in MS has always suffered from a credibility gap. What do sunlight and/or Vitamin D have to do with the immune and nervous systems? The plausibility gap between vitamin D being the key environmental exposure and a role for this hormone in the nervous system has recently been closed. Vitamin D receptors are diffusely expressed throughout the brain and gestational Vitamin D deficiency is associated with gross maldevelopment of the nervous system. It is timely to give consideration to a potential role of sunlight and Vitamin D in preventing MS which is probably increasing in incidence.

Professor Reinhold Vieth

Modern humans first appeared 100,000 years ago, effectively designed through evolution to live in a warm, sunny climate. The UK is so far north that vitamin D produced in summer must sustain us through a five month vitamin D winter without suitable sunlight. Current dietary guidelines for the UK are incorrect in stating that adults below age fifty require no vitamin D. For older adults, official UK guidelines specify only half the minimum intake that doctors now recommend to prevent fractures. Sun-avoidance advice makes the vitamin D problem even worse. The result is an unacceptably high occurrence of what should be regarded as toxic vitamin D deficiency. This is associatedwith higher incidence rates of breast, prostate and bowel cancers. When these cancers do occur vitamin D deficiency increases mortality rates. Vitamin D deficiency accelerates bone loss, promoting osteoporosis and bone fractures. Vitamin D deficiency causes muscle weakness, and impairs ability to balance, this increases falls in the elderly. Vitamin D deficiency increases risk of both juvenile and adult-onset diabetes. Vitamin D supplementation is safe, and essential to health. Official UK guidelines about vitamin D need to be re-evaluated and revised to allow the public to benefit from the wealth of research findings about this nutrient.

Dr Elina Hypponen, a researcher at the Institute for Child Health, London.