Vitamin E // Tocopherol
Any dietary or drug treatment with high doses of micronutrients may override the body's own control mechanisms; therefore, micronutrient therapies may be associated with potential side effects and toxicities. High-dosed micronutrients should not be used without medical supervision.
Results of clinical trials using vitamin E for the treatment of heart disease have been inconsistent.
A randomized, placebo-controlled trial in Great Britain (the CHAOS study) found that supplementing heart disease patients with either 400 IU or 800 IU synthetic alpha-tocopherol (equivalent to 180 mg or 360 mg RRR-alpha-tocopherol) for an average of 18 months dramatically reduced the occurrence of non-fatal heart attacks by 77%. However, alpha-tocopherol supplementation did not significantly reduce total deaths from heart disease (33).
Chronic renal dialysis patients, who have an increased risk of dying from cardiovascular disease, supplemented with 800 IU natural alpha-tocopherol (536 mg of RRR-alpha-tocopherol) for an average of 1.4 years showed a significantly reduced risk of heart attack compared to a placebo (34).
A clinical study showed that vitamin E supplementation of type 2 diabetes mellitus individuals with a specific genetic predisposition for cardiovascular disease (Hp 2-2 genotpye) reduced the incidence of cardiovascular events such as myocardial infarction, stroke, and cardiovascular death (20).
Other intervention trials, which did not stratify the subjects by genotype, did not find significant risk reductions of cardiovascular disease with alpha-tocopherol supplementation in participants who had a history of heart attacks or strokes (35, 36, 37).
In a randomized controlled trial, patients with hypertension were treated with 1 g vitamin C and 400 mg vitamin E. After 8 weeks of treatment the systolic, diastolic and mean blood pressure was significantly lower compared to placebo-treated patients (38).
As diabetes appears to increase oxidative stress and because cardiovascular complications (heart attack and stroke) are among the leading causes of death in diabetics, vitamin E (alpha-tocopherol) supplementation of individuals with diabetes has been proposed.
In individuals with diabetes mellitus, genetic predisposition plays an important role in the susceptibility for cardiovascular disease. Diabetes mellitus individuals carrying a specific variant of the haptoglobin (Hp) gene, the Hp 2-2 genotype, have been shown to have a 2- to 5-fold higher risk for cardiovascular events compared to Hp 1-1 and Hp 2-1 diabetes mellitus individuals (19). This observation has been attributed to increased oxidative stress in the Hp 2-2 diabetics. Supplementing these individuals with vitamin E has been shown to significantly reduce the risk of cardiovascular events such as myocardial infarction, stroke, and cardiovascular death (20) Importantly, 36% of the general population are carriers of the Hp 2-2 genotype.
Studies of the effect of alpha-tocopherol supplementation on blood glucose control have been contradictory: some studies have shown that supplemental vitamin E improves insulin action and glucose disposal in type 2 diabetic (38) and non-diabetic (39, 40) individuals, while other studies have reported minimal to no improvements in glucose metabolism of type 2 diabetics (41, 42).
Increased oxidative stress has also been documented in type 1 diabetes (43). One study reported that supplementing type 1 diabetics with only 100 IU/day synthetic alpha-tocopherol (equivalent to 45 mg RRR-alpha-tocopherol) for one month improved both blood glucose and triglyceride levels (44).
Although there is reason to suspect that alpha-tocopherol supplementation may be beneficial in treatment for type 1 or type 2 diabetes, further evidence from well-controlled clinical trials is needed.
