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Vitamin D

Classification: A

Drug products: ADROVANCE, Benferol, Colecalciferol Meda, D3-Vicotrat, Dekristol Mibe, Detremin, Devitre, Divifarm, Divisun, Fosastad, Fosavance®, Fultium, Kolekalciferol Ebb, Kolekalciferol Evolan, Vigantol, Vitamin D3 Streuli

ATC code: A11CC05, M05BB03

Substances: vitamin d3 100 CWS

Summary

Similar effects in men and women treated with vitamin D have been shown in prevention of fall risk and fractures.

Additional information

Pharmacokinetics and dosing

Vitamin D is inactive, metabolized by hydroxylation in the liver to 25(OH)D and subsequently metabolized in the kidney to 1,25(OH)D which represents the biologically active form [1]. A study of healthy volunteers (20 men, 35 women) randomized to 10 µg cholecalciferol in multivitamin tablets or in fish oil capsules showed a similar increase of 25(OH)D in both men and women after 4 weeks of supplementation [2].

Effects

Mortality

A meta-analysis of eight population based studies in Europe and USA with participants aged 50-79 years (12 842 men, 13 176 women) showed that the median 25(OH)D concentrations were higher in men than in women but the all-cause mortality risk was similar. According to the authors, low 25(OH)D concentrations might be a marker for a poor health status rather than a cause of premature mortality [3]. One of the studies included in this meta-analysis is an U.S. population based survey study with a household interview and a medical examination (7 399 men, 7 700 women) showing the lowest risk of mortality at different intervals of 25(OH)D in men and women (100-119 vs 75-99 nmol/L). The risk of death was increased at levels <40 and >120 nmol/L in men, and at levels <75 and >100 nmol/L in women [4].

A prospective study of health of older adults aged ≥85 years (319 men, 526 women) showed that women but not men had an adjusted increased risk of all-cause mortality at concentrations of 25(OH)D <25 and ≥75 nmol/L (RR 1.6 and 1.5-1.9, repectively) [5].

Cardiovascular (CVD)

In two longitudinal survey studies the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) among US health professionals (51 529 men, 121 700 women), a high vitamin D intake from food and supplements reduced the risk of CVD by 0.84 in men, but not in women [6].

Fall risk

A meta-analysis of pooled data from four studies of vitamin D plus calcium in 1 317 elderly (12% men, 88% women, approximately) showed no overall reduction of the fall risk (RR 0.99). However, in one of the studies in only women (148 women) [7] of vitamin D plus calcium vs calcium a reduced fall risk (RR 0.55) was shown [8].

Fractures, Bone Mineral Density

In a double-blind placebo-controlled intervention study, Danish traditional Muslims (84 men, 89 women, 26 girls of median age 12 years) were randomized to placebo, vitamin D 10 µg or 20 µg daily. In the treatment group, the levels of 25(OH)D increased  (unspecified how much) in girls, 2-3 fold increase in men, and 4-fold in women. The levels of parathyroid hormone (PTH) were decreased in men, women and girls but no effect on markers of bone mass and bone turnover was noted at six months [9]. However, in a cross-sectional study, adolescents 12-15 years of age (111 boys, 111 girls) were randomized to regular diet or a daily supplement of vitamin D and calcium. Total body bone mineral density (BMD) increased with increasing levels of 25(OH)D up to a break-point of 39 nmol/L 25(OH)D in boys and 20 nmol/L 25(OH)D in girls. Above the break-point no further increase in bone mineral density was shown despite increasing levels of 25(OH)D [10].

Hormones

​​​​​​​A clinical study (113 men, 33 women, 74 boys 5–6 years old) showed that women taking daily supplement of vitamin D in the autumn and winter had no seasonal decline in serum levels of Anti-Müllerian hormone (AMH), a sex hormone used as measure of fertility in women, and involved the development of male sex in fetuses [11].

Adverse effects

No studies with a clinical relevant sex analysis regarding adverse effects of vitamin D have been found.

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

In the meta-analysis of eight population based studies in Europe and USA (12 842 men, 13 176 women) mentioned above median 25(OH)D showed that the 25(OH)D concentrations were higher in men than in women [3]. Contrary to this, in a world-wide meta-analysis of 105 studies in men and 277 studies in women (33 266 in all, unknown distribution of participants’ sex) found that women had higher mean levels of 25(OH)D than men (56 vs 50 nmol/L). One of the studies in the age group 70+ found a sufficient intake of 25(OH)D (>15 μg/day) from ordinary diet in 1–3% of men and in none of the women [12].

An open cross-over study, school children (409 boys, 373 girls) 8-11 years old were randomized to ordinary food or to the New Nordic Diet during three months. In the whole study group, the lowest levels of 25(OH)D were found in immigrant girls (80% regarded as deficient, ≤ 50 nmol/L), followed by immigrant boys (+9.4 nmol/L). Among native Danish children, the levels were even higher, with the boys having higher concentrations than the girls (+3.3 nmol/L) [13,14]. A randomized controlled study in 6-14 years old schoolchildren in Thailand (261 boys, 268 girls) showed that girls but not boys had a 4% decline in serum 25(OH)D levels for each increasing year of age. At the age 10 years old, the concentration of 25(OH)D was 19% higher in boys than in girls [15].

