Fasting Mimicking Diet — All the Benefits of Water Fasting Without the Drawbacks

By Dr. Mercola

Most of us want to live a healthy, long life. But what's the best way to switch on your body's ability to promote cellular protection, regeneration and rejuvenation? In this interview, Valter Longo, Ph.D., a researcher and director of the Longevity Institute at the University of Southern California (USC), helps answer that question, as he's investigated this topic for over two decades.

His findings are detailed in the recently released book, "The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight," which also provides the research framework to support his recommendations.

Early on in his career, during his doctoral work, he studied calorie restriction with the late Dr. Roy Walford, who was a pioneer in this area at the time. Calorie restriction involves restricting your calorie intake on a daily basis independently of the types of foods you eat.

As a general rule, you eat just 30 percent or less of your normal calorie amount, until you reach a body mass index (BMI) of about 19. Needless to say, it's quite extreme. And, for all its benefits, it also causes quite a few problems. They eventually discovered that a form of intermittent fasting, dubbed the fasting mimicking diet, provided long-lasting benefits without the drawbacks of long-term calorie restriction.

"I think where the fasting mimicking diet, the periodic nature of what we're doing … is this idea of keeping the benefits by eliminating the problems," Longo says. "And, of course, I had the advantage of having [a background in] molecular biology and the biochemistry, which Walford didn't have, so at the time there was not much known."

Sugar Is a Potent Aging Accelerator

By studying the effects of starvation on yeast, Longo discovered that sugar accelerates aging and premature death, in part by activating two genes known as Ras and PKA, both of which are known to accelerate aging. Longo explains:

"At Walford, we were working with human samples and mice and it was very clear that not knowing about the genes and the molecular biology was going to greatly limit us in moving forward. The gamble was, let's move back to a very simple system and hope that what we learn about aging in this simple system applies back to humans. And I think the gamble worked. We did identify what I call the sugar pathway or the PKA or Ras/PKA, and then the protein pathway, the TOR-S6 kinase. "

Research has demonstrated that these initial findings in yeast hold true in other animals as well, including worms, flies, mice and a group of people in Ecuador who have Laron syndrome, a rare genetic disorder where they lack the receptor for growth hormone. As a result, they cannot grow taller than 4 feet.

Interestingly though, this genetic anomaly also appears to protect them against chronic diseases such as diabetes and cancer — even when consuming a less than ideal diet. According to Longo, there's reason to believe the findings apply to most other people as well, as we now know growth hormone and growth hormone receptor in humans regulates both the TOR and MPK pathways.

"We now suspect there is a network pathway starting with the growth hormone and ending with these transcription factors that we described. These are what I call the captains of protection, that are regulated by the food that you eat," Longo says.

Sugar Avoidance and Fasting Are Powerful Longevity Boosters

Longo was one of the first researchers to identify sugar as an aging accelerator and fasting as a process for improving longevity. In 1997, he published a paper showing yeast could be made to live a lot longer when starved. Shortly after that, they discovered the sugar and protein pathways responsible for this phenomenon.

In essence, what he found was that if you knock out both Ras/PKA and something called LCH-9, which is the S6-Kinase gene in yeast, you could obtain up to a fivefold extension in lifespan. As noted by Longo, "It was clear that the effects of fasting were caused in part by shutting down these two pathways." The question was, does the same apply to humans?

To answer this, Longo looked for equivalents to what they'd identified in yeast. Work done by John Kopchick and Andre Barki showed that, in mice, growth hormone deficiency and growth hormone receptor deficiency caused record longevity extension of 40 to 50 percent. They were also far healthier than normal mice. Half of them were completely disease-free at the time of death. As noted by Longo:

"This is very impressive and remarkable. So, we knew that this was true for yeast and this was true for mice, and the Laron [study] was our way to demonstrate that this is also true for people. To summarize, health and longevity are promoted by either a) having low levels of growth hormone, or b) lack of receptors for growth hormone, so it doesn't matter whether you remove growth hormone or the receptor."

