Tocotrienol Supplementation Led to Higher Serum Levels of Lysophospholipids but Lower Acylcarnitines in Postmenopausal Women: A Randomized Double-Blinded Placebo-Controlled Clinical Trial

Abstract

Osteoporosis is a major health problem in postmenopausal women. Herein we evaluated the effects of 12-week tocotrienols (TT) supplementation on serum metabolites in postmenopausal, osteopenic women. Eighty-nine participants (59.7 ± 6.8 yr, BMI 28.7 ± 5.7 kg/m²) were assigned to 3 treatments: placebo (860 mg olive oil/day), 300mg TT (300 mg TT/day), and 600mg TT (600 mg TT/day) for 12 weeks. TT consisted of 90% δ-TT and 10% γ-TT. In this metabolomic study, we evaluated the placebo and 600mgTT at baseline and 12 weeks. As expected, TT and its metabolite levels were higher in the supplemented group after 12 weeks. At baseline, there were no differences in demographic parameters or comprehensive metabolic panels (CMP). Metabolomics analysis of serum samples revealed that 48 biochemicals were higher and 65 were lower in the 600mg TT group at 12 weeks, compared to baseline. The results confirmed higher serum levels of tocotrienols and lysophospholipids, but lower acylcarnitines and catabolites of tryptophan and steroids in subjects given 600mg TT. In summary, 12-week TT supplementation altered many serum metabolite levels in postmenopausal women. The present study supports our previous findings that TT supplementation helps reduce bone loss in postmenopausal osteopenic women by suppressing inflammation and oxidative stress. Furthermore, the body incorporates TT which restructures biomembranes and modifies phospholipid metabolism, a response potentially linked to reduced inflammation and oxidative stress.

Keywords: clinical trial; dietary supplement; lipids; metabolites; metabolomics (OMICS); vitamin E.

Figure 1

Score plot of principle component analysis (PCA) of the Placebo and the High TT groups at 0 and 12 wk. Placebo at 0 wk (light orange), Placebo at 12 wk (dark orange), 600 mg TT at 0 wk (light blue), 600mg TT at 12 wk (dark blue). Principal component analysis (PCA) showed no differences in serum metabolites between the Placebo and the 600mg TT group, as demonstrated by the lack of separation between the Placebo and the 600mg TT group. Each ball represents the cumulative metabolites from each participant. The 20 light orange balls are from Placebo group at 0 wk, 20 orange balls are from Placebo group at 12 wk, 20 light blue balls are from 600mg TT group at 0 wk, and 20 dark blue balls are from 600mg TT group at 12 wk.

Figure 2

Tocotrienols and their metabolites in serum of the placebo and the 600mg TT groups at 0 and 12 wk. Values represent fold differences in serum tocotrienol and metabolites in placebo and 600mg TT treatment from serum analysis of subjects. Tocotrienols increased with supplementation and were higher compared to the placebo group (A–D).

Figure 3

Effect of tocotrienols supplementation on redox environment biochemical pathways. Proposed actions of tocotrienols on compounds associated with redox pathways based on serum analysis from subjects. Tocotrienols tended to result in lower levels of compounds where the downward arrows are shown.

Figure 4

Effect of tocotrienols supplementation on tyrosine and tryptophan metabolism. Proposed actions of tocotrienols on tyrosine and tryptophan metabolites based on serum analysis from subjects. Tocotrienols tended to result in lower levels of compounds where the downward arrows are shown.

Figure 5

Effect of tocotrienols supplementation on steroid hormone metabolism. Proposed actions of tocotrienols on cholesterol metabolites based on serum analysis from subjects. Tocotrienols tended to result in lower amounts of compounds where the downward arrows are shown.