Vitamin D – has the new dawn for dietary recommendations arrived?

Since the beginning of our new millennium, vitamin D has been the absolute focus of attention: there can be no doubt about that! Whether it be the scientific, clinical or academic communities, government/regulatory organisations, industry, media or indeed the public, everyone has ‘woken up’ to the reality that the functions of this nutrient go far wider than that of the skeletal system. Concomitant with that, there is universal acceptance that we have a high prevalence of people with vitamin D levels lower than is good for their health. Vitamin D is a most unique nutrient – the term ‘vitamin’ is a misnomer since vitamin D is not a ‘vital-amine’ in the true sense of the word but rather it is a pro-hormone – with the main source not being diet but rather ultraviolet B-rays (UVB) from sunlight. This makes vitamin D such a challenging (but exciting!) nutrient to study as in areas of northern latitude, vitamin D can be made from UVB only during the months of April to September. Hence, randomised, controlled trials (RCTs) involving vitamin D should strictly be confined to the winter months when vitamin D is not made endogenously via the act of sunlight on skin, and all dietary vitamin D studies (cross-sectional and longitudinal) need to adjust for sunlight exposure in their analyses (Lanham-New et al. 2011). Vitamin D3 is formed as the direct effect of UV irradiation of the skin. The action of UVB converts 7-dehydrocholesterol to pre-vitamin D, which is then metabolised to vitamin D by a temperature-dependent isomerisation. We know that 7-dehydrocholesterol is a zoosterol, which functions in the serum as a cholesterol precursor, and is converted to vitamin D3 in the skin, therefore operating as pro-vitamin D3. This is particularly important since there is a growing recognition that people who take cholesterol-lowering statin drugs have a problem with vitamin D deficiency, although to date this has attracted relatively little focus. Cholesterol is required by the body to synthesise vitamin D and statin drugs are responsible for reducing cholesterol production and eliminating it, leading many to speculate that statin drug users do not have enough cholesterol to process vitamin D efficiently. Studies, albeit observational in nature, are beginning to show convincingly that statin users have a greater prevalence of vitamin D deficiency, with muscle pain being a common characteristic. This is an area that the clinical field must take forward as a genuine concern in their clinical practice and is a research area that warrants urgent attention. Once vitamin D is metabolised from pre-vitamin D to vitamin D, it is transported via the general circulation and, following enzymatic activity in the liver (by 25-hydroxylase), it is converted to 25-hydroxy vitamin D (25OHD), which is considered to be the best clinical indicator of vitamin D status. The concentration of 25OHD in the blood reflects the vitamin D supply from both the skin and the diet, and with a decent half-life (approximately 3 weeks), it is a good integrated marker of recent vitamin D supply and can thus be used to assess vitamin D adequacy. Using the vitamin D-binding protein, 25OHD is transported to the kidney where it undergoes a final hydroxylation step via the enzyme 1-alpha-hydroxylase to become 1-alpha, 25-dihydroxyvitamin D, also known as calcitriol, which is the active form of vitamin D. What has held the field back is the lack of standardised measurements of 25OHD status, with laboratories worldwide showing alarmingly poor consistency of measurement. Indeed, in the well-publicised paper by Binkley et al. (2004), remarkably different results were yielded from samples, which had been spiked with 20 ng/ml and processed by a number of top vitamin D measuring laboratories using their specific methodologies. This has had ramifications for the field of vitamin D research and is one clear reason why there are such inconsistencies and controversies, nationally and internationally, as to what level of 25OHD status defines Correspondence: Professor Susan A. Lanham-New, Head, Nutritional Sciences Department, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford. GU2 7XH, Surrey, UK. E-mail: s.lanham-new@surrey.ac.uk