Non-alcoholic fatty liver disease (NAFLD)
The term NAFLD encompasses conditions like simple liver steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and is usually associated with metabolic syndrome, obesity, lipid disorders, insulin resistance and type 2 diabetes. Two large RCTs evaluated the efficacy of vitamin E in NAFLD/NASH: In adults the PIVENS trial, and in children the TONIC study. The PIVENS trial included non-diabetic and non-cirrhotic adults with NASH, who received 800 IU vitamin E/day, pioglitazone, or placebo. Compared to placebo, vitamin E treatment was as efficacious or even more so in resolving NASH outcomes than observed with pioglitazone therapy (97). In the TONIC trial, children with NAFLD received 800 IU vitamin E/day, metformin, or placebo. The resolution of NASH in this pediatric population group was significantly higher in the vitamin E than the placebo group (98). In addition to these studies, there are more than a dozen published RCTs reporting beneficial effects of vitamin E on different biochemical or histological markers in patients with NAFLD (99). Based on this evidence, several expert groups and medical societies have concluded that vitamin E administered at a daily dose of 800 IU improves liver histology in non-diabetic adults with biopsy-proven NASH, and should be considered as a first-line pharmacotherapy for this patient population (100).
As oxidative stress is thought to play a role in the development of neurodegenerative diseases with impaired cognitive functions (e.g., Alzheimer's disease) (45), vitamin E supplementation may be beneficial because of its antioxidant effect.
A large placebo-controlled intervention trial in individuals with moderate neurological impairment found that supplementation with 2,000 IU synthetic alpha-tocopherol daily for two years (equivalent to 900 mg/day RRR-alpha-tocopherol) significantly slowed progression of Alzheimer's dementia (46).
In contrast, a placebo-controlled trial in patients with mild cognitive impairment reported that the same dosage of vitamin E did not slow progression to Alzheimer's disease over a 3-year period (47).
In a double-blind, placebo controlled RCT, patients with mild to moderate Alzheimer's disease were recruited and treated with either 2,000 IU/d α-tocopherol, memantine, a combination of both, or placebo. The high-dose α-tocopherol supplementation resulted in slower functional decline in Alzheimer's disease patients (93).
A case-control study in elderly men examining risk factors for ‘vascular dementia’, the second most common type of dementia after Alzheimer’s disease resulting from strokes, found that supplemental vitamin E and vitamin C intake was associated with a significantly decreased risk of vascular and other types of dementia but not Alzheimer's dementia (48). Among those without dementia, vitamin E supplement use was associated with better scores on cognitive tests.
Although these findings are promising, further studies are required to determine the role of vitamin E (alpha-tocopherol) supplementation in the treatment of Alzheimer's disease and other types of dementia.
Cancer cells grow and divide (‘proliferate’) rapidly, and are resistant to programmed cell death (‘apoptosis’). Cell culture studies indicate that the vitamin E ester, alpha-tocopheryl succinate, can inhibit proliferation and induce apoptosis in a number of cancer cell lines (49, 50, 51). Although the mechanisms for the effects of alpha-tocopheryl succinate on cancer cells are not yet clear, the fact that the ester form has no antioxidant activity argues against an antioxidant mechanism (52).
More research is required to determine whether alpha-tocopheryl succinate will be a useful adjunct to cancer therapy in humans.
Uveitis is an eye disorder caused by an inflammation of the ‘uvea’, the middle layer of the eye between the white outer coat of the eye (‘sclera’) and the retina. The uvea contains many of the blood vessels that nourish the eye, so inflammation in this area can affect the cornea, the retina, the sclera, and other important parts of the eye.
A randomized controlled trial in 130 patients with uveitis compared treatment with vitamin E and vitamin C supplements to placebo and found that those who took the vitamins had significantly better visual clarity than the control group (53).
Vitamin E, along with other standard treatments, may also be beneficial for
- treating photodermatitis (54)
- treating inflammatory diseases: ulcerative colitis (55), pancreatitis (56), and osteoarthritis (57)
- slowing progression of Parkinson’s disease (58)
- avoiding miscarriage (59, 94).
Controlled trials are needed to clarify potential benefits of vitamin E in treating these disorders.
Authored by Dr Peter Engel in 2010, reviewed and updated by Dr Szabolcs Peter on 18.06.2017