Taming Oxidative Stress with Tocotrienols

The Mighty Mitochondria is Always Under Attack

Increased oxidative stress is a risk factor for developing chronic diseases. Although normal metabolic processes of the body can contribute to certain amounts of free radicals, the body may be exposed to an excess production of free radicals caused by ongoing exposure to pollutants, toxins, and other stressful factors. High levels of free radicals in the body can damage cells and break down their membranes, resulting in what we know as ageing.

The free radical theory of ageing proposed in the 1950s, reflects on the role of mitochondria in the generation of harmful reactive oxygen and reactive nitrogen species. (ROS/RNS) The ageing process is known to accelerate the overproduction of these volatile species, leading to an increased oxidative burden that needs to be cleared by the body. The longer the ROS/RNS species recirculate inside the body without being cleared, the higher the likelihood of resulting damage/harm to the body. Thus, the ageing process continues.

This deterioration in mitochondrial energetics and function which results in mitochondrial dysfunction is gaining recognition as a major determinant of age-related CVD. From a cardiovascular health perspective, ageing can be viewed as a combination of deteriorating cardiovascular protection mechanisms alongside an increase in disease processes that increase the risk of heart failure. Even in healthy ageing, there is a higher risk of oxidative stress build-up within the mitochondria, which eventually creates a vicious cycle that further damages mitochondria and increases free radicals. This is where tocotrienols’ potent antioxidant capacity is so valuable.

Tocotrienols are Potent Protectors

Tocotrienols are a type of vitamin E that offer a range of health benefits - cell membrane protection, cardiovascular support and even longevity. Tocotrienols are a potent antioxidant and anti-inflammatory component to help improve cell membrane health and heart health. Research has found tocotrienols to have significant health benefits due to their ability to reduce inflammation, protect against oxidative stress and DNA damage, as well as their antioxidant properties. Tocotrienols have been shown to improve heart health, reduce incidence of chronic diseases and boost brain function.

Tocotrienols are found in small amounts in many different foods, (rice bran oil, palm oil, wheat germ, almonds, hazelnuts) but can also be taken as a supplement. While tocotrienols are found in small amounts in variety of foods, annatto seeds are a particularly rich source of the ingredient. Individuals can incorporate annatto seed oil or tocotrienol supplements into their diet to increase their intake of the nutrient.

Annatto is Enough

Annatto seed, also known as achiote, is a natural source of tocotrienols that comes from the nutrition-rich bean pods of the achiote tree‚ a majestic tree (Bixa orellana) which is native to tropical regions of South America. The annatto seed is commonly used as a food coloring and flavoring agent. However, it is also, the richest plant source of tocotrienols, especially delta-tocotrienol, the most potent form of vitamin E.

Studies published on tocotrienols reveal that its strongest attributes are its ability to protect cell membrane health as well as support the healthy function of the cardiovascular system. Annatto seed tocotrienols have also demonstrated significant antioxidant properties that can help to protect cells from damage caused by free radicals. Preliminary clinical studies indicate that annatto tocotrienols may have a protective effect on the brain, helping to reduce the risk of neurological disorders such as Alzheimer's disease. The antioxidant capacity of tocotrienols is also being investigated to protect the cells from environmental stressors such as air pollution or UV radiation.

Studies have found that annatto seed tocotrienols can have a beneficial effect on heart health by reducing cholesterol levels, improving blood flow, promoting healthy CoQ10 levels in the blood, and reducing oxidative stress. Annatto seed tocotrienols may help to lower cholesterol levels and reduce the risk of heart disease.

Tocotrienols, Not Tocopherols, For Superior Protection

The vitamin E family includes tocopherols and tocotrienols with each of the two groups consisting of 4 different isomers (alpha-, beta-, gamma-, delta-). Discovered in 1922, vitamin E has traditionally been associated with only the tocopherols. Tocopherols are found in most vegetables, seeds, nuts, whole grains. Tocotrienols were not discovered until 1986, isolated from palm oil, when it was reported that tocotrienols have 40-60 times more antioxidant capacity than tocopherols and possessed potent inflammation relief. A property that tocopherols offer weakly, if at all, compared to tocotrienols.

