Dr. Ron’s Research Review – June 10, 2020

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This week’s research review focuses on the conflicting results of vitamin E to prevent atherosclerosis.

A study examined vitamin E supplementation and presented a rational basis for understanding the conflicting results among randomized clinical trials, epidemiologic investigations, and animal studies on the use of vitamin E to prevent atherosclerosis. (Robinson et al., 2006)
The possible factors implicated for failure of vitamin E therapy include the following:
Inclusion of patients without biochemical evidence of increased oxidative stress,
The relatively short duration of treatment and the use of suboptimal dosages of vitamin E,
Suppression of gamma-tocopherol by alpha-tocopherol,
The use of vitamin E supplementation without the concurrent use of vitamin C,
The lack of inclusion of biochemical markers of oxidative stress and markers of vascular response,
Inappropriate administration of vitamins relative to meal ingestion, and
Poor patient compliance and the lack of monitoring of vitamin E levels.

Before additional large, randomized clinical trials of vitamin E are performed, the specific biologic and surrogate marker effects of vitamin E in each target population must be defined more carefully. This approach will save resources, minimize untoward side effects, and identify the patients who will benefit the most.
In addition, isoforms of vitamin E differentially regulate inflammation. Most studies focus on the α-tocopherol isoform of vitamin E. The natural forms of vitamin E include α, β, γ, and δ-tocopherol and tocotrienol forms.
It has been reported that α-tocopherol is anti-inflammatory and γ-tocopherol is pro-inflammatory.
Although raising the tissue plasma α-tocopherol and γ-tocopherol levels 50 fold (highly-elevated tocopherols) is anti-inflammatory and can reverse the pro- inflammatory effects of supplemental levels of γ-tocopherol, clinical reports caution that elevation of tocopherols can increase the incidence of high blood pressure, hemorrhagic stroke, all-cause mortality, or post trial cerebral infarction. (Cook-Mills and McCary, 2010)

Dr. Ron


Articles

 

Isoforms of vitamin E differentially regulate inflammation.
            (Cook-Mills and McCary, 2010)  Download
Vitamin E regulation of disease has been extensively studied in humans, animal models and cell systems. Most of these studies focus on the α-tocopherol isoform of vitamin E. These reports indicate contradictory outcomes for anti-inflammatory functions of the α-tocopherol isoform of vitamin E, especially with regards to clinical studies of asthma and atherosclerosis. These seemingly disparate clinical results are consistent with recently reported unrecognized properties of isoforms of vitamin E. Recently, it has been reported that physiological levels of purified natural forms of vitamin E have opposing regulatory functions during inflammation. These opposing regulatory functions by physiological levels of vitamin E isoforms impact interpretations of previous studies on vitamin E. Moreover, additional recent studies also indicate that the effects of vitamin E isoforms on inflammation are only partially reversible using physiological levels of a vitamin E isoform with opposing immunoregulatory function. Thus, this further influences interpretations of previous studies with vitamin E in which there was inflammation and substantial vitamin E isoforms present before the initiation of the study. In summary, this review will discuss regulation of inflammation by vitamin E, including alternative interpretations of previous studies in the literature with regards to vitamin E isoforms.

Vitamin E in humans: an explanation of clinical trial failure.
            (Robinson et al., 2006) Download
OBJECTIVE:  To describe the potential benefits and hazards of vitamin E supplementation and present a rational basis for understanding the conflicting results among randomized clinical trials, epidemiologic investigations, and animal studies on the use of vitamin E to prevent atherosclerosis. METHODS:  We conducted a retrospective review of the pertinent literature found in PubMed from 1981 through August 2005. The published data are analyzed and summarized. RESULTS:  The possible factors implicated for failure of vitamin E therapy include the following: (1) the inclusion of patients without biochemical evidence of increased oxidative stress, (2) the relatively short duration of treatment, (3) the use of suboptimal dosages of vitamin E, (4) the suppression of gamma-tocopherol by alpha-tocopherol, (5) the use of vitamin E supplementation without the concurrent use of vitamin C, (6) the lack of inclusion of biochemical markers of oxidative stress and markers of vascular response, (7) the inappropriate administration of vitamins relative to meal ingestion, and (8) the poor patient compliance and the lack of monitoring of vitamin E levels. CONCLUSION:  Large, randomized clinical trials have not yet substantiated a beneficial effect of use of vitamin E to reduce atherosclerotic risk in humans, despite demonstration of antioxidant effects in vitro and in animals. Only in subsets of patients at high risk for atherosclerosis has a beneficial effect been suggested. Before additional large, randomized clinical trials of vitamin E are performed, the specific biologic and surrogate marker effects of vitamin E in each target population must be defined more carefully. This approach will save resources, minimize untoward side effects, and identify the patients who will benefit the most.

 

References

Cook-Mills, JM and CA McCary (2010), ‘Isoforms of vitamin E differentially regulate inflammation.’, Endocr Metab Immune Disord Drug Targets, 10 (4), 348-66. PubMed: 20923401
Robinson, I, et al. (2006), ‘Vitamin E in humans: an explanation of clinical trial failure.’, Endocr Pract, 12 (5), 576-82. PubMed: 17002935