Fasting Mimicking Diet Looks Pretty Good

post by sarahconstantin · 2018-10-04T19:50:00.695Z · score: 79 (30 votes) · LW · GW · 4 comments

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 1/3 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.

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.

4 comments

Comments sorted by top scores.

comment by Benquo · 2018-10-04T20:37:19.154Z · score: 32 (8 votes) · LW · GW

It seems like the state of the evidence here is:

  • Multiple mechanisms we're reasonably confident should do something useful.
  • Lots of fairly specific, granular experimental evidence from mice, strongly suggesting that FMD works and low-methionine is nearly equivalent, with a mechanism that seems like it should transfer to humans.
  • One RCT showing benefit in short-term biomarkers for the commercial version of FMD in humans relative to the uninterrupted baseline diet.

What we don't have is:

  • Fine-grained experimental evidence in humans directly comparing the commercialized FMD to other sorts of "clean eating."
  • Direct experimental evidence in humans that a low-methionine regime will approximate the commercialized FMD.

Does that seem right?

comment by Richard Meadows (richard-meadows-1) · 2018-10-05T03:23:02.910Z · score: 10 (4 votes) · LW · GW

Hi Sarah, does FMD have any benefits over water fasting, other than the obvious comfort/personal preference? (By water fasting, I mean periodic fasts of 72+ hours, rather than ongoing caloric restriction.)

I don't like counting calories or complicated nutrition packages either. Water fasting appeals to me because it's such a clear bright line, although I'm guessing FMD might be a better fit for most people's preferences - just wondering if there's anything more to it than that? Thanks!

comment by Benquo · 2018-10-04T20:33:06.630Z · score: 10 (2 votes) · LW · GW

If you want to go hardcore, you could try limiting your vegetables etc. to things with very high fat content relative to protein and carbs - avocado, macadamia nuts, olives, heavy cream, butter, and olive oil. This would give you a break from insulin-related metabolism, which has different benefits than the low-methionine state that might be synergistic (because in both cases anabolism is limited. I'd guess that people who rarely or never do anything like actual fasting or keto would benefit from this modification.

This list of foods by methionine content (haven't checked its accuracy) might be helpful.

comment by Dr_Manhattan · 2018-10-04T22:07:37.853Z · score: 6 (3 votes) · LW · GW

Thanks for writing this up - Vassar mentioned you've looked into this, was going to ask you!

One thing that I was a bit suspicious in the book is his strong no-skipping-breakfast recommendation, apparently it's based on a study, but seemed a lot less supported than the rest.