Vitamin D

Vitamin D and Miscarriage

Vitamin D may be useful as immunotherapy in treatment of recurrent miscarriage

We promote vitamin D3 as new immunomodulatory agent in treatment of recurrent miscarriage. Different mechanisms have been proposed to account for the immunosuppressive effect of 1alpha, 25-dihydroxy-vitamin-D3. Portion of the vitamin D activity involves the downregulation of IL-2, IFN-gamma and TNF-alpha genes transcription. Because immunomodulatory effects of vitamin D are very similar to IL-10 effects, acting of vitamin D in immunotherapy of recurrent miscarriage syndrome, preeclamptic and eclamptic pregnancy, as well as pregnancy-induced hypertension, is very reasonable. We propose using of vitamin D as immunotherapy or adjuvant therapy in combination with classic immunotherapies of endangered pregnancies.

Vitamin D reduces inflammation associated with miscarriage

Elevated placental proinflammatory cytokine release is associated with miscarriage, preterm labor and preeclampsia. Specifically, tumor necrosis factor-alpha (TNF-alpha)-induced cytokines may threaten pregnancy outcome. Since trophoblasts produce calcitriol, a hormone with strong immunosuppressive properties, we assessed the effects of this secosteroid on inflammatory cytokines induced in trophoblasts by challenge with TNF-alpha. Vitamin D inhibited the expression profile of inflammatory cytokine genes in a dose-response manner. These data show that vitamin D prevents TNF-alpha induction of inflammatory cytokines through a process likely to be mediated by the vitamin D receptor.

4000 IU Vitamin D daily lowers rates of infection, preterm labor and preterm birth

Researchers randomized 494 pregnant women at 12-16 weeks' gestation into three treatment groups. Group one received 400 International Units (IU) of vitamin D a day until delivery; group two received 2,000 IU and group three received 4,000 IU. The women were evaluated monthly to ensure safety. No adverse events related to vitamin D dosing were found in any of the three arms of the study. Women replete in vitamin D had lower rates of preterm labor and preterm birth, and lower rates of infection. The greatest effects were seen among women taking 4,000 IU of vitamin D per day. Therefore, the researchers recommend this daily regimen for all pregnant women.

Vitamin D required for fetal development; deficiency causes preeclampsia, gestational diabetes

It appears that vitamin D insufficiency during pregnancy is potentially associated with increased risk of preeclampsia, insulin resistance and gestational diabetes mellitus. Furthermore, experimental data also anticipate that vitamin D sufficiency is critical for fetal development, and especially for fetal brain development and immunological functions. Vitamin D deficiency during pregnancy may, therefore, not only impair maternal skeletal preservation and fetal skeletal formation but also be vital to the fetal "imprinting" that may affect chronic disease susceptibility soon after birth as well as later in life.

Vitamin D levels not associated with fertility or pregnancy outcome except late miscarriage

Plasma vitamin D concentrations may affect pregnancy outcomes. To elucidate this further, we studied the effects of pre-conception vitamin D concentrations on chances for pregnancy as well as the effects of vitamin D during pregnancy on the risk of miscarriage, birth weight and length, Apgar score and head circumference. At baseline, median plasma vitamin D was 59 nmol/l (23.6 ng/ml). Of these women, 31% had plasma vitamin D <50 nmol/l, whereas 12% had levels above 80 nmol/l. Plasma vitamin D concentrations did not affect fertility or pregnancy outcomes, although low plasma vitamin D may be associated with an increased risk of late miscarriage (2nd trimester).

Vitamin D and Fertility

Low vitamin D leads to failed IVF attempts

Multivariable logistic regression analysis confirmed vitamin D levels as an independent predictor to success of an IVF cycle; adjusting for age, body mass index, ethnicity, and number of embryos transferred, each ng/mL increase in vitamin d increased the likelihood for achieving clinical pregnancy by 6%.

Having sufficient vitamin D levels is associated with 4 times higher success rate in IVF

Adjusting for age and number and quality of embryos transferred among non-Hispanic whites, the odds of pregnancy were four times higher in vitamin D replete versus deficient patients. Live birth rates mirrored pregnancy rates. Vitamin D status was not associated with ovarian stimulation parameters or with markers of embryo quality. CONCLUSIONS: Vitamin D deficiency is associated with lower pregnancy rates in non-Hispanic whites, but not in Asians, possibly due to their lower IVF success rates. Vitamin D deficiency was not correlated with ovarian stimulation parameters or with markers of embryo quality, suggesting its effect may be mediated through the endometrium.

93% of infertile women were low in vitamin D

Here they studied 67 women who had problems conceiving – and found that 93% of them were low in vitamin D. According to researcher Dr Lubna Pal, “ Of note, not a single patient with either ovulatory disturbance or polycystic ovary syndrome (PCOS) demonstrated normal Vitamin D levels; 39% of those with ovulatory disturbance and 38% of those with PCOS had serum vitamin D levels consistent with deficiency.

