Background/Objectives: Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems. The objective of this study was to assess the effects of tocotrienol-rich fraction (TRF) supplementation on immune response following tetanus toxoid (TT) vaccine challenge in healthy female volunteers. Subjects/Methods: In this double-blinded, placebo-controlled clinical trial, participants were randomly assigned to receive either placebo (control group) or 400 mg of TRF (study group) supplementation daily. Over the 2-month period of the study, volunteers were asked to attend three clinical sessions (that is, on days 0, 28 and 56) and blood samples were obtained from the volunteers during the follow-up. On day 28, all volunteers were also vaccinated with the TT vaccine (20 Lf) intramuscularly. Results: The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group, indicating overall compliance. Volunteers supplemented with TRF showed a significantly (Po0.05) enhanced production of interferon-g and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group. Volunteers from the TRF group produced significantly (Po0.05) lower amounts of IL-6 compared with the placebo group. Anti-TT IgG production was also significantly (Po0.05) augmented in the TRF-supplemented group compared with the placebo group. Conclusions: We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines.

This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P < 0.05) in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P < 0.05) higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response.

Palm oil is a rich source of vitamin E. The tocotrienol-rich fraction (TRF) extracted from palm oil contain 70% tocotrienols and 30% tocopherols. The effect of TRF supplementation on the immune modulation was evaluated in 6-wk-old female BALB/c mice immunized with ovalbumin (OVA) adjuvanted with alum. Mice in control and experimental groups were immunized subcutaneously (s.c.) on days 14 and 28 with a single dose of 50 mg OVA. The mice in the experimental group were orally gavaged daily with 1 mg of TRF from palm oil while those in the control group received carrier oil. The results show that mice in the experimental group produced significantly ( p<0.05) higher levels of interferon-gamma (IFN-g) compared to the control group. There was no significant ( p>0.05) difference in the levels of interleukin-4 (IL-4) produced between the control and experimental animals. Lymphocyte proliferation in response to mitogen or OVA stimulation was significantly ( p<0.05) higher in splenocytes derived from the TRF supplemented mice compared to control mice. These findings show that daily supplementation of palm TRF can induce a strong cell-mediated immune response, i.e., T-helper-1 (Th1) response, which would be beneficial to fight viral infections and cancer.