What type of fasting is best? | Rhonda Patrick
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Fasting activates many of the body's mechanisms that repair damaged DNA and other cellular components. It also promotes the production of ketones, especially beta-hydroxybutyrate, an anti-aging molecule that demonstrates the capacity to delay the onset of aging-related diseases and improve mitochondrial health. There are several types of fasting, including alternate-day fasting, time-restricted eating, and prolonged fasting. Each elicits metabolic changes that can improve health and promote longevity. Time-restricted eating, in particular, has the potential to realign the body's circadian rhythms. In this clip, Dr. Rhonda Patrick describes some of the different types of fasting and identifies the advantages associated with each.
[Mike]: You talked a little bit about time-restricted feeding. Next question I think we'll build on that, which is from Sam Reyes. The question is, "Has there been any evidence suggesting one method of fasting is more beneficial than others? "
[Dr. Patrick]: Right. I think that's a really good question.
[Mike]: It's a very broad question.
[Dr. Patrick]: It's a very broad question, but sort of gives me a chance to describe some of the different types of fasting, which I kind of touched on already. But, you know, you hear in like popular culture, you hear everyone say intermittent fasting and intermittent fasting becomes this like blanket term for all things fasting.
[Mike]: Valter Longo like doesn't like that term because it's just so general.
[Dr. Patrick]: Right. Dr. Valter Longo from USC who is really an expert. He does a lot of research on fasting. He has mentioned how, you know, intermittent fasting can be considered in humans fasting up to about, you know, 24 hours. And then prolonged fasting happens when you get into like the 48-hour mark, so two days or longer. And then, of course, there's time-restricted eating, which has intermittent fasting component to it, but it also has that circadian biology component to it. You want to eat within the time when your metabolism is optimal. And when you're not eating, you're obviously fasting. And so, you know, people end up doing up to 16-hour fasting periods. So if they're eating within an 8-hour window, they're fasting for 16 hours.
[Mike]: Of course, colloquially, that's called 16/8.
[Dr. Patrick]: It's 16/8. Yeah, exactly. So that would also be time-restricted eating. That's something that you're doing on a daily basis. And so, as I had already mentioned with the time-restricted eating, you know, you get the benefits of the fasting part. So you're fasting for 16 hours. Part of the benefits, you know, with that are things like you do start to have repair processes that are activated. In order to repair damage, whether it's damaged to your DNA or, you know, damage to proteins, or just damage, like I mentioned, mitochondria or just pieces of dead cells floating around, that stuff is cleared away and repaired during a fasting state. So you get that with the intermittent fasting and time-restricted eating, which has a fasting component.
In addition, the time-restricted eating, you have the benefits, and this has been shown by Dr. Satchin Panda, Ruth Patterson, others that you're eating within your circadian biology in terms of when your metabolism is at its most optimal. So you don't want to, you know, for example, if you eat your first bite of food at 8:00 a.m. in the morning, and then you're eating dinner at 8:30 or 9:00, you're, you know, you're basically, you've already gone past 12 hours. Your metabolism at 8:30 or 9:00, isn't going to be very good.
And so, and what may end up happening is you're not going to be as insulin-sensitive. So your blood glucose levels are going to be higher. Your fasting blood glucose is going to be higher. Your fatty acid metabolism is not as good. So you're going to start to store fatty acids and adipose tissue rather than using them as energy. So you'll start to like gain more fat mass, which has all sorts of problems.
In addition to that, you may also, your body, because you have been going, it's been like over a 12-hour mark. When you eat that food in the evening, you may be resetting the clock and your body thinks it's resetting the start time of metabolism. So the whole time you're sleeping is when your metabolism is at its best and then you wake up in the morning and it's completely misaligned. So everything is misaligned in terms of your metabolism. So that means that you're always going to have higher blood glucose levels. Your fatty acids are going to be more likely to be stored in adipose tissue rather than used as energy. So that misalignment. So that's the benefit for time-restricted eating or time-shifted feeding as it's called with animal studies.
Then, as you mentioned, Dr. Valter Longo's research, he does a lot of research on what's called prolonged fasting, typically, 48 hours or longer. Again, as you get into that, you may want to do that under medical supervision. Now, he has done a lot of research in animals showing that, you know, if you do a prolonged fast, not only do you have this autophagy start to activate, which we talked about. As the fast becomes more prolonged, you actually start to get the clearing away of cells. Damaged cells, seems to be preferentially damaged cells, that are cleared away.
And in the process of that happening, you actually activate stem cells and sort of replenish those damaged cells with new, healthy young cells. And he's shown this in animals where literally during the fasting period, organs will shrink. And then during the refeeding period, which we'll talk about a little bit later, they regrow. So you're basically getting rid of the damaged cells, mostly it seems, and then you're replenishing them with healthy, new young cells and they're regrowing. That's all been done in animal studies.
He has some preliminary evidence in humans where it as though looking at various markers of like stem-cell activation, for example, that does seem to be happening. But he's got some ongoing studies where they're going to look at that in much more detail. So you know, that's a benefit of the prolonged fasting, which you don't really get from a shorter fast because you need to really have a stronger stress. You have to have your IGF-1 levels really dipped down. That takes time.
[Mike]: And I think that their product ProLon, which, you know, we won't get too much into, but it has some calories per day, but that's like a five-day regimen. So you're really looking at kind of five days to get most of those benefits you discussed.
