Meta analysis adds evidence to anti inflammatory effect for vitamin E supplementation

Meta-analysis adds evidence to anti-inflammatory effect for vitamin E supplementation

Life Extension Update

Tuesday, February 24, 2015. Results of a meta-analysis published on February 11, 2015 in the European Journal of Clinical Nutrition reaffirm an association between a reduction in inflammation and supplementation with vitamin E.

K. Djafarian of Tehran University of Medical Sciences and colleagues selected 12 randomized, controlled trials including a total of 495 participants for their analysis. Trials were limited to those that involved supplementation with 100 international units (IU) per day or more alpha or gamma tocopherol, while reporting serum or plasma levels of C-reactive protein (CRP, a marker of inflammation) before and after treatment.

Pooled analysis of the data uncovered an average reduction of 0.62 milligrams per liter (mg/L) in CRP among subjects that received a vitamin E supplement. CRP levels decreased more among vitamin E-supplemented subjects whose levels were less than 3 mg/L at the beginning of the study in comparison with those whose levels were higher; however, the decline in both of these groups was significant. The decrease in CRP was greater when supplementation occurred for at least six weeks in comparison with less than six weeks.

The authors suggest activation of AP-1 (activation protein 1), suppression of the ability of pro-inflammatory cytokines to induce liver synthesis of CRP, and other potential mechanisms for vitamin E's anti-inflammatory effect. In contrast with other studies, the current analysis indicates that both alpha and gamma tocopherol supplementation may help lower serum CRP.

"It seems that vitamin E supplementation may be a good strategy for decreasing inflammatory conditions in susceptible people, although large well-designed randomized controlled trials are needed to confirm these results," the authors conclude.

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Higher dietary antioxidant capacity associated with lower cardiovascular disease indicators
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In an article published online on January 4, 2013 in the European Journal of Clinical Nutrition, researchers from the University of Connecticut report an association between improved dietary antioxidant capacity and reductions in plasma homocysteine and C-reactive protein (CRP), both of which are markers of increased cardiovascular disease risk.

The study included 4,391 men and women who participated in the National Health and Nutrition Examination Survey (NHANES) 2001-2002. Questionnaire responses concerning diet and supplement use over a 24 hour period were analyzed to provide the antioxidant capacities of 43 nutrients. (The antioxidant capacity of 30 flavonoids was determined from food sources only.) Blood samples were analyzed for serum levels of alpha and gamma tocopherols, six carotenoids and CRP, and plasma total homocysteine.

Total antioxidant capacity (TAC) was correlated with serum vitamin E and carotenoid levels. As TAC rose, the risk of having a total homocysteine level of greater than 13 micromoles per liter decreased. Those whose intake of antioxidants was among the top 25 percent of participants had more than double the chance of having a homocysteine level under 13 micromoles per liter in comparison with those whose TAC was among the lowest fourth. A reduction in the risk of having a CRP level of 3 milligrams per liter or higher was also observed in association with increasing TAC. A significant decline in homocysteine and CRP was observed in association with higher TAC from diet combined with supplements or supplements alone, but not with diet alone.

"Dietary TAC was associated with improved serum antioxidant status and decreased risk factors of cardiovascular disease including serum CRP and plasma total homocysteine concentrations," the authors conclude. "The implicated applicability of dietary TAC needs further validation in prospective cohort studies."

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Health Concern

Chronic inflammation

Of the ten leading causes of mortality in the United States, chronic, low-level inflammation contributes to the pathogenesis of at least seven. These include heart disease, cancer, chronic lower respiratory disease, stroke, Alzheimer's disease, diabetes, and nephritis (Centers for Disease Control and Prevention 2011; Bastard et al. 2006; Cao 2011, Jha et al. 2009; Ferrucci et al. 2010; Glorieux et al. 2009; Kundu et al. 2008; Murphy 2012; Singh et al. 2011).

C-reactive protein (CRP) is an acute-phase protein, one of several proteins rapidly produced by the liver during an inflammatory response. Its primary goal in acute inflammation is to coat damaged cells to make them easier to recognize by other immune cells (Meyer 2010). CRP elevation above basal levels is not diagnostic on its own, as it can raise in several cancers, rheumatologic, gastrointestinal, and cardiovascular conditions, and infections (Windgassen et al. 2011). Elevation of CRP (as determined by a high-sensitivity CRP assay or hs-CRP) has a strong association with elevated risk of cardiovascular disease and stroke (Emerging Risk Factors Collaboration et al. 2010).

Vitamin E functions as an antioxidant in the body. Specifically, vitamin E is incorporated into low-density lipoprotein (LDL) particles and protects them against oxidative damage; it seems to guard against atherosclerosis via other mechanisms as well (Meydani 2001). The gamma-tocopherol form of vitamin E appears to complement the anti-inflammatory action of alpha-tocopherol. Gamma-tocopherol has been shown to inhibit COX-2 and attenuate IL-1β signaling (Jiang 2000; Sjoholm 2001). In a small clinical trial on subjects with metabolic syndrome, the combination of gamma-tocopherol and alpha-tocopherol effectively suppressed C-reactive protein and TNA-α levels compared to placebo (Devaraj 2008). In this study, the combination of both tocopherols performed better than either alone, prompting the investigators to remark "the combination of [alpha-tocopherol] and [gamma-tocopherol] supplementation appears to be superior to either supplementation alone on biomarkers of oxidative stress and inflammation and needs to be tested in prospective clinical trials..."

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