Like Insulin, You Need Growth Hormone, but Not Much

Strength training is typically recommended as a way to optimize health, and one of the effects of this type of training is a boost in growth hormone. So, how do you reconcile the need and health benefits of growth hormone, and its dampening effect on longevity? Longo explains:

"Insulin is a good analogy. You need insulin but a lot of insulin all the time gives you insulin resistance and diabetes, so … it's not so much growth hormone, but IGF-1 and insulin, downstream … [Y]ou can approximate growth hormone activity in general [by the] IGF-1 level, so for example, the Larons have very low growth hormone activity and they have very low IGF-1.

Usually, they say if you go on a low protein diet, you're going to have low growth hormone production, or certainly more growth hormone receptor activity and low IGF-1. So, they usually go together but there are some cases where they can separate … Growth hormone acts on TOR directly, [and] on insulin, and probably in almost any pathway that you can think of. So, they're certainly not the same thing, but it's a lot easier to measure IGF-1."

The Benefits of Protein Restriction

Like me, Longo promotes radically reduced protein consumption. I've often warned that most Americans eat far too much protein for optimal health. Longo recommends limiting protein to 0.31 to 0.36 grams of protein per pound of body weight. For most, that would mean cutting down their protein consumption by about two-thirds. If you weigh 150 pounds, you'd need just 50 grams of protein a day.

As I've mentioned on many occasions, the reason for this recommendation has to do with the way protein interacts with the mTOR pathway, which is involved in aging and age-related diseases. Protein controls the growth hormone, IGF-1 pathway, which also controls TOR signaling and PKA signaling.

When the TOR pathway is deactivated — either by a low protein diet, a drug such as metformin or the supplement berberine — you are therefore protected against the ravages of aging. In recent years, they've also discovered that deactivating the TOR and PKA pathways helps boost regeneration. What this means is that if you eat a lot of protein, a lot of food in general, and have high growth hormone and TOR, then your regenerative potential is placed on hold.

Once you remove these blocks, your stem cells are turned on, and then, during the refeeding phase, your body undergoes a major regeneration and rejuvenation phase. This is in part why intermittent fasting or fasting mimicking is so much better than chronic calorie restriction. The "magic" actually happens during the refeeding phase, after you've gone through a period of starvation.

If you just cut calories but never enter refeeding, you miss the opportunity to rebuild your body. So, while starvation triggers the cleanout process of autophagy and activates stem cells, refeeding triggers rebuilding, and for optimal health, you really need both. According to Longo, the fasting mimicking diet is a real solution for cancer for this reason, as "we've shown clearly that it can selectively remove disobedient cells … [I]t's really clearing a lot of damaged cells."

When and Why Higher Protein Intakes May Be Beneficial

The devil's in the details though, and intermittently giving your body an anabolic burst with extra protein, above the one-third of a gram per pound of body weight, is important for the preservation of muscle mass, and helps optimize your strength training sessions.

As a general guideline, I suggest boosting your protein by about 25 percent on strength training days for this reason. However, going above the recommended one-third of a gram per pound of body weight on days when you're not strength training does not appear to provide any muscle building benefits.

"[O]f course you need sufficient protein … There is no doubt about it. [But] if you're training, the data indicates that above the … 0.31 to 0.37 grams [of protein] per pound, it doesn't really do much more [for] muscle building. So, when they gave athletes that amount or a little bit more than, and then gave them a lot more, a lot more did not make any difference.

It was really about 30 to 35 grams of good quality protein per workout that optimized the muscle synthesis … [C]ertainly, giving excess protein in several studies did not result in higher muscle building. Part of this could be the stem cells.

It could be the cellulite cells, and that's another study we're doing right now, so the high level of protein may in fact block cellulite cells from being activated and that may be part of the problem … It's possible that if you keep [your protein intake] at the normal level and then together with the training, you increase it by 20 to 25 percent … this will help you increase muscle mass."

