by William B. Grant, PhD
A new paper in the open-access journal reported the relation between vitamin D level and mortality rates based on a study of 26,916 individuals from a European consortium [Gaksch, 2017]. The countries involved were Denmark, Germany, Iceland, the Netherlands, and Norway. The average age of the participants at the time of enrollment ranged between 43 years in one German study to 76 years in the Iceland study. Average body mass index ranged from 23 in Denmark to 27 in one of the German studies. Women were slightly more represented than men. By the end of the studies, 6802 participants had died. The average follow-up time varied from 7.5 to 17.8 years. While vitamin D levels can change with time, the authors reported that follow-up time did not affect the findings.
So, what were the findings? All-cause mortality rate was minimal at 85 nmol/L (34 ng/mL). However, the findings were not considered significant for vitamin D levels above 50 nmol/L (20 ng/mL). This result is because there is not a one-in-twenty chance that the results for vitamin D levels above 50 nmol/L would be different from unity. At a vitamin D level of 10 nmol/L, the risk of death was 2.5 times that at 85 nmol/L.
The paper also reported results for cancer and cardiovascular disease (CVD)-specific mortality rates. For CVD, risk increased as vitamin D level declined from 110 nmol/L (44 ng/mL). The risk was significantly reduced above 75 nmol/L (30 ng/mL) based on the 95% confidence intervals. For cancer, there was a U-shaped relation, with highest risk between 45 and 63 nmol/L (18 and 25 nmol/L). However, risk was significantly increased compared to risk at 110 nmol/L for vitamin D level between 30 and 94 nmol/L (12 and 38 ng/mL). There appears to be some interaction between risk of cancer and CVD below 50 nmol/L, i.e., that deaths from one of these diseases affects the risk of dying by the other disease.
These results can be compared to two recent meta-analyses. In the most recent one, based on 32 prospective studies of healthy or sick participants, the minimum risk of death was at 90 nmol/L (36 ng/mL), and was significantly reduced for vitamin D level below 75 nmol/L (30 ng/mL) [Garland, 2014].
In an earlier one, based on 14 prospective studies of healthy people, the minimum mortality rate was found near 80 nmol/L (32 ng/mL) [Zittermann, 2012].
The role of vitamin D in reducing risk of cancer is now supported by three vitamin D randomized controlled trials [Lappe, 2007],[Bolland, 2011],[Lappe, 2016]. However, CVD is not [Veloudi, 2016]. However, CVD mortality rates are reduced with respect to regular outdoor recreational activity, and those people who have the highest outdoor activity levels and highest vitamin D levels have the lowest risk of CVD mortality rate [Donneyong, 2016]. Thus, the findings for CVD in the latest paper may be due to a combination of sun exposure through both vitamin D dependent and independent mechanisms.
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.Lancet Diabetes Endocrinol. 2014 Apr;2(4):307-20.
Donneyong MM, Taylor KC, Kerber RA, Hornung CA, Scragg R. Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III? Nutr Metab Cardiovasc Dis. 2016 Aug;26(8):735-42.
Gaksch M, Jorde R, Grimnes G, Joakimsen R, Schirmer H, Wilsgaard T, Mathiesen EB, Njølstad I, Løchen ML, März W, Kleber ME, Tomaschitz A, Grübler M, Eiriksdottir G, Gudmundsson EF, Harris TB, Cotch MF, Aspelund T, Gudnason V, Rutters F, Beulens JW, van 't Riet E, Nijpels G, Dekker JM, Grove-Laugesen D, Rejnmark L, Busch MA, Mensink GB, Scheidt-Nave C, Thamm M, Swart KM, Brouwer IA, Lips P, van Schoor NM, Sempos CT, Durazo-Arvizu RA, Škrabáková Z, Dowling KG, Cashman KD, Kiely M, Pilz S. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium. PLoS One. 2017 Feb 16;12(2):e0170791. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170791
Garland CF, Kim JJ, Mohr SB, Gorham ED, Grant WB, Giovannucci EL, Baggerly L, Hofflich H, Ramsdell J, Zeng K, Heaney RP. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Pub Health. 2014 Aug;104(8):e43-50.
Lappe J, Travers-Gustafon D, Garland C, Heaney R, Recker R, Watson P. Vitamin D3 and calcium supplementation significantly decreases cancer risk in older women. Poster 3352. 0. American Public Health Association 2016 meeting Oct 31, 2016. https://apha.confex.com/apha/144am/meetingapp.cgi/Paper/368368
Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.Am J Clin Nutr. 2007 Jun;85(6):1586-91.
Veloudi P, Jones G, Sharman, JE. Effectiveness of vitamin D supplementation for cardiovascular health outcomes. Pulse, 2016;4:193-207.
Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: A meta-analysis of prospective cohort studies. Am J Clin Nutr. 2012;95(1):91-100.