Meet Mark

Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

Tell Me More
Stay Connected
February 21 2018

Does the Fasting Mimicking Diet Live Up to the Hype?

By Mark Sisson
93 Comments

Inline_FastingValter Longo is a leading fasting researcher. Since the early 2000s, he’s been one of the top guys running legitimate fasting studies in cancer patients, regular people, and, of course, rodents. He’s gotten great results, elucidating the idea that fasting causes human cells and tissues to enter “survival mode” which allowed them to survive the withering effects of cancer treatment. I’ve cited many of his studies in previous posts.

Several years ago, he came up with an “easier” way to induce the fasting effect in people: the Fasting Mimicking Diet (FMD). Instead of having people skip food altogether—which may not sound crazy to readers of this blog, but probably does to most people—he designed a low-calorie 5-day diet for people to follow at periodic points throughout the year. Longo thinks the FMD is the best way for people to reduce their risk of aging-related diseases, extend lifespan, and live healthier, longer lives. It’s designed to give cancer patients and other people access to the benefits without the mental deprivation that often accompanies true fasting.

The 5-day FMD is a low-protein, high-moderate-carb, moderate-fat diet.

The first day is 1090 calories, with 10% from protein (27 grams), 56% from fat (68 grams), and 34% from carbohydrates (93 grams).

The next four days are 725 calories, with 9% protein (16 grams), 44% fat (35 grams), and 47% carbohydrates (85 grams).

Most of the fat is polyunsaturated and monounsaturated. The protein is plant-based. The carbs come from nuts, seeds, legumes, and grains.

He even came up with a shelf-stable package of FMD food called ProLon. Instead of weighing and measuring your carrots and mac nuts and olives, you could just buy the 5-day supply of dry food and be on your merry way.

It’s certainly an attractive idea—a shortcut to fasting.

Does it live up to the hype? Does it truly improve lifespan in humans?

There’s certainly nothing wrong with it. Let’s get that off the table. It’s a fine idea. Certainly better than what most people do.

I just don’t know if it offers unique benefits to healthy people interested in extending their lives that other eating plans, like keto or Primal or intermittent fasting, don’t offer.

Let’s take a look at some of those benefits.

In rodents, the FMD has been shown to do some pretty cool things:

  • Improve lipids numbers.
  • Reduce body weight (and fat).
  • Activate autophagy.
  • Rejuvenate damaged organs, like the pancreas in type 1 diabetes.
  • Reduce cancer occurrence.
  • Extend life.

The one human trial, done last year, also got positive results.

  • Improved lipids.
  • Reduced body fat and body weight.
  • Lower blood pressure.
  • Lower fasting glucose.
  • Reduced CRP, a marker of inflammation.
  • Reduced IGF-1, insulin-like growth factor.

But there are some issues with the human study.

The subjects weren’t quite healthy at baseline. They were “generally” healthy, and there’s a difference. Over half were obese or overweight. The average body fat percentage was 34%. No one was about to keel over, but these weren’t lean, athletic types.

We don’t quite know what they ate before starting the trial, but the average American doesn’t have a great track record when it comes to dietary quality. They may very well have been going from a standard American diet full of junk food to the healthier approach promoted by the researchers.

They got healthier. They lost weight and body fat. Their biomarkers improved, suggesting a reduction in risk for some of the diseases that characterize aging. That’s real. But it’s also not unique to the fasting mimicking diet.

Furthermore, the people who were the most overweight and unhealthy at baseline reaped the greatest benefits. The lean, healthy people saw fewer benefits, which is understandable—they had fewer problems to solve.

The meatiest results came in rodent studies. The human study shows that overweight and obese folks can really benefit from the proprietary fasting mimicking diet, but that’s about it. It doesn’t show increased lifespan (study was too short). It doesn’t show organ rejuvenation (didn’t measure). It doesn’t show reversal of type 2 diabetes (didn’t try). All those things could very well happen in humans, and I wouldn’t be surprised—but for the time being, those effects have only been shown in rodents. We are not rodents, as I’ve made explicitly clear before and you can hopefully surmise from your own lived experience.

I see another major problem to Longo’s approach and the crux of his argument: It’s predicated on the idea that lower IGF-1 is a Good Thing.

Older folks with lower IGF-1 levels have a lower risk of cancer. That’s true. That’s important, assuming the connection is causal. There’s good reason to believe that it is.

IGF-1 participates in the etiology of ovarian cancer, is involved in breast cancer, helps sustain cancer cell viability, and affects the prognosis of non-small-cell lung cancer, just to name a few. As a growth-promoter, IGF-1 has the potential to promote the growth of cancer cells.

But IGF-1 levels also have a curious association with all-cause mortality. It’s U-shaped, meaning both super low levels and super high levels are linked to increased mortality risk, and that there’s a sweet spot somewhere between where IGF-1 is helping, not hurting. Lower isn’t always better. Somewhere in the middle is the best for longevity.

And for quality of life and overall health, IGF-1 does some good things after all. We don’t manufacture it in order to kill ourselves.

Resistance training, for example, spikes IGF-1. The increase in IGF-1 actually mediates the increase in strength—the beneficial adaptation to the training. Is Longo or any other longevity researcher going to suggest that lifting weights is bad for lifespan and health? (Oh, I’m sure there’s someone…)

IGF-1 counters age-related muscle wasting. I can’t think of a more important physical characteristic for older adults than lean muscle mass.

IGF-1 builds bone strength. Older women with higher IGF-1 levels have stronger bones, and IGF-1 is necessary for bone formation. This goes hand in hand with increasing muscle strength, as resistance training famously builds both muscle and bone.

IGF-1 is necessary for metabolic health. When you inject type 2 diabetic patients with IGF-1, their blood sugar drops, insulin sensitivity increases, and lipids improve.

Dying from cancer is awful. Dying in general, from any number of other maladies, is also bad. We can all agree that we want less of both types of death. We also want good muscle strength, bone mass, metabolic function, and all the rest.

