Sunlight, Vitamin D and Health
House of Commons 2 Nov 2005
Host: Ian Gibson MP
Abstracts
In order of presentation
The Miracle Vitamin D: Importance for Bone Health and Prevention of Common Cancers, Autoimmune Diseases and Cardiovascular Heart Disease
Michael Holick
Professor of Medicine, Physiology and Biophysics; Director of the General Clinical Research Center; and Director of the Bone Health Care Clinic and the Heliotherapy, Light, and Skin Research Center at Boston University Medical Center.
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.
References:
Holick, M.F. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endicrinol Diabetes 2002, 9:87-98
Harris, S.S., Soteriades, E., Stina Coolidge, J.A. et al. Vitamin D Insufficiency and Hyperparathyroidism in a Low Income, Multiracial, Elderly Population. J Clin Endocrinol Metab 2001, 85: 4125-30
Malabanan, A., Veronikis, I.E., Holick, M.F. Redefining vitamin D insufficiency. Lancet 1998, 351: 805-806
Holick, M. F. The Sunlight ‘D’ilemma: risk of skin cancer or bone disease and muscle weakness. Lancet 2001, 357:4-5
Nesby-O’Dell, S., Scanlon, K.S., Cogswell, M.E., Gillespie, C., Hollis, B.W., Looker, A.C., Allen, C., Doughertly, C., Gunter, E.W., Bowman, B.A. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2002, 76:187-192
Garland, C.F., Garland, F.C., Gorham, E.D. Can colon cancer incidence and death rates be reduced with calcium and vitamin D? Am J Clin Nutr 1991, 54:193S-201S
Grant, W.B.. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. American Cancer Society 2002, 94:272-281
Li, Y.C., Kong, J., Wei, M., Chen, Z.F., Liu, S.Q., Cao, L.P. 1,25-dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002, 110:229-238
Holick, M.F. and Jenkins, M. The UV Advantage, ibooks: New York (in press).
Holick, M.F. Vitamin D: Importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004; 79:362-371.
Health consequences of insufficient vitamin D
Armin Zittermann
Heart and Diabetes Center, Northrhein-Westfalia, Ruhr University Bochum, Germany
During the 18th and the 19th century, the process of industrialization and urbanization was associated with low sun exposure of a large percentage of infants, leading to a high prevalence of vitamin D deficiency. As a consequence, rickets, also known as the English disease, was very frequent.
Since the early 20th century, very effective preventive measures such as fortification of infant foods with vitamin D, exposure of young children to artificial UV lamps, and vitamin D supplementation have been performed. Nowadays, rickets is rare in Europe. However, available data indicate that vitamin D insufficiency or even deficiency is a frequent finding in the adult population of westernized countries. Insufficient skin synthesis of vitamin D is the major reason for that.
While elderly subjects and dark-skinned people living at Northern latitude are worst affected, a significant percentage of all age groups is at risk. There is now increasing evidence that vitamin D insufficiency may play a role in the etiology of various chronic diseases which are frequent in industrialized countries. The relation between vitamin D insufficiency and the pathogenesis of several diseases such as osteoporosis, hypertension, cardiovascular disease, and diabetes mellitus is briefly described.
At present, no effective strategies do exist in Europe to improve vitamin D status of those adults who are at risk for vitamin D insufficiency.
Selected publications
· Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R: Vitamin D Supplementation Improves Cytokine Profile In Patients With Congestive Heart Failure: A Double-Blind, Randomized, Placebo-Controlled Trial. (submitted)
· Zittermann A, Schleithoff SS, Koerfer R: Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr 94 (2005) 483-492
· Zittermann A: Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Am J Clin Nutr 78 (2003) 496-497
· Zittermann A: Vitamin D in preventive medicine – are we ignoring the evidence? Br J Nutr 89 (2003) 552-572
· Zittermann A, Schulze Schleithoff S, Tenderich G, Berthold HK, Körfer R, Stehle P: Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 41 (2003) 105-112
· Zittermann A: Seasonal variation in bone turnover: Dependence on calcium nutrition. J Bone Mineral Res 16 (2001) 1733
· Zittermann A, Sabatschus O, Jantzen S, Platen P, Danz A, Dimitriou T, Scheld K, Klein K, Stehle P: Exercise-trained young men have higher calcium absorption rates and plasma calcitriol levels in comparison to age-matched sedentary controls. Calcif Tissue Int 67 (2000) 215-219
· Rettberg P, Horneck G, Zittermann A, Heer M: Biological dosimetry to determine the UV radiation climate inside the Mir Station and its role in vitamin D synthesis. Adv Space Res 22 (1999) 1643-1652
· Zittermann A, Scheld K, Stehle P: Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women. Eur J Clin Nutr 52 (1998) 501-506
Genes, Environment and Prostate Cancer risk:
sunlight and Vitamin D - related genes.
Richard C. Strange
Keele University Medical School, University Hospital of North Staffordshire, Staffordshire, ST4 7PA, England.
Telephone number 01782 554667 e-mail:
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.