Despite vitamin E traditionally being associated with tocopherols, the vitamin E family includes both tocopherols and tocotrienols, it is the delta fraction, called delta tocotrienol, that possesses the most significant properties for cardiovascular and circulatory health.

In fact, evidence suggests that delta tocotrienol has been found to inhibit the production of various pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Compared to tocopherols, tocotrienols are 20-50% more effective at lowering levels of inflammation producing C-reactive protein and improving elasticity of stiff blood vessels.

In addition to its anti-inflammatory effects, delta-tocotrienol also helps to protect cell membrane health by decreasing LDL cholesterol levels and increasing HDL cholesterol levels. Research indicates that tocotrienols may reduce LDL cholesterol and triglyceride levels by up to 28%, significantly lowering heart disease risk.

Unlike tocopherols, delta-tocotrienols have an outstanding potential to provide support for healthy total cholesterol levels as well as LDL cholesterol levels already within the normal range. They also promote regulation of healthy metabolic functioning‚ and support the inner lining of blood vessels which are comprised of endothelial cells. Research also shows that tocotrienols promote healthy levels of coenzyme Q10 in the blood.

Paradoxically, tocopherols, the more widely available form of vitamin E, antagonizes the ability of tocotrienols to suppress HMG-CoA reductase, the primary enzyme involved in cholesterol synthesis. Research suggests that an antagonistic effect occurs when tocopherol is added with tocotrienols which weakens tocotrienols’ ability to impede cholesterol production.

Tocotrienols Tame Oxidative stress

The fire of all chronic illness begins with the spark of inflammation, and it is fueled by vulnerable, undernourished cell membranes. We are only as healthy as our cell membranes, the building blocks of tissues, organs, and body systems. In terms of modulating inflammation, studies have shown that tocotrienols can help reduce the production of certain cytokines and enzymes that are involved in the inflammatory response. The ability for tocotrienols to reduce levels of oxidative stress is significant and can help protect the body from oxidative stress and cellular damage, contributes to ageing and increases the risk of developing chronic diseases.

When oxidative damage can be tamed, the body’s response to inflammation will be less intense. Studies have shown that tocotrienols can help to reduce the production of certain cytokines and enzymes that are involved in the inflammatory response. Due to its strong antioxidant activity, studies reveal that tocotrienols are neuroprotective against stroke and can reduce oxidative stress in the beta-cells of the pancreas, which increases insulin sensitivity levels. Delta-tocotrienol is regarded as the vitamin E vitamer with the most protective cell membrane effects where lipid peroxidation is concerned.

Tocotrienols Heart Health Benefits

Tocotrienols, a form of vitamin E, have been shown to have potential health benefits for heart health and cell membrane protection by reducing both oxidative stress and inflammation. Tocotrienols were first discovered to lower the synthesis of cholesterol. Although the cholesterol drop with tocotrienols is not as dramatic as with statin drugs—approximately 15 to 20% versus 30 to 40%— supplementation of the vitamin does not cause the side effects commonly experienced with statins. (Tan)

Statins mimic the structure of HMG-CoA and acts as a competitive inhibitor for the HMG-CoA reductase. While statins are considered the standard treatment for high cholesterol they deliver undesirable side effects at higher doses, such as abnormal liver function tests, nerve dysfunction and muscle disease, increasing the risk posed to elderly patients.

