Plant-based Diets and Low-Insulin Lifestyles May Suppress Oxidative Stress By Disinhibiting FOXO3a

Mark Frederick McCarty


FOXO transcription factors, notably FOXO3a, promote transcription of a wide range of mitochondrial antioxidant enzymes as well as catalase – an effect thought to contribute to the beneficial impact of caloric restriction on longevity in rodents.  Activated Akt suppresses FOXO3a activity by promoting its exclusion from the nucleus.  Hence, in the many tissues responsive to IGF-I and/or insulin – hormones which stimulate Akt activity – high circulating levels of free IGF-I or of insulin may have a pro-oxidant impact.  Moreover, high insulin levels boost IGF-I bioactivity by inhibiting hepatic production of IGFBP-1, an IGF-I antagonist.  Hence, the combination of a moderate-protein plant-based diet – which down-regulates hepatic IGF-I production via essential amino acid restriction – and a lifestyle that minimizes diurnal insulin levels, would appear likely to offer worthwhile antioxidant protection, possibly contributing to the markedly reduced risk for “Western” cancers and cardiovascular disease characteristic of quasi-vegan societies.  The moderate methionine restriction associated with plant-based diets might also aid this effect by diminishing superoxide production via complex I of the mitochondrial respiratory chain, as observed in methionine-restricted rodents.


plant-based; vegan; low-insulin; FOXO3a; antioxidant; mitochondria


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