The elderly and frail may also need higher protein intakes to prevent sarcopenia (age-related muscle loss), but not by a whole lot. Longo recommends boosting protein intake by 10 to 20 percent around the age of 65, which is when most seniors start losing lean body mass. "I think as long as they maintain [their lean body mass] they don't have to worry about it. But if they start losing it, then both muscle training and increasing protein a little bit is important."

Fasting — A Powerful Metabolic Intervention That Extends Lifespan   

While I was initially hesitant, I now believe multiday water fasting is one of the most powerful metabolic interventions out there. There's really nothing that comes close, and the reason for this is because it switches your cells to a protected "antiaging mode."

It promotes autophagy and replaces cell components with newly generated functional ones, thanks to the activation of stem cells. I now do a five-day water-only fast once a month, and recommend it for most people — as long as you've prepared yourself properly first. A key step that made water fasting easy for me was getting into the habit of intermittently fasting 20 hours a day for at least a month.

If you're on medication, you also need to work with your doctor to ensure safety, as some medications really need to be taken with food and/or can become toxic when your body chemistry normalizes. Those taking hypoglycemic or antihypertensive medication are particularly at risk, as they may end up overdosing.

It's also recommended to continue taking nutritional supplements during your fast. If you take magnesium be aware that it may cause severely loose stools. You also need to take a high-quality salt. Certain health conditions may also need more stringent medical supervision to ensure safety when fasting.

Longo, on the other hand, is not quite as keen on water-only fasting, or even 20-hour intermittent daily fasting, citing findings suggesting intermittent fasting beyond the 13-hour mark raises the risk for gallstones by about 5 percent, as well as other unintended side effects. He also notes that 20-hour intermittent daily fasting is not a strategy used among centenarians, people over 100 years of age.

Water Fasting Versus Fasting Mimicking Diet

It bears mentioning that Longo's fasting mimicking diet is not a water-only fast. The fasting mimicking diet involves restricting your calories to 800 to 1,100 calories per day for five days each month, opposed to no-calorie fasting. It was primarily developed to improve compliance, as many find a five-day water-only fast to be too difficult. The low-calorie strategy also helps reduce the likelihood of adverse side effects, while retaining the benefits.

"We first started with cancer patients about 10 years ago … [T]he National Cancer Institute … funded the research to develop a fasting mimicking diet … The reason it's simple is [because] there's an issue of compliance, but also an issue of safety. [F]irst of all, water-only fasting, or very low calorie fasting … has been done exclusively in clinics. Now, people could do it but they do it in clinics for a reason.

It really revolutionizes your metabolism and to a lot of people, it's going to be dangerous. Hypertension [and] hypoglycaemia [are possible side effects]. The purpose of the fasting mimicking diet was to make it easier on people, but also to make sure they don't go to an extreme state in which then they start having problems, and we saw it in the clinical trial.

We saw, even with the fasting mimicking diet, people can get weaker and can have some problem, but with the water-only fasting, these problems go up by another magnitude … This is why I think the fasting mimicking diet is the way to go.'"

People who should not water fast or be on the fasting mimicking diet include pregnant women, people who are seriously underweight (have low body mass index) and/or suffer from anorexia, seniors over the age of 70 (unless you're exceptionally healthy), anyone who is fragile or people with liver or kidney disease. If you have a chronic disease, be sure to work with your doctor and have him or her closely monitor your condition.

Fasting Mimicking Diet Boosts Effectiveness of Cancer Treatment

The fasting mimicking diet, which is a very low calorie diet, was developed to match the effects of water-only fasting, including the beneficial effects on autophagy, stem cell activation, ketone body production, IGF-1 level, IGFBP1, glucose and more. While Longo is an expert in this field of many years, I am not yet convinced that a very low calorie diet provides as much metabolic benefit as a full five-day water fast as long as one has no contraindications.

