More Evidence That A Low-Fat, Plant Based Diet Extends Healthspan and Lifespan: Low Concentration MUFAs Activate SIRT1

Studies that have looked at whether consuming a diet rich in monounsaturated fatty acids (MUFAs) leads to reduced risk of heart disease have shown mixed results. The confusion arose because it makes a difference whether the MUFAs come from plant or animal products. In the first study to separately examine types of MUFA sources in relation to heart disease, researchers found that while MUFAs from plant-based foods such as olive oil and nuts do indeed lower risk, MUFAs from animal products such as red meats and dairy do not provide benefits. The studies were of calorie matched consumption of the different fat types and did not compare low fat versus high fat consumption (Zong et al, 2018). Much evidence has accumulated that low-fat, plant based diets have numerous positive effects in the human body, including shifting the innate and adaptive immune systems to a less inflammatory state, and one that resolves the inflammation more efficiently (Maguire, 2020). In other words, the low-fat, plant based diet allows one to regain allostais through physiological renormalization, where the body is healthy and in a state of optimal responsiveness (Sterling, 2020).

SIRT1, acting through PPAR-α/PGC-1α to upregulate mitochondrial biogenesis, has a wide-range of biological functions including chromatin structure maintenance, cell cycle control, metabolism, and the regulation of healthspan. Regulation of these pathways is partially dependent upon fatty acids, specifically monounsaturated fatty acids (MUFA) .

One study has found that MUFAs do not modulate SIRT1 activity (Feldman et al., 2013). However, this study employed a fixed concentration of 18:1 (100 μM) and used the H3 peptide as a substrate. As Najt et al (2020) have found, MUFAs do not activate SIRT1 at concentrations above 1 μM and do not enhance SIRT1 activity toward the H3 peptide pathway. Thus low-fat, i.e. low concentrations of MUFAs activate the SIRT1 pathway toward the H3 peptide and provide significant metabolic enahncement. These new mechanistic data translate into a recommended regimen of eating plants that are naturally high in MUFAs, and low in other fats, such as saturated fats. Given that low concentrations of MUFAs activate SIRT1, but high concentrations do not, eating refined oils, even if high in MUFAs, should be avoided.


Feldman JL et al  (2012) Sirtuin catalysis and regulation. J. Biol. Chem.2012; 287: 42419-42427

Maguire G (2020) Thinking and Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts. Berkeley Free Speech Press, Berkeley, CA.

Najt et al (2020) Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1, Molecular Cell (2019). DOI: 10.1016/j.molcel.2019.12.003

Sterling P (2020) What Is Health?: Allostasis and the Evolution of Human Design. MIT Press, Cambridge, MA.

Zong G et al (2018) Monounsaturated fats from plant and animal sources in relation to risk of coronary heart disease among US men and women. The American Journal of Clinical Nutrition, Volume 107, Issue 3, March 2018, Pages 445–453

Published by Dr. Greg Maguire, Ph.D.

Dr. Maguire, a Fulbright-Fogarty Fellow at the National Institutes of Health, is a scientist, innovator, teacher, healthcare professional. He has over 100 publications and numerous patents. His book, "Adult Stem Cell Released Molecules: A Paradigm Shift To Systems Therapeutics" was published by Nova Science Publishers in 2018.

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