plate with chicken and vegetables (696 x 522)

I have written before on caloric restriction (CR) and its effect on reactive oxygen radicals (ROS) and longevity. Basically, it has been shown quite conclusively that a 30-40% reduction in dietary caloric intake (about 1,300-1,400 calories for humans) can result in marked reduction in ROS generation by the electron transport chain in the mitochondria, and in a 20-50% life extension in different species. But as scientists are wont to do, they couldn’t leave good enough alone—they had to dig a bit deeper. And things got a bit more difficult.

In a report published in the Journal of Bioengineering and Biomaterials (vol.36, pp. 545-552, 2004), Sanz and his colleagues from Complutense University in Spain wanted to find out which component of the diet was responsible for the beneficial effects of CR.

They had 2 groups of rats: The control group had a normal diet and consumed as many calories as they wanted (ad libitum in scientific lingo; hence ad lib). The other group also consumed total calories ad libitum but their caloric intake of the proteins in the diet was kept at a 40% lower level than the controls.

The results were very interesting and somewhat unexpected: After 7 weeks on this regimen, the liver of the protein-restricted animals showed 30-40% decreases in mitochondrial production of ROS and in oxidative damage to nuclear and mitochondrial DNA. They were able to identify that the decrease in ROS generation occurred at complex I of the electron transport chain, the same location where such a reduction occurs on a CR diet.

Sanz and his coauthors conclude that

“the results suggest that part of the decrease in aging rate induced by caloric restriction can be due to the decreased intake of proteins acting through decreases in mitochondrial ROS production and oxidative DNA damage.”

And they conclude the paper with this hopeful note for us mortals who’d rather eat and enjoy our short stay on earth than live long and die famished:

“Interestingly, these tissue oxidative stress-linked parameters (generation of ROS and oxidative damage to nuclear and mitochondrial DNA) can be lowered by restricting only the intake of dietary protein, probably a more feasible option than caloric restriction for adult humans.”

Voilá! No pain, all the gain.

Maybe. But consider the fact that amino acids (the building blocks of proteins) are essential for generating new muscle tissue. A 40% reduction in normal protein intake is bound to result in reduced muscle tissue synthesis. Want proof? Just look at a picture of practitioners of CR: they look emaciated, skin hanging over their skeleton. This couldn’t be good for you. As my mother would say, “Oy Vey, who would want to live like that? Only a Meshugener (a nut).”

To the rescue in rides, the French cavalry made of scientists from Université d’Auvergne published a report this month (FASEB Journal, vol. 20, pp. 2439-2450, 2006). They compared 21-month old rats (really old) on a 40% across the board caloric reduction diet with a group of rats of the same age who were on a diet that overall had a 40% reduction in diet, but that the protein component of the diet was not reduced at all. And what did they find?

Exactly as you would intuitively guess: The rats receiving the higher protein diet made more muscle fibers and their muscle strength was increased. Also, their mitochondrial function was better than in the control group; they made more ATP, and their electron transport activity was improved, with a lowered rate of ROS generation.

So, who to believe? I tend to put more credence on the French study, and not because it makes more intuitive sense; biology works in mysterious ways, and it never fails to surprise. The French study was longer term (5 months) as opposed to the Spanish study (7 weeks). The Spanish investigators could have easily missed the longer term effects of relative protein deprivation. Furthermore, the French study measured not only biochemical parameters like ROS production, but also parameters on the tissue level, like muscle fiber synthesis, and physiological parameters such as muscle strength. The Spanish study measures ROS generation only. In other words, the French study measured more parameters that are important in real life. Reminds me of my days in medical training when I felt a bit cheated when my patient died with all the blood tests being perfectly normal.

What’s my take on this issue? I think the jury is still out and more studies are clearly needed to clarify the role of proteins in the CR diet. In the meantime, I would recommend consuming normal amounts of proteins, especially from plants (legumes) and fish or chicken. Beef in moderate amount is OK too.

Remember the motto of the royal house of Windsor: “Everything in Moderation”. The queen mother was living proof; she died at 100 years of age.