We welcome the response from Dr. Grant et al to our paper (04 February 2015). They argue that new trials should include persons with low initial 25-hydroxyvitamin D (25(OH)D) concentrations. This is in line with our recommendations for further research (see box in article). The lower initial 25(OH)D concentration, the more potential benefit would be expected, and trials predominantly including persons with higher 25(OH)D could fail to demonstrate an effect. Under these circumstances we assume that they also would agree that smaller increases in 25(OH)D concentrations have beneficial health potentials even if their proposed target of 75 nmol/l is not reached. Although 75 nmol/l has been recommended as a target level by the Endocrine Society task force, the evidence is not clear as discussed by the Institute of Medicine and others who advocate a target of 50 nmol/l. As noted in our article, this discussion is also complicated by the large variations between laboratories in the determination of 25(OH)D. For example, in a Swedish study, the mean concentration of 25(OH)D varied between 85 nmol/l, 70 nmol/l and 60 nmol/l when identical samples from 204 individual were analysed at three different laboratories. This implies that at worst, 75 nmol/l in one laboratory could correspond to 50 nmol/l in another. Even though there are current efforts to improve standardisation between laboratories, this is a major limitation when interpreting 25(OH)D concentration in the literature.
Grant el al also point to a large body of evidence supporting that chronic disease risk can be reduced by higher 25(OH)D. We are well aware of this literature, and it is both biologically plausible and supported by observational studies that vitamin D might help prevent some chronic diseases. However, the question posed in our review is whether vitamin D supplements should be recommended to prevent chronic diseases, and our major message is that such an intervention has not been proven effective thus far, since evidence from clinical trials is lacking. In a situation of widespread use of high dose vitamin D supplementation, potential harms by high intakes should not be ignored, as emphasised by Dr. Schwarz in his response to our manuscript (08 February 2015). In this respect, 75 nmol/l would not pose a safety issue in individuals, but if this is a general minimum target concentration in a population, many individuals would potentially reach much higher concentrations, which often will stay undetected, as a close monitoring would be very resource consuming and unrealistic in most settings.
We agree with Dr. Saiz et al (05 February 2015) that most benefit of vitamin D plus calcium supplements would be expected in high risk populations with poor vitamin D status and low calcium intake. However, the recommendation of vitamin D supplements in doses of 600-800 IU (15-20 µg) per day combined with calcium (0-1000 mg/day, depending on current dairy intake) is in accordance with nutritional recommendations in the general elderly population. As outlined, it has also been related to a modestly decreased risk of all-cause mortality.
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2. Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, et al. IOM committee members respond to Endocrine Society vitamin D guideline. J Clin Endocrinol Metab 2012; 97:1146-52.
3. Bouillon R, Van Schoor NM, Gielen E, Boonen S, Mathieu C, Vanderschueren D, et al. Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. J Clin Endocrinol Metab 2013;98(8):E1283-304.
4. Snellman G, Melhus H, Gedeborg R, Byberg L, Berglund L, Wernroth L, et al. Determining vitamin D status: a comparison between commercially available assays. PloS One 2010;5:e11555
Competing interests: HEM and PL have none. KH received payment for performing independent food safety assessments concerning vitamin D as a member of the Norwegian Scientific Committee for Food Safety’s panel on nutrition, dietetic products, novel food and allergy. She also received an honorarium from Renapharma for a lecture in an educational symposium for general practitioners in November 2012. The funding company had no influence on the content of the lecture.