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New rodent study on CR vs. Protein Restriction

Dean Pomerleau

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I stumbled across an new paper [1] which contrasts the impact of calorie restriction vs. protein restriction (PR) in C57BL/6 mice. Interestingly, and contrary to some other studies I've seen (e.g. see Dr. Greger's video on CR vs. PR), it didn't find that PR induced the same kind of changes to hormone levels (e.g. < IGF-1) or improvements in glucose regulation as CR. The protein restricted mice were restricted to get the same percent of calories from protein from their diet as the CR mice, but their absolute level of protein intake (i.e. grams of protein) was nonetheless a lot higher than the CR mice, because the PR mice were eating an ad lib number of calories (and as a result didn't lose weight).


Plus, the percent of protein wasn't all that low (the PR groups were 16%, 14% and 12% protein vs. 20% protein for control diet). Plus the protein in the chow fed to all the rats was all casein, which is high in the two amino acids thought to be inversely related to the CR-effect - methionine and cysteine. Not only that, but the mice chow used in the study had additional cystine, which is in very closely related to cysteine (in fact metabolically interchangeable to some extent). 


So it seems to me this wasn't a very good test of the hypothesis that restricting specific amino acids (methionine and cysteine) has similar effects on health markers (and lifespan) as CR. But I thought it was an interesting study nonetheless. 


It would seem to bolster the hypothesis (as outlined in Dr. Greger's video) that it is restriction in protein high in these two amino acids (i.e. animal products), and not protein restriction in general, that could mimic CR.


Go vegan :) .





[1]  The effects of graded levels of calorie restriction: II. Impact

of short term calorie and protein restriction on circulating
hormone levels, glucose homeostasis and oxidative stress in
male C57BL/6 mice
Sharon E. Mitchell1, Camille Delville1, Penelope Konstantopedos1, Jane Hurst2,
Davina Derous1, Cara Green1, Luonan Chen3, Jackie J.D. Han4, Yingchun Wang5,
Daniel E.L. Promislow6, David Lusseau1, Alex Douglas1, John R. Speakman1,5
Keywords: calorie restriction, protein restriction, glucose homeostasis, oxidative stress, adipokines
Received: April 01, 2015 Accepted: May 20, 2015 Published: June 01, 2015
Limiting food intake attenuates many of the deleterious effects of aging,
impacting upon healthspan and leading to an increased lifespan. Whether it is the
overall restriction of calories (calorie restriction: CR) or the incidental reduction in
macronutrients such as protein (protein restriction: PR) that mediate these effects is
unclear. The impact of 3 month CR or PR, (10 to 40%), on C57BL/6 mice was compared
to controls fed ad libitum. Reductions in circulating leptin, tumor necrosis factor-α and
insulin-like growth factor-1 (IGF-1) were relative to the level of CR and individually
associated with morphological changes but remained unchanged following PR. Glucose
tolerance and insulin sensitivity were improved following CR but not affected by PR.
There was no indication that CR had an effect on oxidative damage, however CR
lowered antioxidant activity. No biomarkers of oxidative stress were altered by PR. CR
significantly reduced levels of major urinary proteins suggesting lowered investment
in reproduction. Results here support the idea that reduced adipokine levels, improved
insulin/IGF-1 signaling and reduced reproductive investment play important roles in
the beneficial effects of CR while, in the short-term, attenuation of oxidative damage
is not applicable. None of the positive effects were replicated with PR.
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Thanks, Dean! I agree with your doubts about whether the experimental design permits answers to some important questions (important for us human CR practitioners), but the paper is worth a read.


I'd love to see some short-term human studies looking at the same dep. variables across varying levels of protein and amino acid intake.



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