High or low vitamin D associated with lower sperm count, motility and morphology

Sperm concentration, sperm progressive motility, sperm morphology, and total progressively motile sperm count were lower in men with vitamin D ≥50 ng ml when compared to men with 20 ng ml ≤ vitamin D <50 ng ml. Total sperm count and total progressive motile sperm count were lower in men with vitamin D <20 ng ml when compared to men with 20 ng ml ≤ vitamin D <50 ng ml. The adjusted means of various hormonal parameters did not show statistical difference in the different categories of vitamin D. In conclusion, serum vitamin D levels at high and low levels can be negatively associated with semen parameters.

High vitamin D levels associated with higher sperm motility and morphology

Vitamin D serum levels correlated positively with sperm motility and progressive motility, and men with vitamin D deficiency (<25 nM) had a lower proportion of motile, progressive motile and morphologically normal spermatozoa compared with men with high vitamin D levels (>75 nM). Vitamin D increased intracellular calcium concentration in human spermatozoa, increased sperm motility and induced the acrosome reaction (necessary for fertilization) in vitro. CONCLUSIONS: Vitamin D increased intracellular calcium concentration, sperm motility and induced the acrosome reaction in mature spermatozoa, and vitamin D serum levels were positively associated with sperm motility, suggesting a role for vitamin D in human sperm function.

Extra vitamin D increases litter size in pigs and has a trend towards higher pregnancy rates

A 23% increase in pregnancy rate was observed in 2,500 IU vitamin D fed gilts compared with 500 IU vitamin D fed control (78% vs. 55%, respectively; not statistically significant). Litter size was larger (control = 10.2; vitamin D = 12.7) in vitamin D fed gilts compared with control fed gilts. Notably, mean fetal weight was not decreased in vitamin D fed gilts as frequently occurs when litter size is increased. Overall, feeding vitamin D to first-service gilts before and during gestation improved both maternal and fetal vitamin D status and improved maternal reproductive performance.

Vitamin D deficiency leads to fewer offspring in mice

Vitamin D deficiency was verified by lack of detectable serum 25-hydroxycholecalciferol. Deficient mice had fewer pups per litter than controls (7.1 vs. 8.4).

Vitamin D and Hormones

Vitamin D deficiency impairs egg production, elevates LH and FSH

Vitamin D deficiency caused uterine hypoplasia and impaired folliculogenesis in mice. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice.

Vitamin D stimulates estrogen and progesterone production by the placenta

Estrogen and progesterone synthesis in human placenta is stimulated by calcitriol (vitamin D). Vitamin D stimulated in a dose-dependent manner estrogen and progesterone secretion (the secretion of these hormones by the placenta is vital to preventing miscarriage).

Vitamin D stimulates progesterone and estrogen production in the ovary

In vitro, Vitamin D stimulated progesterone production in the ovary by 13%, estradiol production by 9%, and estrone production by 21%. Insulin and vitamin D acted synergistically to increase estradiol production by 60%. Vitamin D alone stimulated IGFBP-1 production by 24% (IGFBP-1 is lower in women who miscarry), however, in the presence of insulin, vitamin D enhanced insulin-induced inhibition of IGFBP-1 production by 13%. Vitamin D stimulates ovarian steroidogenesis and IGFBP-1 production in human ovarian cells likely acting via vitamin D receptor. Insulin and vitamin D synergistically stimulate estradiol production. Vitamin D also enhances inhibitory effect of insulin on IGFBP-1 production.

Excess Vitamin D reduces the function of the corpus luteum and decreases progesterone

The following results were observed: 1) disturbance of the menstrual cycle, 2) hypofunctional changes in the corpus luteum in the ovary, and the epithelium, endometrium and uterine gland in the uterus with a decrease in the serum progesterone level and 3) hypercalcemia with a decrease in calcitonin or parathyroid hormone levels in serum with morphological changes including atrophy and cyst-formation in the parathyroid. However, the above changes were reversible, and recovery was observed after administration of the compound was discontinued. These results indicate that the hypercalcemia caused by vitamin D disrupts endocrinological homeostasis which in turn temporarily disrupts the female reproductive system.

High Vitamin D associated with 56% lower pregnancy rate in IVF

The aim of the present study was to measure serum and follicular fluid 25-OH vitamin D and glucose levels in women who underwent IVF-ET treatment and to further investigate whether the circulating 25-OH vitamin D and glucose levels correlate with IVF success. METHODS: Group A with less than 20 ng/ml, group B with vitamin levels between 20.1 and 30 ng/ml and group C with more than 30 ng/ml vitamin concentration. RESULTS: Serum vitamin levels of all women studied were significantly correlated with folicular fluid vitamin levels. Follicular fluid vitamin levels significantly correlated with the quality of embryos in total, while the quality of embryos of group C were of lower quality as compared to those of groups A and B. Follicular fluid glucose levels were lower in women of group C as compared to the respective levels of groups A and B. Clinical pregnancy rate demonstrated in 14.5% in women of group C and 32.3% and 32.7% in groups A and B, respectively. CONCLUSION: The data suggests that excess serum and follicular fluid vitamin levels in combination with decreased follicular fluid glucose levels have a detrimental impact on the IVF outcome.

