The link between vitamin D intake and protection from cancer dates from the 1940s when Frank Apperly demonstrated a link between latitude and deaths from cancer, and suggested that sunlight gave "a relative cancer immunity."
Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. The former, produced in the skin on exposure to UVB radiation (290 to 320 nm), is said to be more bioactive. The latter is derived from plants and only enters the body via the diet.
Both D3 and D2 precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.
There is growing evidence that 1,25(OH)2D has anticancer effects, but the discovery that non-kidney cells can also hydroxylate 25(OH)D had profound implications, implying that higher 25(OH)D levels could protect against cancer in the local sites.
The Health Professionals Follow-Up study, a prospective study of over 50,000 US male health professionals, is the first study to examine total cancer incidence and factors that determine 25(OH)D levels.
The research, led by Edward Giovannucci from Harvard School of Public Health, used data from 1095 participants who had plasma 25(OH)D levels measured, and then computer-predicted levels for the whole cohort.
The scientists then linked the 25(OH)D levels to determinants of vitamin D exposure, like dietary and supplemental vitamin D, geographical residence, skin pigmentation and leisure-time activity.
Vitamin D levels were strongly linked to physical activity and skin colour - darker skinned people produce less vitamin D on exposure to the sun, relative to fair-skinned people.
Dietary vitamin D was also a strong predictor of vitamin D levels, but supplements had only a slight effect, consistent with the common use of the less active vitamin D2 in multivitamins, say the researchers.
"In this cohort analysis, a 25(OH)D increment of 25 nanomoles per litre (nm/L) was associated with a 17 per cent reduction in total cancer incidence, a 29 per cent reduction in total cancer mortality, and a 45 per cent reduction in mortality of digestive-system cancer," wrote Giovannucci in the April issue of the Journal of the National Cancer Institute (vol. 98, pp. 451-459).
The RDA of 400 International Units (IU), equal to 10 micrograms per day, raises plasma levels of 25(OH)D by a modest 7 nm/L.
"Achieving a 25(OH)D increment of 25 nm/L may require a vitamin D supplementation of at least 1500 IU per day, a safe but not generally encouraged level," said Giovannucci.
The best source of vitamin D is from sun exposure, with a fair-skinned person estimated to produce up to 20,000 IU after 20-30 minutes in the sun. However, sun exposure is discouraged due to the risk of skin cancer.
In an accompanying editorial, Gary Schwartz from Wake Forest University and Willian Blot from the Vanderbilt University Medical Center said clinical trials of high dose vitamin D supplementation and the risk of cancer should be "undertaken speedily".
"The potential for cancer prevention by vitamin D (in pill form) must now proceed to the clinical trial testing arena," said the editorial.
Schwartz and Blot said that the cohort results were likely to boost enthusiasm for the vitamin for cancer prevention, but cautioned that observational epidemiological studies had limitations that should not be overlooked.
Unlike beta-carotene and vitamin E, both of which were heralded as cancer preventatives only to be questioned by further studies, the evidence for vitamin D is strong, said the editorial.
"The biological evidence for inhibition of carcinogenesis is strong and, often, was predicted by the prior epidemiological findings on sunlight exposure."
The vitamin's protection is proposed to be multifaceted, by reducing the formation of blood vessels in tumours (angiogenesis), stimulating the mutual adherence of cells, and enhancing intercellular communication through gap junctions. All this adds up to stop proliferation of cancerous cells by contact inhibition.
Sara Hiom, head of health information at Cancer Research UK, said that the study was one of the most robust that suggested an association between low vitamin D levels and an increased risk of cancer incidence and mortality in men.
"The authors suggest that it may be wise to review daily recommended doses of vitamin D as these may currently be too low. As the sun is also an important source of the vitamin, Cancer Research UK's SunSmart campaign will continue to advise safe enjoyment of the sun without burning," she said.
Calls for raising the recommended daily allowance of the vitamin based on a growing body of science is also reaching consumers, whose awareness of these health links is increasing and outlets have reported massive boosts in sales.
Britain's largest supermarket chain, Tesco, said in January that it had witnessed a 400 per cent increase in the sales of vitamin D supplements since the end of December.