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With 4000 new vitamin D research publications each year, there is good possibility to find single studies that support your opinion. Even though there are strong beliefs in the area of vitamin D effects, the problem is that vitamin D supplementation in meta-analyses of randomized clinical trials, our most rigorous method to evaluate treatment efficacy, has not at present been unequivocally proven to reduce disease burden (1, 2). Even in the case of bone health and in contrary to common assumptions, vitamin D supplementation alone does not provide a clear positive effect on bone mineral density (3) and does not reduce rates of falls (4, 5) or fractures (2, 6). Furthermore, compared with more moderate intakes, there is no proof that a mineral rich diet in childhood will render a better bone health at old age (7). However, we need to define true vitamin D deficiency in a better way – a message emphasized in my editorial (8). Naturally, a lower limit for sufficient vitamin D status does exist but it might be lower than many presently think (9).
Regarding the large proportion with vitamin D deficiency in Scotland, this number is dependent on both the definition of deficiency, which is a moving target, and the analytical method to determine vitamin D status. In the study by Purdon et al (your reference No 2), plasma 25-hydroxyvitamin D was measured using the DiaSorin chemiluminecent immunoassay (Liaison). We know that this assay underestimates the actual serum/plasma concentration of 25-hydroxyvitamin D, and therefore overestimates the proportion with vitamin D insufficiency, compared to the gold standard method (LC-MS/MS) (10-12). This inaccuracy may have large impacts on the clinical interpretation. While a third of the Scottish population had sub-optimal serum 25-hydroxyvitamin D concentrations (<25 nmol/L by DiaSorin Liaison), the large majority (99%) of people living close to the Arctic Circle in Sweden have adequate serum 25-hydroxyvitamin D concentrations (by LC-MS/MS) even during the second half of the dark winter (13). Only a modest part of this large discrepancy in vitamin D status between the populations can be explained by different food fortification and dietary intake patterns (14) and a more likely explanation is the different methods used in the analysis of serum 25-hydroxyvitamin D. The Liaison assay provided by DiaSorin has recently been modified such that the difference compared to the gold standard is smaller, but the difference still exists (15).
References
1. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.
2. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. The lancet Diabetes & endocrinology. 2014;2(4):307-20.
3. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2014;383(9912):146-55.
4. Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. The lancet Diabetes & endocrinology. 2014;2(7):573-80.
5. Bolland MJ, Grey A, Reid IR. Differences in overlapping meta-analyses of vitamin D supplements and falls. J Clin Endocrinol Metab. 2014;99(11):4265-72.
6. Moyer VA, Force* USPST. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158(9):691-6.
7. Slemenda CW, Peacock M, Hui S, Zhou L, Johnston CC. Reduced rates of skeletal remodeling are associated with increased bone mineral density during the development of peak skeletal mass. J Bone Miner Res. 1997;12(4):676-82.
8. Michaelsson K. Calcium supplements do not prevent fractures. BMJ. 2015;351:h4825.
9. Gallagher JC, Jindal PS, Smith LM. Vitamin D does not increase calcium absorption in young women: a randomized clinical trial. J Bone Miner Res. 2014;29(5):1081-7.
10. Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab. 2004;89(7):3152-7.
11. Enko D, Fridrich L, Rezanka E, Stolba R, Ernst J, Wendler I, et al. 25-hydroxy-Vitamin D status: limitations in comparison and clinical interpretation of serum-levels across different assay methods. Clin Lab. 2014;60(9):1541-50.
12. 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(7):e11555.
13. Ramnemark A, Norberg M, Pettersson-Kymmer U, Eliasson M. Adequate vitamin D levels in a Swedish population living above latitude 63 degrees N: The 2009 Northern Sweden MONICA study. Int J Circumpolar Health. 2015;74:27963.
14. Burgaz A, Akesson A, Oster A, Michaelsson K, Wolk A. Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter. Am J Clin Nutr. 2007;86(5):1399-404.
15. Wyness SP, Straseski JA. Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s. Clin Biochem. 2015.
•
Competing interests:
No competing interests
26 October 2015
Karl Michaëlsson
Professor, senior consultant
Department of Surgical Sciences, Uppsala University
UCR/MTC, Dag Hammarskjölds väg 14b, 752 37 Uppsala, Sweden
Re: Vitamin D supplements may be needed when calcium supplements are not
Muddy bathwater
With 4000 new vitamin D research publications each year, there is good possibility to find single studies that support your opinion. Even though there are strong beliefs in the area of vitamin D effects, the problem is that vitamin D supplementation in meta-analyses of randomized clinical trials, our most rigorous method to evaluate treatment efficacy, has not at present been unequivocally proven to reduce disease burden (1, 2). Even in the case of bone health and in contrary to common assumptions, vitamin D supplementation alone does not provide a clear positive effect on bone mineral density (3) and does not reduce rates of falls (4, 5) or fractures (2, 6). Furthermore, compared with more moderate intakes, there is no proof that a mineral rich diet in childhood will render a better bone health at old age (7). However, we need to define true vitamin D deficiency in a better way – a message emphasized in my editorial (8). Naturally, a lower limit for sufficient vitamin D status does exist but it might be lower than many presently think (9).
Regarding the large proportion with vitamin D deficiency in Scotland, this number is dependent on both the definition of deficiency, which is a moving target, and the analytical method to determine vitamin D status. In the study by Purdon et al (your reference No 2), plasma 25-hydroxyvitamin D was measured using the DiaSorin chemiluminecent immunoassay (Liaison). We know that this assay underestimates the actual serum/plasma concentration of 25-hydroxyvitamin D, and therefore overestimates the proportion with vitamin D insufficiency, compared to the gold standard method (LC-MS/MS) (10-12). This inaccuracy may have large impacts on the clinical interpretation. While a third of the Scottish population had sub-optimal serum 25-hydroxyvitamin D concentrations (<25 nmol/L by DiaSorin Liaison), the large majority (99%) of people living close to the Arctic Circle in Sweden have adequate serum 25-hydroxyvitamin D concentrations (by LC-MS/MS) even during the second half of the dark winter (13). Only a modest part of this large discrepancy in vitamin D status between the populations can be explained by different food fortification and dietary intake patterns (14) and a more likely explanation is the different methods used in the analysis of serum 25-hydroxyvitamin D. The Liaison assay provided by DiaSorin has recently been modified such that the difference compared to the gold standard is smaller, but the difference still exists (15).
References
1. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.
2. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. The lancet Diabetes & endocrinology. 2014;2(4):307-20.
3. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2014;383(9912):146-55.
4. Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. The lancet Diabetes & endocrinology. 2014;2(7):573-80.
5. Bolland MJ, Grey A, Reid IR. Differences in overlapping meta-analyses of vitamin D supplements and falls. J Clin Endocrinol Metab. 2014;99(11):4265-72.
6. Moyer VA, Force* USPST. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158(9):691-6.
7. Slemenda CW, Peacock M, Hui S, Zhou L, Johnston CC. Reduced rates of skeletal remodeling are associated with increased bone mineral density during the development of peak skeletal mass. J Bone Miner Res. 1997;12(4):676-82.
8. Michaelsson K. Calcium supplements do not prevent fractures. BMJ. 2015;351:h4825.
9. Gallagher JC, Jindal PS, Smith LM. Vitamin D does not increase calcium absorption in young women: a randomized clinical trial. J Bone Miner Res. 2014;29(5):1081-7.
10. Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab. 2004;89(7):3152-7.
11. Enko D, Fridrich L, Rezanka E, Stolba R, Ernst J, Wendler I, et al. 25-hydroxy-Vitamin D status: limitations in comparison and clinical interpretation of serum-levels across different assay methods. Clin Lab. 2014;60(9):1541-50.
12. 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(7):e11555.
13. Ramnemark A, Norberg M, Pettersson-Kymmer U, Eliasson M. Adequate vitamin D levels in a Swedish population living above latitude 63 degrees N: The 2009 Northern Sweden MONICA study. Int J Circumpolar Health. 2015;74:27963.
14. Burgaz A, Akesson A, Oster A, Michaelsson K, Wolk A. Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter. Am J Clin Nutr. 2007;86(5):1399-404.
15. Wyness SP, Straseski JA. Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s. Clin Biochem. 2015.
•
Competing interests: No competing interests