UNIQUE Tocotrienol by A.C. Grace Company

POSSIBLY EFFECTIVE

• Diabetes. Oral tocotrienols may improve glycemic control in adults with type 2 diabetes. Details: A meta-analysis of 8 clinical trials of adults with type 2 diabetes shows that taking a tocotrienol-rich fraction, primarily derived from palm fruit, 250-400 mg daily for 2-18 months leads to slight improvements in glycated hemoglobin (HbA1c) when compared with placebo (112286). The benefit was primarily among those with a higher baseline HbA1c, a duration of diabetes less than 10 years, and in studies with a duration of less than 6 months. Most studies were rated high quality with a low risk of bias, but most were also small with moderate heterogeneity. Most of the studies were conducted in Malaysia, where tocotrienol-rich palm oil was already regularly consumed as part of the diet, potentially limiting the generalizability of the findings to other populations with different baseline tocotrienol intakes.

POSSIBLY INEFFECTIVE

• Hypercholesterolemia. Oral tocotrienols are not likely to induce clinically meaningful improvements in cholesterol levels. Details: A meta-analysis of 19 small clinical trials shows that taking tocotrienols 50-600 mg daily for 1-6 months does not decrease levels of total cholesterol, low density lipoprotein (LDL) cholesterol, or triglycerides when compared with control. Tocotrienols were shown to increase levels of high-density lipoprotein (HDL) cholesterol by a modest and clinically insignificant amount. Sub-group analyses did not find that baseline lipid levels, or dose and duration of tocotrienol supplementation, notably alter results (104430). These findings are limited because the studies included not only patients with hypercholesterolemia, but also healthy patients and patients with various conditions such as type 2 diabetes, metabolic syndrome, and kidney disease. Tocotrienols have also been studied in combination with tocopherols (28730,85107,104430) and polymethoxylated flavones (99694) without notable benefit.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral tocotrienols have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: A small study in healthy adults over 40 years of age with self-diagnosed, subjective memory decline shows that taking a specific combination supplement (BGG Japan Co.) containing tocotrienols 50mg and astaxanthin 9 mg daily for 12 weeks modestly improves composite and verbal memory when compared with placebo (105099). This study was funded by the supplement manufacturer.
• Aging. Although there is interest in using oral tocotrienols for aging, there is insufficient reliable information about the clinical effects of tocotrienols for this condition.
• Alzheimer disease. Although there is interest in using oral tocotrienols for Alzheimer disease, there is insufficient reliable information about the clinical effects of tocotrienols for this condition.
• Alopecia areata. Although there is interest in using topical tocotrienols for alopecia areata, there is insufficient reliable information about the clinical effects of tocotrienols for this condition.
• Breast cancer. It is unclear if oral tocotrienols are beneficial for improving early breast cancer outcomes or preventing recurrence. Details: Clinical research in Malaysian patients with early-stage breast cancer shows that taking tocotrienols 200 mg daily, in conjunction with tamoxifen 20 mg daily for up to 5 years, does not improve survival or reduce the rate of cancer recurrence when compared with taking tamoxifen with placebo (99697). The validity of this study is limited by the lack of randomization and insufficient power to evaluate an effect on cancer-related mortality.
• Chronic kidney disease (CKD). Although there is interest in using oral tocotrienols for CKD, there is insufficient reliable information about the clinical effects of tocotrienols for this condition.
• Diabetic nephropathy. It is unclear if oral tocotrienol-rich vitamin E is beneficial for slowing diabetic nephropathy progression. Details: A small clinical study in patients with diabetic nephropathy shows that taking a specific tocotrienol-rich vitamin E supplement (Tocovid SupraBio, Hovid Nutriworld) 200 mg twice daily for 12 weeks seems to modestly reduce serum creatinine, with a corresponding increase in estimated glomerular filtration rate (eGFR), when compared with placebo. According to a sub-group analysis, these improvements remained statistically significant in patients with low tocopherol levels (less than 42 mcmol/L) at baseline, but not in those with higher levels at baseline (103010). Another small clinical study shows that taking this same supplement regimen for 12 months reduces serum creatinine levels and improves eGFR at 8 months, but not 12 months, when compared with placebo. In a subgroup analysis of patients with stage 3 chronic kidney disease, these benefits persisted at 12 months when compared with placebo (107390).
• Familial dysautonomia. It is unclear if oral tocotrienols are beneficial for familial dysautonomia outcomes. Details: A small clinical study in patients with familial dysautonomia shows that taking tocotrienols 100 mg for 3-4 months decreases the number of hypertensive crises by at least 50% in about 80% of patients when compared to baseline (28720). However, another small clinical study shows that taking tocotrienols 50 mg or 100 mg daily for 3 months improves subjective symptom reports, but does not improve objective clinical measurements, when compared to baseline (99700). The validity of these findings is limited by small study sizes and the absence of comparator groups.
• Hypertrophic scars. It is unclear if topical tocotrienols improve hypertrophic scar appearance or vascularity. Details: A clinical study in adults with recently healed surgical scars shows that applying a cream containing 5% tocotrienols twice daily for 6 weeks does not improve scar appearance or vascularity at the end of treatment or 10 weeks after treatment completion when compared with a placebo cream (99699). It is unclear if a cream containing a greater concentration of tocotrienols might be beneficial.
• Impaired glucose tolerance (prediabetes). It is unclear whether oral tocotrienols are beneficial in patients with prediabetes. Details: A small clinical trial in adults with untreated prediabetes shows that taking delta-tocotrienol 300 mg orally daily for 12 weeks reduces fasting plasma glucose and insulin levels and improves glycated hemoglobin and the homeostatic model assessment for insulin resistance (HOMA-IR) when compared with placebo (107856).
• Metabolic syndrome. Oral tocotrienols have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: A moderate sized clinical trial in adults with metabolic syndrome shows that taking delta-tocotrienols 500 mg and resveratrol 300 mg daily for 24 weeks improves body weight, waist circumference, blood pressure, fasting blood glucose, serum triglycerides, total cholesterol, high-density lipoprotein cholesterol, and markers of inflammation and oxidative stress compared with placebo (112144). It is unclear if these effects are due to the tocotrienols, resveratrol, or the combination.
• Nonalcoholic fatty liver disease (NAFLD). Small clinical studies suggest that oral tocotrienols may modestly improve steatosis and other outcomes in patients with NAFLD. Details: A small clinical trial in adults with NAFLD shows that taking tocotrienols 200 mg twice daily for one year might reduce steatosis, as measured by ultrasound hepatic echogenic response, when compared with placebo (99695). Another small clinical trial in overweight or obese adults with NAFLD shows that taking a specific product (American River Nutrition, Inc.) containing 90% delta-tocotrienol and 10% gamma-tocotrienol, as 300 mg twice daily for 24 weeks, modestly reduces fatty liver index (FLI), hepatic steatosis measured by ultrasound, and liver enzyme levels when compared with placebo (104428). These findings are limited because liver biopsy was not used to determine disease progression. Assessment by liver ultrasound examination has limited accuracy when used in obese patients and when testing for steatohepatitis or fibrosis.
• Postmenopausal conditions. It is unclear if oral tocotrienols are beneficial for improving symptoms in postmenopausal patients. Details: A small clinical study in postmenopausal patients shows that taking a specific product (DeltaGold70) 430 mg or 860 mg daily, containing 300 mg or 600 mg tocotrienols, respectively, for 12 weeks does not improve quality of life, body weight, or body fat percentage when compared with placebo (99690).
• Stroke. It is unclear if oral tocotrienols are beneficial for improving outcomes in patients after stroke or transient ischemic attack (TIA). Details: Observational research in patients after an ischemic stroke or TIA has found that taking tocotrienols 400 or 800 mg daily for one year is associated with reduced resistance to aspirin in patients using aspirin with clopidogrel, but not in patients using only aspirin or only clopidogrel, when compared with placebo (104429).
• Wound healing. Although there is interest in using topical tocotrienols for wound healing, there is insufficient reliable information about the clinical effects of tocotrienols for this condition. More information is needed to rate tocotrienols for these uses.