Perhaps I’ve come off a bit too harsh on FMD. I don’t intend to. Longo is a great researcher, and the fasting mimicking diet obviously works. Where I take issue is the assertion that it is uniquely beneficial for longevity and health, or that “lower IGF-1” is what we should all be striving for. That simply hasn’t been proven. It may be true.—but I suspect the reality is far more complex than that.

Thanks for reading, folks. Take care, and be sure to let me know what you think about the FMD down below!

whole30kit_640x80

If you'd like to add an avatar to all of your comments click here!

93 thoughts on “Does the Fasting Mimicking Diet Live Up to the Hype?”

Leave a Reply

Your email address will not be published. Required fields are marked *

  1. Since the FMD is not fasting, but is just an extremely restricted calorie diet, I believe there is more benefit from actually fasting? I’ve read that the healing process, autophagy, is immediately halted when even just a small amount of protein is eaten. Since the FMD includes protein, seems that wipes out some of the greatest benefits of fasting. As for myself, I do a 6-day, water only, fast every month and it is improving some chronic health issues. No reason to “mimic” when it’s easier, cheaper and more beneficial to just fast.

    1. Correct unfortunately there’s nothing fasting in this regiment it’s just extreme caloric reduction and all the benefits that come with caloric reduction which seems to be identical to real fasting.

    2. How does water-only fasting affect gut bacteria? What do they live on while you’re not consuming anything? I’m interested in trying a shorter water fast to help correct blood sugar issues and give my liver/gallbladder a break. But I have motility issues in the intestines and don’t want to wipe out all my good bacteria while starving off the bad (which is what antibiotics do).

    3. My interpretation of Longo isn’t that he thinks FMD is better than regular fasting. He said in interviews that he just found he couldn’t get research funds to test real fasting because the medical establishment was afraid of it. They thought it was dangerous, they thought people wouldn’t follow it, etc. FMD was a way he came up to mimic fasting but one that he could get backing for.

      1. Geez thank you for explaining this. Even the large amount of people on here who follow a Paleo, whole foods plus meat ect. Diet are a miniscule tiny fraction of the population. Like you had mentioned it’s for backing and compliance of 98% of people who could benefit from this who will never go on a good woe.

  2. I generally listen to my body. I don’t fast, but from time to time don’t I eat as much, mainly because I feel full. I have a pretty good appetite and keep it healthy as much as possible.

  3. I’d still rather fast completely for 3 days instead of doing the 5 day FMD, realizing the FMD would be good for beginners to fasting. Would love to read more about this in the future.

    1. I would too, although even three days is too long for me. (16 to 18 hours of daily IF is my personal sweet spot.) I found out years ago that I would be hungry an hour after eating a small a.m. meal, such as a banana. Whereas if I fasted completely I wouldn’t be hungry at all until at least lunchtime.

      1. Intermittent fasting is great. And it is seven days a week lifelong thing without any silly weighing of foods. I love it and I really enjoy the fast period. Its not all about denial its about satisfaction and rest

    2. Apparently, there are important benefits from Time Restricted Feeding and Intermittent Fasting and Keto diets that overlap with the benefits from longer fasts.
      BUT there are benefits from a 5 day fast that do not kick in for an 3 days and less.

      I’m on a 3-day fast right now. Easy enough. Minerals help. Going for a 5-day next month.

      Supposedly, the FMD generates full results of a 5-day water fast. At least what they are paying attention to so far. It seems that a 5-day fast is the gold standard for metabolic improvement and most of the drugs/supplements they are researching are ones that will affect one or more of the pathways that 5-day fasts hack.

    1. It’s tricking the body into inducing the same response as fasting without a full-on fast. By getting almost all calories from fat and a hair from protein and carbs, insulin never really rises because that’s a response to carb and protein intake. Plus at about 700 calories a day, you are really only eating 1/3 to 1/5th of your calorie needs. It may be that a 5 day mimicked fast is more beneficial than a 2 or 3 day full fast, because duration does matter in fasting, and day 5 is when some of the magic starts to happen. And even for someone who is fairly disciplined and used to shorter fasts, a 5 days full fast would be difficult for most people, so this may be the best way to get the benefits fairly regularly because people simply won’t do a longer fast otherwise…

  4. Can you review his Longevity Diet also? Some of his advice is quite challenging wrt primal diet principles, especially the suggestion to avoid red meat and eat low protein. How well are his diet recommendations backed up by research? Also his FMD recommendation is supposed to be in part because of some evidence of harm with longer fasting and evidence that you need 4-5 days to get real benefits. Can you address this?

    1. I’d third this- would love Mark’s take on The Longevity Diet overall. Victor makes some specific recommendations that are counter standard keto/paleo and he acknowledges these differences. He’s especially hard on non-fish animal protein and easy on starch.

    2. It is mostly a vegan diet with very little fish. I can guess what Mark thinks about it but would be great to hear him counter some of his claims (like that there is hardly any research on the long-term effect of eating paleo/keto).

      1. The “No research on long-term effects of eating an ancestral diet” claim is hilarious 🙂 There might be a huge variation in our genetic tendencies and in what an ancestral diet looks like in different corners of the earth, but ancestral diets have the ultimate long-term study.

        1. when he says “research” he means controlled research, not life experience (which is primarily what humans have so far when it come to diet of all sorts). Also, the “long-term study” we humans have given “ancestral diets” shows pretty bleak results – lifespans ranging from 30 – 60 years on the average until just the last century. It seems to me that almost anything could beat that.

          1. I’d say the 30-60 life span you mention has less to do with diet and more to do with a combination of constant wars, lack of sanitation, disease, poor understanding of medicine, unsafe working environments, higher infant mortality rates etc.

          2. Don’t mistake average lifespan for possible or even common lifespan. Increases in average lifespan in the last two hundreds years are mainly due to much lower infant mortality rates. In old ages, humans who made it past the first five years (and didn’t die from violence later) often lived to their seventies. Check out the book Factfullness by Hans Rosling for many interesting points like this.

