Role of Palm Oil Vitamin E in Preventing Pre-eclampsia: A Secondary Analysis of a Randomized Clinical Trial Following ISSHP Reclassification

Abstract

Background: Preeclampsia is a significant cause of maternal and perinatal mortality worldwide. Oxidative stress plays a key role in its pathophysiology, hence antioxidants such as tocotrienol may be preventive against preeclampsia. In 2018, the ISSHP revised the definition of preeclampsia. In accordance with the new definition, we report a secondary data analysis from a clinical trial comparing palm oil vitamin E in the form of tocotrienol-rich fraction (TRF) against placebo, in preventing preeclampsia.Method: A randomized double-blind controlled trial was conducted in 2002–2005 to assess the benefits of TRF in preeclampsia prevention. A total of 299 primigravidae were recruited. The intervention group was supplemented with TRF 100 mg daily in super-olein capsules, whereas the placebo group was prescribed super-olein capsules without TRF, beginning from 12 to 16 gestational weeks until delivery. The primary outcome measure was incidence of preeclampsia.Results: The total incidence of pregnancy induced hypertension (PIH) was 5%, whereas the incidence of preeclampsia was 2.3%. The odds of developing PIH (adjusted OR 0.254; 95% CI: 0.07–0.93; p–value 0.038) and preeclampsia (adjusted OR 0.030; 95% CI: 0.001–0.65; p-value 0.025) were significantly lower in the TRF arm compared to the placebo arm.Conclusion: Antenatal supplementation with palm oil vitamin E in the form of TRF is associated with significant reductions in the incidence of preeclampsia and PIH in a single urban tertiary hospital. Palm oil vitamin E deserves further scrutiny as a potential public health preventive measure against preeclampsia and PIH.

Tocotrienol in Pre-Eclampsia Prevention: A Mechanistic Analysis in Relation to the Pathophysiological Framework

“…The lack of effects of palm TRF on these subjects is expected because they were not hypertensive [ 91 ]. By contrast, Aminuddin et al demonstrated that palm TRF at 100 mg daily from 12–16 gestational weeks to delivery substantially reduced the risk of pregnancy-induced hypertension (odds ratio [OR]: 0.254; 95% confidence interval [CI]: 0.07–0.93) and pre-eclampsia (OR: 0.030, 95% CI: 0.001–0.65) amongst pregnant women [ 23 ]. However, the CI values for both effects were very large, which implies that the effect might not be consistent for all patients.…”

“…Given this limitation, a direct translation of the effects of tocotrienol on blood pressure from existing animal models may be problematic because it is not tested in a pre-eclampsia model. Preliminary data from Aminuddin et al [ 23 ] suggested that tocotrienol could be used as a preventive agent rather than a reversal agent, based on animal studies. More comprehensive human clinical trials with larger sample size are required to prove the effects of TRF in preventing hypertension amongst women with pre-eclampsia.…”

“…Only one clinical trial has looked at a tocotrienol-predominant preparation in preventing pre-eclampsia [ 23 ]. In this randomised double-blind placebo-controlled trial involving 299 primigravidae without any other risk factors for pre-eclampsia, the risk of pre-eclampsia was remarkably reduced by 83%.…”

“…However, the effects of another form of vitamin E, tocotrienol, in pre-eclampsia prevention have been less explored. Only one study examined the effects of tocotrienol-rich fraction (TRF) derived from palm oil with promising outcomes [ 23 ]. In this study, TRF reduced the risk of pre-eclampsia by 64% [ 23 ].…”

“…Only one study examined the effects of tocotrienol-rich fraction (TRF) derived from palm oil with promising outcomes [ 23 ]. In this study, TRF reduced the risk of pre-eclampsia by 64% [ 23 ]. Before embarking on expanding such clinical trials further, scrutinising the currently accepted pathophysiology of pre-eclampsia and the potential targets of tocotrienol in general would be prudent.…”