Considering the potential benefits as well as adverse effects of sun exposure: can all the potential benefits be provided by oral vitamin D supplementation?
Prog Biophys Mol Biol. 2006 Sep;92(1):140-9. Epub 2006 Feb 28.
Lucas RM, Ponsonby AL.
National Centre for Epidemiology and Population Health, The Australian National University, Canberra 0200, Australia. Robyn.lucas at anu.edu.au
Exposure to ultraviolet radiation (UVR) is associated with both adverse and beneficial health effects. While many of the adverse effects of excessive exposure are well known, the adverse effects of insufficient UVR exposure are less clear-cut, but may include a heightened risk of several cancers and autoimmune disorders as well as of bone diseases such as rickets, osteomalacia and osteoporosis. Although some of the postulated beneficial effects of UVR exposure may occur through the maintenance of adequate levels of vitamin D, it is not clear that this can account for all of these effects. We briefly review the epidemiological literature with respect to vitamin D, UVR exposure and autoimmune diseases. We further outline alternative pathways, whereby UVR could alter the risk of development of some cancers and autoimmune disorders, independent of effects on vitamin D synthesis. Recognition of the beneficial effects of UVR exposure has led to a reconsideration of sun avoidance policies. It is important to recognize that all of the beneficial effects of UVR exposure may not occur only through UVR-induced vitamin D synthesis. Thus maintaining current sun avoidance policies while supplementing food with vitamin D may not be sufficient to avoid the risks of insufficient exposure to UVR. PMID: 16616326
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Arguments for vitamin D supplementation of food:
- Widespread reach to people in the community without them having to take any action, e.g. additional supplements;
- Easy, with the cooperation of industry;
- Should ameliorate those disorders associated with vitamin D insufficiency and deficiency;
- May be particularly important to high risk groups, e.g. the elderly, deeply pigmented persons with limited UVR exposure, indoor-dwellers; or those with a proven susceptibility to the adverse effects of UVR exposure, including persons with a prior history of skin cancer and transplant recipients.
Arguments against vitamin D supplementation of food:
- Cannot be sure what dose is being delivered and who is getting it:
- If the dose received is insufficient then the problems of vitamin D insufficiency and limited UVR exposure remain, i.e. may not get the benefit of the direct immunosuppressive effects of UVR exposure, which may be important. Although there is supplementation of milk and breakfast cereals (optional) in the US, vitamin D insufficiency is not uncommon (Looker et al., 2002). There are now calls to increase vitamin D fortification of foods (Calvo et al., 2005), including mandatory supplementation of cereal-grain products with vitamin D (Newmark et al., 2004).
- Excessive doses may cause toxicity. But even modest levels within the normal range may be associated with an increased risk of prostate cancer (Tuohimaa et al., 2004). Risk of excessive doses may be increased in individuals who are also taking supplements or vitamin D as medication (in addition to routine dietary supplementation). Long term supplementation may be associated with an adverse blood lipid profile (Heikkinen et al.,1997).
- Is vitamin D the whole story—there may be specific UVR effects that are not mediated via vitamin D adequacy (as outlined in the text).
Arguments for limited (safe) UVR exposure:
- Toxic levels of vitamin D do not occur through UVR exposure (Zittermann, 2003);
- There may be beneficial effects of UVR exposure that are not mediated thru vitamin D;
- Cheap, easy;
- Current sun avoidance messages are probably not appropriate, especially for particular populations, e.g. deeply pigmented persons living at high latitude, but also persons with a largely indoor lifestyle.
Arguments against limited (safe) UVR exposure:
- Difficult to provide advice for optimal individual UVR exposure:
- Due to skin pigmentation, dietary habits, clothing habits and regional and seasonal variation in ambient UVR;
- Difficult to establish the (individual) balance between excessive and insufficient exposure;
- Liberalizing the sun safe message may offer people an excuse to over-expose;
- Sun exposure/vitamin D levels may be important at particular stages of development (critical periods). This means there needs to be particular care with revised sun exposure messages.
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- Mouse MS: UVB but not Vitamin D reduced incidence - April 2010
- Hypothesis: Sun provides more than vitamin D – June 2012
Abstracts of other papers of interest co-authored by LUCAS - - - - - - - -
Int J Epidemiol. 2008 Jun;37(3):654-67. Epub 2008 Feb 14.
Lucas RM, McMichael AJ, Armstrong BK, Smith WT.
National Centre for Epidemiology and Population Health, The Australian National University, Australia. robyn.lucas at anu.edu.au
BACKGROUND: WHO's global burden of disease studies, undertaken since 1996, apportion the total global disease burden, measured in disability-adjusted life years (DALYs), to specific diseases and injuries. Recent assessments of the relative burden due to specific environmental risk factors, plus an understanding of the nature of the risk factor, may guide resource allocation in risk factor management. We report here the global disease burden due to ultraviolet radiation (UVR) exposure.