  5. One thing people don’t realize is that “fasting” means reducing calories to near zero. Low calorie consumption is not fasting. The body interprets low calorie consumption as starving and reacts differently.
    Even short term, true fasting causes drastic recovery and repair functions in the body. This includes more energy and less need for sleep. This is so the body can be ready to hunt for the next meal.
    On the other hand, continuous low calorie consumption causes an entirely different set of reactions in the body. These reactions include a slowed metabolism and reduced fat utilization because the body interprets low calories as a starvation situation.
    I have type two diabetes. Periodic fasting allows me to keep my glucose levels normal where diet and medication alone do not.

    1. Thank you, Bill. That’s the most succinct explanation of something I was wondering about: that starvation-mode is from low calories, not no calories.

    2. Your analysis is based on a diet that uses insulin as its source of fuel , rather than a high fat diet that burns Ketoes as fuel…

      Additionally, it takes at least three days of fasting for the cells to reach the point of rejuvenation at the mitochondrial level with stem cells….

  6. I read his book and find it quite interesting but haven’t tried it yet but will to see how I feel. I also find it quite interesting that he does believe in a traditional 3 meal a day model and breakfast should be skipped. So not a big believer in more than 12 hours of fasting a day and thinks it may even be harmful.

    1. Dave… Don’t you mean “he does believe in a traditional 3 meal a day model and breakfast should NOT be skipped.” I just read his book, and that’s what I took away. In fact, he recommends 2 meals + 1 snack/day for most.

    2. I was hoping to see this covered in the article by Mark. A lot of these comments are basically saying that IF does the same thing but is easier to implement. But in reality Longo suggests that IF (such as 16/8) is actually BAD for you. I suspect that this comes down to the desire to reduce IGF-1.

  7. I think it’s better to follow this sage advice: “Keep it simple, stupid.” Eating a Mediterranean diet and a moderate restriction of calories combined with intermittent fasting gives you significant health benefits and it is much easier to do than this FMD diet. The Greeks have been eating this way for thousands of years and the Greek Orthodox Church uses intermittent fasting on a regular basis. I should know–my wife is Greek and we have a home south of Athens. Of course today many Greeks are eating the same junk that most Americans eat and those that do are suffering the consequences of their poor choices.

    1. I agree with this advice. I hit the gym Mon-Fri so I have 3 square meals plus the protein shake after my workout. If I’m hungry apart from that, I have a small healthy snack. On weekends, when I’m not in the gym, I eat when I feel like it or don’t eat if I don’t feel like it. I have played with intermittent fasting in the past. I did a 21 hour fast once a week. While I did not find it difficult to not eat, I found it difficult to stop eating once the fast was over. I think female bodies, generally speaking, may have more varied results with IF.

  8. I very much liked this article. Although not all questions answered it addressed what is for me a “paradox” of sorts. That is….how is there a reduction in all cause mortality with the practice of fasting or FMD ….which lowers many risk factors including IGF-1 …AND a similar reported reduction in ACM in persons engaging in resistance training to increase muscle mass, which also requires relatively high protein consumption, also driving up growth pathways in which includes IGF-1 upregulations? Shouldn’t these two interventions…..be at odds with each other?

    mark’s thoughtful article confronts this “paradox” where others have not. The answer seems to be ” we do not understand ” exactly how some very complex metabolic responses actually interplay…and that context, as always, appears to matter. \\

    And that it is premature or perhaps even wrong to conclude that a program to lower IGF-1 is an “unmitigated” good.

    1. Hap,
      I’ll take a crack at a partial explantation for the paradox, or at least some context. A few thoughts:
      – My understanding is that myokine anti-aging signaling is a big part of how strength training not only extends life but reduces aging
      – I would bet a lot (and my experience has been) that once one has built muscle to a level close to their genetic potential (which takes about 3-5 years for a given muscle) that it takes relatively little protien to maintain and slowly continue to improve. Almost certainly not enough protein (and leucine and methionine/glycine balance are likely the real issues AFAIK) to be in the danger zone of the “u” curve but plenty to maintain the anti-aging signalling. This should be further enhanced by cycling protein to coincide with heavy workouts, something longo apparently favors.
      – From what I’ve read (i haven’t read longo) low IGF-1 has a minor anti-aging affect but extends ACM by reducing cancer and certain other issues which are not purely aging. However myokines produce a true anti-aging affect but have only a moderate risk reduction for cancer and infection. IOW, anti-aging and reducing ACM are loosely related but not the same thing. Infections, cancer and accidents are what seem to kill the people who maintain youthfulness until late in life.
      – I believe there have also been some mouse studies that showed that low IGF-1 had to be present early in life to get the major benefit however that seems questionable to me.
      – Where this really becomes an issue IMO is not regarding protein but rather regarding decisions around whether to use IGF-1 boosting methods to enhance injury recovery, and my guess is that the benefits of enhanced recovery will outweigh any risks from temporarily elevated IGF-1, but who knows.
      – For bonus points, another strong guess is that any harm from animal protein (very unlikely) is far outweighed by the loss of nutrients from liver, egg yolks, and meat.

      So it seems like the practical takeaway is 1) left weights 2) don’t assume you have to go high protein but do get high quality protein 3) pursue strategies like fasting and low carb that should reduce the risk of cancer 4) avoid chronically elevated insulin at all costs, and 5) do what maximizes your quality of life.

      1. Interesting response. We are starting to appreciate the crosstalk through myokine signalling between muscle, brain, bone, and other peripheral tissues. What you say is reasonable but not yet supported by rigorous research. Even so, we can’t wait for that nor should we.

        It has been pretty well demonstrated that increased muscle mass reduces ACM AND it is goes that doing so requires initiating the stress/recovery/adaptation process…which means lifting weights with as much incremental intensity as necessary to keep a person on the upwards curve. Recovery and adaptation requires rest and substrate (protein, and lots of it). We are talking 1.6gm+/kg body weight to drive the program. During this time the growth pathways will be very stimulated…..seemingly at odds with ginger recommendations of Longo…..for longevity and health.

