Bioavailability of tocotrienol in human studies
Tocotrienols exhibit a plethora of unique biological activities, including neuro-protection, radio-protection, anti-cancer, anti-inflammation and lipid-lowering. However, the plasma concentrations of tocotrienols were found to be lower compare to tocopherols. Fu et al. has published a review article: Bioavailability of tocotrienols: evidence in human studies in Nutrition & Metabolism.
The pharmacokinetics of tocotrienols has been studies using single dose of tocotrienol-rich fractions (TRF) derived from palm oil. Tocotrienols were mainly detected in the HDL cholesterol at 4 to 8 hours before clearance. The rapid clearance of tocotrienols from the plasma within 24 hours could be partly due to the low affinity of α-tocopherol transport protein for tocotrienols. Human clinical studies suggest that the plasma concentrations of tocotrienols can be increased by at least 2-fold in the fed state. The significant increase in tocotrienol bioavailability under fed state was probably attributed to the increase of TAG from meal followed by bile secretion. A dosing schedule of tocotrienols twice daily is sufficient for the plasma concentration to reach the steady state within 3 days. An acute dose of mixed tocotrienols ranging from 200 to 1011 mg were considered to be safe for human consumption with no adverse events.
The review article also discussed the therapeutic efficacy of tocotrienols based on three variables: dose, formulation and study population. The authors concluded that the outcome of clinical evaluations is not only affected by the bioavailability of tocotrienols, but also closely dependent on the study designs.
Vitamin E Supplementation is Beneficial in Mild to Moderate Alzheimer’s Disease
Alzheimer’s disease (AD) affects millions of people in the world with symptoms of deteriorating memory and loss of bodily functions. Currently there is no cure for this disease and researches focus on preventing the onset and slowing the progression of the disease.
A clinical study published in JAMA found that patients with mild to moderate Alzheimer’s disease benefited from high dose of Vitamin E supplementation with delayed disease progression over a study period of 5 years.
613 patients participated in the Trial of Vitamin E and Memantine in Alzheimer’s disease (TEAM-AD). The participants were randomized to receive either 200O IU/d α-tocopherol, 20 mg/d of memantine (NMDA antagonist), the combination, or placebo. The participants were assessed every 6 months for functional abilities to perform daily living activities such as dressing or bathing, cognitive function and dementia severity, memory, language and praxis functions in AD using a range of questionnaires and instruments. The time on which caregivers spend assisting AD patients in daily activities were also surveyed. Drug compliance was monitored by measuring the serum levels of α-tocopherol and memantine.
The patients receiving Vitamin E have a delay of 19% per year or approximately 6.2 months in the clinical progression compared to the control, followed by a reduction of 2 hour/d of caregiver time. Despite the high dose of α-tocopherol used in this study, the annual mortality rate in the group receiving α-tocopherol (7.3%) was not increased compared to those in the placebo group (9.4%).
Vitamin E has neuroprotective benefits which are largely attributed to its antioxidant properties. Palm tocotrienols alleviate oxidative stress by free radical scavenging as well as interacting with antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. Oxidative stress plays a major role in the development and progression of AD. A series of clinical studies by Mangialasche et al. have shown that high plasma levels of vitamin E tocotrienol are associated with reduced Alzheimer Disease risk. The plasma levels of vitamin E tocotrienols could be used as a biomarker for diagnosis of cognitive impairment when combined with MRI measures.
The study highlights Vitamin E’s potential in benefiting AD patients. Tocotrienol, being a more potent antioxidant, may confer neuroprotection similar to α-tocopherol.
Tocotrienol Supplementation Improves Lipid Profiles in Chronic Hemodialysis Patients
Scientists have found tocotrienol supplementation lower plasma triglyceride levels in patients undergoing chronic hemodialysis. The study was conducted by Professor Pramod Khosla’s group in Wayne State University. End-stage renal disease patients on chronic (at least 3 months prior to the study) dialysis treatment were recruited from a local dialysis clinic in Detroit. 81 Patients were randomized to receive either 180 mg tocotrienol rich fraction or placebo daily for 16 weeks. The patient compliance was measured by pill counting. After 12 weeks supplementation, the group receiving tocotrienol supplementation have decreased plasma triglyceride levels from 144 ± 91mg/dL to 113± 47 mg/dL (p <0.05). The triglyceride levels remained low (103± 45 mg/dL) at week 16. In the control group, the plasma triglyceride levels were unchanged. Triglycerides are produced from energy sources like carbohydrates. High plasma triglyceride levels (> 150 mg/dL) indicate increased risk of cardiovascular diseases. In end-stage renal disease patients, dyslipidemia is highly prevalent with elevated plasma triglyceride levels. This study indicated the lipid-regulation and potential cardio-protection effect of tocotrienol in these patients. The triglyceride-lowering effect of tocotrienol observed in this clinical study agrees with a previous publication by Davos Life Science, in which supplementation with 120 mg γδ-tocotrienol in 10 hypercholesterolemic subjects for 8 weeks led to a 28% reduction in plasma triglyceride levels. Both the tocotrienol supplementation group and the control group have decreased levels of total cholesterol, higher levels of high density lipoprotein cholesterol (HDLC) and decreased levels of low-density lipoprotein cholesterol (LDLC) at week 16. This could be due to the effect of the cholesterol-lowering drug statin of which 30-40% of the patients were taking concurrently. This study reinforced the cardiovascular benefits of palm-derived tocotrienols in lowering triglyceride levels in subjects with mild to moderate dyslipidemia. Reference: