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The Lancet 2001; 357:4-6
DOI:10.1016/S0140-6736(00)03560-1
Sunlight ?D?ilemma: risk of skin cancer or bone disease and muscle weakness Michael F Holick
a
Vitamin D is a fat-soluble vitamin found naturally in cod liver oil and oily fish, added to some foods, and produced in the skin with help from the sun.1 Land-based organisms have been producing sunlight-mediated vitamin D for over 300 million years. Early in evolution, as vertebrates left their calcium-enriched ocean environment for terra firma, they depended on the cutaneous synthesis of vitamin D for increasing the efficiency of intestinal absorption of scarce sources of dietary calcium.
Vitamin D is rare in the diet consumed by human beings. In countries where some foods are fortified with vitamin D, the assumption is that dietary fortification is more than adequate to satisfy everyone's requirement for the vitamin. Little recognition is given to sunlight as the major source of vitamin D for most people. Publicity about risk of skin cancer with exposure to sunlight has led to the wide spread avoidance of exposure to the sun. Consequently, vitamin D insufficiency has become epidemic in adults over the age of 50 years.2?5
Sniadecki1 recognised the relation between rickets and lack of exposure to sunlight in 1822. 100 years later, Hess and Unger1 reported that exposure of children to sunlight treated and cured rickets. Vitamin D's main function is to preserve calcium and phosphorus homoeostasis by increasing the efficiency of intestinal calcium and phosphorus absorption in order to maintain signal transduction, metabolic activities, and neuromuscular function, and to promote skeletal mineralisation. Several compelling studies have shown that sunlight is the most important source of vitamin D.
Circulating concentrations of 25-hydroxyvitamin D (a barometer for vitamin-D status) are maximum in late summer and minimum at the end of winter.1,2,5,6 Arab women who protect all of their skin with clothing are commonly vitamin-D deficient, as are blacks because their increased skin pigmentation greatly reduces the production of vitamin D3 in the skin.6,7 When nursing-home residents in New Zealand were exposed to 15 or 30 minutes of sunlight two to three times a week, their circulating concentrations of 25(OH)D increased sharply.8
In 1997, the Institute of Medicine of the US National Academy of Sciences recommended new adequate intakes for vitamin D.7 On the assumption that young and middleaged adults were more likely than older people to be exposed to sunlight, the recommendations were 200 IU (5 μg)/day for adults up to the age of 50, 400 IU/day for people aged 50?70, and 600 IU/day for those aged 70 and above. Is this enough? H Glerup and colleagues9 provide convincing evidence that more attention should be paid to exposure to sunlight as the major source of vitamin D. They conducted a cross-sectional study in middle-aged veiled and non-veiled Arab women and age-matched Danish women who lived in Denmark. They found that both veiled and non-veiled Arab women who had a dietary intake of 1?04 μg (about 40 IU/day) of vitamin D were vitamin-D deficient (25[OH]D, 7?1 [SEM 1?1] nmol/L and 12?6 [2?6], respectively; normal range >20 nmol/L), as were ethnic Danish Moslems (17?5 [2?3] nmol/L), whose estimated vitamin-D intake, including food supplementation, was about 600 IU/day.
The Danish controls, with an estimated daily oral intake of 300 IU, were not vitamin-D deficient (47?1 [4?]6 nmol/L). Serum parathyroid hormone measurements revealed that 57%, 55%, and 20% of the veiled Arab women, non-veiled Arab women, and ethnic Danish Moslems, respectively had hyperparathyroidism secondary to vitamin-D deficiency, compared with only 2% of the Danish controls.
Secondary hyperparathyroidism can increase mobilisation of calcium from the skeleton sufficiently to precipitate or exacerbate osteoporosis. The phosphaturia it induces decreases serum phosphorus, which, in turn, causes a mineralisation defect leading, in many cases, to osteomalacia. Muscle weakness is a more subtle and insidious consequence of vitamin D deficiency.10 Glerup and colleagues9 reported muscle pain in 88% of Arab women, compared with 32% among Danish controls. Muscle weakness as measured by rising from a chair or ascending a staircase was experienced by 32% of Arab women but only by 14% of the Danish controls, and muscle cramps by 72% of Arab women, compared with none of the Danish controls. Glerup and colleagues10 suggest that, in the absence of sunlight, 1000 IU of vitamin D is necessary to maintain adequate 25(OH)D concentrations. This point is consistent with the observation that healthy men confined to a submarine for 3 months were barely able to maintain adequate circulating concentrations of 25(OH)D while receiving 600 IU of vitamin D daily.1 Once exposed to sunlight, their 25(OH)D increased by 40% in a month.1
Are there any other consequences of vitamin-D deficiency? There is a latitudinal association with increased risk of dying of breast, colon, prostate, and ovarian cancer.11 Black men, who are prone to vitamin-D deficiency, have a higher risk of prostate cancer and a more aggressive form of the disease. A suggestion is that it is the lack of exposure to sunlight and associated chronic vitamin-D insufficiency that is associated with the increased risk of dying of these cancers.11?13 The possibility that vitamin D is important for cellular health is now appreciated. The prostate, colon, breast, and probably many other tissues have the enzymatic machinery to convert 25(OH)D to its active form, 1,25(OH)2D,14 which is a potent hormone for regulating cell proliferation and perhaps limiting the metastatic activity of some cancers (figure).