        The muscle/strength curve is parabolic and reaching genetic potential is probably not a goal. However, getting above some percentage, maybe arbitray, like 80+ or 90+ is resonable. How would someone know that they have reached this level? Beyond the scope of what we can discuss right now….so take it on faith to some degree that it is a lot of work, but worth it…even if just eliminating the frailty of the aging phenotype.

        there will be a point where the gains are small (or non evident)at which time it would be reasonable to back off significantly on the protein and seek to maintain. It may also be reasonable to engage in cycles of intended growth gains through mechanical load and nutrient excess and intended nutrient deficit….for initiation of cell survival programs (ie autophagy, FOXO etc). The muscle mass will certainly address the chronically elevated insulin issue and BTW it is pretty difficult to increase lifting without carbs. carb limitation is most necessary when you are not strong.

        Again, I think you are on to something. Muscle myokine signalling and crosstalk tells the system that you are vigorous (somewhat youthfull) and to “act ” like it.

        A recent article in Medscape studied the outcomes of patients with various cancers undergoing therapy who were randomized to strength and aerobic training throughout their therapy and afterwar (4 year follow up). Significant benefits reported.

  9. Longo designed the diet to “mimick” fasting in the sense that all the complete water fasting induced changes in the biomarkers that they could measure, were reproduced with the low protein/calorie/sugar diet.

    Very low methionine, being only 19g plant protein daily is probably key. Still, I agree, a complete 3day water fast would be a more assured way of gaining the benefits than trying to come up with one’s own version, or paying for the commercial version- if one could even find a doctor who would prescribe it.

    The effects on the immune system were also very exciting. During the fast white blood cell count declined significantly but upon refeeding, bounced back to higher levels and a more youthful ratio of T cells to Macrophages!

    1. From the Buck Institute of Aging
      A Janet Tomiyama, Jeffrey M Milush… Elissa S Epel “Long-term calorie restriction in humans is not associated with indices of delayed immunologic aging: A descriptive study.” Nutr Healthy Aging 4:2 147-156

    2. According to Longo a 3 day fast does not achieve the results that a 5 day fast will.

      According to biomarkers a 5 day FMD “fast” gets more results than anything shorter, including water fasts.

  10. As Dr Fung has pointed out, it is often much harder to eat small amount than to eat nothing. If I am fasting I generally feel no hunger at all, but if I even eat a small amount, then it’s like a switch is flipped an no nearby food is safe…This FMD is actually anti-fasting and seems like trying to weld the principles of low-carb and mainstream thinking together. It seems likely to do more harm that good by leading well-intentioned people who give it a try down a path that will just cause the same problems as other low-calorie diets.

    1. FMD is not really a diet…….that’s a misnomer of sorts. It is an “intervention” and as I understand it was developed with the goal of being a medical intervention and adjunct therapy. In the book Longevity Diet (yes I read it), there is clearly an attempt to make fasting or FMD part of a therapeutic “cleansing” or “resetting”…but not a substitute for general diet advice. I think Longo presumed (correctly) that human diet preferences are either entrenched (for a bunch of reasons) or that adopting some alien diet advice would see compliance problems. Hence, while not backing down on the general dietary prescription…..he throws in the FMD sort of suggesting that substantially beneficial (ie all these biomarker wonders) and that the benefits persist awhile even if one goes back to eating “normally”.

  11. Trying to keep up with all the wellness trends and studies out there is like drinking from a fire hose; really appreciate what Mark does to summarize and synthesize information like this. It seems to be kind of a “fasting lite” approach which I would think might have benefits. I try to eat all my meals (which are primal) within 8 (sometimes stretches to 9) hours each day, at this point that is the extent to which I wish to fast. But, will certainly keep an open mind and as always I get good perspectives and learn things from what others post here.

  12. Just tried it two weeks ago at the suggestion of my new doctor (another story). I was a little apprehensive since I’ve been LCHF for the past 3 years. I am fat adapted and do IF and extended day fasts without a problem. My longest fast has been 72 hours and typically I do 36 hours once a week. As described the carb total is high since I generally target 30g total carbs per day. So, I bought the Prolon package to try – it was expensive. My impressions/results: 1) It was easy to follow. I didn’t get hungry in fact it was quite filling. 2) There were electrolytes included that seems to be properly sufficient for the 5 days. 3) Although the instructions were to cut back on exercise, I went ahead with my normal program (HITT & Resistance training 2X week) without a problem. 4) Although I didn’t test ketones, I don’t think I got into ketosis due to the carbs but I did feel pretty good by day 3. 5) I had a weight loss of 6 lbs of which 3 lbs has returned 2 later. 6) My fasting glucose fell 14 points (99 to 85) during FMD and continued to fall and remain lower (high 70s) for the next 2 weeks. A surprise since during my normal fasting routine it falls and then goes back up to high normal within a couple of days. 7) I get more blood work in 6 weeks so I’m anxious to see the results.
    Overall, FMD was a surprisingly good experience for me. My doc would like me to do it for another two months (once per month) so I’ll probably try it again. But like most of you, extended fasting and LCHF is probably my ongoing lifestyle.

    1. Paul that is Interesting especially your fasting glucose results. How much does it cost? Since your Dr prescribed does insurance cover it?

      1. $250 for one package, there seems to be a small quantity discount. So far no insurance coverage.

  13. I love fasting but we do need science to catch up. Longo really subscribes to low protein diets to promote longevity, and his diet has very little protein. On the other hand it seems pretty important to have muscle mass as you age, and for that you need protein. We need to learn what the sweet spot is for that, as I don’t really believe reasonably strong muscles and lifespan can be mutually exclusive. As I am only 53 and working on muscle-building so I can do sports activities more easily, I am currently eating on the higher end of protein. As I get older I hope we will know more about the optimal amount of protein to not hurt longevity.

  14. I do intermittent fasts (16 to 20 hours) a few times per week. I occasionally go for 24 hours. I eat a low glycemic, moderate protein diet with some HIIT, strength training, yoga and MBSR thrown into the mixture. Prior to trying the FMD, which I have done four times in the past year, the idea that a calorie restricted diet could mimic fasting seemed counter to what I understood of the body’s response to true fasting. I even doubted the claims of those who include bulletproof coffee as part of intermittent fasting; the calories in the butter (even the few in the coffee) were likely to convince the body it wasn’t really fasting. Reading of the apparent ability of the FMD to mirror true fasting makes it rather remarkable. I have done FMD with ease and kept my regular work schedule while doing so. I doubt I could do a five or even three day fast and lead my normal life. Some people, I am sure, can do so. I do skip vigorous exercise during the FMD, opting to go for long walks or easy bike rides.