(Read more about TOCOTRIENOLS)

POSSIBLY SAFE ...when used orally and appropriately. Tocotrienols have been used with apparent safety at doses of up to 600 mg daily for up to 18 months (99690,99695,99696,104427,104428,112286). Tocotrienols have also been used with apparent safety at a dose of 200 mg daily for up to 5 years (99697). There is insufficient reliable information available about the safety of tocotrienols when applied topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about TOCOTRIENOLS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Concomitant use of tocotrienols with anticoagulant or antiplatelet agents might increase the risk of bleeding. However, this has not been reported in humans.  Details Taking tocotrienols orally inhibits experimentally-induced platelet aggregation in humans (3237,104429). Theoretically tocotrienols might increase the risk of bleeding if taken with antiplatelet or anticoagulant drugs. However, tocotrienols 400-800 mg daily have been used with aspirin and/or clopidogrel for 1 year with no clear cumulative antiplatelet effects and no reports of bleeding (104429).

(Read more about TOCOTRIENOLS)

General ...Orally, tocotrienols appear to be well-tolerated. No adverse effects have been reported in clinical trials.
Most Common Adverse Effects:
Topically: Mild itching.

Dermatologic ...Topically, a cream containing 5% tocotrienols has been reported to cause mild itching in 7% of patients in one clinical study (99699). Contact dermatitis has been reported in 33% of patients using a cream containing vitamin E as a mixture of tocopherols and tocotrienols (4721). However, it is unclear if this effect resulted from tocopherols, tocotrienols, or the combination.

(Read more about TOCOTRIENOLS)