Click to enlarge image
Figure. Metabolism and function of vitamin D
There are two take-home messages from the work of Glerup and colleagues.10 First, although there is no question that chronic excessive exposure to sunlight can increase risk of skin cancer and cause skin damage,15 recommendations on sun protection should be moderated.
Second, fortification of foods with vitamin D should be widened, especially in Europe. The fear of vitamin-D intoxication that swept Europe in the 1950s16 and resulted in laws forbidding fortification of milk and other products is antiquated. Vitamin-D deficiency causes rickets in children and osteopenia and osteomalacia in adults, exacerbates osteoporosis, and increases muscle weakness and pain. It may also predispose to the growth and metastatic activity of some of the more common cancers.
Because latitude, season, skin pigmentation, sunscreen use, and ozone air pollution can greatly influence the cutaneous production of vitamin D,1 there can be no simple recommendation for the amount of exposure to the sun to satisfy the body's requirement for vitamin D. Exposure of the body in a bathing suit to 1 minimal erythemal dose (MED) of sunlight is equivalent to ingesting about 10
000 IU of vitamin D. Thus, exposure of 6?10% of the body surface to 1 MED is equivalent to ingesting about 600?1000 IU of vitamin D. Exposure of hands, arms, and face two to three times a week to a third to a half of an MED (about 5 min for skin-type-2 adult in Boston at noon in July) in the spring, summer, and autumn is more than adequate. Excessive exposure to sunlight cannot produce vitamin-D intoxication;1
anybody wishing to stay outside longer than recommended above should apply a sunscreen with a sun-protection factor of 15 to prevent sunburn and the damaging effects of excessive sun exposure. Another means of guaranteeing vitamin-D sufficiency, especially in nursing-home residents, is to give 50000 IU of vitamin D once a month. A simple remedy for vitamin D deficiency is 50000 IU of the vitamin once a week for 8 weeks.3
With adequate exposure to sunlight, dietary vitamin D becomes unnecessary. It is remarkable how exposure to sunlight a few times a week can reduce the risk of osteoporosis, osteomalacia, muscle weakness, fractures, and maybe some of the common cancers but also induce a feeling of wellbeing.
<!--start simple-tail=-->References
1. Holick MF. McCollum Award Lecture, 1994: Vitamin D: new horizons for the 21st century. Am J Clin Nutr 1994; 60: 619-630. MEDLINE
2. Dawson-Hughes B, Harris SS, Dallal GE. Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Am J Clin Nutr 1997; 65: 67-71. MEDLINE
3. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998; 351: 805-806. Full Text | PDF (123 KB) | MEDLINE | CrossRef
4. Gloth FM, Gundberg CM, Hollis BW, Haddad HG, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA 1995; 274: 1683-1686. MEDLINE
5. McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992; 93: 69-77. MEDLINE | CrossRef
6. Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw S, Shary J. Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest 1985; 76: 470-473. MEDLINE
7. Sedrani SH. Low 25-hydroxyvitamin D and normal serum calcium concentrations in Saudi Arabia: Riyadh region. Ann Nutr Metab 1984; 28: 181-185. MEDLINE
8. Reid IR, Gallagher DJA, Bosworth J. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Ageing 1985; 15: 35-40. MEDLINE
9. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000; 247: 260-268. MEDLINE | CrossRef
10. Glerup H, Mikkelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without osteomalacic bone involvement. Calcif Tissue Int 2000; 66: 419-424. MEDLINE | CrossRef
11. Garland CF, Garland FC, Gorham ED. Can colon cancer incidence and death rates be reduced with calcium and vitamin D?. Am J Clin Nutr 1991; 54: 193S-201S.
12. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Cancer 1992; 70: 2861-2869. MEDLINE | CrossRef
13. Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000; 11: 847-852. MEDLINE | CrossRef
14. Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev 1998; 7: 391-395. MEDLINE
15. Gilchrest BA. Sunscreens: a public health opportunity. N Engl J Med 1993; 329: 1193-1194. MEDLINE | CrossRef
16. British Pediatric Association. Hypercalcemia in infants and vitamin D. BMJ 1956; 2: 149.
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<!--end simple-tail-->Affiliations
a. Vitamin D, Skin, and Bone Research Laboratory, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
DOI:10.1016/S0140-6736(00)03560-1
Sunlight ?D?ilemma: risk of skin cancer or bone disease and muscle weakness Michael F Holick
aVitamin D is a fat-soluble vitamin found naturally in cod liver oil and oily fish, added to some foods, and produced in the skin with help from the sun.1 Land-based organisms have been producing sunlight-mediated vitamin D for over 300 million years. Early in evolution, as vertebrates left their calcium-enriched ocean environment for terra firma, they depended on the cutaneous synthesis of vitamin D for increasing the efficiency of intestinal absorption of scarce sources of dietary calcium.
Vitamin D is rare in the diet consumed by human beings. In countries where some foods are fortified with vitamin D, the assumption is that dietary fortification is more than adequate to satisfy everyone's requirement for the vitamin. Little recognition is given to sunlight as the major source of vitamin D for most people. Publicity about risk of skin cancer with exposure to sunlight has led to the wide spread avoidance of exposure to the sun. Consequently, vitamin D insufficiency has become epidemic in adults over the age of 50 years.2?5
Sniadecki1 recognised the relation between rickets and lack of exposure to sunlight in 1822. 100 years later, Hess and Unger1 reported that exposure of children to sunlight treated and cured rickets. Vitamin D's main function is to preserve calcium and phosphorus homoeostasis by increasing the efficiency of intestinal calcium and phosphorus absorption in order to maintain signal transduction, metabolic activities, and neuromuscular function, and to promote skeletal mineralisation. Several compelling studies have shown that sunlight is the most important source of vitamin D.
Circulating concentrations of 25-hydroxyvitamin D (a barometer for vitamin-D status) are maximum in late summer and minimum at the end of winter.1,2,5,6 Arab women who protect all of their skin with clothing are commonly vitamin-D deficient, as are blacks because their increased skin pigmentation greatly reduces the production of vitamin D3 in the skin.6,7 When nursing-home residents in New Zealand were exposed to 15 or 30 minutes of sunlight two to three times a week, their circulating concentrations of 25(OH)D increased sharply.8
In 1997, the Institute of Medicine of the US National Academy of Sciences recommended new adequate intakes for vitamin D.7 On the assumption that young and middleaged adults were more likely than older people to be exposed to sunlight, the recommendations were 200 IU (5 μg)/day for adults up to the age of 50, 400 IU/day for people aged 50?70, and 600 IU/day for those aged 70 and above. Is this enough? H Glerup and colleagues9 provide convincing evidence that more attention should be paid to exposure to sunlight as the major source of vitamin D. They conducted a cross-sectional study in middle-aged veiled and non-veiled Arab women and age-matched Danish women who lived in Denmark. They found that both veiled and non-veiled Arab women who had a dietary intake of 1?04 μg (about 40 IU/day) of vitamin D were vitamin-D deficient (25[OH]D, 7?1 [SEM 1?1] nmol/L and 12?6 [2?6], respectively; normal range >20 nmol/L), as were ethnic Danish Moslems (17?5 [2?3] nmol/L), whose estimated vitamin-D intake, including food supplementation, was about 600 IU/day.
The Danish controls, with an estimated daily oral intake of 300 IU, were not vitamin-D deficient (47?1 [4?]6 nmol/L). Serum parathyroid hormone measurements revealed that 57%, 55%, and 20% of the veiled Arab women, non-veiled Arab women, and ethnic Danish Moslems, respectively had hyperparathyroidism secondary to vitamin-D deficiency, compared with only 2% of the Danish controls.
Secondary hyperparathyroidism can increase mobilisation of calcium from the skeleton sufficiently to precipitate or exacerbate osteoporosis. The phosphaturia it induces decreases serum phosphorus, which, in turn, causes a mineralisation defect leading, in many cases, to osteomalacia. Muscle weakness is a more subtle and insidious consequence of vitamin D deficiency.10 Glerup and colleagues9 reported muscle pain in 88% of Arab women, compared with 32% among Danish controls. Muscle weakness as measured by rising from a chair or ascending a staircase was experienced by 32% of Arab women but only by 14% of the Danish controls, and muscle cramps by 72% of Arab women, compared with none of the Danish controls. Glerup and colleagues10 suggest that, in the absence of sunlight, 1000 IU of vitamin D is necessary to maintain adequate 25(OH)D concentrations. This point is consistent with the observation that healthy men confined to a submarine for 3 months were barely able to maintain adequate circulating concentrations of 25(OH)D while receiving 600 IU of vitamin D daily.1 Once exposed to sunlight, their 25(OH)D increased by 40% in a month.1
Are there any other consequences of vitamin-D deficiency? There is a latitudinal association with increased risk of dying of breast, colon, prostate, and ovarian cancer.11 Black men, who are prone to vitamin-D deficiency, have a higher risk of prostate cancer and a more aggressive form of the disease. A suggestion is that it is the lack of exposure to sunlight and associated chronic vitamin-D insufficiency that is associated with the increased risk of dying of these cancers.11?13 The possibility that vitamin D is important for cellular health is now appreciated. The prostate, colon, breast, and probably many other tissues have the enzymatic machinery to convert 25(OH)D to its active form, 1,25(OH)2D,14 which is a potent hormone for regulating cell proliferation and perhaps limiting the metastatic activity of some cancers (figure).
