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Positive effects of the fasting-mimicking diet may persist for up to three months after completion. An individual's health status dictates how frequently they should practice a fasting-mimicking diet. For example, an athlete on a strict diet may prefer twice a year, whereas an obese person may choose monthly. Some individuals favor this strategy for weight loss as it requires them to struggle for five days and then allows them to eat without restrictions for the remainder of the month. In this clip, Dr. Valter Longo explains how frequently the fasting-mimicking diet can be practiced and his hope that it may support sustained weight loss.
Rhonda: I have a couple of questions. So first the...you measure these biomarkers at baseline and then after the three cycles. Do you think if you were to have measured...you measured them immediately after the third cycle, or...?
Valter: One week.
Rhonda: One week? Okay. So, do you think...
Valter: And three months. And we also measured again three months
Rhonda: Oh you did? And how were they...that was my question. So, what were they like three months later? Do you have to keep doing it every, you know, month?
Valter: Yes. I mean, there were, about 60% of the effects were still there. So you could tell that they were smaller, but 60% of the changes were still significant. So, yes. So this is why we say that on average people probably need to do it once every four months, and it's also important to point out that, you know, until millions of people do it, it should be on a need-to-do-it basis, right?
So, if you are an athlete, you have a great diet, you know, low protein, pescetarian, and you do all the right things, you exercise, etc., you probably only need to do it once or twice a year. It's not very many people in that category, maybe like 5% of the population.
And then as you move to a problem state of course, then, you know, the minimal risk that is associated with doing a fasting-mimicking diet is a good risk to take, because of course any drug that you take, any intervention that you do is going to have risks.
And so now I think people, there's over 25,000 people that have done the fasting-mimicking diet, the prolon, the same diet that was tested clinically.
We've had very few severe side effect reports, right? And even the ones that had severe side effects, they fully recovered and there was no evidence that it was the diet that caused them, right? So, it's very good news, right?
Then when you get to, this is what in the FDA terms would be considered a phase four, when you say, well, let's keep monitoring this once it's out in the market and see, you know, are there people that eventually show side effects that we didn't see in the FDA trials, right? Of course we didn't do FDA trials, but...So we have done phase one and phase two, and skipped phase three, and now we're in phase four.
Rhonda: Wow, that's really great. Twenty-five thousand people, that's a lot. So you were mentioning the frequency changes, the frequency of doing this fasting-mimicking diet may change according to someone's health status and how, what their lifestyle is. So someone that's obese or has high cholesterol, high triglycerides, high fasting blood glucose, all these markers that you mentioned, may want to do it more frequently like...
Valter: Well much more frequently, yeah. So, somebody that has those problems, say obese, multiple markers for disease, or risk factor for disease, then once a month, yeah. And that's what the doctors have been doing. So they put them on once a month, and then monitor the changes. If it works, then you can keep it going. It doesn't mean they're going to do it once a month for their entire life. The hope is that you slowly...And that's also very important, this idea, especially with obese people, we'll see how it works, but this idea that you can go back to your diet after five days, right? This is very mentally, to people is very important. Say, "Well, struggle for 5 days, but then leave me alone for the next 25." That I think is both potentially at the mechanistic level, but also the psychological level it could be a good way to go.
Rhonda: So I'll just tell you, I have a friend of mine who was morbidly overweight, I mean, he was morbidly obese, he was, I think at his highest weight was about 400 pounds, and had tried all sorts of types of diets, you know, and never could really get anything to work and the compliance was low. But then he started doing these prolonged water fasts. Now he was doing, you know, five, seven days, and he was doing it frequently, like once a month, and he's lost 200 pounds. And I think for him, and he does exactly what you said. He likes food. He likes food, and he likes to eat certain foods, but he's found something that works for him, where he can, he just, you know, once a month he does a five-day fast, and then he goes back and he eats his...
Valter: I want to talk to this guy.
Rhonda: Yeah, I would absolutely like to put you in touch with him. He's actually applying to medical school now, but he's a very smart guy. He's a lawyer, and now he's going back to medical school because he's become very interested in obesity and all this stuff.
Valter: So we're running our trial in Holland on diabetes patients, many of which are going to be obese, and yeah. So, that's our hope, that hey, you know, people always ask, you know, there's famous papers that have shown what they call the yo-yo diets, right? They've shown that these can actually lower your metabolism. If you have this prolonged starvation period, it can lower your metabolism and then you tend to gain weight.
But in mice and in humans we're seeing really the opposite, you know? Doing it this way. So if you take somebody and you put him like say two months on a very low calorie diet, and you make him exercise, that seems to be a problem. Why? Because of course they can't keep doing that. And then when you eventually go back to a normal diet, your metabolism is now slow.
But doing it like this for these five days, particularly in the fasting-mimicking diet, seem to be not doing that. So the body doesn't quite ever switch to a slower metabolism because it's so short. So I think, we'll see, but I think it may very well represent a very good way to psychologically and also physiologically get the people to help them have a long-term plan to lose weight.
A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.
A waxy lipid produced primarily in the liver and intestines. Cholesterol can be synthesized endogenously and is present in all the body's cells, where it participates in many physiological functions, including fat metabolism, hormone production, vitamin D synthesis, and cell membrane integrity. Dietary sources of cholesterol include egg yolks, meat, and cheese.
A diet that mimics the effects of fasting on markers associated with the stress resistance induced by prolonged fasting, including low levels of glucose and IGF-1, and high levels of ketone bodies and IGFBP-1. More importantly, evidence suggests these changes in the cellular milieu are associated with a sensitization of cancer cells to chemotherapeutic drugs while simultaneously also conferring greater stress resistance to healthy cells.[1] Evidence also continues to emerge that properties of the fasting-mimicking diet, particularly its ability to cause immune cell turnover, may also make it useful in the amelioration of auto-immune diseases like multiple sclerosis.[2]
[1] Cheng, Chia-Wei, et al. "Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression." Cell Stem Cell 14.6 (2014): 810-823. [2] Choi, In Young, et al. "A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms." Cell Reports 15.10 (2016): 2136-2146.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
The postmarketing surveillance stage. A clinical trial conducted to identify and evaluate the long-term effects of new drugs and treatments over a lengthy period for a greater number of patients. Phase IV research takes place after the FDA approves the marketing of a treatment.
A type of intermittent fasting that exceeds 48 hours. During prolonged periods of fasting, liver glycogen stores are fully depleted. To fuel the brain, the body relies on gluconeogenesis – a metabolic process that produces glucose from ketones, glycerol, and amino acids – to generate approximately 80 grams per day of glucose [1]. Depending on body weight and composition, humans can survive 30 or more days without any food. Prolonged fasting is commonly used in the clinical setting.
[1] Longo, Valter D., and Mark P. Mattson. "Fasting: molecular mechanisms and clinical applications." Cell metabolism 19.2 (2014): 181-192.
A molecule composed of a glycerol molecule bound to three fatty acids. Triglycerides are the primary component of very-low-density lipoproteins (VLDL). They serve as a source of energy. Triglycerides are metabolized in the intestine, absorbed by intestinal cells, and combined with cholesterol and proteins to form chylomicrons, which are transported in lymph to the bloodstream.
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