Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients

Abstract

Purpose

Chronic hemodialysis patients experience accelerated atherosclerosis contributed to by dyslipidemia, inflammation, and an impaired antioxidant system. Vitamin E tocotrienols possess anti-inflammatory and antioxidant properties. However, the impact of dietary intervention with Vitamin E tocotrienols is unknown in this population.

Patients and methods

A randomized, double-blind, placebo-controlled, parallel trial was conducted in 81 patients undergoing chronic hemodialysis. Subjects were provided daily with capsules containing either vitamin E tocotrienol-rich fraction (TRF) (180 mg tocotrienols, 40 mg tocopherols) or placebo (0.48 mg tocotrienols, 0.88 mg tocopherols). Endpoints included measurements of inflammatory markers (C-reactive protein and interleukin 6), oxidative status (total antioxidant power and malondialdehyde), lipid profiles (plasma total cholesterol, triacylglycerols, and high-density lipoprotein cholesterol), as well as cholesteryl-ester transfer protein activity and apolipoprotein A1.

Results

TRF supplementation did not impact any nutritional, inflammatory, or oxidative status biomarkers over time when compared with the baseline within the group (one-way repeated measures analysis of variance) or when compared with the placebo group at a particular time point (independent t-test). However, the TRF supplemented group showed improvement in lipid profiles after 12 and 16 weeks of intervention when compared with placebo at the respective time points. Normalized plasma triacylglycerols (cf baseline) in the TRF group were reduced by 33 mg/dL (P=0.032) and 36 mg/dL (P=0.072) after 12 and 16 weeks of intervention but no significant improvement was seen in the placebo group. Similarly, normalized plasma high-density lipoprotein cholesterol was higher (P<0.05) in the TRF group as compared with placebo at both week 12 and week 16. The changes in the TRF group at week 12 and week 16 were associated with higher plasma apolipoprotein A1 concentration (P<0.02) and lower cholesteryl-ester transfer protein activity (P<0.001).

Conclusion

TRF supplementation improved lipid profiles in this study of maintenance hemodialysis patients. A multi-centered trial is warranted to confirm these observations.

Keyword:

• vitamin
• tocotrienol-rich fraction
• lipid profiles
• hemodialysis
• end-stage renal disease
• nutrition intervention

Supplementary materials

Table S1 Energy, macronutrient, and micronutrient intake during the course of the study

Figure S1 Percentage of capsule “consumption” in placebo (n=38) and TRF (n=40) group during the course of the study.

Notes: The figure shows percentage of capsule consumption (disappearance) for non-dialysis days, measured by pill counting method for 16 weeks of the study. Values are expressed as mean ± standard error of the mean. No significant differences for each week between the two groups were noted, as tested by independent t-test.

Abbreviation: TRF, tocotrienol-rich fraction.

Figure S2 Change in TAG levels among statin and non-statin users in placebo and TRF groups.

Notes: Changes in TAG and HDLC were calculated by deducting baseline values. Data are reported as mean ± standard error of the mean. a and b denote differing marginal differences (P<0.08), tested by independent t-test.

Abbreviations: HDLC, high-density lipoprotein cholesterol; TAG, triacylglycerol; TRF, tocotrienol-rich fraction.

Figure S3 Cumulative days of missed treatment in placebo (n=38) and TRF (n=40) groups.

Notes: This figure is for illustrative purposes only. Data are presented as absolute number of days of missed dialysis sessions during each month of study course. The total number of days missed was 122 versus 180 for the TRF and placebo groups, respectively.

Abbreviation: TRF, tocotrienol-rich fraction.

Acknowledgments

The authors thank Dr James Sondheimer, MD, for his critical review of the manuscript. The authors are also especially thankful to Rami Hanna, Rajeev Shahani, Eno Latifi, and Aisha Chaudri for technical assistance, and the Great Lake Dialysis Clinic nurses and laboratory technician, Charles Vaughn, for their help and cooperation. The authors thank Dr Kalyana Sundram, Deputy CEO of MPOC for input into TT dosages.

Author contributions

ZAMD was involved in the study’s design, data acquisition, analysis, interpretation, and preparation of the manuscript. BT contributed to study design, monitoring, and supervision during data acquisition and review of the manuscript. MS, RO, JA, and ST shared equal contribution in data collection, supervision of the subjects, and review of the manuscript. PK was instrumental in the study’s design, monitoring data acquisition and providing critical comments during manuscript preparation. All authors took part in drafting the article or revising it critically for important intellectual content.

Disclosure

The current work was supported in part by a grant from Malaysian Palm Oil Council. TRF and placebo capsules were formulated and donated by Carotino (Malaysia) Sdn. Bhd. ZAMD was supported by the Malaysian Ministry of Higher Education and Universiti Putra Malaysia. The authors declare no other conflicts of interest.