Click to enlarge image
Figure. Metabolism and function of vitamin D
There are two take-home messages from the work of Glerup and colleagues.10 First, although there is no question that chronic excessive exposure to sunlight can increase risk of skin cancer and cause skin damage,15 recommendations on sun protection should be moderated.
Second, fortification of foods with vitamin D should be widened, especially in Europe. The fear of vitamin-D intoxication that swept Europe in the 1950s16 and resulted in laws forbidding fortification of milk and other products is antiquated. Vitamin-D deficiency causes rickets in children and osteopenia and osteomalacia in adults, exacerbates osteoporosis, and increases muscle weakness and pain. It may also predispose to the growth and metastatic activity of some of the more common cancers.
Because latitude, season, skin pigmentation, sunscreen use, and ozone air pollution can greatly influence the cutaneous production of vitamin D,1 there can be no simple recommendation for the amount of exposure to the sun to satisfy the body's requirement for vitamin D. Exposure of the body in a bathing suit to 1 minimal erythemal dose (MED) of sunlight is equivalent to ingesting about 10
000 IU of vitamin D. Thus, exposure of 6?10% of the body surface to 1 MED is equivalent to ingesting about 600?1000 IU of vitamin D. Exposure of hands, arms, and face two to three times a week to a third to a half of an MED (about 5 min for skin-type-2 adult in Boston at noon in July) in the spring, summer, and autumn is more than adequate. Excessive exposure to sunlight cannot produce vitamin-D intoxication;1 anybody wishing to stay outside longer than recommended above should apply a sunscreen with a sun-protection factor of 15 to prevent sunburn and the damaging effects of excessive sun exposure. Another means of guaranteeing vitamin-D sufficiency, especially in nursing-home residents, is to give 50
000 IU of vitamin D once a month. A simple remedy for vitamin D deficiency is 50000 IU of the vitamin once a week for 8 weeks.3With adequate exposure to sunlight, dietary vitamin D becomes unnecessary. It is remarkable how exposure to sunlight a few times a week can reduce the risk of osteoporosis, osteomalacia, muscle weakness, fractures, and maybe some of the common cancers but also induce a feeling of wellbeing.
<!--start simple-tail=-->References
1. Holick MF. McCollum Award Lecture, 1994: Vitamin D: new horizons for the 21st century. Am J Clin Nutr 1994; 60: 619-630. MEDLINE
2. Dawson-Hughes B, Harris SS, Dallal GE. Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Am J Clin Nutr 1997; 65: 67-71. MEDLINE
3. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998; 351: 805-806. Full Text | PDF (123 KB) | MEDLINE | CrossRef
4. Gloth FM, Gundberg CM, Hollis BW, Haddad HG, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA 1995; 274: 1683-1686. MEDLINE
5. McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992; 93: 69-77. MEDLINE | CrossRef
6. Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw S, Shary J. Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest 1985; 76: 470-473. MEDLINE
7. Sedrani SH. Low 25-hydroxyvitamin D and normal serum calcium concentrations in Saudi Arabia: Riyadh region. Ann Nutr Metab 1984; 28: 181-185. MEDLINE
8. Reid IR, Gallagher DJA, Bosworth J. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Ageing 1985; 15: 35-40. MEDLINE
9. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000; 247: 260-268. MEDLINE | CrossRef
10. Glerup H, Mikkelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without osteomalacic bone involvement. Calcif Tissue Int 2000; 66: 419-424. MEDLINE | CrossRef
11. Garland CF, Garland FC, Gorham ED. Can colon cancer incidence and death rates be reduced with calcium and vitamin D?. Am J Clin Nutr 1991; 54: 193S-201S.
12. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Cancer 1992; 70: 2861-2869. MEDLINE | CrossRef
13. Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000; 11: 847-852. MEDLINE | CrossRef
14. Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev 1998; 7: 391-395. MEDLINE
15. Gilchrest BA. Sunscreens: a public health opportunity. N Engl J Med 1993; 329: 1193-1194. MEDLINE | CrossRef
16. British Pediatric Association. Hypercalcemia in infants and vitamin D. BMJ 1956; 2: 149.
Back to top
<!--end simple-tail-->Affiliations
a. Vitamin D, Skin, and Bone Research Laboratory, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
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