    1. So bulletproof coffee could be a type of mimicked fasting? Interesting.

  15. Hmm… I think something like “Eat Stop Eat” would be considerably easier to do, and perhaps just as effective.

  16. Intermittent Fast Five is much easier. You pretty much eat what you want when you open the eating window about 5p until 10p. Or you do 4p – 9p. Etc. 19 hrs fasting except water then open window. I exercise in that fasting time. Some, open window at 2p for a healthy snack, then eat dinner with family at 5p. Done with food by 7pm. The food tastes so good after the fast. Some do this 3-5 days a week, some aim for everyday. Flexible program, eat less, more plants, exercise!!

  17. Just read Longo’s book, and the IGF-1 issue was confusing to me, too. He does, actually, recommend “relatively intense weight-training sessions” followed by 30+ gm of protein intake for muscle synthesis (as well as daily vigorous walking. HOPE YOU WILL WRITE MORE ABOUT IGF-1, MARK! Maybe the point is to spike IGF-1 occasionally (e.g., 1-2x/day, allow for periods of not eating daily when it will drop low, hit the sweet spot in between, and then have periodic fasting days?? I’m in that “older” group, continue moderate strength-training/HIIT on alternate days + try to eat somewhat more protein to sustain muscle mass (which is much harder now than it ever was before). The idea that I may be setting the stage for cancer or early ACM by doing this is disconcerting. Would appreciate learning more from you about this very confusing topic.

    1. I second your motion, highly.

      Question for Mark…what is the lowest amount of protein we can get by with, without losing muscle mass?

    2. “Maybe the point is to spike IGF-1 occasionally (e.g., 1-2x/day, allow for periods of not eating daily when it will drop low, hit the sweet spot in between, and then have periodic fasting days??”

      This is what I wanted to point out to Mark. A mistake we may make is to consider things must remain static. Many times a stresser that would harm over long term helps if cycled. There is speculation arising that IGF-1 may be like this. Not low, not high, but cycled.

  18. Is this type of diet followed by any of the 5 Blue Zone populations? If not, it’s simply speculation – with a bit of profit if one purchases the proffered product

    1. I echo Larry’s query. I’ve read quite extensively on diet and its impact on health and longevity. Which includes some books and research on the Blue Zone peoples, who are documented as the longest living. One notes that these folks don’t adhere to a particular diet, certainly one that is Keto or incorporates intermittent fasting, certainly with no (voluntary) 1-6 day fasts. There is relatively little animal protein consumption (not available; too expensive). Most of the 5 Blue Zone people’s diet is plant based, with a good deal of legume consumption, again because it’s available and inexpensive. There is no gym or workout facility attendance, just calorie burning pretty much evenly throughout the day due to type of work and general lifestyle. Low stress and community are factors. Alcohol consumption plays a role through moderate imbibing. There is no tobacco or pharmaceutical use documented. No obesity due to activity levels and food harvested from native lands during season.

      Simple. So, like Larry, if the above works through evidence based research on humans humans vis-a-vis lab rodents, I ask why do we need to posit an experimental dietary protocol which has not been proven to work in humans over against one that has through these Blue Zone folks?

      1. Longo’s general diet recommendations in the Longevity Diet are pretty much based on the Blue Zones type diets. He has personally studied people in these zones, as well, for his research.

        Regarding intermittent fasting, he says that most of the people in these zones don’t tend to eat for longer than 12 hours a day, so that is also his recommendation, though he allows for longer periods, as well.

        From an evolutionary and ancestral health perspective, our predecessors very likely had to go for even longer periods of time without food, which is why we are well-adapted to fasting.

  19. Hi Mark have you heard of Dr. Satchin Panda from the Salk Institute in La Jolla, CA? He has a time restricted feeding idea which makes more sense to me. If feels more like the way I was raised eating — a longer period of “fasting” after dinner. My mother used to frown on us coming back into the kitchen looking for after dinner snacks since for her, the whole idea was if you had eaten dinner, plus the previous two meals, you probably were set until breakfast. She wasn’t a sadist about some dessert, but not eating for hours. Since eating more primally, I find I’m not always as hungry as I used to be.

    Dr. Panda’s idea is to eat within an 8 to 12 hour window and to fast otherwise. The fasting is supposed to help with blood glucose. Heck, he even put his own mother on this regimen when she visited. I know I’ve read of this elsewhere, but it just jibes with me, not putting my mother on this but the eating window. I tried to read Dr. Longo’s book and also watch some podcasts with him but he seems to be more interested in his food pouches. I want to eat real food.

  20. Mark Sisson – just a quick note from a 58 year old healthy male who has been reading your blogs and communications for over 8-9 years now. Just a sincere note of thanks for continuing to send out your wise, reasoned, actually-saying-something communications all these years. You are unique in that regard and virtually the only Paleo-Keto thought leader I consistently follow. I’ve always enjoyed what you say and how you say it – not a waste of time like most. I’ve been strong into nutritional and life wellness for quite awhile now and am aging well, feel great. I’m careful in my buying practices – though I’ve bought 2-3 of your books over the years – but I just very much appreciate your wonderful intelligent free advice. It is unique in this crowded space of online communities.

  21. I’m worried how reliable a source I can call this now. Dr Longo’s research shows a rebound effect of IGF-1 in the refeeding window. I won’t defend the FMD, but what I do know leads me to believe you forgot to scratch the rest of that lottery ticket. His studies are also showing IGF-1 and FoxO3 may be inversely related while prolonged fasting, and if that doesn’t get you excited then look up what FoxO3 does.

