A lot of people don’t like the term “anti-aging”. Many see it as a negative. A resistance to, and denial of the very normal part of our life cycle.
The phrase doesn’t bother me personally but because the term may prejudice some readers, I will try to put this into context.
In the marketplace, anti-aging is about getting rid of those visible signs of living. Hey, who doesn’t want to look good? There’s nothing wrong with that, and well all partake to some degree.
In the field of biology, physiology, and health, anti-aging is viewed more along the lines of optimal cellular health, energy production and energy output. It’s about preserving those features as long as possible in the name of supporting optimal repair and maintenance of cell, tissue and organ structure and, in turn, function. All with the purpose of delaying chronic disease in a way that has a real impact.
Through THAT lens, nutrition’s impact on physiology is fascinating, and more excitingly, something that can be leveraged to your advantage. That’s where annatto and one of the darlings of anti-aging, tocotrienols, comes in.
What is annatto?
Chances are, you’ve never heard of the achiote tree (Bixa orellana) which is native to tropical regions from Mexico to Brazil. The seeds and pulp have been used for hundreds of years for a variety of purposes and are used heavily in Latin America as a dye, medicine, and as an ingredient in many foods.
As a condiment, cooking ingredient, annatto’s flavour can be described as earthy, musky, and slightly peppery. Annatto seeds are usually steeped in oil or ground to a powder prior to adding to recipes. However, annatto seeds also contain another ingredient that’s been studied for a while but largely unknown by the general public: tocotrienols.
What are tocotrienols?
You’ve heard of vitamin E but you may not know that vitamin E isn’t a single nutrient like vitamin C is. In fact, vitamin E refers to a family of eight similarly, not identically, structured molecules, or isomers (1).
There are four fat-soluble tocopherols: alpha, beta, gamma and delta, and four fat-soluble tocotrienols: alpha, beta, gamma and delta.
Vitamin “E” has been around as a supplement for decades. When it first hit the market, it was sold as alpha-tocopherol. Not only that, but supplemental alpha-tocopherol also came (and still does) in two forms: 1] “natural”, as it’s found in nature (denoted as “d-alpha-tocopherol) and 2] synthetic, derived from petroleum (denoted “dl-alpha-tocopherol) (2).
Early research in 1922 focused on a compound derived from wheat germ that was capable of preventing spontaneous abortions in rats (referred to as a “dietary fertility factor”). The compound was later called alpha-tocopherol from the Greek ‘tokos’ or “birth” and ‘pherein” or “to bear or carry”.
Because of this essential role, alpha-tocopherol got all the attention Just as vitamin K2 was overshadowed by vitamin K1 for the past 80 years, alpha-tocopherol has overshadowed the other members of the vitamin E family, not the least of which are the tocotrienols. Sadly, confusion and misinformation followed and today is the rule and not the exception.
Today, most health and nutrition professionals remain in the dark.
FUN FACT: most “vitamin E” studies only used alpha-tocopherol and most of those used the synthetic version. In the case of alpha-tocopherol, natural sourced IS NOT the same as synthetic versions derived from petroleum. The consensus is, that’s why early vitamin E studies were unimpressive or failed.
As stated above, tocotrienols make up one half of the vitamin E family. They aren’t commonly found in nature like their tocopherol siblings but when they are, they’re present in lower amounts.
Tocotrienols are found in palm, rice bran, barley, and wheat germ oils. Another popular source for tocotrienols is the achiote tree (Bixa orellana), also known as annatto. Using annatto extracts, supplements can be formulated to safely provide a number of tocotrienols that experts and research have shown to have beneficial effects on health.
Seeds of the annatto tree
Tocopherols vs tocotrienols
When it comes to optimal human health, preventing and correcting both functional and clinical nutrient deficiencies is crucial. Therefore, from a purely basic nutritional point of view, vitamin E as alpha-tocopherol has correctly been identified as an essential nutrient since it’s the form that can reverse a “vitamin E” deficiency.
However, leveraging nutrition for increased healthspan goes beyond just preventing clinical deficiencies. Preventing a deficiency is like just crossing the finish line; you will finish the race BUT it’s certainly not your personal best.
Although tocotrienols are structurally similar to tocopherols, each of the eight molecules has slightly different properties. Like a big family with several kids, each sibling has their own strengths and weaknesses. The same goes with tocotrienols, each one behaves differently, and the group of four offer different benefits (3).
