The Jaminets cite six scientific papers as support for the idea that protein restriction will promote longevity. All of these papers report on experiments done with rodents (mice or rats). I have read five of the papers (I did not read the sixth because it appeared not to be original research) and have some thoughts about them.
The first is “Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age” by Sun et al. In this study, after a 7 day control period during which all mice received “standard laboratory chow,” they shifted 51 of the mice to “a diet containing a synthetic mixture of amino acids in lieu of natural sources of protein and including methionine at 0.43% per weight,” and an equal number were shifted first to “an equivalent diet containing 0.23% methionine by weight and after two further weeks [at the age of 12 months] were shifted to a diet containing 0.15% methionine.”
According to Sun et al:
“The control diet, prepared by Purina Test Diets, Inc. (Richmond, IN), was based upon the AIN-76 formulation. It was compounded using 43% cornstarch, 20% sucrose, 8% corn oil, 5% dextrin, 5% cellulose, 3.6% glutamic acid, vitamin and mineral mix, choline, and a set of defined amino acids in lieu of a protein source.”
The experimental diet was identical in all respects except for the ratio of methionine in the amino acid mix. In short, this diet contains no whole foods, only refined carbohydrates, amino acids, oils, vitamins, and minerals, and contained a large dose of each sucrose and corn oil rich in omega-6 fatty acids. Therefore, I find it hard to extrapolate the results to a whole food diet.
Sun et al report the results of this intervention on life span:
“Median longevity was 948 days in the control group (95% confidence interval 884–1,003 days) compared with 1,011 days (95% confidence interval 931–1,085 days) in the Meth-R group, an increase of 7%.”
Thus, we can say that in mice fed a diet of refined nutrients, if after the first third of their lives you switch them to a low methionine diet, they will gain an average of 63 days of life.
Assuming that you could achieve a similar precision of methionine restriction and the same would happen in humans, a 7% increase in lifespan would add 4.9 years to a base of 70 years, 5.6 years to a base of 80 years, 6 years to a 90 year lifespan, and 7 years to a base of 100 years. This for enduring two thirds of your life—say, 60 years-- eating a protein- or methionine restricted diet. I personally don’t find those results compelling enough for me to restrict my protein intake. I’m gambling a lifetime of restriction for a mere 7 extra years, assuming I don’t die accidentally in the mean time.
The second paper, “Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance” by Miller et al. From the methods portion of this paper, we find that they used the same base diet of purified nutrients used by Sun et al:
“The control diet, prepared by Purina Test Diets, Inc. (Richmond, IN, USA), was based upon the AIN-76 formulation, and contained 0.43% methionine by weight. It was compounded using 43% corn starch, 20% sucrose, 8% corn oil, 5% dextrin, 5% cellulose, 3.6% glutamic acid, vitamin and mineral mix, choline, and a set of defined amino acids in lieu of a protein source. Amino acid concentrations were as follows: 0.93% arginine, 0% cystine, 2.31% glycine, 0.27% histidine, 0.82% isoleucine, 1.11% leucine, 1.15% lysine, 0.43% methionine, 1.16% phenylalanine, 0% tyrosine, 0.82% threonine, 0.18% tryptophan and 0.82% valine. Related diets containing 0.1–0.15% methionine were also prepared by the same company for our use, in which cornstarch was substituted for the diminished methionine; the diet containing 0.15% methionine is available as Catalogue no. 52501 (58MK).”
Miller et al describe their method:
“When the mice were 6 weeks old, half of them were placed on a diet containing 0.43% methionine (‘control’ mice) at age 6 weeks, and the other half were placed on a diet containing lower levels of methionine, initially 0.1%, but then increased at 4 months of age to 0.12% and again at 6 months of age to 0.15% to diminish the incidence of rectal prolapse and early death.” [Italics added]
Wonderful. They admit here that the diets with restricted methionine apparently increased the incidence of rectal prolapse and early death. In fact, in the results portion of the paper they state:
“It is clear that the experimental group had a higher risk of death in the first year of the protocol, but that this effect was diminished when methionine levels were raised to 0.15%. Survival at ages beyond 365 days was much higher in mice receiving the Meth-R diet. The log-rank test found the difference between the two groups significant at P = 0.02 when all mice were considered, and at P < 0.0002 when only those surviving more than 365 days were considered.”[Italics added]
So the difference in life span reached the highest significance only when they did the calculations leaving out the mice who died early deaths on the methionine deficient diet. Miller et al report the results on life span:
“Maximum lifespan of the control mice, estimated as the mean age of the oldest 10% to die (1144 ± 26 days, mean ± SD, n = 4), is significantly less (P < 0.002 by Student's t-test) than the corresponding value for the restricted mice (1261 ± 32 days, a minimum estimate with 5% of the mice still living).”