  22. Thanks Mark for this nice asessment. My name is Joseph Antoun, CEO at L-Nutra, the company that licenses ProLon the Fasting Mimicking Diet (FMD) from the University of Southern California. I wanted to write here as I was much inspired by the time that you took to review the FMD which very few bloggers/reviewers do (this is the first time I respond to any blog/review and we currently get one or two per day). I also wanted to write to clarify many of your/your readers questions/misstatements.
    I read few saying that ‘if you eat, even a little bit then the body is not fasting’ which is not true and hence the Fasting mimicking name. The University of Southern California spent 2 decades and some $20 Million dollars of NIH grants to discover cellular nutrition sensing pathways and a diet that does not trigger the pathways and therefore mimics fasting. This is why top scientific and medical peer-reviewed journals such as Cell, Science Transnational Medicine, Cancer Cell, Cell Metabolism, etc. report our trials and the USPTO issued to USC 5 FMD patents (with 16 others under review). Regarding autophagy, not only the FMD induces autophagy but it goes much further to induce stem cell regeneration, which is a step further in stressing the body with fasting. The best illustration of the above is the stem cell regeneration of the diabetic pancreas in mice (http://www.cell.com/fulltext/S0092-8674(17)30130-7) or the regeneration of immunity and damaged organ in auto-immune diseases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899145/) or the regeneration of immunity in cancer (https://www.ncbi.nlm.nih.gov/pubmed/27411588). We are currently in human trials on many of these conditions.
    FMD is a novel category so I understand, respect and happy to read all the questions about it. Would love to do an interview/blog Mike to answer all the interesting questions your audience is bringing. But for sure the FMD lives to the hype that you are hearing about and yes the ProLon two trials were not focused on autophagy or stem cell based healing as much as proving the safety and efficacy on age related markers but the subsequent articles that aim at diseases/regeneration provide more answers.
    Have a Fastinating day!

    1. Joseph, thanks for your reply. I was about to write something similar here, and I was with you until I read the word Fastinating. Smh. But anyway, since you’re doing human trials, I’ll share my experience with your diet.

      I’m a scientist and I was at USC when the 3-day-fast-stem-cell-regeneration paper came out. I have an autoimmune condition similar to rheumatoid arthritis, and for several years it was mostly in remission due to following a strict paleo-primal-phd style diet. But if I ate something problematic, the bad reaction would typically persist for more than a month. Such a reaction had happened a week or 2 before I read the paper, and the next day I stopped eating altogether. I went 4 days just to be sure.

      The results were dramatic – upon refeeding the symptoms had completely disappeared and I had more energy and mental clarity than I’d had for a long time. I have repeated the four day fast maybe 5-7 times since then, both following a flare-up of symptoms and also when I felt ok and just wanted to see what would happen when my immune system was functioning closer to baseline. The fast again helped if I had symptoms, but didn’t have much effect in their absence, besides 10-12 pounds of weight loss and hunger.

      One final note on the hunger – it wasn’t fun but I’ve experienced much worse. Before changing my diet in response to autoimmune onset, I regularly got migraines and was overweight despite numerous attempts to control food consumption. If I even missed a meal, I felt orders of magnitude worse than I did at any time during any of my 4 day fasts. Given the vast differences in the subjective experience of hunger, I don’t think I could have finished the fast or a FMD without first eliminating the foods that caused the underlying issue.

      Thanks for your work, and I look forward to seeing more of it.

    2. I’m so glad you chimed in, and I hope that Mark will take you up on the interview. I have had a recurrence of cancer, and upon reading Longo’s research, I did fasting before and after chemo, and then periodic fasts during the subsequent years. I’m just a study of one, but glad I did it since I’m almost 5 years clear now after my recurrence that happened at 2 years.

      Upon reading Investigator’s post below, I’m interested to know more about how it influences autoimmune disease and the gut flora since my son has Crohn’s disease.

      1. Jill, nice to hear your self-study, I’ve never met anyone else who’s done this. My 2c on the connection to gut flora and Chron’s disease (* I am not an MD *): different immune diseases may have different triggers (such as foods or viruses), and different dose-response relationships (such as how much gluten is needed to set off a Celiac). The amount of exposure to a trigger determines how much (or what part of) the immune system is activated, and then the activated immune system sets off inflammatory cascades, which are thought responsible for things like IBD.

        The immune/inflammatory response depends on (1) environmental exposure and (2) sensitivity of the immune system to the exposure. So we do what we can to identify environmental triggers and reduce exposure to them. Paleo/primal diets can function as elimination diets in this regard. Precision nutrition also has a nice article on this topic (https://www.precisionnutrition.com/elimination-diet).

        We also do what we can to reduce the sensitivity of our immune system to the triggers. This is where gut flora may be important – a nice large healthy population of good bacteria may defend against invading triggers along with the immune system, effectively reducing the amount of trigger to which the immune system is exposed. The Art of Fermentation by Sandor Katz is a fantastic book about trying to make delicious fermented foods do exactly this.

        Another way to reduce the sensitivity of the immune system to exposure is the reason we’re here: read paper, starve self 3-4 days, death to overly-sensitive immune cells, eat again, stem cells make new immune cells, inflammatory cascades shut off and we feel better. Until the next time we suffer massive exposure to the trigger, and the process begins again.

        1. I suggested in a previous blog post that it would be worthwhile for either Valter or Mark to make the cross town drive and engage in some serious dialogue.

  23. Valer Longo is one of the most rigorous researchers in the world in the study of cell biology and gerontology. You can try to learn something from his carefully framed peer-reviewed research and randomized control trials. The alternative is Mark, who claims that Longo asserts that FMD is uniquely beneficial for longevity and health, or that “lower IGF-1” is what we should all be striving for. I would like to see evidence of these claims.

    1. Yes, this. As I read Mark’s post (albeit late), I couldn’t help but wonder how he attributed those claims to Longo and the FMD. Instead, Longo seems to claim that 5-day fasting gives the greatest results in their studies and that the FMD has been developed to invoke the same mechanisms to popularize fasting in the interest of public health, offering a reliable, prescribable meal kit for those who cannot or will not do a water fast but wish to reap the benefits. Kudos.

