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Healthco: 2014 HCS

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Red Palm Tocotrienols Tocomin Suprabio and the Healthy Aging Brain Structure

Tocotrienols, a class of vitamin E with an unsaturated side chain, have been gaining increasing attention of cardiologists, gastroenterologists, clinicians and nutritionists. Compared to tocopherols, tocotrienols are found in tissues in extremely low concentration, where they function as potent antioxidants. The main areas of interest have been their effect on cardiovascular and liver health. However, recently completed clinical research has drawn attention to the benefits of tocotrienols in neurological tissue, particularly, in the brain white matter.

Compared to grey matter which consists of neuron bodies and associated largely with higher cognition, white matter consists primarily of myelinated neuron extensions and coordinates communication between different regions of the brain. Myelin, an electrically isolating material, which is approximately 70 percent lipids and 30 percent protein, is synthesized by specialized cells located alongside the neuron extensions. Research in the white matter structure in general and the age-related loss of myelin in particular has been the focus of the neurological science for the last several decades.

So-called white matter lesions can be detected by magnetic resonance imaging (MRI) as areas of hyperintensity, and have been shown to correlate with the aging process in the brain.1 The underlying mechanism leading to the formation of the lesions is believed to be agerelated loss of myelin. These areas of hyperintenisity can be found on the brain MRI in healthy people without any symptoms of cognitive impairment sometimes as early as in their 30s. The number and the volume of white matter lesions steadily increase with age, and may eventually have an unwelcomed effect on cognitive well-being.

Because of previous findings regarding the protective effect of red palm tocotrienols on the white matter of the brain, an international group of scientists conducted the following clinical trial. The goal of the trial was to investigate whether long-term supplementation with tocotrienols would have effect on the white matter lesions in healthy volunteers without cognitive symptoms in whom the areas of hyperintensity (aka, white matter lesions) have been detected on the MRI. The study commenced in 2007, and the results have been published in Stroke, a peer-reviewed medical journal, in May of 2014.2 

The study adhered to the “gold standard” protocol in clinical research, and was randomized, double-blind and placebo-controlled. After screening 1,300 volunteers age 35 years or older, 177 eligible healthy volunteers were found to have white matter lesions, 121 agreed to participate, and 88 with the average age of 52 years have successfully completed a two-year study. There were 46 and 42 participants in the tocotrienol and placebo group, respectfully. Mixed tocotrienols (200 mg of twice a day for two years) were provided as highly bioavailable self-emulsified Tocomin Suprabio from red palm oil; and the placebo was in the form of matching capsules administered using the same regimen. No other dietary changes were implemented during the trial.

Another clear advantage of this trial was the utilization of fully automated software to compute the measurements of the white matter lesions on the brain MRI. Compared to the visual methods of generating lesion size, which is often subject to human error and observer’s bias, the automated method provided high confidence in the results.

After one year of supplementation the difference in white matter lesion volume was not statistically significant between the groups. However, after two years of supplementation, the white matter lesion volume was significantly larger in the placebo group than in the tocotrienolsupplemented group (Figure 1).

With the exception of five complaints of loose stool during the first week, tocotrienol supplementation was well tolerated and did not result in the withdrawal from the study. No significant difference was observed in the blood chemistry parameters between the groups.

This study is the first human clinical evidence to demonstrate that long-term supplementation with mixed tocotrienols can attenuate the development of agerelated white matter lesions in healthy adults without signs of cognitive impairment. The mechanism is complex, and includes antioxidant effect. Additionally, tocotrienols have been shown to support the normal ability of neurons to withstand the effect of an excitatory neurotransmitter, such as glutamate normally present in the brain.3 

The findings were both statistically significant (p<0.05) as well as clinically and nutritionally relevant to the science of the aging brain. It is worth emphasizing that the extent of the tocotrienol supplementation’s effect correlated with its duration (years rather than months), which is in line with the expectations for achieving detectable results using a nutrient-based intervention.

References: 

1 Longstreth WT, Jr., Manolio TA, Arnold A, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke. Aug 1996;27(8):1274-1282.

2 Gopalan Y, Shuaib IL, Magosso E, et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. May 2014;45(5):1422-1428.

3 Khanna S, Roy S, Ryu H, et al. Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. J Biol Chem. Oct 31 2003;278(44):43508-43515.