It’s for this reason that referring to vitamin E as alpha-tocopherol and vice versa misses the mark.
Tocotrienols are definitely a less common form of vitamin E than tocopherols. That’s because there’s a lot more tocopherols in our diets and because most vitamin E supplements (I’m guessing over 90% of those on the market), consist exclusively of tocopherols.
FUN FACT: Gamma tocopherol is the predominant tocopherol in the American diet which is found abundantly in corn and soybean oil (4). This is different in Europe where alpha-tocopherol is more common because olive and sunflower oil is the cooking oils of choice.
The role of dietary tocopherols on health is well understood. This is certainly true for alpha-tocopherol where its role in supporting reproduction, as well as, protecting your cells from oxidation (rusting) is established. Sadly, gamma-tocopherol hasn’t shared the same fame. It’s not for a lack of information, there’s plenty of that to go around but rather a lack of understanding by both health and nutrition professionals (5, 6, 7, 8, 9, 10, 11, 12).
Because tocotrienols are not as abundant in the food supply, researchers are increasingly interested in how supplementing with tocotrienols might improve health.
Health benefits of tocotrienols
Experts believe that tocotrienols, such as annatto tocotrienols have many health benefits — some that are even more powerful than those found in the more common tocopherols. These include improved brain health and functionality, anticancer activity, improved skin health, lower degrees of inflammation and more (13, 14)
Loving your circulatory system (cardiovascular) isn’t just about the myopic focus on LDL cholesterol. There’s a lot more to the story but we never hear about it because of the singular, medication-focus (statins) on LDL cholesterol concentration.
How well the blood vessels of your heart expand and relax (endothelial function), and whether or not inflammation is present, are arguably more important where cardiovascular disease is considered than just “LDL” (15, 16, 17, 18, 19, 20). Not to mention LDL particle number (ApoB) and particle size [Lp(a)].
Overall though, evidence supports tocotrienols’ biological properties when it comes to cardiovascular disease protection (21). They do this in a couple of ways; by balancing several blood lipid concentrations (total cholesterol, LHDL, and LDL cholesterol, and triglycerides) and by lowering homocysteine.
As a driver of inflammation, blood homocysteine (Hcy) level is also an important risk factor for CVD (22, 23). One study found that tocotrienols lowered homocysteine better than folate, the usual Hcy-lowering nutrient (24). By lowering elevated Hcy levels, tocotrienols may help to reduce the risk for CVD via its inflammation-lowering properties.
Brain and neuro protection
To be alive means there’s inevitable collateral damage to bodily tissues. It’s simply the consequence of breathing oxygen, burning glucose (sugar) and fat for energy, a.k.a. “metabolism”. It all brings with it a certain amount of oxidation and inflammation.
All tissues are susceptible but the brain is especially so. It’s a real energy hog, using about 25% of your total energy requirements 24/7. Luckily, your body produces most of the antioxidant defenses it needs, provided it has all the building blocks (adequate vitamins, minerals, etc). Some of those antioxidant defenses, such as alpha & gamma-tocopherol vitamin E, vitamin C, beta and alpha-carotene, lycopene, and more, come from your diet.
The reality is, over the course of a lifetime, the normal wear and tear of normal brain activity contribute to cognitive decline. Because both tocopherols and tocotrienols offer antioxidant and anti-inflammatory protection within cell membranes including neurons (brain cells), vitamin “E” is of interest as far as cognitive health is concerned.
Blood levels of tocopherols and tocotrienols are associated with Alzheimer’s disease and cognitive impairment (28, 29). Those with higher levels of tocotrienols have about a 64% lower risk of developing Alzheimer’s disease.
Animal studies demonstrate amazing neuroprotection by tocotrienols helping to prevent oxidative-induced brain cell death and reduce DNA damage, as well as, improving various cognitive functions (30).
Alpha tocotrienols is regarded as the most potent neuroprotective form of natural vitamin E (31). It has been shown to prevent brain cell death caused by over-stimulation by the neurotransmitter glutamate (32, 33, 34, 35).
Tocotrienols have been shown to uniquely benefit the heart via many cardio-protective mechanisms (36):
- Reduces pro-inflammatory proteins (cytokines)
- Helps to reduce the risk for, and progression of atherosclerosis, a disorder of inflammation
- Reduces blood levels of a potent marker, and driver of, inflammation: CRP (C-reactive protein)
- Helps to reduce blood sugar-related damage (Advanced Glycation End-products or AGEs) to blood vessels, tissues, blood cells and lipoproteins (LDL, HDL cholesterol)
- Turns down the production of adhesion molecules, compounds that cause blood cells such as platelets and white blood cells to stick to blood vessel walls which can lead to a blockage
Tocotrienols, especially the delta-tocotrienol form, have been shown to have greater anti-proliferative (growth preventing) and pro-apoptotic (causes cells to self destruct) than tocopherols in malignant cancer cell lines (37). Anything, nutrient, phytochemical, or drug, that can prevent cancer cell growth and/or cause those cancer cells to “commit suicide”, greatly reduces the risk of cancer cells to take hold in your body.
Studies on vitamin E and cancer produced mixed results for years. It’s now understood that the likely explanation was the huge variability in the type of vitamin E used (natural versus synthetic alpha tocopherol), huge differences in dosages and whether or not the supplement had some, or all eight of the now recognized different vitamin E isomers (38).
In a mouse study of pancreatic cancer, tocotrienols were found to dramatically extend the life of the mice supplemented with tocotrienols. Comparing survival rates after 16 weeks of treatment, only 10% of the mice that got the placebo were alive. Thirty percent of the mice that were treated with the chemo drug gemcitabine were still alive after 16 weeks whereas 70% of the tocotrienol treated mice were still alive. Combining gemcitabine AND tocotrienols resulted in a remarkable 90% survival rate (41).
Oxidation (think rusting) is a risk factor for cancer. Damaged cells, DNA, proteins, etc can lead to mutations resulting in an accumulation of damage. What’s unique about tocotrienols as far as cancer is concerned is that there really are a multi-targeting nutrient. They really kick cancer, or early stages of it, where it counts. They exert protective effects against all steps in the progression of cancer (42).
Possible anti-cancer mechanisms of tocotrienols
Apoptosis (cell self-destruction)
Cell cycle arrest
Slows tumour growth
Anti-angiogenesis (inhibits new blood vessel growth)
Deprives tumour of nutrients and oxygen
Inhibits HMG-CoA reductase enzyme
Inhibits metastasis (spreading)
“Turns off” cancer-causing genes
Prevents the initiation of cancer
“Turns on” cancer-fighting genes
Prevents the initiation and progression of cancer
One of the more exciting mechanisms (at least to me) is that of apoptosis. Every person on the planet has loads of pre-cancerous and cancerous cells in their body at any given time. The good news is, your body has many defenses to prevent them from growing to the point where they cause disease. One such mechanism is apoptosis.
Tocotrienols help to trigger apoptosis, a.k.a. “programmed (cancer) cell death”. This prevents a tumor from ever getting a toe-hold in your body (43, 44). Apoptosis is also vital in shrinking existing tumors, a factor that will influence more research looking into the concurrent use of tocotrienols, alone or with conventional chemotherapy drugs (45, 46).
Chronic, unchecked inflammation is incompatible to health. Many medical conditions like cardiovascular disease and cancer share a common pathway in chronic inflammation. Most aspects of degenerative, chronic disease, so-called diseases of aging are, in part, due to increased inflammation. But, these diseases and conditions, in turn, drive more inflammation.
The problem is due to a constant ‘upregulation’ of inflammatory signals. Any time there’s inflammation, your immune system is involved. Anything that causes inflammation via cell or tissue damage (alcohol, drugs, several medications, infections, toxins, stress, high intakes of sugar, etc) constantly tells the immune system to send in cells to find the trauma – over time, this leads to tissue abnormalities.
Anything that can temper, quell, mitigate, or reduce chronic, unchecked inflammation is a good thing and tocotrienols have been shown to help (47).
Bone health and fractures
Tocotrienols are emerging as major contributors to better bone health. They help promote greater bone density while preventing bone loss.
- Tocotrienols can prevent, and reverse bone loss while promoting fracture healing in models of osteoporosis and steroid treatment (48, 49, 50).
- They reduce oxidative-induced inflammatory bone loss (51, 52, 53), while turning on genes that promote bone formation and turning off genes that lead to bone destruction (54).
- Helps to reduce postmenopausal osteoporosis bone turn over (55)
Like your brain, your liver is very metabolically active. The best liver health diet can go a long way to protecting your liver for a lifetime. In addition to reducing the risk for liver cancer (56), tocotrienols may just be the thing you’re looking for to treat non-alcoholic fatty liver disease (NAFLD) (57).
