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Mechanism posted a topic in CR Science & TheoryAn argument against prolonged fasting (>24 hours): In their book “the perfect health diet” by Paul Jaminet Ph.D. and Shou-Ching Jaminet Ph.D., the authors note that “Long fasts do not upregulate autophagy more than short fasts do. In mice, autophagy peaks within the first twenty-four hours of a fast and then drops back to normal levels within forty-eight hours of fasting.” While this is in mice, since they published their work similar findings have come out in humans too. Further, they note that “Although long fasts do not upregulate autophagy, they do lead to a more exaggerated drop in autophagy upon resumption of feeding. Mice starved for forty-eight hours experience complete suppression of autophagy when feeding is resumed.  In rats starved for five days, autophagy is completely eliminated throughout the first day of refeeding and takes several more days to return to normal.  Regarding this delay in resumption of autophagy, they cite “a study of famine victims who had lost 25 percent of body weight during a famine and then were given unlimited food found that only 4.9 percent had detectable infections when refeeding began, but 29.1 percent had overt infections two weeks later. […] the infections that flared up were all intracellular infections—the kind that are fought by autophagy.” .Those authors, who saw increased malaria following fasting, concluded “Severe undernutrition can suppress certain infections, mostly those due to intracellular pathogens and especially P. falciparum. Refeeding reactivates suppressed infection and can increase vulnerability to certain new infections especially of viral origin. Based on this, they argue that, “with autophagy suppressed [ by prolonged fasts ] pathogens are free to multiply,” and therefore: “in order to maximize immunity, we want our fasts to be shorter than twenty-four hours. Such short fasts are long enough to induce the highest rates of autophagy—thus maximizing immunity. Longer fasts would not increase autophagy, but would increase the period of immune suppression after the fast ends. Long fasts make infections worse, not better.” They did endorse shorter fasts  in the 16-24 hour range, citing the work in alternate day fasts. They also noted a couple of healthy population that practice some version of least partial intermittent fasting, Orthodox Christians following a Mediterranean diet  and the Kitavans,  “who are noted for their absence of disease […] where the “main and only cooked meal is at sunset, after the gardening has been completed, and generally consists of yams, taro, and occasionally fish, wild fowl, pork, or sea fowl eggs. During the day mangoes, breadfruit, bananas, and green coconuts and their milk may be eaten while working.”  We should probably acknowledge here that besides not quite practicing complete intermittent fasting, these populations may be healthy for other reasons. But I think their basic point here is that we have pretty good empirical data on safety of practicing a lifetime of shorter <24 hour fasts in real populations. In contrast, we have less empirical data for the long-term health impact - including any cumulative metabolic damage from the hypothetical proliferation of intracellular parasitic and opportunistic infection -- of practicing lifelong regular prolonged complete fasts >24 hours. Has delayed resumption of autophagy with prolonged fasts been raised as a concern here in the past? Interested in thoughts and perspectives on their arguments for keeping fasts <24 hours. References* * Link to their book via Amazon provided above, repaginated references obtained from http://perfecthealthdiet.com/notes/#Ch40  Mortimore GE et al. Quantitative correlation between proteolysis and macro- and microautophagy in mouse hepatocytes during starvation and refeeding. Proceedings of the National Academy of Sciences of the United States of America 1983 Apr;80(8):2179–83, http://pmid.us/6340116.  Pfeifer U, Bertling J. A morphometric study of the inhibition of autophagic degradation during restorative growth of liver cells in rats re-fed after starvation. Virchows Archive B: Cell Pathology 1977 Jun 24;24(2):109–20, http://pmid.us/407706.  Murray MJ et al. Infections during severe primary undernutrition and subsequent refeeding: paradoxical findings. Australian and New Zealand Journal of Medicine 1995 Oct;25(5):507–11, http://pmid.us/8588773.  Carlson AJ, Hoelzel F. Apparent prolongation of the life span of rats by intermittent fasting. Journal of Nutrition 1946 Mar;31:363–75, http://pmid.us/21021020. Hat tip to Mark Sisson: The myriad benefits of intermittent fasting, February 16, 2011, www.marksdailyapple.com/health-benefits-of-intermittent-fasting/.  Sarri KO et al. Greek Orthodox fasting rituals: a hidden characteristic of the Mediterranean diet of Crete. British Journal of Nutrition 2004 Aug;92(2):277–84, http://pmid.us/15333159. Trepanowski JF, Bloomer RJ. The impact of religious fasting on human health. Nutrition Journal 2010 Nov 22;9:57, http://pmid.us/21092212.  Malone MJ. Society—Trobriands, http://lucy.ukc.ac.uk/ethnoatlas/hmar/cult_dir/culture.7877 [link does not work but is the citation provided at http://perfecthealthdiet.com/notes/#Ch40 ]