A multicenter study  in the Midwest in the US of 385 patients (20% men, 80% women, approximately) who had undergone surgical repair of a hip fracture showed that the median levels of 25(OH)D were higher in men than in women (16.9 vs 14.4 ng/ml) [16,17].

A prospective cohort study of data from a randomized clinical trial in hemodialysis patients (31 men, 21 women) during 4-5 weeks showed that patients’ sex, but not serum concentration of 25(OH)D, was a predictor of changes in parathyroid hormone (PTH). During the study period PTH decreased in men but increased in women (-61 vs +14 pg/mL) [18]. Another study of hemodialysis patients (48 men, 36 women) showed higher mean levels of 25(OH)D in men than in women (72 vs 47 nmol/L), this was also shown in multivariate analysis [19].

Updated: 2019-02-26

Date of litterature search: 2016-09-15

References

  1. Food and Drug Administration. Clinical Pharmacology and Biopharmaceutics Review - FOSAMAX PLUS (alendronate and cholecalciferol). Food and Drug Administration [www]. [updated 2005-07-04, cited 2016-11-17]. länk
  2. Holvik K, Madar AA, Meyer HE, Lofthus CM, Stene LC. A randomised comparison of increase in serum 25-hydroxyvitamin D concentration after 4 weeks of daily oral intake of 10 microg cholecalciferol from multivitamin tablets or fish oil capsules in healthy young adults. Br J Nutr. 2007;98:620-5. PubMed
  3. Schöttker B, Jorde R, Peasey A, Thorand B, Jansen EH, Groot Ld et al. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014;348:g3656. PubMed
  4. Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, Yetley EA, Looker AC, Schleicher RL et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the US nationally representative NHANES. J Clin Endocrinol Metab. 2013;98:3001-9. PubMed
  5. Granic A, Aspray T, Hill T, Davies K, Collerton J, Martin-Ruiz C et al. 25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study. J Intern Med. 2015;277:456-67. PubMed
  6. Sun Q, Shi L, Rimm EB, Giovannucci EL, Hu FB, Manson JE et al. Vitamin D intake and risk of cardiovascular disease in US men and women. Am J Clin Nutr. 2011;94:534-42. PubMed
  7. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res. 2000;15:1113-8. PubMed
  8. Latham NK, Anderson CS, Reid IR. Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc. 2003;51:1219-26. PubMed
  9. Andersen R, Mølgaard C, Skovgaard LT, Brot C, Cashman KD, Jakobsen J et al. Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study. Br J Nutr. 2008;100:197-207. PubMed
  10. Wu F, Laslett LL, Zhang Q. Threshold Effects of Vitamin D Status on Bone Health in Chinese Adolescents With Low Calcium Intake. J Clin Endocrinol Metab. 2015;100:4481-9. PubMed
  11. Dennis NA, Houghton LA, Jones GT, van Rij AM, Morgan K, McLennan IS. The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys. J Clin Endocrinol Metab. 2012;97:2450-5. PubMed
  12. Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int. 2009;20:133-40. PubMed
  13. Damsgaard CT, Dalskov SM, Petersen RA, Sørensen LB, Mølgaard C, Biltoft-Jensen A et al. Design of the OPUS School Meal Study: a randomised controlled trial assessing the impact of serving school meals based on the New Nordic Diet. Scand J Public Health. 2012;40:693-703. PubMed
  14. Petersen RA, Damsgaard CT, Dalskov SM, Sørensen LB, Hjorth MF, Ritz C et al. Vitamin D status and its determinants during autumn in children at northern latitudes: a cross-sectional analysis from the optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. Br J Nutr. 2016;115:239-50. PubMed
  15. Houghton LA, Gray AR, Harper MJ, Winichagoon P, Pongcharoen T, Gowachirapant S et al. Vitamin D status among Thai school children and the association with 1,25-Dihydroxyvitamin D and parathyroid hormone levels. PLoS One. 2014;9:e104825. PubMed
  16. Pieper CF, Colon-Emeric C, Caminis J, Betchyk K, Zhang J, Janning C et al. Distribution and correlates of serum 25-hydroxyvitamin D levels in a sample of patients with hip fracture. Am J Geriatr Pharmacother. 2007;5:335-40. PubMed
  17. Harrington JT, Broy SB, Derosa AM, Licata AA, Shewmon DA. Hip fracture patients are not treated for osteoporosis: a call to action. Arthritis Rheum. 2002;47:651-4. PubMed
  18. Indridason OS, Pieper CF, Quarles LD. Predictors of short-term changes in serum intact parathyroid hormone levels in hemodialysis patients: role of phosphorus, calcium, and gender. J Clin Endocrinol Metab. 1998;83:3860-6. PubMed
  19. Del Valle E, Negri AL, Aguirre C, Fradinger E, Zanchetta JR. Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis. Hemodial Int. 2007;11:315-21. PubMed
  20. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-11-08.] Socialstyrelsens statistikdatabas

Authors: Maria Enghag

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson