The vitamin E family consists of two subgroups: tocopherols and tocotrienols. These two subgroups can be broken down further into their corresponding isomers (alpha, beta, gamma, and delta), totaling eight vitamin E isomers. Research suggests that vitamin E tocotrienols exert clinically relevant benefits in cardiometabolic health. The annatto plant is the richest known source of naturally occurring tocotrienol-rich, tocopherol-free vitamin E isomers. 

Typical commercial vitamin E supplements are low or absent in tocotrienols and, instead, are high in alpha-tocopherol. Interestingly, human studies reveal that if simultaneously administered, alpha-tocopherol may attenuate the bioavailability of tocotrienols and may interfere with the potential clinical benefits of tocotrienols. When supplemented without the presence of tocopherol isomers, vitamin E tocotrienols may promote cardiometabolic health in numerous ways. 

Healthy Lipid Metabolism 

The unique chemical structure of tocotrienols has been shown to support healthy lipid metabolism and synthesis. A meta-analysis of 15 clinical trials highlighted that the individuals who received tocotrienol supplementation (≥ 200 mg/day) exhibited increased high-density lipoprotein (HDL) cholesterol status compared to a placebo.Individuals with high cholesterol (n = 31) receiving tocotrienol supplementation displayed decreased total cholesterol by 15%, low-density lipoprotein (LDL) cholesterol by 18%, and triglycerides by 14%. Furthermore, cytokines associated with cardiovascular disease and their gene expression, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, and IL-8, were downregulated by 39% to 64%. Patients with type 2 diabetes (n = 19) who received 3 mg of tocotrienol-rich fraction per kg of body weight exhibited decreased serum total lipids by 23%, total cholesterol by 30%, and LDL-cholesterol by 42% (from 179 mg/dL to 104 mg/dL) within 60 days of supplementation.

Supporting Healthy Inflammatory Responses 

Vitamin E tocotrienols help to promote healthy inflammatory responses, which may help support cardiovascular health and age-related diseases. In individuals (n = 31) receiving 250 mg/day of tocotrienol supplementation, notable serum inflammatory markers were reduced: C-reactive protein (CRP), nitric oxide (NO), and malondialdehyde (MDA) were decreased by 40%, 40%, and 34%, respectively. Total antioxidant status, on the other hand, increased by 22%. It is important to note that normal NO status is necessary for cardiovascular health and blood pressure regulation. However, an overproduction of NO is associated with unregulated inflammatory responses. Systematic reviews of randomized controlled trials (RCTs) have further supported the role of tocotrienols in promoting healthy inflammatory responses, such as modulating the nuclear factor kappa β signaling pathway. 

Helping Maintain Endothelial Health

Nearly half of American adults have hypertension (48.1%), and only 1 in 4 adults have their hypertension under control (22.5%). Hypertension is associated with endothelial injury that can worsen the atherosclerotic process – a major risk factor for cardiovascular disease. In human studies, tocotrienols have demonstrated the ability to support endothelial health. In vitro and animal studies have shown that tocotrienols may help maintain healthy blood pressure, potentially mitigate atherosclerotic lesions, and help attenuate the effects of endothelial inflammation. Specifically, gamma-tocotrienol has been shown in animal models to significantly reduce systolic blood pressure and improve endothelial NO synthase activity, both of which are key in supporting normal blood flow and circulation. However, more human clinical studies are needed before definitive conclusions can be drawn.  

Promoting Metabolic Health 

Clinical studies have demonstrated the potential benefits of tocotrienol supplementation on individuals with metabolic syndrome (MetS). Combining tocotrienols with other nutrients that promote healthy inflammatory responses, such as quercetin, resveratrol, and B vitamins, may synergistically affect metabolic health, as observed in clinical trials.In a 24-week RCT with 82 patients with MetS, groups consuming 500 mg/day of delta-tocotrienols and 300 mg/day of resveratrol for 24 weeks exhibited a significant reduction in waist circumference, blood pressure, mean fasting plasma glucose, and serum triglyceride and an increase in HDL cholesterol. A decrease in high sensitivity-CRP, IL-6, TNF-α, and MDA, as well as an increase in total antioxidant capacity, was also observed compared to the placebo group.

Promoting Healthy Glucose Metabolism 

One hundred and ten patients with T2DM on a hypoglycemic agent were randomly divided to consume 250 mg/day of tocotrienols or a placebo for 24 weeks. Compared to the placebo, the experimental group exhibited improved glycemic control, reduced inflammation (analyzed through high sensitivity-CRP, TNF-α, and IL-6), and decreased oxidative stress (analyzed through MDA). An RCT of 77 patients with prediabetes demonstrated that individuals consuming 300 mg/day of tocotrienols exhibited significantly improved glycemic status and glucose utilization compared to the placebo. 

Learn more about how tocotrienol supplementation can support blood sugar balance, according to a 2023 systematic review and meta-analysis.  

Explore how vitamin E tocotrienols may support eye health for those with type 2 diabetes. 

Summary

Research is still uncovering the exact role of tocotrienols in cardiometabolic health. In vitro and in vivo studies demonstrate how tocotrienols may benefit cardiometabolic health by promoting healthy lipid metabolism, inflammatory responses, and glucose metabolism and supporting endothelial and metabolic health. Moreover, tocotrienols may play a role in healthy aging and bone health, displaying a wide range of clinical benefits. Tocotrienol supplementation, such as annatto-derived tocotrienols, may be warranted for certain individuals seeking to promote cardiometabolic health.  

By Danielle Moyer Male, MS, CNS, LDN