METHODS: A systematic literature review identified nine diseases with sufficient evidence of a causal relationship with UVR exposure and for which the population attributable fraction (PAF) for UVR could be estimated. For cutaneous malignant melanoma and cataract, the PAF was directly applied to disease burdens already calculated by WHO. For seven other diseases, we developed population-level exposure-disease relationships and used these to calculate disease incidence and mortality, and thence disease burden. We also estimated the disease burden from rickets, osteomalacia and osteoporosis that might result if global UVR exposure was reduced to very low levels.
RESULTS: UVR exposure is a minor contributor to the world's disease burden, causing an estimated annual loss of 1.6 million DALYs; i.e. 0.1% of the total global disease burden. A markedly larger annual disease burden, 3.3 billion DALYs, might result from reduction in global UVR exposure to very low levels.
CONCLUSIONS: Sun protection messages are important to prevent diseases of UVR exposure. However, without high dietary (or supplemental) intake of vitamin D, some sun exposure is essential to avoid diseases of vitamin D insufficiency. PMID: 18276627 CLICK HERE for PDF
Vitamin D deficiency and pregnancy: from preconception to birth.
Mol Nutr Food Res. 2010 Aug;54(8):1092-102.
Lewis S, Lucas RM, Halliday J, Ponsonby AL.
Public Health Genetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia. Sharon.lewis at mcri.edu.au
Vitamin D is important for bone health, as well as an increasing number of other health outcomes. Here we discuss the evidence relating to vitamin D in pregnancy, from preconception to the perinatal period. During pregnancy extra calcium required for fetal skeletal growth is attained by both maternal bone resorption and increased absorption from dietary sources, necessitating increased maternal vitamin D. Many women have low vitamin D status during pregnancy and may require supplementation, although optimal serum levels and intake required to achieve those levels is not yet well defined. Evidence from animal studies, with some supportive human evidence, suggests that fertility may be impaired in mothers with low vitamin D. During pregnancy, maintaining vitamin D and calcium levels may decrease the risks of pre-eclampsia, while gestational diabetes mellitus appears to be more common in those with low vitamin D status, although there is insufficient evidence of causality. The evidence in relation to increased risks of bacterial vaginosis and caesarean section similarly requires confirmation in carefully designed observational and experimental studies. This review outlines the emerging evidence that maternal vitamin D status during pregnancy is important for the health of the mother and offspring across a range of possible health outcomes. PMID: 20440696
Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies.
BMC Public Health. 2010 Jun 11;10:331.
Lai JK, Lucas RM, Clements MS, Roddam AW, Banks E.
National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACT, 0200, Australia. jeffrey.lai at anu.edu.au
BACKGROUND: Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk.
METHODS: We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers.
RESULTS: The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.1395%CI 0.98-1.29; 801 cases), with no significant difference between trials of <800 IU/day and > or = 800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (chi(2)(1) (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (chi(2)(16) (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (chi(2)(9) (heterogeneity) = 149.68, p < 0.001).
CONCLUSIONS: Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID: 20540727 – full text on-line
Assessing vitamin D status: pitfalls for the unwary.
Mol Nutr Food Res. 2010 Aug;54(8):1062-71.
Lai JK, Lucas RM, Clements MS, Harrison SL, Banks E.
National Centre for Epidemiology and Population Health, The Australian National University, Canberra, ACT, Australia. jeffrey.lai at anu.edu.au
The use of vitamin D testing has grown rapidly in the recent times as a result of increased interest in the role of vitamin D in health. Although the generally accepted measure of vitamin D status is circulating 25(OH)D concentration, there is little consensus on which assay method should be used. Commonly used assays include competitive protein-binding assay, RIA, enzyme immunoassay, chemiluminescence immunoassays, HPLC, and LC-MS/MS, each with its own advantages and disadvantages. However, there is significant interassay and interlaboratory variability in measurements. Our simulation of the published data showed that using a deficiency cut-point of 50 nmol/L, 57% of samples assessed using a chemiluminescence immunoassay were classified as deficient compared with 41% of samples assessed using LC-MS/MS; a 20% misclassification rate. Similar rates of misclassification were seen at 75 nmol/L. This has implications for clinical practice and decision limits for vitamin D supplementation, suggesting that cut-points should be assay specific rather than universal and that greater harmonization between laboratories is required. Newer assays using alternative biological samples to determine the circulating 25(OH)D have been proposed and advances in the genetics of vitamin D and the role of vitamin D-binding protein may improve future assay accuracy. PMID: 20397196