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The fasting-mimicking diet can affect biomarkers and disease risk in a positive way. In a clinical trial, researchers subjected people to three cycles of a fasting-mimicking diet and measured biomarkers including cholesterol, triglycerides, fasting glucose, IGF-1, blood pressure, and C-reactive protein. After the diet, people with previously elevated biomarkers returned to healthy levels, while those with normal levels remained the same. These results are unlike caloric restriction, which continues to drive biomarkers lower even in healthy people. The fasting-mimicking diet appears to be resetting or rejuvenating the system. In this clip, Dr. Longo describes the promising research that suggests that one's risk for diseases over the next 10 years may be drastically reduced.
Rhonda: So you do have evidence, and this is a recent publication of yours, that the fasting-mimicking diet in healthy subjects can, it seems, affect biomarkers that are related to aging in a positive way.
Valter: Yes, aging and as well biomarkers for aging, as well as risk factors for diseases, right? So this was a clinical trial, a randomized clinical trial with three cycles of the fasting-mimicking diet once a month for five days, for three months in a row, and then of course we looked at baseline and it was a randomized crossover. So, in each case you'll have a group of controls, a group on a control diet and a group on the fasting-mimicking diet, and then the crossover.
And yeah, the results are remarkable. I mean, first of all, if you are a healthy person with say a healthy or a low blood pressure, nothing happens to you. And this is a really nice distinction with calorie restriction for example, right? Earlier we were talking about, you know, are they all going to the same place? I don't think so.
So calorie restriction, chronic, it keeps driving your markers down. Right? So, even if you started...I mean, if you look at Biosphere 2, and these were then confirmed by Fontana and others, if you look at Biosphere 2, even people that had at the beginning a low blood pressure, they kept dropping, and by the end of it, they had pressure like 85/55.
And same thing for cholesterol, same thing for triglycerides, almost everything, usually drop to very low levels. Fasting glucose.
The fasting-mimicking diet itself, it seems to...you know, if you have a blood glucose of 75, nothing changes, it doesn't drop it even more. If you had a fasting glucose of 106, almost in every case, it brings you back to normal. This is very interesting, and also very good for doctors. So now we have close to 3,000 doctors just in the U.S. that are recommending the prolonged fasting-mimicking diet, what was tested in the clinical trial, and this is a very important feature.
So, the three cycles decreased, in normal people did nothing, in people that had...I mean, I shouldn't say did nothing. Did nothing that you can see in terms of markers, because they already had good levels of these markers. But in people that had elevated cholesterol, it decreased cholesterol. The people that had the elevated triglycerides, it decreased triglycerides. People that had the elevated IGF-1, probably people eating on a high protein diet, it dropped IGF-1. And the highest people dropped dramatically, you know, it came down about 60 points.
And the people that had the high fasting glucose, came down. People with blood pressure that was elevated, both the systolic and diastolic, had major effects. The people that had CRP, systemic inflammation, in almost every case they moved back to the normal range.
So it's really powerful I think in resetting the system somehow, that it's getting out of the...its functional ideal state, it resets it, and I think it really rejuvenates. Now we're doing...we're trying to calculate based on published profiles, and also methylation profiles, is this rejuvenating you? And also A and B, after three cycles, what is your risk for diseases in the next 10 years at baseline, and what is your risk after three cycles? And we suspect there's going to be a drastic change, just...You know, if you think about it, it's three months, right? Is just...
Rhonda: And this was a five-day fast each? It was one week...
Valter: Yeah, five days of...three cycles of a five-day fasting-mimicking diet, and then we measured again, and of course all these things that I just say change. But what if we go to the databases and we plug in the numbers, and we say, tell me, you tell me, what is the risk now compared to before? So we haven't finished that yet, but I think soon enough. And I'll just say there's very...the results look very promising.
A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.
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.
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 ring-shaped protein found in blood plasma. CRP levels rise in response to inflammation and infection or following a heart attack, surgery, or trauma. CRP is one of several proteins often referred to as acute phase reactants. Binding to phosphocholine expressed on the surface of dead or dying cells and some bacteria, CRP activates the complement system and promotes phagocytosis by macrophages, resulting in the clearance of apoptotic cells and bacteria. The high-sensitivity CRP test (hsCRP) measures very precise levels in the blood to identify low levels of inflammation associated with the risk of developing cardiovascular disease.
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.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
One of the most potent natural activators of the AKT signaling pathway. IGF-1 stimulates cell growth and proliferation, inhibits programmed cell death, mediates the effects of growth hormone, and may contribute to aging and enhancing the growth of cancer after it has been initiated. Similar in molecular structure to insulin, IGF-1 plays a role in growth during childhood and continues later in life to have anabolic, as well as neurotrophic effects. Protein intake increases IGF-1 levels in humans, independent of total caloric consumption.
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 biochemical process involving the addition or subtraction of a methyl group (CH3) to another chemical group. In epigenetics, a methyl group is added to an amino acid in a histone tail on DNA, altering the activity of the DNA segment without changing its sequence. Under- and over-methylation are referred to as hypomethylation and hypermethylation, respectively.
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.
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.
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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