[Dr. Patrick]: So ProLon, that's the name for their fasting mimicking diet, which was developed by Dr. Valter Longo. And it has a very specific macronutrient content. So a specific amount of fat and protein and carbohydrates and a total caloric cap. So, you know, I think that like the first day it's up to 1,000 calories and then the second, the fifth day, you're getting a little bit, a little over 700 calories a day. And he has shown, again, he's shown in animal studies, the same benefits with the organ shrinking and then regrowing. And then he sent some clinical studies in humans showing a variety of metabolic benefits. You're getting, you know, of course, improved glucose levels, insulin sensitivity, he shows IGF-1 does go down and, you know, cholesterol, like there's benefits with your cholesterol metabolism, things like that. So that's also another sort of, part of fasting or it's fasting [inaudible 00:19:20].
[Mike]: So same idea of a prolonged fast that you mentioned where you're getting the autophagy and the stem cell production over a multiple-day fast, except in this case, bringing low calories into the equation. Ostensibly, it'd probably make it just easier for people to stick with than a water-only fast.
[Dr. Patrick]: It definitely seems like it's easier for people to stick with, or at least try out. You know, in animals, he has shown that you do get a lot of the same benefits as a water fast, but you have to remember, you know, animals have a much faster metabolism than humans.
[Mike]: Sure. Right. Great point.
[Dr. Patrick]: And in fact, if you fast a mouse or rodent for 48 hours, they lose 20% of their body weight. Well, a human loses, maybe 2%.
[Mike]: I can tell you from experience that doesn't happen. I've tried, but, no.
[Dr. Patrick]: So the question then becomes, well, you know, how much of the organ shrinking, regrowing you get with just a fasting mimicking for five days versus, you know, actually not eating or... You know, so there's lots of little nuances that aren't quite figured out yet, but certainly there are benefits and he's shown that in humans.
[Mike]: So just to wrap up the question, it sounds like... You know, the question is, is a fast type more beneficial than other? It sounds like there are different instruments, different tools for different outcomes. And, you know, maybe combining some of these modalities may be doing, you know, time-restricted feeding, circadian more regularly. And periodically, to kind of get those cleansing benefits, metabolic cleansing, you do maybe a longer one if, again, if your doctor says it's okay and you're cleared for it. Could that be a good sort of sequencing for people?
[Dr. Patrick]: Yeah. And I think that's a good summary. And I think I should probably also mention another benefit that comes from the both intermittent fasting and certainly a prolonged fasting is your body shifts from glucose metabolism, metabolizing carbohydrates, to fatty acid metabolism.
[Mike]: Ketones.
[Dr. Patrick]: And you get to production of ketone bodies, like beta-hydroxybutyrate, which is in and of itself been shown by people like Dr. Eric Verdin to be anti-aging in a sense where there it's a signaling molecule that's been shown to activate genetic pathways in the body that are known to delay age-related diseases that are known to help increase repair processes. It's been shown to reduce damage that's generated by your mitochondria, which are, you know, basically what's generating most of the energy inside of your cells. But that whole process of generating energy, known as metabolism, generates a lot of, you know, very harmful reactive byproducts and beta-hydroxybutyrate lowers that. So it kind of makes your mitochondria more efficient. That's another benefit with the intermittent fasting and certainly the prolonged fasting.
[Mike]: Cool.
A type of intermittent fasting in which a person fasts every other day. On “fasting” days, dietary intake is limited to 0–25% of typical caloric intake; on “feeding” days, energy take is not restricted. Scientific evidence suggests that ADF results in weight loss and improved metabolic parameters and may be an effective weight loss strategy in humans.
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.
A chemical produced in the liver via the breakdown of fatty acids. Beta-hydroxybutyrate is a type of ketone body. It can be used to produce energy inside the mitochondria and acts as a signaling molecule that alters gene expression by inhibiting a class of enzymes known as histone deacetylases.
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 gene encoding a transcription factor (CLOCK) that affects both the persistence and period of circadian rhythms. CLOCK functions as an essential activator of downstream elements in the pathway critical to the generation of circadian rhythms. In humans, polymorphisms in the CLOCK gene have been associated with increased insomnia, weight loss difficulty, and recurrence of major depressive episodes in patients with bipolar disorder.
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]
Fasting-Mimicking Diet Breakdown
- Day 1 - consists of 1,090 total calories (10% protein, 55% fat and 34% carbohydrate)
- Days 2 through 5 - consists of 725 total calories (9% protein, 44% fat and 47% carbohydrate)
[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.
A molecule composed of carboxylic acid with a long hydrocarbon chain that is either saturated or unsaturated. Fatty acids are important components of cell membranes and are key sources of fuel because they yield large quantities of ATP when metabolized. Most cells can use either glucose or fatty acids for this purpose.
A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:
- Time-restricted eating
- Alternate-day fasting
- Periodic fasting (multi-day)
Molecules (often simply called “ketones”) produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, or prolonged intense exercise. There are three types of ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are readily used as energy by a diverse array of cell types, including neurons.
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.
Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.
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 that allows cells to perceive and correctly respond to their microenvironment, which enables normal cellular function, tissue repair, immunity, cognition, and more. Hormones and neurotransmitters are examples of signaling molecules. There are many types of signaling molecules, however, including cAMP, nitric oxide, estrogen, norepinephrine, and even reactive oxygen species (ROS).
A cell that has the potential to develop into different types of cells in the body. Stem cells are undifferentiated, so they cannot do specific functions in the body. Instead, they have the potential to become specialized cells, such as muscle cells, blood cells, and brain cells. As such, they serve as a repair system for the body. Stem cells can divide and renew themselves over a long time. In 2006, scientists reverted somatic cells into stem cells by introducing Oct4, Sox2, Klf4, and cMyc (OSKM), known as Yamanaka factors.[1]
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