A network meta-analysis of randomized controlled trials using a variety of interventions to help with gestational hypertension was published in The Journal of Fetal-Maternal & Neonatal Medicine. Gestational hypertension, defined as hypertension that begins after 20 weeks into pregnancy (without proteinuria) affects 10-15% of women. Pre-eclampsia, a combination of gestational hypertension and the coexistence of at least one other new onset condition (such as proteinuria, maternal end-organ dysfunction, etc.), is the leading cause of fetal and maternal death, as well as a risk for cardiovascular disease, multiple pregnancy complications, type 2 diabetes, and more. This analysis included 50 trials involving nearly 60,000 women and was not restricted to a single type of intervention, but included exercise (yoga, walking), aspirin, and nutritional supplements. Twelve of the studies were rated as low bias, 6 as high bias, and the remaining as unclear.
Overall, calcium combined with aspirin was associated with the largest reduction in risk, approximately 88% lower than compared to placebo. Aspirin alone was associated with a 32% reduction and calcium alone with a 45% reduction. Compared to usual care, exercise was associated with a 61% lower risk for gestational hypertension. No other included supplements showed a significant benefit.
This study offers helpful guidance but has several limitations, some of which the authors point out. For one, all trials with any vitamins (e.g., vitamin D, vitamin C) were combined into one group titled “vitamin,” potentially diluting the effects of any specific vitamin. A close look at the 5 cited “vitamin” studies found that 4 used vitamin C, vitamin E, or a combination of the two, and 1 used vitamin D. The latter utilized 1000 IU/day cholecalciferol among women with a baseline 25-OH vitamin of at least 25 nmol/l; potentially, the exclusion of women with lower baseline levels may have masked a benefit, 1000 IU/day may not be a sufficient dose, and a lack of benefit with vitamins C and E may have drowned out the benefit from vitamin D. For example, among women with low baseline levels, supplementation with 4000 IU was associated with a 1.2% rate of pre-eclampsia events, whereas a 400 IU dose was associated with a significantly higher rate of 8.6% in an open-label but randomized and controlled trial. A previous meta-analysis of calcium and vitamin D found that the combination, as well as vitamin D alone, significantly lowered pre-eclampsia risk, and a 2024 meta-analysis found that vitamin D significantly reduced the risk of pre-eclampsia by 45% (and pre-term labor by 30%). At the very least, measuring 25-OH vitamin D levels and supplementing women with suboptimal levels seems supported. It’s also worth noting that a 2024 study published in the New England Journal of Medicine found a low dose of calcium (500 mg per day) was equivalent to a higher dose (1500 mg) in preventing pre-eclampsia among women in India and Tanzania.
Not included in the network meta-analysis (it is unclear why) were studies related to omega-3 fatty acid supplementation. A 2024 meta-analysis published in Clinical Nutrition ESPEN found a 37% lower risk for pre-eclampsia with omega-3 supplementation, as well as a 55% lower risk for severe pre-eclampsia. A Mendelian randomization study published in Lipids in Health and Disease also suggests that higher levels of omega-3 fatty acids are protective against gestational hypertension.
The network meta-analysis included studies evaluating magnesium, but only 2 very small ones from 1992 and 1997, both of which reported a lower rate of gestational hypertension with magnesium supplementation (yet the meta-analysis did not find an overall benefit). A 2022 meta-analysis found that oral magnesium was associated with a 24% risk reduction for developing pre-eclampsia, with a stronger effect observed among women at higher risk (46% risk reduction in studies including normal- and high-risk women).
A supplement with emerging evidence for its use in preventing gestational hypertension is L-arginine, the precursor for endogenous synthesis of nitric oxide. Gestational hypertension and pre-eclampsia have been associated with disrupted signaling of nitric oxide. Indeed, placental hypoperfusion appears to release agents that cause endothelial dysfunction, oxidative stress, and a hyperinflammatory state, which may drive the pathogenesis of pre-eclampsia. For example, reduced nitric oxide bioavailability may cause vasoconstriction of the placental bed, increased systemic vascular resistance, and maternal hypertension (reviewed here).
A 2025 systematic review and meta-analysis published in BJOG included 20 randomized and controlled trials and 3 non-randomized trials, and found that L-arginine supplementation was associated with a 48% reduced risk of pre-eclampsia, and a 77% lower risk for severe pre-eclampsia. It was also shown to reduce maternal blood pressure among women with pre-eclampsia, as well as fetal growth restriction. Only one study evaluated L‐citrulline and found no benefit. However, the authors report the main limitation of this meta-analysis was the “absence of large, prospectively registered trials reporting on our primary outcomes”, and that all included studies had some risk of bias. Well-controlled, well-conducted trials would certainly be welcome. In a real-world setting, it’s also important to combine complementary approaches, especially among higher-risk women; for example, encouraging regular exercise as well as appropriate supplementation.
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