Vitamin D has a critical role in skeletal health and maintaining serum calcium levels. Calcium is needed for a variety of cellular and metabolic processes in the body. Large amounts of vitamin D can be produced in the skin when exposed to UV-B radiation. It is therefore a paradox that in Europe, Caucasians living in higher latitude countries, such as Scandinavia and Iceland, have higher serum vitamin D compared with those living in lower latitude. In a recent study of adult-type lactase persistence (LP), it was shown that Caucasian of European descent, who carried the C-13910T LP allele, had higher levels of total serum 25-hydroxyvitamin D compared with those who were lactase non-persistent. This was attributed to higher consumption of dairy. We postulated that the distribution of the LP C-13910T allele in Caucasian populations may explain the vitamin D concentration pattern seen in Europe.
Baseline mean total serum 25 hydroxyvitamin D concentration from a clinical trial of post-menopausal women with osteoporosis was correlated to published LP frequencies in European populations.
In multiple regression analysis, mean total serum 25 hydroxyvitamin D concentrations in both winter and summer were in turn correlated to LP phenotype frequency (winter: r2 = 0.51, p < 0.05; summer: r2 = 0.4, p < 0.05).
High frequency of LP in northern Europe may explain high mean total serum 25 hydroxyvitamin D concentrations despite low UV-B radiation exposure.
Your institute does not have access to this article
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Bouillon R, Suda T. Vitamin D: calcium and bone homeostasis during evolution. Bone Rep. 2014;3:480.
Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.
Bendik I, Friedel A, Roos FF, Weber P, Eggersdorfer M. Vitamin D: a critical and essential micronutrient for human health. Front Physiol. 2014;5:248.
Aune D, Navarro Rosenblatt DA, Chan DSM, Vieira AR, Vieira R, Greenwood DC, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101:87–117.
Rosen CJ. Vitamin D insufficiency. N Engl J Med. 2011;364:248–54.
Alharbi O, El-Sohemy A. Lactose intolerance (LCT-13910C>T) genotype is associated with plasma 25-hydroxyvitamin D concentrations in Caucasians: a Mendelian Randomization Study. J Nutr. 2017;147:1063–9.
American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for prevention of falls and their consequences. J Am Geriatr Soc. 2014;62:147–52.
Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, et al. The Nonskeletal effects of vitamin D: an endocrine society scientific statement. Endocr Rev. 2012;33:456–92.
Shore RM, Chesney RW. Rickets: part I. Pediatr Radiol. 2013;43:140–51.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.
Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. 2007;85:649–50.
McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med. 1992;93:69–77.
Maalouf NM. The noncalciotropic actions of vitamin D: recent clinical developments. Curr Opin Nephrol Hypertens. 2008;17:408–15.
Marwaha RK, Tandon N, Reddy DRHK, Aggarwal R, Singh R, Sawhney RC, et al. Vitamin D and bone mineral density status of healthy schoolchildren in northern India. Am J Clin Nutr. 2005;82:477–82.
Harris SS, Soteriades E, Coolidge JAS, Mudgal S, Dawson-Hughes B. Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population 1. J Clin Endocrinol Metab. 2000;85:4125–30.
Grant WB, Cross HS, Garland CF, Gorham ED, Moan J, Peterlik M, et al. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe. Prog Biophys Mol Biol. 2009;99:104–13.
Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68:854–8.
Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol. 2017;13:466–79.
Vieth R, Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007;22:64–8.
Göring H, Koshuchowa S. Vitamin D—the sun hormone. Life in environmental mismatch. Biochemistry. 2015;80:8–20.
Göring H, Koshuchowa S. Vitamin D deficiency in Europeans today and in Viking settlers of Greenland. Biochemistry. 2016;81:1492–7.
Holick MF, The vitamin D epidemic and its health consequences. J Nutr. 2005;135:2739–48.
Biancuzzo RM, Clarke N, Reitz RE, Travison TG, Holick MF. Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation. J Clin Endocrinol Metab. 2013;98:973–9.
van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25:671–80.
van Schoor N, Lips P. Global overview of vitamin D status. Endocrinol Metab Clin North Am. 2017;46:845–70.
Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2014;111:23–45.
Spiro A, Buttriss JL. Vitamin D: an overview of vitamin D status and intake in Europe. Nutr Bull. 2014;39:322–50.
Andersen R, Mølgaard C, Skovgaard LT, Brot C, Cashman KD, Chabros E, et al. Teenage girls and elderly women living in northern Europe have low winter vitamin D status. Eur J Clin Nutr. 2005;59:533–41.
Helgi Library. Fish Consumption Per Capita in Norway|Helgi Library. 2017. http://www.helgilibrary.com/indicators/fish-consumption-per-capita/norway/ Accessed 14 December 2017.
Bergholdt HKM, Nordestgaard BG, Varbo A, Ellervik C. Lactase persistence, milk intake, and mortality in the Danish general population: a Mendelian randomization study. Eur J Epidemiol. 2018;2:171–81.
Ding M, Huang T, Bergholdt HK, Nordestgaard BG, Ellervik C, Qi L. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. BMJ. 2017;356:j1000.
Kuchuk NO, van Schoor NM, Pluijm SM, Chines A, Lips P. Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective. J Bone Miner Res. 2009;24:693–701.
Liebert A, López S, Jones BL, Montalva N, Gerbault P, Lau W, et al. World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection. Hum Genet. 2017;136:1445–53.
