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Could Fasting Protect the Brain From Disease? A Neuroscientist Weighs in

By | August 20th, 2018

Could tricking your body into believing it’s only consuming water for several days improve your brain or protect it from diseases like Alzheimer’s? Valter Longo, the creator of the fasting mimicking diet (FMD) and director of USC’s Longevity Institute, thinks it’s possible. According to Longo, restricting yourself to a small vegan diet that consists of olives, nuts, kale chips, soup and other supplements—things Longo says the body does not recognize as food—for several days every so often could be beneficial for your cells.

While Longo and his team found that the fasting mimicking diet prevented cognitive decline in mice, they are now conducting a clinical trial on participants who have mild cognitive impairment or are in the early stages of Alzheimer’s disease. He said they should know whether or not this diet could improve cognition in humans within a year and a half. Because many drug interventions for treating Alzheimer’s have been unsuccessful, he is hopeful that the diet could be an alternative treatment for the disease.

Being Patient spoke to Longo about the diet, the benefits of fasting and how people can implement this diet in their day-to-day lives. 

Being Patient: You created the fasting mimicking diet. Can you tell us more about the diet?

Valter Longo: The fasting mimicking diet is the result of decades of work looking into how we can improve longevity with nutrition. Historically, interventions have been chronic, meaning that you have to do something every day. I think the fasting mimicking diet is one of the first attempts to ask, based on discoveries, whether you can do something once every month, every three months or every six months for just five days, and whether that changes the way the body is protected long-term or how the body regenerates. Following this diet may lead to rejuvenation, or becoming a little bit younger.

Being Patient: What is the theory behind why fasting could be beneficial? 

Valter Longo: I first started doing dietary restriction in mice and humans, but then I moved back to E. coli bacteria in yeast. The remarkable thing is that if you take bacteria—and these were my findings in the early ‘90s—or yeast that we use to make bread, then starve it and put it in water, the bacteria or yeast become very resistant. This illustrates a simple idea: If you are an organism and you find yourself starving all of a sudden, you have to go into a protective mode—try to survive as long as possible with as little food as possible until the food comes around again. That’s the major idea behind fasting. To protect yourself and start breaking yourself down, a lot of cells commit suicide and start eating themselves. It’s very counterintuitive, but it makes sense if you’re trying to survive a period where there’s no external food and you’re relying on internal resources to stay alive. During this process, junk is cleared up within cells and when you go back to eating normally, a process of rebuilding occurs.

Being Patient: A lot of people mention that after they fast, their mind feels clear. Why is that?

Valter Longo:
Fasting is potentially a true reset, meaning that it forces the brain to move away from just using sugar as an energy source; instead, it starts using byproducts of fat as an energy source. Ketogenesis is activated and the brain starts relying 50/50 on ketone bodies and glucose. In this process, we suspect—as we see everywhere else in the body—that autophagy, or the process of clearing up junk within the cells, is activated and possibly clears bad cells as well. A lot of the benefits occur when you go back to eating normal food. Fasting itself could be viewed as a good and bad thing: In some sense, it gets rid of junk, but it also gets rid of a lot of components. The refeeding has the job of rebuilding. You put the cells back together now in a way that is more functional and works better than the original cells.

Being Patient: You suggest people should follow the fasting mimicking diet for five days. Why is your diet called the fasting mimicking diet?

Valter Longo:
It’s a fasting mimicking diet because water-only fasting can cause hypoglycemia and low blood pressure. There are also concerns about people passing out. The fasting mimicking diet involves understanding the connection between proteins, amino acids and TOR—a gene that responds to high levels of amino acids—or the connection between sugar and types of protein. We first tried to understand the molecular biology and then asked, “What if we trick the system into thinking it is just receiving water?” We can now provide about 50 percent of the normal level of calories with this diet, but the system detects it as water-only fasting. Everything changes according to a water-only fasting diet. In some ways, it removes the majority of issues, as well as a lot of the burden that comes with having to do water-only fasting, which is extremely difficult for people. We can maintain the same effects.

Being Patient: If someone has already been diagnosed with dementia, will this diet help them?

Valter Longo: We don’t know. We have tested the diet in mice and it helps prevent cognitive decline, so the mice can learn and remember better. Soon, we’ll be publishing some data on humans who don’t have dementia, and in a month or so, we’ll start a randomized clinical trial at one of the largest hospitals in Genova, Italy. That trial is going to look at those in the early stages of Alzheimer’s or who have mild cognitive impairment. We are hopeful. I think the great advantage to the fasting mimicking diet, compared to drug interventions for Alzheimer’s, is that it revolutionizes the brain’s metabolism. A lot of the targeted approaches have not worked for Alzheimer’s. Maybe there is something that is much more wide-acting, much more programmed and evolved as a process that could have a better chance of treating this disease. It doesn’t mean it’s going to work, but it could have a better chance of achieving this reset of the brain, which we’re already seeing somewhat in mice.

Being Patient: How many people will be in your trial and how long will the trial last before you know it’s having an impact?

