How high-dose vitamin D3 supplementation assists the prevention and treatment of pre-eclampsia during pregnancy

Pre-eclampsia is a fairly common condition in pregnant women (affecting around three million women globally per year) resulting in highly elevated blood pressure, which threatens the lives of both the mother and the unborn child. High-dose vitamin D supplementation has been shown to be effective in preventing the onset of the condition as well as ameliorating the symptoms in patients who have already presented with the condition. A new paper provides a plausible metabolic mechanism for the beneficial effect of vitamin D.

Pre-eclampsia is a serious condition in pregnant women, usually occurring after the 20th week of gestation, where highly elevated blood pressure begins to cause organ damage. Pre-eclampsia is a progression of gestational hypertension (GH) and occurs in around 25% of GH cases. Globally, the condition affects around three million women per year. 

Complications of the condition include kidney impairment, hepatic rupture, hemorrhage and pulmonary edema. There is a serious risk of both maternal and neonatal death if left untreated. Pre-eclampsia has a fatality rate of around 20%. There are many risk factors including anemia, diabetes, and obesity. The cause of pre-eclampsia has until recently been assumed to be due to problems with the vasculature in the placenta, but recent theories favor a mismatch in terms of the competing oxygen demands of the mother and fetus (1).

The treatment of pre-eclampsia has remained unchanged for many years. In cases where the blood pressure cannot be brought down to normal levels, sadly it is often necessary to terminate the pregnancy to prevent the death of the mother.

Vitamin D deficiency is common in pregnant women (5–50%) and breast-fed infants (10–56%), even where maternal vitamin supplementation is practiced, because of the difficulty in maintaining normal vitamin D levels (i.e. 32 ng/mL or more). It has been shown that vitamin D deficiency in early pregnancy can be a factor in the onset of pre-eclampsia (2). In addition, in patients suffering pre-eclampsia, administration of oral-dose vitamin D can decrease the severity of complications (3).

A new paper by Zabul et al. (4) proposes a mechanism for the use of high-dose vitamin D3 supplementation in both the prevention and treatment of pre-eclampsia. A feature of the condition is that the production of placental progesterone is compromised.

Progesterone is normally sourced from the conversion of cholesterol. This process is catalyzed by the heme-containing protein side-chain cleavage cytochrome P450. However, cytochrome P450 also hydroxylates vitamin D3 to 20-hydroxyvitamin D3, which is further converted to a series of other biologically active metabolites. Zabul et al (4) showed that in the placentas of pre-eclampsia patients, the cytochrome P450 appears to undergo suicidal oxidation leading to the destruction of heme and an increase in oxidative stress. It is proposed that vitamin D3 could act as a competitive inhibitor of placental cytochrome P450, preventing the production of lipid peroxides and moderating progesterone synthesis—both of which are important factors in the onset of pre-eclampsia.

1. Dennis AT and Castro JM, “Hypertension and haemodynamiocs in pregnant women – is a unified theory for pre-eclampsia possible?”, Anaesthesia 2014, 69: 1183-1196.
2. Bodnar LM, Catov JM, Simhan HN et al., “Maternal Vitamin D deficiency increases the risk of preeclampsia”, J Clin Endocrinol Metab 2007, 92:3517-3522.
3. Mulligan ML; Felton SK, Riek AE and Bernal-Mizrachi C, “Implications of vitamin D deficiency in pregnancy and lactation”, Am J Obstet Gynecol 2010, 202,429.e1-429.e9.
4. Zabul P, Wozniak M, Slominski A et al, A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia”, International Journal of Molecular Sciences 2015), 16(6): 13043-13064.