The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 11 No. 6 • October 2008

White Wine Has Cardioprotective Effects by Activating a Cell Survival Pathway, Including the Longevity-Associated Gene FOXO3a

White wine, though lacking in polyphenols (plentiful in red wine) has been shown in a new study1 to protect against heart injury in myocardial ischemic-reperfusion (heart attack, where blood flow is first blocked and then restored) in rats. This protection was provided by a different set of natural constituents, including caffeic acid (twice as much in white wine as in red), tyrosol, and shikimic acid.

The authors report that “In human case control studies, red and white wine demonstrated equal effects on fibrinolytic [clot-busting] factors and collagen-induced platelet aggregation.” Moreover, tyrosol and caffeic acid have been found to modulate oxidative stress and inflammatory reactions.1 Previous work by these scientists reported white wine reduced heart cell death (infarct size) during experimental heart attacks. The researchers conducted this new study of myocardial ischemic-reperfusion injury in rats to determine the effects of white wine under these conditions on protective signaling from Akt, FOXO3a, eNOS, and the redox transcription factor NFkappaB. The experimental animals (subject to ischemia-reperfusion) received white wine by gavage (pumped into their stomachs). A wine sham group received white wine by gavage but did not receive the ischemia-reperfusion treatment.

The results showed that white wine decreased the infarct size to approximately 21% as compared to 39% in the control IR (ischemia-reperfusion) group. There was a significant decrease in the apoptosis (programmed cell death) of cardiac cells and of endothelial cells in the treated group vs. the untreated. “On the whole, white wine treatment has demonstrated progressive, significant increase in left ventricular function as compared to the untreated group.” The results for the biochemical pathways included finding that white wine significantly increased the phosphorylation (i.e., activation) of Akt (1.5-fold in the wine shams and 2.6-fold in the wine ischemia-reperfusion experimental group), significantly increased eNOS (in both the wine shams and the wine ischemia-reperfusion groups), and increased levels of phosphorylated FOXO3a in both wine shams and wine ischemia-reperfusion groups, while significantly increasing the DNA binding of NFkappaB in both wine sham and wine/ischemia-reperfusion groups as compared to controls.

The activation of Akt has been shown in other studies to inhibit cardiomyocyte apoptosis and also to preserve function in surviving cardiomyoctes.1 The authors note that “Recently, we have demonstrated that bromelain [a pineapple proteolytic enzyme] induces cardioprotection against ischemia-reperfusion injury through the Akt/FOXO3a pathway in rat myocardium.” [Emphasis added] Increased eNOS activity has also been shown to have cardioprotective effects, reducing cardiomyocyte apoptosis and infarct size in a rat model of ischemia-reperfusion injury.1 Induction of NFkappaB has been shown to occur under conditions where eNOS is low (as occurs during ischemia-reperfusion) and provides cytoprotection to cardiomyocytes.

FOXO3a Genotype Strongly Associated with Human Longevity

In a new paper2 scientists report finding that “genetic variation within the FOXO3a gene was strongly associated with human longevity. . . . Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity, and this was associated with homozygosity [two copies of the same version of the gene] for the FOXO3A GG genotype. . . . two copies of the G allele conferred about twice the protective effect (suggesting an additive effect), roughly tripling the odds of living close to a century.” It would be interesting to see what effect the human FOXO3a genotype would have had on the protective effects of white wine if the above experiment had been done in transgenic rats. Another possible study is to examine the prevalence of the FOXO3a GG genotype in human heart attack survivors as compared to nonsurvivors.


  1. Thirunavukkarashu et al. White wine-induced cardioprotection against ischemia-reperfusion injury is mediated by life-extending Akt/FOXO3A/NFkappaB survival pathway. J Agric Food Chem 56:6733-9 (2008).
  2. Willcox et al. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105(37):13987-92 (2008).

A man can never have too many
books, too much red wine, or too much ammunition.
— Rudyard Kipling

As long as I don’t read the newspapers, I feel fine.
— Otto Hahn, received Nobel Prize in Chemistry, 1944

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