Fasting and Fasting Mimicking Diet for treatment of autoimmune diseases | Valter Longo
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Studies in animals reveal that prolonged fasting and a fasting-mimicking diet result in decreased organ size. Upon refeeding, however, the organs return to their normal size. This shrinking and re-expanding effect does not occur with caloric restriction or shorter duration fasts. During shorter fasts, the body does not break down cellular components because digestion is still ongoing and glycogen (a storage form of carbohydrate) is still available. The characteristic cycle of targeted destruction and renewal has been shown in multiple sclerosis patients and animal models to temporarily reduce total white blood cell levels. In this clip, Dr. Longo discusses his work that indicates that the fasting-mimicking diet holds promise for the treatment of autoimmune diseases, particularly multiple sclerosis.
Rhonda: The shrinking of the organs and then sort of in the refeeding phase the re-growing, is kind of something I wanted to talk to you about as well, this rejuvenation process, because you've obviously shown this now in several different studies both with fasting and fasting-mimicking diet in animals, where they lose a significant amount of their different organs, right? And I think that you...maybe you want to talk about this, the...what...
Valter: Yes. So in mice for example, if you look at the weight of most organs, and this of course was known for calorie restriction long term. But with fasting, and fasting-mimicking diet, this happens much more rapidly. So the organs will be smaller, and at the end of the days of fasting-mimicking diet, and then you refeed and of course they go back to the normal level, right? So there is really, there is this shrinking and re-expanding effect.
Now, we don't know how much of it is cells becoming smaller, versus cells being killed, but clearly there is killing of cells. And certainly of course we are also very interested in, is there preferential killing of the damaged cells? And we've started to show that in our multiple sclerosis mouse model, and also the human study, there was evidence that the white blood cell level temporarily was reduced during the, at the end of the fasting cycles and then went back to normal. So yeah, so we suspect that there are these fasting-dependent, depletion of both intracellular components, you know, autophagy, and cellular components, and then we've shown the stem cell to be activated, and then the stem cell during the refeeding part.
And that's another very important point, is that differentiates it to most of other interventions, right? All of a sudden...even the intermittent fasting. Because you don't have enough time. If you do like even one day, it barely even gets you into the ketogenic mode, right? And of course if you do it for one day, you wouldn't want to break down too many of the components. That's probably...having all the glycogen and having all the digestion takes 30 hours to complete the food digestion, from the time you eat to the time that all the calories have been taken up, it takes probably over a day.
So that's a very important distinction between the prolonged fasting and everything else, including calorie restriction, which does not have the refeeding moment, right?
So, if the rebuilding happens during refeeding and you never have it, then of course you're missing out the reconstruction part, which is as important as the destruction part.
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.
The practice of long-term restriction of dietary intake, typically characterized by a 20 to 50 percent reduction in energy intake below habitual levels. Caloric restriction has been shown to extend lifespan and delay the onset of age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast.
The biological process in which a cell matures and specializes. Differentiation is essential for the development, growth, reproduction, and lifespan of multicellular organisms. Differentiated cells can only express genes that characterize a certain type of cell, such as a liver cell, for example.
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.
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)
An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.
A diet that causes the body to oxidize fat to produce ketones for energy. A ketogenic diet is low in carbohydrates and high in proteins and fats. For many years, the ketogenic diet has been used in the clinical setting to reduce seizures in children. It is currently being investigated for the treatment of traumatic brain injury, Alzheimer's disease, weight loss, and cancer.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
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]
The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.
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