For a concise list of qualities found to affect one's risk of miscarriage, see:

Vitamin D and Obesity

Obesity lowers vitamin D

Increased body weight has a significant negative effect on 25-OH- and 1,25-(OH)2-vitamin D concentrations, but no association with PCOS was observed.

Vitamin D and Insulin Resistance

Insulin sensitivity increased by 60% with normalization of vitamin D levels

In a study published in 2004, the authors saw a 60% improvement in insulin sensitivity in healthy, vitamin D replete adults.

Vitamin D important for glucose regulation

Vitamin D has increasingly been shown to be important not only for bone health, but also for glucose regulation, immune function, and good uterine contractility in labor.

Supplemental vitamin D improves insulin resistance in PCOS women

Aim of this study was aimed to determine the effect of vitamin D replacement therapy on glucose metabolism, insulin, and testosterone levels in obese, insulin-resistant women with PCOS. Only 2 women were within the normal limits of vitamin D levels as >20 ng/ml. Three weeks after the administration of the single dose of 300,000 units of vitamin D orally, 25-hydroxyvitamin D3 significantly increased from 16.9 to 37.1 ng/ml and only 2 women were detected to have vitamin D levels <20 ng/ml. Although glucose and insulin levels were decreased non-significantly, homeostasis model assessment of insulin resistance significantly decreased from 4.41 to 3.67. No significant alterations were witnessed at the levels of DHEAS, total and free testosterone, androstenedione. In conclusion, women with PCOS have mostly insufficient vitamin D levels, and vitamin D replacement therapy may have a beneficial effect on insulin resistance in obese women with PCOS.

Vitamin D improved the FFA-induced insulin resistance in muscle cells.

Supplemental vitamin D did not improve insulin resistance in type 2 diabetics

High-dose vitamin D improved systolic blood pressure and B-type natriuretic peptide levels, but not endothelial function, insulin resistance or glycosylated haemoglobin in patients with type 2 diabetes.

Vitamin D and Autoimmunity

A genetic defect of the vitamin D receptor gene can predict Hashimoto's Autoimmune Thyroiditis.

Vitamin D boosts anti-inflammatory IL-10 activity

We studied here the effect of the physiologically active metabolite, 1,25-dihydroxyvitamin D3 (vitamin D) and its synthetic analogue calcipotriol (MC 903) on the expression of the IL-10R in HaCaT cells by RT-PCR. IL-10 receptor gene expression was effectively induced in the range of 10-8-10 -9 M. Upregulation by vitamin D was about 10-fold, by calcipotriol 12-fold. Induction of the receptor for the anti-inflammatory cytokine IL-10 may be involved in the antipsoriatic action of vitamin D derivatives.

Increasing Vitamin D Levels

400 IU is adequate; 2,000 IU is upper limit; Vitamin D3 is more potent and preferred

The Institute of Medicine publishes an Adequate Intake recommendation which is an estimate of the amount of vitamin D that appears to maintain normal functioning. The current daily AI of vitamin D to prevent rickets in healthy children and bone pain (osteomalacia) in adults is based on age. Birth through 50 years of age, 200 IU; Adults ages 51 to 70, 400 IU; Adults greater than 70 years of age, 600 IU daily. The upper intake levels for vitamin D are 1000 IU for infants 0 to 12 months and 2000 IU for everyone over one year of age. Many experts now recommend using vitamin D supplements containing cholecalciferol (vitamin D3) in order to meet these intake levels. This seems to be more potent than another form of vitamin D called ergocalciferol.

2,000 IU is upper limit; Excess vitamin D causes excess calcium

Too much of the pill variety of Vitamin D can cause a dangerous buildup of calcium in the body. 2,000 IUs is the upper daily limit, although newer clinical trials conducted in healthy adults and conclude that the data support a UL as high as 10,000 IU/day. Vitamin D from sunshine has no such limit, because the sustained heat on the skin is thought to photodegrade previtamin D3 and vitamin D3 as it is formed.

Vitamin D Information

Vitamin D lowers progesterone and estrogen

Per increase of 10 nmol/l of vitamin D (50 nmol/l is considered optimal), progesterone multiplicatively decreased by a factor of 10%  and estrogen decreased by a factor of 3% after adjustment for age, body mass index, ethnicity, season, alcohol use, smoking, and physical activity. Women recruited during the winter months were given 4 weekly doses of 28,000 IU of vitamin D3 (equivalent to daily doses of 4,000 IU over 4 weeks). This dose was selected to increase the range of vitamin D, but remain within the normal range, and, as expected, the highest levels of vitamin D we observed remained below the levels observed in some highly sun-exposed individuals. Among the 37 women with values before and after supplementation, mean progesterone decreased from 23 to 16 nmol/l and mean estrogen decreased from 446 to 418 pmol/l, although neither change reached significance. CONCLUSIONS: Higher levels of vitamin D may reduce progesterone and estrogen.

Other topics covered under Vitamins: