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Tocotrienols as adjunct therapy for chronic diseases, a comprehensive review

Highlights

  • Includes over 3 decades of published research (preclinical & human studies)
  • Research related to common diseases addressed
  • Applications for cardiovascular, cerebrovascular, neurodegenerative diseases & more

Summary

This comprehensive review summarizes the body of evidence supporting the use of tocotrienols to help prevent and treat non-communicable, chronic diseases. Over 30 years of preclinical and human studies are reviewed to guide clinicians in the use of tocotrienols as adjunct therapy.

Key findings are summarized below:

Lipid Metabolism. Tocotrienols improve lipid profiles in preclinical and human studies. This action is attributed to the ability to inhibit the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-Co reductase) needed for cholesterol synthesis, modulate lipogenic gene expression, alleviate oxidative stress and stimulate the breakdown of apolipoprotein B. These actions help reduce total, LDL- and VLDL-cholesterol and triglyceride levels as well as increase HDL-cholesterol levels.

Cardiovascular Diseases (CVD). Tocotrienols protect against CVD in animal studies. This effect is attributed to modifying pro-survival and anti-survival proteins, decreasing hypercholesterolemic proteins and cytokines, decreasing creatine phosphokinase, and increasing nitric oxide production. However, research in humans is limited and results are inconsistent. One potential reason for inconsistent findings in human studies is differences in preparations that affect bioavailability.

Cerebrovascular Diseases. Tocotrienols exert a protective effect on cerebrovascular disorders. This action is attributed to the ability to decrease brain lesions, oxidative stress and brain infarct volume as well as increase adaptive arteriogenesis. In one randomized, double-blind, placebo-blind study,1 EVNol SupraBio™ mixed tocotrienols significantly attenuated the progression of white matter lesions (a marker for cerebral small vessel disease) in adults at risk for CVD (see study summary for more details).

Osteoporosis. In rat models of osteoporosis, tocotrienols promote bone growth and prevent the progression of bone loss. These effects are attributed to antioxidant, anti-inflammatory, and gene-modulating actions that increase bone microstructure and biomechanical strength. Human studies are limited; however, one randomized, double-blind, placebo-controlled study2 involving postmenopausal women with osteopenia indicates tocotrienols exert osteoprotective effects by suppressing bone remodeling regulators, an action that may be mediated in part by reducing oxidative stress.

Arthritis. Animal studies suggest that tocotrienols may protect against arthritis-induced joint damage. This action is attributed, in part, to the ability to reduce oxidative stress and inflammation.

Muscle Diseases. Animal studies indicate tocotrienols may have anti-sarcopenic properties. This action is attributed to antioxidant, anti-inflammatory, and metabolic effects such as increasing the regenerative capacity of skeletal muscle mass and strength, decreasing oxidative stress in myoblasts, and other cell-signaling actions. However, more research is needed to confirm efficacy in humans and clarify the mechanism(s) of action by which tocotrienols could protect against arthritis-induced cartilage damage.

Peptic Ulcers. Animal studies indicate tocotrienols protect against peptic ulcers primarily via antioxidant and anti-inflammatory mechanisms and by helping to maintain gastric protective factors. Based on these findings, the authors note that supplementation with tocotrienols may be useful to avoid gastric lesions caused by stress or other aggressive agents or as a part of the treatment regime in critically ill patients. However, no clinical studies have been completed to date that investigate the use of tocotrienols in patients with gastric lesions.

Neurodegenerative Diseases. The neuroprotective effect of tocotrienols has been shown in preclinical studies and is attributed to the ability to reduce oxidative stress and promote cell survival. However, results from human studies, including those involving patients with Parkinson’s disease, are inconsistent.

Wound Healing. Preclinical studies indicate tocotrienols may offer value for wound healing. This action is attributed to the ability to accelerate wound healing, promote angiogenesis, collagen production and related factors, and improve scar management. Interestingly, both topical and oral administration have been shown to produce positive results on wound healing properties.

Obesity & Diabetes. The anti-obesity effect of tocotrienols has been shown in preclinical studies, including the ability to reduce body weight and total and visceral fat mass in obese rodents fed a high-fat diet. Clinical studies are needed to confirm similar effects in humans. Tocotrienols improve glycemic control in preclinical and human studies; however, clinical research is lacking to assess the potential hypoglycemic effect of tocotrienols in people who are obese.

Cancer. Tocotrienols have been extensively studied in cancer cell lines (i.e., breast, lung, liver pancreas, prostate, cervix, skin, brain, stomach, and colon) and have demonstrated anti-cancer properties. These properties are attributed to modulating intracellular signaling pathways, which can inhibit cell proliferation, induce apoptosis and cell cycle arrest, suppress angiogenesis, and inhibit metastasis. Evidence in humans is limited, and most trials are preliminary. A Phase 1 trial with patients with pancreatic cancer and a Phase 2 trial with patients with ovarian cancer showed promising effects, while a Phase 3 trial with patients with breast cancer failed to show benefits. More clinical trials are needed to confirm the safety, efficacy, and tolerability of tocotrienols as a novel chemopreventive or adjuvant agent.

The authors also discuss the pharmacokinetic and safety profiles of tocotrienols and provide a comparison of tocotrienols to tocopherols. They note several opportunities for more research. To date, clinical trials have only addressed the effect of tocotrienols for hyperlipidemia, CVD, osteoporosis, Parkinson’s disease, diabetes, and certain cancers. However, results from preclinical and population-based research suggest tocotrienols may offer benefits for arthritis, sarcopenia, peptic ulcer, Alzheimer’s disease and wound healing.

 

References

1. Gopalan Y, Shuaib IL, Magosso E, et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014;45(5):1422-8. PMID: 24699052.

2. Shen CL, Yang S, Tomison MD, Romero AW, Felton CK, Mo H. Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial. Osteoporos Int. 2018;29(4):881-891. PMID: 29330573.

Reference

Wong SK, Kamisah Y, Mohamed N, et al. Potential role of tocotrienols on non-communicable diseases: a review of current evidence. Nutrients. 2020;12(1). Review.

PMID: 31963885