      And the IGF-1 has been shown to rebound after the fast, which Dr. Longo knows. In fact, this seems be one of several reasons why he has come to prefer 5 day fasts to long-term calorie restricted diets which will keep IGF-1 down.

  24. Any fasting suggestions for someone who is underweight? Is love to do a 7 day fast, but after 3 days my energy gets extremely low and I worry it isn’t safe…

    1. Hey Jon,
      I’m actually on day four of a five day fast. You can certainly attempt a 7 day fast but I will tell you that the research points to five days being the real sweet spot. Everyone is a little bit different of course but there are days that are harder than others. Between the evening of day three and the mid point of day four are difficult for me. There are couple of tricks you can use to maintain. I will occasionally drink black coffee in significant moderation. I also make sure that I am drinking mineral rich water to insure that all my metabolic processes stay on line as well as continue with transdermal Magnesium. Cold showers and Wim Hoff breathing seem to really keep me alert and energetic. The more fat adapted you become the easier it is. Regular IM helps a great deal as well. Hope that helps and good luck!!

      1. Can you expand on that? Your 5 day comment? What sources are you pulling from, and the sweet spot for what elements of all this? I’ve read and done the 3+ days related to immune regeneration. And most agree it is easier after day 4. Is this what you’re talking about? And what goes downhill after day 5?
        –thanks!

    2. Jon, my situation is similar to yours with regard to weight. I don’t have one pound to lose. My Integrative MD suggested I do three cycles of FMD, and I bought one of the expensive ProLon kits. He did tell me he didn’t want me to lose weight-that was his one concern. (Well, how would you not lose weight starving for five days?) I should have given it more consideration before spending the money and committing. Well, this evening is my third day, and I caved and quit. I have lost several pounds, am having heart palpitations, and am extremely weak to the point I cannot easily function. I didn’t know how I’d make it through two more days of work this week. Feel like a total failure. Was hoping to “reset” my immune system; I have three autoimmune diseases that are out of control. Also have ApoE 3/4 allele and thought this might be a good thing for me but because I have no reserve, I guess not. Will IF help in the same way? I can easily handle 14-18 hours or a little more between meals from time to time. Im not a graze eater. Any opinions out there? I realize this discussion is old; I’m a newcomer to the newsletter.

      1. Linda, this is my first post here. Started Mon-Fri 16:8 IF 2 1/2 yrs ago at 62 with one meal on Sat and Sun. Just finished my first 4 day fast ten days ago, but drinking two basically bulletproof coffees each day. My goal was to prevent insulin spikes and keep protein/carb zero to enable Autophagy via mTor regulation. Broke fast at 95 hours with bone broth, then two eggs/cheese/bacon in a high-fiber wrap. It was strange not to eat, but the PF was a very positive experience and I plan on doing it again next month. Lost 9 lbs, gained back 3, think I’m stabilized now. Anyway, I believe Autophagy would be the right path for immune system reset and cell renewal, especially concerning T-cells. I don’t understand how one could be hitting mTor with the carbs and protein on the FMD and not shut down Autophagy. My two-cents. BTW, I’ve already lost 48 lbs (222 down to 174) on my IF regimen and HIIT with moderate weight training. Best of luck to you in fighting off your autoimmune condition!

      2. I am finding that taking minerals really makes a difference with the heart palpitations and weakness.

        Mineral salt (pink himalaya or sea salt) and Magnesium spray

  25. Hi Mark, would taking a fish/krill oil supplement in the morning break the fast?
    Because i know putting fats in morning coffee does, so would the omega-3 supplement do the same?

  26. Why is there a place to put comments and questions and the author does not give feedback or answer questions?

    1. Gracie, thanks for your note. This is a community board. I jump in on occasion and respond, but I also know my readers bring impressive knowledge and experience to the table – as well as support for others who share their questions here. I also respond to some questions in detail in Monday’s “Dear Mark” posts as well. Thanks again for being here. – M

  27. Hi,

    An interesting series on fasting on your blog. I have done severel IF protocols ever since Martin Berkhan started sort of a movement back in the day. Also tried a few five day fasts as well.
    I mainly do this for health benefits as I have come to believe they are real, however today I ran into a study that claimed there may actually be some serious health risks involved in the long run. The outcome of this study really took me by surprise, as the results are pretty much the direct opposite of all the things I read before, like decreased insulin sensitivity, increase in free radicals and even pancreas damage. I would love to hear about your thoughts on this study. Here is a link: https://www.sciencedaily.com/releases/2018/05/180520090903.htm

  28. Mark, I think if you don’t want to be thought of as being too harsh on Longo, you might not want to use the term “hype” in your title. 🙂

    To Mike, it is not just extreme calorie reduction. In fact the macronutrient distribution is quite precise; protein is 9%. Apparently, he has NOT found that the protein knocks out autophagy. And his experience has shown that even for people with cancer, who could very much benefit from water-only fasting, most of them do NOT think it’s easier. They’d rather take their chances, i.e., die, even if it is cheaper to take in nothing but water.

    (In England, a sizable percentage of people in a study lost the sight in one eye from simply not putting some drops in the eye every day. The drops were not painful or unpleasant, and paid for by the health system. And these were people who had ALREADY LOST THE SIGHT IN THE OTHER EYE.)

    Let’s not assume everyone or even most people are willing to be as astute as you are in their diets.

    In fact, we see plainly that hundreds of thousands of people (deaths from CVD, cancer, and diabetes; estimated about 80% caused by lifestyle) a year are willing to take their chances on SAD and meds; many of them die rather than give them up and just lose 5% of their weight by just about any means, never mind water fasting, low carb, or high carb.

    Nothing is “better” if the majority of people aren’t going to keep at it. I don’t claim that a high percentage would follow repeated cycles of FMD long enough to benefit their conditions, but if I had to put money on it, I’d go with FMD over water fasting. Most of us aren’t going to live long enough to find out who’s right.

    I myself lost about 20% of my weight over a period of years simply by sticking to three meals of non-sweet foods 5 days a week. I wasn’t being precise about it, but my weekday diet was close to 40/30/30. Kept it off for five years. Then I started doing FMD and dabbled in other IF, but those drove me back to eating packages of Cheezits and cookie dough at a time and such after years of not doing that. I have also been leaning towards- don’t panic, I’m the one to pay the price- high unrefined carb and lost 10 more lbs.

