Lifestyle and Environment Nutrition and Metabolic Health

Dietary supplements and prevention of preeclampsia

Ushida T, Tano S, Matsuo S, Fuma K, Imai K, Kajiyama H, Kotani T

Published April 2025 Hypertension research : official journal of the Japanese Society of Hypertension
DOI 10.1038/s41440-025-02144-9 PMID 39930022 PMC PMC11972965

RRM Academy Synopsis

Calcium supplements lower preeclampsia risk when intake is low

Calcium supplements roughly halved preeclampsia risk in pregnant women with low calcium intake, a 2025 review of earlier meta-analyses reports. The review also covered vitamins, minerals and antioxidants. Its authors find calcium the only supplement with substantial evidence.

Key Findings

  • A 2022 meta-analysis of 30 studies (n = 20,445) found that calcium supplementation reduced the risk of preeclampsia (RR 0.49, CI 0.39–0.61).
  • The calcium effect appeared in populations with low calcium intake (RR 0.45, CI 0.35–0.58). Among populations with adequate intake, the reduction was not significant (RR 0.62, CI 0.37–1.06).
  • A 2020 meta-analysis of 27 vitamin D studies (n = 4777) reported less preeclampsia (OR 0.37, CI 0.26–0.52). Three more recent systematic reviews, one a 2024 Cochrane review, found no clear benefit.
  • Cochrane reviews from 2015 found no significant reduction with vitamin C, alone or combined (RR 0.92, CI 0.80–1.05), or vitamin E combined with other supplements (RR 0.91, CI 0.79–1.06).
  • A 2018 Cochrane review found that omega-3 fatty acids tended to reduce preeclampsia, a result that was not significant (RR 0.84, CI 0.69–1.01; 20 studies, n = 8306).

Interpretation

The article reviews published systematic reviews and meta-analyses. It reports no new trial data. The authors rate the calcium evidence as high quality. They frame the question around Japanese women, whose average calcium intake is low. Vitamin D reviews disagree, and the authors call for large trials. The authors found no prevention studies for L-carnitine, resveratrol, astaxanthin or S-equol.

RRM Context

The review frames preeclampsia prevention around the concept of preconception care. It lists assisted reproductive technologies among the main risk factors. Restorative reproductive medicine treats health before conception as part of fertility care for both partners. Nutrition belongs to that picture.

Abstract

Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE. In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE. Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan. According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions. We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE.

Topics

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Lifestyle and Environment › Nutrition and Metabolic Health › Dietary Patterns
Takafumi Ushida, Sho Tano, Seiko Matsuo, Kazuya Fuma, Kenji Imai, Hiroaki Kajiyama, Tomomi Kotani
T Ushida, S Tano, S Matsuo, K Fuma, K Imai, H Kajiyama, T Kotani
PMID 39930022 39930022 DOI 10.1038/s41440-025-02144-9 10.1038/s41440-025-02144-9 Ushida et al. 2025, Ushida 2025