I want to address the big picture before I dig into details. I will start by presenting some CR studies and Protein Restriction Studies or some combination thereof.

First: 
Protein Restriction Makes No Difference

Differential effects of dietary caloric and protein restriction in the aging rat. This study begins by noting that in previous calorie restriction studies, protein was reduced in all of the rats’ diet so the individual effects of CR and protein reduction are unclear. The test groups consisted of two main groups: A CR’ed group and a Non-CR’ed group. The Non-CR’ed group had three sub-groups with protein intakes of 18,30, or 42%. The CR group’s calories were restricted by 1/3 and thus the three CR sub-groups had protein intakes of 12, 20, or 28%.  The researchers concluded the results showed CR in general was associated with increased longevity, but protein restriction was not shown to have any effect, positive or negative.

NOTE/ISSUES: First note that I only had access to the abstract, so I can’t make pointed agruements. What I want to know is the details of the diet besides protein percentage, which may or my not be in the paper. What kind of protein, carbs, and fat? Since there is the possibility protein restriction in general may not lead to longevity, but some detail about protein restriction, knowing the diet is important before passing judgment. However, this could bring a certain aspect of protein restriction to light (such as methionine or maybe damage from AGEs) if the Met happened to be limited or the protein was low AGEs, etc.

Second:
Protein Restriction Alone Mimics CR Bio Marker Changes But Only A Slightly Increased Longevity Effect By Itself
Dietary Protein Restriction Decreases Oxidative Protein Damage, Peroxidizability Index, and Mitochondrial Complex I Content in Rat Liver. The researchers note that in typical CR experiments, calories are restricted by 40%  which correlates to a protein restriction (PR) of 40% unless the diet is specifically modified. This study measured the following bio markers (known to be affected by CR) after a 7 week protein  restricted diet: mitochondrial ROS production, membrane saturation, and endogenous DNA, protein, and lipid oxidative damage. The findings showed that the rats on PR displayed changes in the measured bio markers similar to what is seen in CR, thus the authors suggest that PR is likely responsible for at least some of the CR effects.

The researchers do point out that many studies looking at PR show increased longevity, but the increase has never been equivalent to the CR effect. 16 different PR studies found a mean longevity increase of 19.2% with a mean PR of 68%, which suggest that a PR of 40% should show a 11.5% longevity increase in contrast to the 40% longevity increase seen with a 40% CR diet.

NOTE/ISSUES: This study did not look at the total life span effect, but only bio markers for 7 weeks. Also, since the PR rats only had protein reduced but not other nutrients, their calories were therefore reduced by 8.5% (but a CR diet of only 8.5% would not affect bio markers like this). Also, the authors note that the effects could be related to the effective methionine restriction, and not protein in general. This suggests protein restriction may play a part in the effect of calorie restriction, but the mechanism is unknown.

Third:
High Protein is Good? Or is it the CR?
The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. The researchers fed 6 groups of mice different diets to observe types of dietary restriction on life span.   
Group 1: Non-purified diet, ad libitum (averaged ~110kcal/week), min 23% protein and 4.5% fat 
Group 2: *control group*, 85kcal/week, 25% cal restriction after weaning, 20% casein protein 
Group 3: 50kcal/week, 55% cal restriction, protein + vitamin + mineral content equal to group2,restricted AFTER weaning, 35% casein protein 
Group 4: 50kcal/week, 55% cal restriction, protein + vitamin + mineral content equal to group2, restricted BEFORE weaning, 35% casein protein 
Group 5: 50kcal/week, 55% cal restriction, vitamin + mineral equal to group2,
BUT *protein* was gradually reduced over life span and replaced by carbs:
weaning – 4mo = 35% casein protein
4mo-12mo = 25% casein protein
12mo-24mo = 20% casein protein
24mo – death = 15% casein protein 
Group 6: 40kcal/week, 65% cal restriction after weaning, protein +vitamin + mineral equal to group2 (paper did NOT specifically state the % protein, but my calculation gives ~43% protein)

Results:
Groups 3-6 had a mean an max life span 35-65% of Group 1, and 20-40% of Group 2.
Group 6 lived longest.
Longevity (shortest-longest) = 1<2<5<4<3<6

NOTES/ISSUES:
The purified diets used casein protein; we have all sorts of protein choices available as humans. Which means we could have more or less AGE exposure by choice. Also, the methionine levels were constant in this experiment with the exception of group 5.

Group 5′s protein was gradually replaced by *carbohydrates*: half sucrose and half corn starch. Doesn’t seem the healthier choice! More sugar and starch? Hum….I don’t like that one bit. I would like to find a study where the protein was replaced with fat (and not trans fat either!). Personally, I think this is where the experiment messed up. I feel that the results of this group have been negatively affected by the increased starch and sugar. I can’t take this result too seriously, but I also realize that in the 1980′s (when this study was done), everyone thought carbs were good and fat was bad. So, I can’t criticize their carb choice logic, but I still think the nature of the added carbs was not ideal, and may have shewed the results negatively.

Also, other studies showing protein restriction alone, while having statistically significant increases in longevity, do not compare to the much greater effects of calorie restriction. With only one group at the high level of restriction and the only protein reduced group being bunk, IMO one does not have enough evidence to make the conclusion that a high protein is ideal. Especially if the protein was low Met or low AGEs because there could be an aspect of protein restriction being shown without the detailed analysis to know what is actually going on. Now, it may not make a huge difference one way or the other, but I just don’t feel this study proves anything conclusive besides how *awesome* CR is.

My Final Statement On This Broad Issue:
First, this is by no means a comprehensive review of all papers. I had to resort to free papers and abstracts, and I had trouble finding papers that focused on the broad picture. Many of the papers I found got more into the details of PR, which I will be delving into in the next few posts in this series. During my initial research for this post, not only did I realize how complex this problem is, but I also realized the difficulty of finding studies I think accurately research the issue. I have yet to see even an abstract that I think may show the type of experiment I am looking for, not to say they doesn’t exist, but I didn’t have luck locating anything like what I wanted. So, PLEASE send any papers my way that you feel are representative of this issue.

I am currently dissatisfied with these findings, and feel in this situation, the details cannot be ignored for the large picture. However, with that being said, I’m not sure protein restriction will have a profound effect on calorie restriction, but I am also not sure that a high protein diet is the best either. Right now I am taking “the middle way” approach, but I may change my mind after I look more at the evidence for IGF-1 and Methionine. I also may decided that veggie or animal protein is superior, and I also want to explore the fat relationship.

 Please, if you are capable of supporting research you feel passionate about, DO IT! I am hoping to join the 300 in 2010 if the slots don’t fill up. Until then, I will blog so I can contribute in my own way. Science needs your help!