Research Studies Supporting the Heart-Healthy Benefits of Tocotrienols:

There have been several research studies exploring the potential benefits of tocotrienols for cardiovascular health. These studies have produced promising results. Some of the potential benefits of tocotrienols for cardiovascular health include:

  1. Supports heart health by providing antioxidant and anti-inflammatory benefits. Tocotrienols have been shown to have strong antioxidant properties, which can help protect the body from oxidative stress and cellular damage.
  2. Helps maintain healthy cholesterol levels. High levels of cholesterol in the blood can increase the risk of cardiovascular disease. Tocotrienols have been shown to have cholesterol-lowering effects, which may help support cardiovascular health. Tocotrienols can reduce high cholesterol levels by inhibiting HMG-CoA reductase, a rate-limiting enzyme that is involved in cholesterol synthesis.
  3. Supports healthy blood pressure levels. High blood pressure is a major risk factor for cardiovascular disease. Tocotrienols have been shown to have blood pressure-lowering effects, which may help support cardiovascular health.

Research has also shown that tocotrienols can help reduce the risk of heart disease by lowering triglycerides and improving vascular reactivity. Studies have demonstrated that tocotrienols can prevent low density lipoprotein oxidation which is one of the main causes of cardiovascular disease. Additionally, dietary supplementing with tocotrienols has been linked with improved blood flow, reduced platelet aggregation, enhanced antioxidant effects, increased HDL levels, decreased LDL levels and improved lipid profiles overall.

Dietary tocotrienols appear to have a preventative role in the development of atherosclerosis in both animals and humans. Alpha-tocotrienol is 40 times more effective than alpha-tocopherol in reducing oxidative stress and damage. However, Additionally, tocotrienols appear to modulate the expression of the PPAR family of nuclear receptors, which are associated with higher risk of atherosclerosis/CVD.

Regardless of isomer or vitamer type, low serum vitamin E is an independent predictor of atrial fibrillation. Given what we know about the potent antioxidant activity, compared to vitamin C and tocopherols, tocotrienols could potentially further reduce the risk of post-operative atrial fibrillation.

Tocotrienol Takeaways

Tocotrienols are the most bioactive form of vitamin E. There is evidence that tocotrienols are better suited to more easily diffuse through the phospholipid bilayer of the cell membrane because of their unsaturated isoprenoid tail compared to the phytyl tail of tocopherol.

In terms of heart health, tocotrienols have been found to reduce cholesterol levels, improve blood flow, and reduce oxidative stress, which are all factors that can contribute to heart disease. Additionally, tocotrienols have been shown to have a protective effect on the heart by reducing oxidative damage to the heart and blood vessels and toning down inflammatory responses.

Based on current evidence, tocotrienols are a safe and potential option to improve heart health, especially for the elderly, who can be more susceptible to the adverse effects of more aggressive pharmaceutical interventions. Clinical research on annatto seed and tocotrienols has shown promising results for various health benefits, and so far, the supplement form of tocotrienols derived from annatto seeds has been found to be safe for most people. Clinical trials studying the effects of tocotrienols have used doses of 50-400 mg/day for periods of 2 weeks to 18 months have not been associated with any adverse effects, even in the elderly.

Research indicates that daily intake of annatto seed extract provides numerous long-term benefits due the abundance of beneficial antioxidants like delta-tocotrienol. There are multiple potential benefits related to consuming annatto seed extract including but not limited to promoting a healthy response to inflammation, protection against oxidative stress and DNA damage, prevention of LDL oxidation leading towards improved heart health outcomes; enhancement in cognitive performance; improvement in lipid profiles leading towards overall better cardiovascular health, as well as other potential long-term benefits yet unknown. Although further human trials are needed before any definitive conclusions can be drawn regarding the anti-inflammatory properties of tocotrienols specifically, no adverse effects have been reported. Anyone interested in improving their health should consider adding annatto-based tocotrienols to their wellness regimen.

 

References

  1. Ramanthan N. 2018 - Tocotrienol is a cardioprotective agent against ageing-associated cardiovascular disease & its associated morbidities.
  2. Khor BH,2020. MASR - Effects of tocotrienol supplementation on inflammation & oxidative stress markers.
  3. Annatto seed monograph. Alt Med Review.
  4. Srineeraja P, - Review - Pharmacological Properties of Bixa Orellana.
  5. Tan B, 2019. Using Tocotrienols to Address Lifestyle & Metabolic Disease