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  • Does Calorie Restriction And / Or Its Molecular Mimics Confer Life-Prolonging Benefits In Humans As It Does In Laboratory Animals?

    December 28, 2017: by Bill Sardi

    Researchers continue to piece together data to show that the lifespan and healthspan doubling effect of a calorie restricted diet observed in fruit flies, roundworms and laboratory mice, is applicable to humans.

    Last year (2016) an extensive analysis concluded that the “health benefits of calorie restriction are conserved in monkeys and suggest that calorie restriction mechanisms are likely translatable to human health.”

    And a team of researchers report that a two-year controlled trial of a calorie restricted diet in middle-aged humans concludes: “sustained calorie restriction is feasible in non-obese humans.”

    We know from historical records that humans deprived of food but not malnourished experience a 30-34% reduction in mortality as evidenced by populations that experienced food shortages during WWI and WWII.

    In modern times the same CR phenomenon is exhibited on the Island of Okinawa where food intake is 40% less than the average adult in the U.S. resulted in 4-5 times more centenarians than any other industrialized country (50 in every 100,000 were 100-years of age).

    Various short-term controlled human studies also confirm that food restriction confers longevity.  The most recent analysis of human studies concludes: “data from human studies show that CR remains the cornerstone in the prevention and treatment of obesity and its complications. Moderate CR achieved through intermittent fasting or restricting feeding in combination with regular physical activity most likely exerts additional beneficial health effects even in non-obese individuals.”

    So now the question of whether small molecules such as resveratrol, quercetin, curcumin, known as molecular mimics of a calorie restricted diet, can exert the same biological effect without having to adhere to a food deprivation diet?

    A review of molecules that are known mimics of calorie restriction found resveratrol to be the “best CR mimetic.”  Furthermore, it has recently been reported that in the short-term (30-days) resveratrol produces similar effects in obese humans to those induced by calorie restriction.  The bridge has been crossed from the animal lab to humans and from diet to pills.

    Given all of the above information, a question remains: Have all of the users of resveratrol pills, many who began taking these pills as early as 2004 when a Harvard professor first revealed an association between a calorie restricted diet, the Sirtuin1 survival gene and the red wine molecule resveratrol, taken those pills in a vain attempt to achieve superlongevity?

    University-based researchers recently examined the effect of a calorie restricted (CR) diet and so-called CR mimetics like resveratrol upon expression of genes in laboratory animals.  These researchers added various molecular mimetics of CR like resveratrol to the diet of different strains of laboratory mice such as resveratrol and quercetin.

    Unexpectedly, these researchers found synthetic resveratrol by itself exerted little epigenetic activity.

    However, these researchers referred to research they conducted and published in 2008 which showed that resveratrol in combination with other small molecules had a profound, rapid effect in replicating the biological effects of a calorie restricted diet.

    The researchers noted: “We previously reported that a nutraceutical mixture containing an even lower dose of resveratrol plus inositol hexaphosphate (IP6) and quercetin mimics gene expression profile of CR.”  (Longevinex®)

    In a rodent study conducted by these researchers nine years ago, a calorie-restricted diet activated 198 genes over a short-term (3 months) and resveratrol activated 225 genes.  If these animals were fed a calorie-restricted diet over their lifetime (~3 years) a prior study showed 831 genes would be significantly activated.  Strikingly, the nutrient combination of resveratrol/quercetin/rice bran IP6 activated 1711 genes, 82% of these genes being activated in the same direction (turned off or on – expressed or silence) as a calorie restricted diet.

    That study showed a commercially available dietary supplement (Longevinex®) to be the closest thing to a CR diet ever demonstrated.  That is still the case today.

    Special note: If what was reported in these laboratory animals applies to humans, consumers would have to adhere to a life-long calorie-restricted diet or life-long resveratrol to achieve a full longevity effect, or take Longevinexv and achieve a superior effect in a short time.  This may help explain whey plain synthetic resveratrol had no measurable effect in a short-term gene array/animal study mentioned above.

    Furthermore, among all of the molecules tested, these researchers said: Sirtuin3, the sirtuin-family gene that operates in the mitochondria (power plants of the cell), facilitates at least some of the health benefits of CR in retarding aging.  However, unexpectedly none of the tested calorie restriction mimetics appeared to act by Sirtuin3 induction.  These researchers concluded: “stronger mimicry of calorie restriction may be achieved by combining different calorie restriction mimetics.” (Longevinex®)

    Longevinex® has been shown to activate the Sirtuin3 mitochondrial gene far better (+295%) than plain resveratrol.  ©2017 Bill Sardi,

    Chart: Comparative Activation Of Sirtuin3 Gene: Resveratrol vs Longevinex

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