Benefits of 40% CR with 1% Restriction (????) Part 4. Lingering Questions

[Guest guest]

Hi folks:

But many many questions remain. Here are a few of the more obvious

of them:

The principal question is whether it will be confirmed that the

restriction of just Met (or perhaps a small group of amino acids)

will result in substantial extension of maximum lifespan.

Second, if it is confirmed, then what is the optimal Met intake as a

percentage of total calories? The RDA has been set to prevent any

chance of deficiency. Is it then overly generous? I doubt that at

the time they set the RDA for Met, and protein in general, they had

in mind that it might be dangerous in excess. The fact that an

experiment in rats which restricted Met by 94% reported a substantial

extension of lifespan but no protein deficiency problems could be

interpreteted to suggest that the RDA may be dramatically in excess

of the optimal intake.

Third, once the optimal Met intake is established, what is the

optimal total caloric intake to go along with that amount?

Fourth, are there other amino acids the restriction of which would

also be desirable?

Fifth, if we were to eat everything except Met ad lib, but restricted

Met to the RDA, and allowed our body weights to rise to 300 pounds,

how would our biomarkers for CVD and diabetes compare with those of

the WUSTL subjects? Is it just variations in Met that are

responsible for the lion's share of all these effects? The benefits

demonstrated in the Met restriction paper referenced above certainly

suggest it might be. But does that seem likely?

Sixth, is it just reduced Met intake that explains the 70% reduction

in cancer deaths in CR mice? Al has referred me to two papers,

rather old, which suggest that there is an expanded need for either

Met or homocycteine to assist in the replication of cancer cells.

Perhaps this could be the mechanism? Or does excessive Met reduce

our immune response to cancer cells? Or is restricted Met intake the

factor responsible for the reductions in inflammation, and for large

improvements in CRP and IL-6 readings in people on CRON?

Seventh, is it primarily excessive Met intake that is responsible for

the increased insulin resistance seen in obese people? And reduced

Met for the huge decline in fasting insulin in people on CR?

Also interesting is the fact that while the average BMI in the US has

increased significantly in the past thirty-odd years, while fat

intake has declined, the percentage of deaths attributed to CVD has

fallen substantially. Might the explanation be that fat content,

especially animal fat, is, in a very general sense, often a marker

for Met?

Al has also raised the point that it possibly may not be the Met, per

se, that is the problem. But instead harmful effects of conversion

of Met to other products. If so then it may be that biomarkers for

these harmful products might be test parameters to consider in

examining whether it is the quantity of methionine or the metabolism

of it that is responsible for the apparent negative effects.

The intuitive answer to most of these questions would seem to

be " No " . But if Met restriction extends lifespan significantly then

one might suppose it must be doing things to reduce the incidence of,

or progression of, the principal causes of death as well as retarding

aging. How else could the apparent benefits be explained?

Remember those chinese centenarians, who were eating only 40g of

protein daily? The way they managed that was, largely, by eating

about half their caloric allotment in the form of sweet potatoes. Is

it likely pure coincidence that the Met content of sweet potatoes is

a very low 0.19%? As a personal working assumption I believe this

low Met intake likely made a significant contribution to the

longevity of these chinese centenarians. But this is nowhere even

remotely close to being proven.

And how about the empty calorie foods we all (certainly including me)

regularly scorn here? Is it really constructive to eat foods that

provide us with substantial amounts of the nutrients we know for

certain we do need, but in many cases in amounts well beyond what are

necessary, if at the same time they are accompanied by additional Met

which, it seems, may be perceptibly increasing our aging rate?

Sometimes I see that my daily intake of a certain nutrient is ten or

more times the RDA. Isn't it likely there is a point at which the

health benefit returns to be had from from additional quantities of

these vitamins and elements are not only diminished, but diminished

to zero? Or perhaps even below zero? And if so then possibly health

would be better promoted - instead of piling up more and more of

these nutrients - by satisfying our caloric needs with the addition

of Met-free (perhaps largely 'empty') calories? I do not know the

answer. But it seems to me like a legitimate question.

Also, since most of the Met we consume comes from animal products, if

the primary route by which CR extends lifespan is Met restriction

then why do we not see vegans living 30% longer than the rest of us?

Some Seventh Day Adventist data does suggest longer lives for

vegetarians. The number I have seen is a sizeable seven years. But

not the 30% to 40% seen in animal CR experiments. This is a piece of

the puzzle that doesn't seem quite to fit.

Up until now I have spent quite a bit of time thinking how to prevent

the more common 'diseases of aging', and CR has seemed to be the most

effective route to take to achieve that. But now it looks like in

addition we should be considering the factors that affect, and trying

to find ways to measure, our biomarkers for *aging rate*. Is there a

practical way to measure our own rate of mtDNA damage and

mitochondrial ROS production? And it looks like Met restriction may

be a very important component of such a strategy. Does the aging

rate simply act to vary how soon the diseases of aging appear? Or is

it an additional factor helping to determine an individual's

potential lifespan, largely independent of the diseases of aging,

which can be avoided by other means?

So there are many unanswered questions, of which the above are just a

few. As always we do not have conclusive evidence to permit us to

come to a definitive conclusion. But my take on this, fwiw, is that

while I am more than prepared to reverse my view if future studies

suggest that to be appropriate, right now on balance it seems to me

that substantially reduced Met intake may be very helpful.

So I am now starting to shift my Met intake down in the direction of

the RDA. It seems unlikely to me that reducing Met intake to the RDA

level, if that is practically achievable, eating foods I have long

believed to be healthy, could present a risk to health. And it seems

to me that waiting several decades for decisive proof, before making

the change, is not a viable alternative. But it is a gamble either

way. This is yet another case of placing our bets, based on what we

THINK we now know, where we imagine they might produce the best

health returns. But sometimes when one bets one loses. An example

of which might be putting too many egg whites in one's basket?!

For a little perspective. Based on my target BMI of 21, and using the

41·0 mg/kg.day number for an 'ad lib Met' number ............. for

me 30% restriction gives a total Met intake amount of 1·93g. 40%

restriction gives 1·65g. 50% ..... yields 1·38g. 60% ..... 1·1g.

70% ...... 0·83g, and the RDA represents between 75% and 80%

restriction. The last day I listed everything I ate, CRON-o-Meter

told me I consumed 0·9g of methionine. That is somewhere between 65%

and 70% restriction for me. That is pretty good, but it was simply

because I didn't happen to eat any fish, egg whites or fat-free

cottage cheese that day. I finished off the last of my egg whites

this morning, so I don't think I want to look to see what my Met

number was for today!

Maybe now Jeff should add another criterion to his Nutrition

Challenge: concoct a diet plan that, as well as satisfying all the

other requirements, contains not more than the RDA for Met?

More coming .......................

Rodney.