Tocotrienols: A new generation of vitamin E for brain, heart and liver health

During Elizabethan times, it was believed the three main organs of the body were the brain, the heart and the liver. Shakespeare so famously romanticized these organs in "Twelfth Night" as the residences of judgment (brain), sentiments (heart) and passion (liver):

Duke Orsino: when liver, brain and heart, / These sovereign thrones, are all supplied, and fill'd / Her sweet perfections with one self king!"

Twelfth Night, Act 1 Scene 1, line 41-43

Today, we know the brain, heart and liver are not the only main organs of the human body, but their normal functions are certainly critical for the overall well-being of the body, and interestingly, tied intricately to the presence of a particular shared molecule classthe tocotrienols.

Tocotrienols are hitherto the lesser-known members of the vitamin E family. Unlike the better-known tocopherols (in particular, alpha-tocopherol), tocotrienols are distinguished by having an unsaturated side chain with three double bonds in their isoprenoid tail, a feature which confers them with far superior properties. So notable are these qualities that it has led to American celebrity doctor Mehmet Oz (better known as Dr. Oz), proclaiming that red palm oil, which is naturally rich in tocotrienols, as perhaps the "most miraculous find of 2013."

Indeed, with an increasing volume of revolutionary findings unfolding each day in the scientific field of tocotrienols, this class of molecules (consisting of alpha-, beta-, gamma- and delta-tocotrienols) is poised to take center stage as the vitamin of the next decade.

Superior antioxidant

Within a biological context, tocotrienols are better antioxidants than tocopherols. One particular study described alpha-tocotrienol having up to 40 to 60 times the potency compared to alpha-tocopherol.¹

The magic lies in the structural difference of tocotrienols molecular side-chains. While both tocotrienols and tocopherols possesses the same chromanol head group that confers antioxidant attributes, it is the unsaturated side chain of tocotrienols that enables their enhanced performance over tocopherols (tocopherols have saturated side chains). Unsaturated double bonds cause the tocotrienol molecule to pucker," and this contracted structure in turn facilitates a few advantages, including a higher mobility and a more uniform distribution within cell membranes, as well as a higher regeneration efficiency (from the exhausted form" back into the active form").

But tocotrienols are not merely superior antioxidants."

Currently, the three major areas being studied actively in connection with tocotrienols are brain health, heart health and liver health. Supplementation with tocotrienols is suggested to confer significant benefits to this trio of organs.

Brain health

According to the World Health Organization (WHO), stroke results in the fourth highest burden of disease worldwide. Moreover, the risk of suffering from a stroke doubles for every decade after the age of 55.

In both rodent² as well as canine studies,³ consumption of tocotrienols significantly reduced lesion and brain cell death during a stroke event. Similarly, a randomized, double-blind study conducted by researchers from Universiti Sains Malaysia  showed the molecule helped mitigate the increase of white matter lesions in humans. Researcher Yuen Kah Hay, Ph.D., presented this study at the Palm International Nutra-Cosmeceutical Conference 2013.

How is this achieved? When stroke occurs, the brain releases a substance called glutamate, and glutamate-induced toxicity is what causes the subsequent neuronal death and degeneration. Tocotrienols help circumvent glutamate-induced toxicity via a few mechanisms:

Given that glutamate-induced toxicity is also implicated in conditions such as brain traumas, Huntington's disease and Alzheimer's disease (AD), tocotrienols are suggested to be beneficial under these circumstances, too. Incidentally, a recent study of 250 human subjects by Karolinska Institute of Sweden reported subjects with AD or mild cognitive impairment were found to have lower blood tocopherol and tocotrienol levels.⁸

Heart health

Every year, more than half a million in the United States die of cardiovascular disease (CVD). The disease remains the number one killer for adults, accounting for one in every four deaths.

Conditions are commonly caused by an underlying predicament known as atherosclerosis, a process marked by a build-up of cholesterol in the inner lining of the arteries. This consequently narrows and obstructs the bloods passageway, causing angina, heart attack or even heart failure.

Supplementation with tocotrienols has been shown to reduce atherosclerotic lesions in animals genetically programmed to develop atherosclerosis. In one particular study, rabbits fed a high-cholesterol diet displayed regression of atherosclerotic conditions.⁹ The nutrient appears to be effective in supporting not only prevention, but also the treatment of these conditions, and they work by targeting more than one stage of disease progression.

Cholesterol production in the body typically involves an enzyme called HMG-CoA reductase. The enzyme helps make mevalonatea compound that is converted by the body to cholesterol. Tocotrienols can potentially lower cholesterol levels by reducing the amount of HMG-CoA reductase within cells.¹⁰

Moreover, during atherosclerosis, oxidized low-density lipoprotein (LDL) cholesterol within the blood is first engulfed by immune cells called monocytes. These cells subsequently lodge themselves to endothelial cells lining the blood vessel walls. The process is highly dependent on adhesive molecules" on the surface of endothelial cells and tocotrienols have been shown to hamper the production of these sticky" molecules.

Liver health

Fatty liver disease commonly occurs when excessive fat is deposited within liver cells. While the condition may not be harmful in general, damage typically occurs when fat accumulation exceeds 5 to 10% of the liver weight. When this happens, liver cells are destroyed by oxidative and inflammatory processes, concomitant with the formation of scar fibers (causing liver fibrosis or cirrhosis).

In animals with fatty liver and liver fibrosis, consumption of tocotrienols suppressed both the accumulation of fatty triglycerides in the liver, as well as the resulting liver damage.¹¹

Given that detrimental liver conditions typically involve damaging components, which are fundamentally oxidative and inflammatory in nature, it is not difficult to understand why tocotrienols are beneficial. Apart from being potent antioxidants, tocotrienols also display anti-inflammatory characteristics. Complex as they are, inflammatory processes almost invariably involve a pathway called the NF-B pathway, and tocotrienols have been shown to suppress this exact pathway via diverse mechanisms.¹²

In a separate study conducted by the Ohio State University on humans with end stage liver disease (which is the progressive destruction of the liver due to various conditions, including fatty liver disease and viral infections), tocotrienols supplementation improved the MELD (Model for End-stage Liver Disease) scores in half of all subjectsa strong indicator to assess the severity of the disease, and is seen as a reliable marker for mortality.¹³

In the pursuit of better judgment (brain), sentiments (heart) and passion (liver)

In light of these wide-ranging benefits, the perception of tocotrienols being just an alternate form of vitamin E" is beginning to change. Tocotrienols are a single class of molecules that provide the anchoring foundation to the well-being of arguably three of the most important yet highly vulnerable organs in the human body. Perhaps Shakespeare was referring to tocotrienols when he mentions of the one self king" that has filled" and supplied" the three sovereign thrones."

T.C. Long is co-founder and managing director of The Vance Group, a oleochemicals and nutraceuticals company in Asia. Vance Nutraceuticals is the nutraceuctical division of The Vance Group, and manufactures FSSC 22000 certified palm-based tocotrienols.

Isaac Loh is the business analyst of The Vance Group. Loh obtained his bachelor's of art degree in biochemistry and molecular biology at Fitzwilliam College, University of Cambridge, England.