Fasting Mimicking Diet Looks Pretty Good

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Epistemic sta­tus: pretty much fac­tual.

CW: diets, calories

One of the odd things about work­ing on longevity is that now peo­ple ask me for lifestyle ad­vice.

Or they ask me what I, per­son­ally do to live longer.

Mostly my re­sponse has been a lame “um, noth­ing?”

There are, as of now, no in­ter­ven­tions shown to make hu­mans live longer or slow or re­verse the hu­man ag­ing pro­cess. And, of the in­ter­ven­tions re­ported to make an­i­mals live longer, many are doubt­ful, and many are too risky or un­pleas­ant to make the cost-benefit trade­off look good for healthy peo­ple.

Also, as a per­sonal mat­ter, I’m just not very in­ter­ested in my own “lifestyle op­ti­miza­tion” for the most part. My mo­ti­va­tion is about helping peo­ple, not es­pe­cially staving off death for my­self; I think I’m more men­tally pre­pared for death than most peo­ple my age. Cer­tainly I’ve thought about it more con­cretely. (BTW, if you too like to know all the gory and tech­ni­cal de­tails about how peo­ple die, this blog by an ICU nurse is gold.)

And “lifestyle op­ti­miza­tion” turns out to be heav­ily about diet and ex­er­cise, and…I con­fess, diet cul­ture re­ally creeps me out. Not at all my thing.

That said, there is a lifestyle in­ter­ven­tion that seems pretty ev­i­dence-based and also pretty low on risk and in­con­ve­nience: the Fast­ing Mimick­ing Diet, de­vel­oped by Valter Longo of USC.

It’s ac­tu­ally been tested in a clini­cal trial on 100 healthy par­ti­ci­pants, where it im­proved a bunch of bio­mark­ers re­lated to ag­ing and dis­ease (re­duced IGF and blood pres­sure, though no change in glu­cose, triglyc­erides, choles­terol, or CRP.)

The re­ally good re­sults are in mice, where it res­cues both Type I and Type II di­a­betes as well as a mouse model of MS, re­duces tu­mors by 45% and der­matitis by 50%, in­creases mes­enchy­mal stem cells by 45x, im­proves mo­tor and cog­ni­tive perfor­mance, and re­sults in an 11% lifes­pan ex­ten­sion.

So, what is the FMD?

It’s a 5-day low-calorie, low-carb, low-pro­tein diet, fol­lowed by a pe­riod of eat­ing how­ever you would by de­fault.

Caloric re­stric­tion (re­duc­ing calorie in­take about 13 from baseline or ad-lib) is prob­a­bly the most repli­cated lifes­pan- and healthspan-ex­tend­ing in­ter­ven­tion in an­i­mals. It’s about 30-40% life ex­ten­sion in mice and rats. In mon­keys, it ex­tends lifes­pan lit­tle if at all, but de­lays age-re­lated dis­ease and hair loss. How­ever, the side effects are non­triv­ial — hu­mans on CR ex­pe­rience weak­ness, lethargy, de­pres­sion, mus­cle wast­ing, and neu­rolog­i­cal defic­its. (Un­dereat­ing also stunts growth in chil­dren and ado­les­cents, and un­der­weight in women causes in­fer­til­ity, mis­car­riage, and preterm birth.)

Mice seem to get most of the benefits of CR, in­clud­ing an equally ex­tended lifes­pan, from an isocaloric but low-pro­tein or low-me­thio­nine diet. Low-pro­tein diets are safe for hu­mans and might not be as dam­ag­ing to qual­ity of life, but they do definitely in­hibit phys­i­cal fit­ness/​perfor­mance.

Alter­nate-day fast­ing in mice has a bunch of benefits, in­clud­ing lifes­pan ex­ten­sion of 10-30% de­pend­ing on mouse strain, as well as re­duc­tion in can­cer in­ci­dence, and lower lev­els of neu­ral dam­age in mouse mod­els of Alzheimer’s, Hunt­ing­ton’s, Park­in­son’s, and acute brain in­jury. In a ran­dom­ized con­trol­led trial in hu­mans, al­ter­nate-day fast­ing caused weight loss but no im­prove­ment in metabolic/​car­dio­vas­cu­lar pa­ram­e­ters.

The FMD seems like the least amount of dietary re­stric­tion that is still known to cause life ex­ten­sion. 5 days/​month of low calorie in­take isn’t that big a com­mit­ment.

Valter Longo sells patented pack­aged foods for the FMD, but they’re pricey ($300 for five days).

What I find more aes­thetic, and cheaper, is an adapted ver­sion, which I’m try­ing now:

For the first five week­days of ev­ery month, eat noth­ing but (non-potato) veg­eta­bles, cooked in fat if de­sired. The rest of the time, eat what­ever you want.

It’s low-calorie and low-pro­tein while con­tain­ing vi­tam­ins, but it skips the calorie-count­ing and al­lows you to ac­tu­ally cook tasty food.

Since I’m breast­feed­ing, which is about a 500-calorie daily ex­pen­di­ture, it’s a lit­tle harder on me than it would be by de­fault, so I’m adding the mod­ifi­ca­tion of if you feel weak or light­headed, eat a fat source un­til you stop feel­ing that way. I ex­pect this is prob­a­bly a good con­ser­va­tive mea­sure for peo­ple in gen­eral.

This ought to be gen­er­ally safe for healthy adults un­der 65. The clini­cal trial re­ported no ad­verse effects more se­ri­ous than fa­tigue.

It’s definitely not a good idea for chil­dren, di­a­bet­ics, preg­nant peo­ple, or peo­ple with di­s­or­dered eat­ing.

If you ba­si­cally be­lieve the sci­ence that pe­ri­ods of lit­tle or no food pro­mote good metabolic pro­cesses (au­tophagy, re­duced in­flam­ma­tion, in­creased neu­ro­ge­n­e­sis & stem cell pro­duc­tion) but you don’t want the nasty side effects of pro­longed caloric re­stric­tion, some kind of in­ter­mit­tent or pe­ri­odic fast­ing seems like a sen­si­ble thing to try.

I don’t think there’s any di­rect ev­i­dence that the FMD is bet­ter than in­ter­mit­tent fast­ing for health, but it seems eas­ier to do, and maybe a bit bet­ter in terms of re­sults from ran­dom­ized hu­man tri­als.

If you (like me) re­ally don’t like the aes­thet­ics of diet­ing — “spe­cial” pre-pack­aged foods, ap­pear­ance in­se­cu­rity, calorie count­ing, hav­ing to make ex­cuses to the peo­ple around you for eat­ing “weirdly” — a home­brew FMD is pretty ideal be­cause you are spend­ing very lit­tle time “on a diet”, and you are eat­ing nor­mal things (veg­eta­bles). Also, it’s not nec­es­sar­ily a weight-loss diet, and you can con­cep­tu­al­ize it as pri­mar­ily about health, not looks.

I don’t ex­pect it to have non­triv­ial lifes­pan effects on hu­mans, but it might be good for healthspan or dis­ease risk, and that seems worth­while to me.

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