In this study, the restricted mice lived an average of 117 extra days, which is 10% longer than the unrestricted animals. Note that they achieved this difference by only considering “the mean age of the oldest 10% to die,” in other words, by factoring out the animals that died early in the methionine deficient group. That is one way to get the conclusion you want.
Again, assuming this could translate to whole foods and humans, you spend your whole life on a border line deficient diet, hoping to avoid early death or rectal prolapse, so that you can live an extra 7 to 10 years. You decide if the cost justifies that benefit.
The third study is “Low Methionine Ingestion by Rats Extends Life Span” by Orentriech et al. In this study, “60 Fischer 344 male rats obtained from Taconic Farms were prefed for 2 wk a nonpurified diet (Ralston Purina, St. Louis, MO) were randomly assigned to one of two groups receiving a purified diet containing either 0.86% or 0.17% L-methionine.”
Like Sun et al, they used AIN-76 formulated food, too unlike natural foods to provide a solid base for generalizing to natural diets. The results:
“Rats fed low methionine (0.17%) starting at 4-6 wk of age showed greater median (1059 vs. 818 d) and maximum (1252 vs. 1116 d) life spans than those fed 0.86% methionine (Fig. 1).When the methionine concentration of the diet was reduced below 0.12% no rats survived for longer than 1 mo (data not shown).”
So the rats on the methionine-restricted diets lived a median of 241 extra days, and when looking at maximum life spans, 136 extra days. The abstract states the restricted animals lived 30% longer, a number derived by only considering the median life span of each group, as 241 is 30% of 818. Considering maximum life spans, the difference was only 12%.
There was a cost to the lifelong methionine restriction leading to a 30% greater lifespan:
“On the other hand, rats fed a 0.17% methionine diet from 42 d of age failed to gain weight throughout their lives (Fig. 2). At the end of 90 d of feeding 0.17% methionine to rats, the reproductive organs (testes, seminal vesicles) were smaller and lung and heart were larger (relative to body size) than in rats fed 0.86% methionine.”[Italics added]
The average body mass of restricted rats was 100g from 42 d of age onward, whereas the unrestricted rats had an average body mass of 400g. The unrestricted animals had a body mass 4 times than of the restricted animals, comparable to wild rats which may achieve body mass of 500 g. This along with the reduced size of the reproductive organs indicates that the greater life span was achieved by restriction of body growth to juvenile size.
Put in human proportions, if 120-150 pounds is adult size, the restricted rats in this study attained weight comparable to about 30-40 pounds. Assuming this applied in some measure to humans eating natural foods, would you trade attainment of mature body size for a 30% increase in life span?
Because this study restricted the rats’ methionine intake from the age of 42 days on, his does not tell us anything about how methionine restriction will affect the lifespan of an adult beginning methionine restriction later in life after attaining mature stature.
Further, this study only shows that if you’re using a purified diet to feed rats, they will live 30% longer if you restrict their methionine intake to a level that stops the growth process early in life. It does not compare rats on a low methionine refined food diet to rats on a whole foods, self-selected, species appropriate diet. I would like to see a study examining the difference in life span between rats eating their natural diet for a lifetime, and rats eating this toxic mixture of refined corn oil, sugar, and corn starch. I really don’t see how anyone can make conclusions about the effect of whole food proteins on human life spans by doing or reading any of these studies of rats eating refined amino acid mixtures.
The fourth paper, “Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans” by López-Torres and Barja, is not even an original experiment, so I did not take the time to track it down for comment.
The fifth study, “Excess methionine suppresses the methylation cycle and inhibits neural tube closure in mouse embryos” by Dunlevy et al, reports that “exogenous methionine unexpectedly caused frequent NTD in cultured mouse embryos.” (Thanks to Matt Schoeneberger from S.P.E.E.D. for assistance getting ahold of this article.)
From the materials and methods section:
“Random-bred CD1 mice were purchased from Charles River, UK. Embryos were generated by timed matings, explanted at embryonic day (E) 8.5 and cultured in rat serum as described previously [11,12]. Methionine, ethionine, cycloleucine, folic acid or 5-azacytidine (Sigma–Aldrich) were dissolved in PBS and added to cultures as 1% (v/v) additions. The same volume of PBS alone was added to control groups.”
Thus, in this study they cultured mouse embryos outside of the uterus in a solution that contained isolated methionine, resulting in frequent neural tube defects in the embryos. At most this study shows that when you culture mouse embryos in rat serum instead of the uterus, with the addition of isolated methionine, you get “unexpected” neural tube defects (NTD). This may show that isolated methionine is a toxin for mouse embryos growing in rat serum, but doesn’t say anything about the effect of natural foods like meat on embryos of any species growing as nature designed, in utero.
Outside of a laboratory experiment like this, methionine would reach the embryo by route of the mother consuming methionine-rich whole foods which would contain a full complex of amino acids along with nutrients that reduce the incidence of NTD, such as pyridoxine (vitamin B6), cobalamin (B12), or folate, all of which could modify the outcome. The condition of culturing in rat serum lies so far outside the natural course of mouse development that I don’t understand why anyone would assume that this experiment tells us anything about the effect of natural methionine-rich whole foods on the intrauterine development of any species.
The last study, “The atherogenic effect of excess methionine intake” by Troen et al, reports on their experiment with adding isolated methionine to a standard diet:
“Mice were acclimated on a standard rodent maintenance diet recommended by the American Institute of Nutrition and fed ad libitum for 1 week (AIN-93M) (51). They were then systematically assigned to four groups of similar mean body weights and fed for 10 weeks with control and experimental diets formulated on the basis of Hoffman et al. (15) with vitamin-free, ethanol-precipitated casein and the appropriate vitamin mix (Harlan TEKLAD, Madison, WI). A control group continued eating the control AIN-93M diet. Two diets were formulated to induce hyperhomocysteinemia through combined folate, vitamin B12, and vitamin B6 deficiency with or without methionine enrichment: diet “M+B-,” a methionine-enriched/B vitamin-deficient diet, and diet “B-,” a B vitamin-deficient diet with control levels of methionine. A third, methionine- and B vitamin-enriched diet, “M+B+,” was used to determine the effects of dietary methionine enrichment without hyperhomocysteinemia.”
The base AIN-93M diet consists of, by weight, 47% corn starch, 16% dextin, 14% vitamin-free casein, 10% sucrose, 5% cellulose, 4% soybean oil, and the remainder as isolated vitamins, minerals, L-cystine, and t-butylhydroquinone. Again, a fully refined nutrient diet, to which they added additional refined, isolated methionine and B-group vitamins for the experimental arms. Again, I don’t see how this can tell us anything about diets composed of whole foods, which still contain unknown components which may modify the effects of any of the components in these refined diets.
The results of methionine-enrichment included increased atherosclerosis:
“Dietary methionine enrichment significantly increased aortic lesion area beyond the baseline vascular pathology of control mice (Fig. 2). The methionine rich, B vitamin-deficient diet (M+B) resulted in a nearly 2-fold increase in lesion area compared with controls (lesion area was 45,923 ± 2,804 μm2 vs. 24,557 ± 1,712 μm2, respectively, P < 0.05). B vitamin enrichment (M+B+) only partially mitigated this increase despite completely normalizing homocysteine levels (lesion area was 37,936 ± 1,298 μm2, P < 0.05 vs. controls).”
Strictly speaking, this study only tells us that adding isolated methionine to a diet, thereby altering the overall ratio of amino acids, increases atherosclerosis. In short, this study shows us that isolated methionine has a toxic, and that its toxic effect can’t be reduced by ingesting isolated B-vitamins. So, don’t add isolated methionine to your diet!
This study does not tell us that natural foods rich in methionine have the same effect, because they did not test natural foods. In all these studies, the situation is the same as with T. Colin Campbell’s research using isolated casein, not whole milk products, to promote cancer in laboratory animals. You can’t draw conclusions about whole foods or diets based on whole foods from experiments done with isolated nutrients.
Just to experiment, for a couple of days Tracy and I reduced our meat intake by half. I reduced my meat intake from more than a pound daily to just about one-half pound, and, as the Jaminets suggest, replaced the protein with starchy carbohydrates (potatoes and sweet potatoes). For both Tracy and I, this resulted in a noticeable decline in mood and a dramatic increase in hunger and intestinal gas, along with a disruption of bowel function.
So I remain unimpressed with the results of these studies, and find in them no reason to believe that making any attempt to deliberately restrict my protein intake by conscious decision will have any significant effect on my longevity. Which brings me to another point.
One of the benefits I have received from paleo dieting has been a sharpening of my primal, unconscious guidance system. Basically, the longer I have eaten in a “primal” fashion, the less conscious effort I find myself putting into food selection. I follow my natural inclination to eat meat, fat, vegetables, fruits, and nuts in amounts determined by appetite rather than reason, and I get rewarded with pleasant moods, smooth digestion, abundant energy, and good health. Every time I interfere with this by trying to impose on my food selection some guidance from the haughty conscious mind, I have negative results, almost always appearing first in the digestive tract and mood.
The lesson I take from this is that the conscious mind does not know enough to regulate food intake, and, so long as I eat practically primal foods, I am better off if I leave regulation of food intake to primal wisdom of the body.
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