Vitamin D

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].