Szilagyi A, Leighton H, Burstein B, Xue X. Latitude, sunshine, and human lactase phenotype distributions may contribute to geographic patterns of modern disease: the inflammatory bowel disease model. Clin Epidemiol. 2014;6:183–98.
National Accounts of OECD Countries. OECD data, Volume 2017 Issue 2. 2017. https://data.oecd.org/gdp/gross-domestic-product-gdp.htm Accessed 14 December 2017.
Ségurel L, Bon C. On the evolution of lactase persistence in humans. Annu Rev Genom Hum Genet. 2017;18:297–319.
Silanikove N, Leitner G, Merin U. The interrelationships between lactose intolerance and the modern dairy industry: global perspectives in evolutional and historical backgrounds. Nutrients. 2015;7:7312–31.
Enattah NS, Jensen TGK, Nielsen M, Lewinski R, Kuokkanen M, Rasinpera H, et al. Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture. Am J Hum Genet. 2008;82:57–72.
Gerbault P, Liebert A, Itan Y, Powell A, Currat M, Burger J, et al. Evolution of lactase persistence: an example of human niche construction. Philos Trans R Soc Lond B Biol Sci. 2011;366:863–77.
Itan Y, Jones BL, Ingram CJ, Swallow DM, Thomas MG. A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol Biol. 2010;10:36.
Ingram CJE, Mulcare CA, Itan Y, Thomas MG, Swallow DM. Lactose digestion and the evolutionary genetics of lactase persistence. Hum Genet. 2009;124:579–91.
Gallego Romero I, Basu Mallick C, Liebert A, Crivellaro F, Chaubey G, Itan Y, et al. Herders of Indian and European cattle share their predominant allele for lactase persistence. Mol Biol Evol. 2012;29:249–60.
Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007;39:31–40.
Shrier I, Szilagyi A, Correa JA. Impact of lactose containing foods and the genetics of lactase on diseases: an analytical review of population data. Nutr Cancer. 2008;60:292–300.
Gerbault P, Moret C, Currat M, Sanchez-Mazas A. Impact of selection and demography on the diffusion of lactase persistence. PLoS One. 2009;4:e6369.
Ranciaro A, Campbell MC, Hirbo JB, Ko W-Y, Froment A, Anagnostou P, et al. Genetic origins of lactase persistence and the spread of pastoralism in Africa. Am J Hum Genet. 2014;94:496–510.
Heyer E, Brazier L, Ségurel L, Hegay T, Austerlitz F, Quintana-Murci L, et al. Lactase persistence in Central Asia: phenotype, genotype, and evolution. Hum Biol. 2011;83:379–92.
Wang YG, Yan YS, Xu JJ, Du RF, Flatz SD, Kühnau W, et al. Prevalence of primary adult lactose malabsorption in three populations of northern China. Hum Genet. 1984;67:103–6.
Enattah NS, Trudeau A, Pimenoff V, Maiuri L, Auricchio S, Greco L, et al. Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans. Am J Hum Genet. 2007;81:615–25.
Shaukat A, Levitt MD, Taylor BC, MacDonald R, Shamliyan TA, Kane RL, et al. Systematic review: effective management strategies for lactose intolerance. Ann Intern Med. 2010;152:797.
Sibley E. Genetic variation and lactose intolerance: detection methods and clinical implications. Am J Pharm. 2004;4:239–45.
Zhong Y, Priebe MG, Vonk RJ, Huang C-Y, Antoine J-M, He T, et al. The role of colonic microbiota in lactose intolerance. Dig Dis Sci. 2004;49:78–83.
Deng Y, Misselwitz B, Dai N, Fox M. Lactose intolerance in adults: biological mechanism and dietary management. Nutrients. 2015;7:8020–35.
He T, Priebe MG, Harmsen HJM, Stellaard F, Sun X, Welling GW, et al. Colonic fermentation may play a role in lactose intolerance in humans. J Nutr. 2006;136:58–63.
Szilagyi A. Adaptation to lactose in lactase non persistent people: effects on intolerance and the relationship between dairy food consumption and evalution of diseases. Nutrients. 2015;7:6751–79.
Flatz G, Rotthauwe HW. Lactose nutrition and natural selection. Lancet. 1973;2:76–7.
Luca F, Perry GH, Di Rienzo A. Evolutionary adaptations to dietary changes. Annu Rev Nutr. 2010;30:291–314.
Muehlhoff E, Bennett A, Mcmahon D. Milk and Dairy Products in Human Nutrition. Rome: Food and Agriculture Organization of the United Nations; 2013. http://www.fao.org/docrep/018/i3396e/i3396e.pdf Accessed 9 March 2018.
Raw Milk. What’s In It? http://www.raw-milk-facts.com/what_is_in_raw_milk.html Accessed 9 March 2018.
Berridge MJ. Calcium signalling remodelling and disease. Biochem Soc Trans. 2012;40:297–309.
Norman AW. Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutr. 1998;67:1108–10.
Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res. 2007;23:525–35.
Li S-S, Gao L-H, Zhang X-Y, He J-W, Fu W-Z, Liu Y-J, et al. Genetically low vitamin D levels, bone mineral density, and bone metabolism markers: a Mendelian Randomisation Study. Sci Rep. 2016;6:33202.
We thank Nils Reinton for critically reading the manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
About this article
Cite this article
Sorthe, J., Moghaddam, A. Lactase persistence may explain the paradoxical findings of high vitamin D concentrations in Europeans living in areas of low UV-B irradiation. Eur J Clin Nutr 73, 585–593 (2019). https://doi.org/10.1038/s41430-018-0179-x