Valter Longo: I think there will be 80 people: 40 are going to be the control and on a placebo diet and 40 will be on the fasting mimicking diet. They have to do three cycles, so that’s a process that will last about six months. We should have the initial data within a year and a half from now. We always say the same thing: The fasting mimicking diet is a low-calorie diet and we’re not really recommending the diet for people who are 70 or older. However, now we’re developing a fasting mimicking diet for Alzheimer’s patients that is higher in calories, suitable for the clinical trial and hopefully, for others. If you reach the point where you can’t wait and want to consider trying this diet before we get our results, you should talk to your neurologist. A lot of neurologists will say, “No, you’re going to have to wait until the end of the clinical trial,” which is fair. But many people cannot wait, so a neurologist and dietician can decide whether or not a patient should try this, if they’re running out of options. It’s a difficult decision, but we’ve seen it used on cancer, diabetes or multiple sclerosis patients who may not have other alternatives, so I think it’s also reasonable to consider trying it for Alzheimer’s or cognitive problems. The doctor and dietician should handle treating a patient with the fasting mimicking diet as if it were a clinical trial.

Being Patient: How can people implement this diet in their day-to-day lives? 

Valter Longo: There’s a company that sells a kit. I don’t have any financial gain from it, but I’m the founder of the company, and the project is called Prolon. I founded the company to get the product out there, although the income goes to charity. Prolon is a box that contains all of the food that someone would consume for five days. They have to go through a questionnaire, which either sends them to a dietician or a doctor, and if they don’t want to go to an additional dietician, then they can just speak to a dietician who works for the company on the phone. The dietician will tell them what to watch out for. Once they get the box, they stop everything else they’re eating and just drink water, plus what’s in the box, for five days. This can be done once a month or once every six months. If someone’s very healthy, they probably only need to do it once every six months.

Being Patient: What is inside of the box?

Valter Longo: My book, The Longevity Diet, has all of the details. The income from the box goes to my foundation, the Create Cures Foundation, so we can continue to do this type of work. The box includes olives, walnuts, hazelnuts, kale chips, soups, ranging from tomato soup to broccoli soup, etc. It’s five days of a vegan diet, but it’s very special and complex. It took us years and years to develop. Even after we knew what ingredients we wanted to put in there, it took us years to get the factories to make it correctly. We make it look simple, but it’s not as simple as it looks. Even the tomato soup is completely revolutionized to serve its purpose.

Food
Valter Longo said that olives and walnuts are included in the fasting mimicking diet.

Being Patient: You mentioned that it could be dangerous to follow this diet if you are 70 or older. How does fasting impact people in various age groups differently?

Valter Longo:
Every person is different, meaning someone could have diabetes or another condition, so everybody should be handled differently. In the clinical trial, we had 100 subjects, who were between 20–70 years old. They did not have any problems. An additional 70,000 people have now done the Prolon fasting mimicking diet and we’ve collected surveys from about 2,000 people and 150 doctors. Thus far, we haven’t seen problems reported by patients or doctors, so it looks like there’s a pretty good safety record within this group who are between 20–70 years old. After 70 years old, we found that protein intake would be problematic and we also suspect that if you’re 70 or older and you follow the diet too frequently, it wouldn’t be good. If most 70 or 80 year olds tried the fasting mimicking diet once in a while, they’d probably be fine, but I think their geriatrician should make that decision and monitor them. 

FMD
According to Valter Longo, those who are 70 or older should consult a geriatrician before trying the fasting mimicking diet.

Being Patient: You mentioned that refeeding after fasting is important. How does fasting have a long-lasting impact, rather than just making someone have better cognition within the moment?  

Valter Longo: We’ve very clearly shown that in the mice studies and in the clinical trials, the effects are long lasting. About 60 percent of the effects were there three months after the last cycle, but the less you follow a good diet and exercise, the more likely the effects of the fasting mimicking diet will go away more quickly. If someone is obese, has high cholesterol and high blood pressure, they probably should follow the diet once a month. If somebody is a 35-year-old athlete in perfect shape and follows a pescetarian diet that is low protein with high nourishment, they may only need to follow the diet twice a year. However, each person should talk to a dietician or doctor at least once when they get started to make sure that there aren’t reasons why they shouldn’t do it, or to see if they should do it differently.

Being Patient: How often do you fast?

Valter Longo: When I tend to gain weight, I don’t eat lunch. Today, I didn’t have lunch. I follow the fasting mimicking diet twice a year because I have an ideal diet and exercise regimen.

Being Patient: Have you researched the benefits of just following 12- or 15-hour fasts? Is there a benefit to doing really short spurts of fasting?

Valter Longo: I always say that I don’t call that fasting—I call that eating. I think 12 hours is great and it’s what people have always done. If you look at centenarians and everybody else, eating for 12 hours, then fasting for 12 hours is a normal eating pattern. When you fast for 16 hours, there are some benefits. You’ll probably lose weight, but there are also problems: Gallstone formation goes way up for people who fast regularly for 16 or more hours, and they may need their gallbladder removed. If people skip breakfast, they also face an increased risk of cardiovascular mortality, so I would not fast for 16 hours unless you have to. I would stick with 12 hours. These are very different fasting regimens than what the fasting mimicking diet involves. It takes two to three days for the brain and most of the body to switch to a ketogenic mode, and it takes two to three days for it to even begin to break down all of these components. Five days is the minimum amount of time that’s needed to do a full reset, and then the refeeding provides an opportunity to rebuild everything that’s been broken down.

This interview has been edited for length and clarity.

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