The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health .
Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D , which would explain why low vitamin D status is reported in a wide range of disorders .
In elderly people , restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival
Low serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) have been associated with many non-skeletal disorders .
However , whether low 25(OH)D is the cause or result of ill health is not known .
Prospective study of predictors of vitamin D status and cancer incidence and mortality in men.
BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day
The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health .
Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D , which would explain why low vitamin D status is reported in a wide range of disorders .
In elderly people , restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival
Low serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) have been associated with many non-skeletal disorders .
However , whether low 25(OH)D is the cause or result of ill health is not known .