In a randomized trial of 87 adults with NAFLD, those that received 200 mg or mixed tocotrienols for one year, had a significantly greater rate of normalization of liver status (58).
But that’s not all, another study compared tocotrienols to alpha-tocopherol to assess the impact of tocotrienols on delaying the progression of end-stage liver disease. Over 50% of of patients getting the tocotrienols saw benefit compared to just 20% of those receiving alpha-tocopherol (59).
Metabolic syndrome & diabetes
Elevated blood insulin and blood sugar ages you. Long before the official diagnosis of diabetes, dysregulation in the insulin and blood sugar control that leads to diabetes, accelerates aging. Over 80% of diabetics will die of a heart attack or stroke because as a result of this metabolic derangement.
Anything that can help to offset the damage of chronic elevated blood sugar and insulin levels is welcomed news. Tocotrienols have been shown to
- Improve blood sugar and kidney function in animal models (60).
- Lower blood sugar and balance blood lipids which lead to sclerosis (blockage) of the vessels in the kidneys. Prevents the deposits of damaged proteins in the kidney (which leads to decrease kidney function) (61).
- Improve insulin sensitivity (helps insulin work better) (62).
- Prevent glycation [added of sugar molecules] of the proteins and fats that make up your various cells and tissues (63).
- May improve the impact/experience of neuropathy, or metabolic/diabetes-associated nerve damage (64).
Like many fat-soluble compounds such as lycopene, beta-carotene, or omega-3 fats, tocotrienols accumulate in the layers of the skin. Given their antioxidant and anti-inflammatory properties, they’ve been investigated for skin health.
Compared to tocopherols, about 15% of the fat-soluble antioxidants found in the skin are tocotrienols compared to 1% for tocopherols (65)
A Japanese study using a low 2 mg dose of a potent antioxidant called astaxanthin along with 40 mg of tocotrienols for 4 weeks found improved skin elasticity, reduced wrinkles, and reduced swelling under the eyes (66).
Tocotrienols exhibited stronger protection to the skin against UVB induced damage in these studies, as compared to alpha-tocopherol. This could probably be explained by the fact that dietary tocotrienols were selectively taken up into the skin but not alpha tocopherol (67).
Are tocotrienols safe?
Tocotrienol safety has been examined using standard toxicological and pharmacological studies. Using rat models, doses up to 2500 mg/kg of body weight per day didn’t cause any adverse effects (68). To put that into perspective, I weight 72 kg (160 pounds), this would be the equivalent of 180,000 mg or 180 grams per day.
Safety studies on humans have found them to be safe even at extremely high doses (69). In another study, Japanese researchers show that the No-Observed- Adverse-Effect Level (NOAEL) for tocotrienols is 120 mg/kg body weight/day for male rats whereas female rats are 130 mg /kg body weight/day (70).
Studies have not uncovered any consistent, serious side effects associated with the use of tocotrienols.
How much tocotrienols should you take?
It depends on the goals; maintaining general good health or to support a chronic disease. Studies that found beneficial effects of tocotrienols used the following amounts:
- 100-200 mg per day for general health promotion
- Mild chronic condition 300-450 mg per day
- Advanced chronic condition 450-600 mg per day
However, because tocotrienols do have anticoagulant properties, there’s a theoretical risk of interactions with blood-thinning medications or if you have a blood clotting disorder. Speak with your doctor first if you’re thinking of supplementing.
Vitamin E is a family of eight similar, yet differently structured molecules. “Vitamin E” is not just alpha-tocopherol.
Within this family, tocotrienols have long been overlooked for their role in human health. Because you can survive without them, tocotrienols are not technically essential nutrients but that doesn’t mean they can’t offer health-promoting benefits.
If fact, research has shown just the opposite. Tocotrienols influence gene activities, support various enzymes involved in human metabolism and help to quash the inflammation, glycation, and other processes that contribute to age-related diseases.
Tocotrienols are increasingly being recognized for their potential roles in protecting against cancer, heart disease, stroke, diabetes, liver disease, neurodegenerative diseases, and even osteoporosis.
As one of the best sources of tocotrienols, annatto has become a go-to source for these potent allies of anti-aging. Including tocotrienols as part of your “longevity” supplement protocol may be worth considering.