The unique effects of multi-day prolonged fasts (requires more than 48 hours) - Valter Longo
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A prolonged fast has additional benefits compared to an overnight fast. Overnight the body still has liver glycogen and is not forced to begin burning fat. However, after two days of fasting, or a fasting-mimicking diet, the body starts to burn visceral fat as energy. The brain stops using sugar and begins using ketone bodies, such as beta-hydroxybutyrate as fuel. Further changes are seen, as the immune system, and organs including the liver and the heart shrink. In this clip, Dr. Valter Longo explains the benefits of a prolonged fast.
Rhonda: Eating within a certain time frame, and eating two meals a day, actually is what I do. I usually try to eat within a 10-hour, and I fast for about, you know, 14 hours. But I'm really interested in the autophagy benefits, and in the stem cell, being able to make more hematopoietic stem cells, and I'm wondering what a human would have to do to get it? Like is my 14 hours of fast every night doing that, or do I have to do a 4-day prolonged fast, which I can't? I mean, I wouldn't do that, like, unless I had some, sort of, supervision, or possibly this fasting-mimetic diet, which you mentioned. You've shown in several different studies and many different ways, it mimics fasting, and it's this low-sugar, low-protein, high-fat diet. So, you know, is that something that...
Valter: Yeah. I think there are different advantages. I mean, there's obviously some overlap, so I would say if you're on the perfect diet, which is a vegan pescetarian diet, low-protein, high-nourishment like I do always. It's like two meals a day, 12-hour restriction, and then, the rest that I just said, if you're on that, you're not gonna need as many fasting-mimicking diets, right? But the fasting-mimicking pushes you into a mode that you don't normally get with all these interventions. Why? Because overnight, most of that 14 hours, you got some glycogen to burn, right? So, you're not really needing to do much of a switch to anything else.
And that's fine, and I think it's good, you know, shouldn't go over that because it's just a continuous thing, you know. You don't wanna push the system too much into these extreme modes all the time. It's different from the fasting-mimicking diet because, as I said, you know, the fasting-mimicking diet I really, by day two of the diet, and only by day two or so of the diet, the system starts switching to a ketogenic mode. You start burning visceral fat as your major source of energy. Your brain starts moving from burning sugar, to burning ketone bodies, beta-hydroxybutyrate.
So, as I said, everything starts shrinking, the immune system starts shrinking, the liver, the heart, even the oligodendrocytes, as we've shown in our multiple sclerosis paper. So, yeah, so, that, you're not gonna get with anything else, and you're only gonna get it with these prolong fasting-mimicking diet. Now, is it possible that if you did some of these things many, many times that this would be equivalent to a fasting-mimicking diet? Yes, it's possible, but again, we don't know because, theoretically, that shouldn't be enough because you're never gonna get to this shrinking and rebuilding. But even if it was like that, then I think that, again, it's hard to change people's behavior all the time, so we felt that by doing these periodic interventions, we get a much better chance of getting there.
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 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 highly branched chain of glucose molecules that serves as a reserve energy form in mammals. Glycogen is stored primarily in the liver and muscles, with smaller amounts stored in the kidneys, brain, and white blood cells. The amount stored is influenced by factors such as physical training, basal metabolic rate (BMR), and eating habits.
An immature cell that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets. Hematopoietic stem cells are found in the peripheral blood and the bone marrow and give rise to both the myeloid and lymphoid lineages of blood cells. The process by which blood cells are produced is known as hematopoiesis.
Myeloid cells include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, and megakaryocytes to platelets. Lymphoid cells include T cells, B cells, and natural killer cells.
A metabolic pathway in which organisms produce ketones. Ketogenesis occurs primarily in the mitochondria of liver cells via the breakdown of fatty acids and ketogenic amino acids. Insulin is the major hormonal regulator of ketogenesis; however, glucagon, cortisol, thyroid hormones, and catecholamines can induce greater breakdown of free fatty acids, thereby increasing the substrates available for use in the ketogenic pathway. The primary ketones used by the body for energy are acetoacetate and beta-hydroxybutyrate.
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.
A type of glial cell that is involved in the production of myelin, providing support and insulation to axons in the central nervous system. A single oligodendrocyte can extend its processes to 50 axons, wrapping approximately 1 micrometer of myelin sheath around each axon.
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 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]
- ^ Takahashi, Kazutoshi; Yamanaka, Shinya (2006). Induction Of Pluripotent Stem Cells From Mouse Embryonic And Adult Fibroblast Cultures By Defined Factors Cell 126, 4.
Restricting the timing of food intake to certain hours of the day (typically within an 8- to 12-hour time window that begins with the first food or non-water drink) without an overt attempt to reduce caloric intake. TRE is a type of intermittent fasting. It may trigger some beneficial health effects, such as reduced fat mass, increased lean muscle mass, reduced inflammation, improved heart function with age, increased mitochondrial volume, ketone body production, improved repair processes, and aerobic endurance improvements. Some of these effects still need to be replicated in human trials.
An excess of visceral fat, also known as central obesity or abdominal obesity. Visceral fat, in contrast to subcutaneous fat, plays a special role involved in the interrelationship between obesity and systemic inflammation through its secretion of adipokines, which are cytokines (including inflammatory cytokines) that are secreted by adipose tissue. The accumulation of visceral fat is linked to type 2 diabetes, insulin resistance, inflammatory diseases, certain types of cancer, cardiovascular disease, and other obesity-related diseases.[1]
- ^ Fontana, Luigi; Eagon, J. Christopher; Trujillo, Maria E.; Scherer, Philipp E.; Klein, Samuel (2007). Visceral Fat Adipokine Secretion Is Associated With Systemic Inflammation In Obese Humans Diabetes 56, 4.
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