    I’ve done the FMD protocol (okay, the cheap internet versions) seven times over the past couple of years. I didn’t have a lot of blood work done, but found out that without my actually intending it and without any real consistent added exercise, I put on muscle, lost fat, and lost the greatest percentage of it around my middle torso. That wasn’t even my intent, but I’ll take it.

    I am willing to keep doing it for the next 6 years, or until I’m 70, as is recommended. I could probably extend my life with other changes as well, but I’m not sure I’d want to live longer under those circumstances. I think I’d have better results working on good social support-which can be negatively impacted by extreme dietary restrictions- practicing gratitude, and volunteering.

    That being said, a sincere THANK YOU to Mark for your continued effort to get people to use at least some alternative to SAD. Lord knows it’s needed.

  29. High levels of insulin are known to cause systemic problems including fat storing and resistance. Lowering levels of insulin improves insulin sensitivity and helps people lose weight and has shown to be anti-ageing.
    The only thing that lowers insulin is not eating! So good old’ fashion fasting will help. Regular intermittent fasting for 24hrs twice a week has improved my health and blood work too.

  30. I have read this article and comments with interest, having just spent some time watching the videos of Valter Longo being interviewed about different forms of fasting here http://l-nutra.com/fasting-mimicking-diet-2/ (scroll down to see them). I found his arguments quite compelling.

    I have just been diagnosed as pre-diabetic, despite being physically very active, slim, with a BMI of 19 and with no extra abdominal fat. I have followed the 5:2 protocol for over 4 years. The diagnosis was totally unexpected and I have spent the days since the diagnosis eating a very low carb diet with as much fat as I can manage within the meals. I don’t want to become underweight but have lost 3lb in 3 weeks so will up my weight/resistance work to try to add weight through extra muscle. I also bought a blood glucose monitor and have been testing my glucose levels before and after meals to get a picture of what’s going on.

    Having read previously about the FMD, as well as other types of fasting, I decided to research to see if I could find a way of ‘resetting’ my system to get the pancreas working properly again. I’m not keen to spend the amount of money that Prolon charges for the FMD packages though I do hear Longo’s point about the pouches being carefully constructed to include all the nutrients etc. that are necessary to benefit the participant, which could be hard to imitate in a DIY version. I’m still thinking about the options but, in the interim, may change from the 5:2 (which appears to have let me down) to the 12/12 fasting-feeding window that he recommends (he thinks longer than 12 hours is harmful) whilst still keeping to a low carb, high fat diet.

    1. I was similar to you until I read the book, “Dr. Neal Barnard’s Program for Reversing Diabetes”. It solved all my issues. It was different than what I followed for years but worked wonders. I now need to take no meds. Give it a try

  31. Important to note that Longo advocates the “refeeding” stage after the 5-day with high protein that rebuilds IGF1 to the “other side of the U”

  32. lowering IGF1, he’s only doing it periodically. so, I would doubt it would have a negative effect that you felt cautioned about. Also, a study looking at meat containing diet vs vegan diet… IGF1 was only 13% lower in the vegan diet. So, basically, i’m saying, our body will continue to make IGF1, because it must need it. But the world keeps eating more and more protein and higher calorie diets. Maybe our increased cancer risks have at least some influence from IGF1 being higher than we need it to be from eating copious amounts of animal protein. just one way to infer.

    1. The most current research would suggest that eating a diet where the largest portion of calories come from fats like avocado, nuts and nut oils, olive oil, coconut oil, etc.–followed by fairly low carb and low protein, is the healthiest and most age defying way to eat. This is very high fat, very high vegetables, beans, some fruit, a little grain and meat/dairy, preferably fish. This is an extra green version of the mediterranean diet, basically. I think what you infer about eating so much animal protein is probably correct. But the sugars/simple carbs are the worst and seem to feed disease and inflammation more than protein.

  33. Reading Valter Longo’s book. His answer to the protein question which comes up several times in this thread seems to be this so far–

    1. Muscle does not need a lot of protein to maintain, after it has been built up over 3 to 5 years.

    2. He still does his army routine he did when he was 19 (not sure if he sticks to the time). That was 70 push ups and 60 situps in two minutes, and running 2 miles in 10 minutes.

    There may be more, and I’ll try to update if there is. I’m early in the book

  34. So, I’m on day 5 of Longo’s ProLon plan right now. It was interesting…and I’m online at present to find any writings on following it with two days of straight fasting (guessing its ok to do, but want to be sure I don’t see any warnings against it). My reasons for doing it are that I’d badly fallen off my paleo wagon due to extreme stress and life changes…still have to be strictly gluten free due to Celiac (which ensures I can’t fall TOO far off! Ha)…but too much “safe” sugars and the addition of more corn and carbs of all sorts saw my insulin response suffer and weight gain starting to happen. So I gave this a shot to help with a reset of sorts. But yes, it does feel a tad at odds with a kicking paleo lifestyle. There is abundance there that seems utterly non-existent with longevity diet. But the fasting aspect? I like it as a counter to the abundance found in paleo diet. It helps tone it down a little for me (I can veer towards too much bacon and paleo baked goods really easily). Where I think it has faltered for me is in having any food at all. I think that part is a crutch for those who need the mental act of eating….but honestly, the act of eating these sparse calories only made me want to eat more. So it kind of hurt the process a little for me. I would ha e powered through any hunger or cravings much easier without having his little chocolate nut bars to look forward to on three of the nights with dinner. Trying to really bust sugar cravings with this and I’m not sure that’s going to be achieved here (hence the desire to go a couple more days minus all food). But I do feel lighter, more clear, released a bit from the grasp of “comforting foods” I was a bit stuck in….and prob down 5 lbs, but I don’t own a scale, so can’t know exact numbers (could be more!)

  35. I listened to Valter Longo on Kevin rose’s podcast. Longo actually states that he thinks daily intermittent fasting for longer than 12 hours is detrimental to health!