All:
I've previously posted a series of studies showing that alternate-day fasting does not provide the metabolic effects of CR in humans, despite the fact that it has some parallel effects in rodents (eg, improved insulin sensitivity) -- although intermittent feeding raises IGF-1 whereas CR lowers it in mice (3) and, crucially, alternate-day fasting without lowering Calories does not extend lifespan even in rodents. (See also here and here). Now, as pointed out by Al Pater on the CR Society list, we have yet another human study, once again showing no effect on major CR-related parameters:
BACKGROUND: Intermittent fasting (IF) was shown to increase whole-body insulin sensitivity, [see below on this previous report ((2) below -MR] but it is uncertain whether IF selectively influences intermediary metabolism.
DESIGN: Glucose, glycerol, and valine fluxes were measured after 2 wk of IF and a standard diet (SD) in 8 lean healthy volunteers in a crossover design, in the basal state and during a 2-step hyperinsulinemic euglycemic clamp, with assessment of energy expenditure and phosphorylation of muscle protein kinase B (AKT), glycogen synthase kinase (GSK), and mammalian target of rapamycine (mTOR). We hypothesized that IF selectively increases peripheral glucose uptake and lowers proteolysis, thereby protecting protein stores.
RESULTS: No differences in body weight were observed between the IF and SD groups. Peripheral glucose uptake and hepatic insulin sensitivity during the clamp did not significantly differ between the IF and SD groups. Likewise, lipolysis and proteolysis were not different ... IF decreased resting energy expenditure. IF had no effect on the phosphorylation of AKT but significantly increased the phosphorylation of glycogen synthase kinase. Phosphorylation of mTOR was significantly lower after IF than after the SD.
CONCLUSIONS: IF does not affect whole-body glucose, lipid, or protein metabolism in healthy lean men despite changes in muscle phosphorylation of GSK and mTOR. The decrease in resting energy expenditure after IF indicates the possibility of an increase in weight during IF when caloric intake is not adjusted. (1)
Re (2): as they note in the full text,
Although Halberg et al showed an increased glucose infusion rate during the hyperinsulinemic clamp in their study we were not able to discern differences in peripheral or hepatic insulin sensitivity despite equal diets and a crossover design. The lack of an effect on peripheral insulin sensitivity was strengthened by the data on phosphorylated AS160-thr642-a downstream target of AKT that is involved in the translocation of GLUT4 to the plasma membrane. Insulin-mediated phosphorylation ofAS160 was shown to be decreased in patients with type 2 diabetes and after short-term fasting, but it is uncertain whether IF selectively influences intermediary metabolism. Such selectivity might be advantageous when adapting to periods of food abundance and food shortage.
Certainly, none of the other human intermittent fasting studies have suggested improved glucose metabolism or insulin sensitivity.
Re the more interesting effect on mTOR:
pmTOR-ser2448 [the residue whose activating phosphorylation rapamycin blocks -MR] was not different between the IF and SD groups in the basal state but was significantly lower during the clamp after IF ... [We found no differences in the total muscle content of AKT, GSK-3, or mTOR … Because we did not assess protein synthesis rates, we cannot support that the lower mTOR phosphorylation in the basal state after IF than after the SD reflects lower protein synthesis, as shown earlier for short-term fasting (14). LBM was not affected, although the duration of our study may have been insufficient to observe measurable effects on muscle mass
This would be more promising ... but again, the rodent data is pretty clear that whatever the narrow metabolic benefits of EOD/ADF/IF may be, it doesn't retard aging except when it's associated with an actual reduction in Caloric intake.
See the full text here.
-Michael
1. Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism.
Soeters MR, Lammers NM, Dubbelhuis PF, Ackermans MT, Jonkers-Schuitema CF, Fliers E, Sauerwein HP, Aerts JM, Serlie MJ.
Am J Clin Nutr. 2009 Sep 23. [Epub ahead of print]
PMID: 19776143
2. Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F.
Effect of intermittent fasting and refeeding on insulin action in healthy men.
J Appl Physiol. 2005 Dec;99(6):2128-36. Epub 2005 Jul 28.
PubMed PMID: 16051710.
3. Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6216-20. Epub 2003 Apr 30. PubMed PMID: 12724520; PubMed Central PMCID: PMC156352.
Edited by Michael, 28 September 2009 - 04:19 PM.