One of the strong recommendations in Longo's book is to actively incorporate the fasting mimicking diet if you're undergoing treatment for cancer. Not only will it radically improve the effectiveness of the cancer therapy, but it will also decrease its side effects.

"This has been a difficult battle. We work with the top oncology hospitals in the world: MD Anderson, Mayo Clinic, USC Norris Cancer Center. So, we really didn't want to be the rebels here. We really fought for the patients. We fought very hard, but also, we wanted them to agree with us. We wanted the oncologists to basically say, 'Yes. This is a good way to do it.' And in the end, I think, what we all agreed on was the following.

Now there are a number of new clinical trials that are almost finished, with hundreds of patients and fasting mimicking diets. So those, I think, are going to be conclusive … [In cases of] more advanced cancer, metastatic, [where] there are really not many options … we said the oncologist should seriously consider doing the fasting mimicking diet together with standard of care. And that's the beauty of this [diet]. It works very well with standard of care.

We've now shown it for kinase inhibitors, we've shown it for chemotherapy. All kinds of chemotherapy, all kinds of cancers, and now we have more data coming up with all kinds of new therapy. For example, now we're looking at immunotherapy … It makes the cancer visible to the immune system, and [can then be] attacked by the immune system, so I would say, yes, absolutely [talk] to your oncologist … At least they should read the clinical trials that are already published …  

The safety concerns, I think now, are really minimal and the potential benefits are very high … In mice, we consistently see cancer-free survival even in the metastatic models. Meaning that the mice are essentially cured in combination with the chemo or the therapy … I think it's important to talk to patients about this, and give them an opportunity, particularly where they don't have any viable options."

Fasting Mimicking Diet as an Antiaging Strategy

In his book, Longo cites animal research showing the fasting mimicking diet in combination with treadmill exercise resulted in greater maintenance of muscle mass and a decrease in sarcopenia. Interestingly, neither strategy worked on its own. In this case, the mice got a low-calorie diet twice a month for four days at a stretch. In between, they ate normally.

As a result, they lost visceral fat but not muscle mass. This, Longo says, "really separates the fasting mimicking diet from most, if not all of other diets, in which there is always fat and water and muscle lost in the weight loss process. "Longo's research also shows the fasting mimicking diet reduces inflammation and inflammatory diseases such as dermatitis.

Cancers are reduced by nearly 50 percent. Importantly, cancers are also significantly postponed, and many tumors are also benign rather than malignant. Cognition is also improved. In mice that received the fasting mimicking diet twice a month were cognitively doing much better than the mice on the regular diet.

Another area of improvement is the immune system, which undergoes a transformation to a more youthful state. Overall, there's a reduction in risk factors for diabetes, cardiovascular disease and cancer, and an improvement in markers for aging. "So, as expected, [the diet] is really going after multiple systems and causing multisystem regeneration and rejuvenation, leading to improved performance," Longo says.

More Information

In summary, one of the primary messages in Longo's book is the importance of cycling — the episodic fasting and refeeding is really part of the key that makes this strategy so beneficial. Importantly, it also helps circumvent the negative effects that can occur during continuous fasting or chronic underfeeding. Longo adds:

"I would also point out that it's not cycling that needs to be every month. It can be, but we basically say, if you're obese and have high cholesterol and high blood pressure, yes, you probably have to do it every month, until you're healthy. But if you're the average person who may have high cholesterol and that's it, this could be once every three months. So, every 90 days, you do it for five days, and I think that's very reasonable.

From the clinical trial, we show there are long-lasting effects. If we measure the effects of three cycles of the fasting mimicking diet, three months after the end of the third cycle, we still see about 60 percent of the changes there. So … it might take three to six months for these changes to be completely wiped out."

To learn more about this beneficial "antiaging" strategy, be sure to pick up a copy of Longo's book, "The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight." If you are like me and are really interested in living healthier, longer, it can point you in the right direction.

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