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Valter Longo yet another (interesting) podcast


mccoy

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Valter Longo must be one of the most interviewed guys in the latest coupla years.

 

I just listened to the stemtalk interview (Ken Ford is usually biased on the ketogenic diet, but he's been evidently able to overcome this bias), where new aspects on his proposals are underlined: IGF-1 and its sweet spot, local and general IGF-1. No coffe when fasting and when on his FMD.

 

One pretty interesting issue is that about the 'phantom carbon sources', nutrients which are utilized by the body but not recognized as nutrients. Fibers? Else?

 

I googled  'phantom carbon sources' but found no relevant results so far .

 

https://www.ihmc.us/stemtalk/episode-64-valter-longo-talks-about-the-fasting-mimicking-diet-and-the-keys-to-longevity/

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Mccoy,   a Google search for carbon sources that activate pro-growth pathways  or  carbon sources that activate pro-pro-aging pathways  yielded some apparently relevant articles.  I haven't had the time yet to delve into them.

 

 

Replicative and Chronological Aging in Saccharomyces cerevisiae

 
 
One issue surrounding studies of replicative aging in yeast involves the choice of growth conditions, which can have major effects on experimental outcome (see section on chronological life span below). For the vast majority of replicative aging studies, growth on rich medium in the presence of 2% glucose (YPD, Yeast Peptone Dextrose) is the method of choice. It is clear, however, that life span can be affected by these choices. For instance, lowering glucose concentration, a condition that is used to model dietary (or calorie) restriction in multicellular eukaryotes, causes life span extension in many, but not all, strain backgrounds. Alternate carbon sources have also been tested to a lesser extent. Budding yeast is a facultative anaerobe that generates most of its energy in the presence of ample glucose through fermentation, with only limited respiratory metabolism. Since most mammalian tissues rely primarily on respiration rather than fermentation, it has been argued that use of a respiratory carbon source such as glycerol may make for more relevant comparison to human aging (Botta et al., 2011). This assertion has yet to be rigorously evaluated. A relatively small number of studies have also examined RLS using synthetic defined (SD) medium, which is commonly used in the chronological life span assay (below), but a direct comparison of life span on SD versus YPD has not been performed. In summary, there is a need for a broader understanding for how different environmental factors, including the nutritional status of the growth medium, influence yeast RLS.

 

 

The article has many more references to carbon sources-- the quote is just an example.  It's a dense article and I haven't digested it in the least.

 

 

Also Google carbon source substitution.

 

 

Tor1/Sch9-Regulated Carbon Source Substitution Is as Effective as Calorie Restriction in Life Span Extension

Min Wei ,Paola Fabrizio ,Federica Madia,Jia Hu,Huanying Ge,Lei M. Li,Valter D. Longo

 

Published: May 8, 2009

https://doi.org/10.1371/journal.pgen.1000467

 

 

 

Abstract The effect of calorie restriction (CR) on life span extension, demonstrated in organisms ranging from yeast to mice, may involve the down-regulation of pathways, including Tor, Akt, and Ras. Here, we present data suggesting that yeast Tor1 and Sch9 (a homolog of the mammalian kinases Akt and S6K) is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis. During chronological survival, mutants lacking SCH9 depleted extracellular ethanol and reduced stored lipids, but synthesized and released glycerol. Deletion of the glycerol biosynthesis genes GPD1, GPD2, or RHR2, among the most up-regulated in long-lived sch9Δ, tor1Δ, and ras2Δ mutants, was sufficient to reverse chronological life span extension in sch9Δ mutants, suggesting that glycerol production, in addition to the regulation of stress resistance systems, optimizes life span extension. Glycerol, unlike glucose or ethanol, did not adversely affect the life span extension induced by calorie restriction or starvation, suggesting that carbon source substitution may represent an alternative to calorie restriction as a strategy to delay aging.

 

 

Longo et al have an article in the book "Calorie Restriction, Longevity and Aging" (2010)  where they briefly discuss glycerol and carbon source substitution (p.101-102), citing the above mentioned article.

 

https://books.google.ru/books?id=zWgEkmHwjo8C&pg=PA102&dq=%22carbon+source+substitution%22&hl=en&sa=X&redir_esc=y#v=onepage&q=%22carbon%20source%20substitution%22&f=false

 

In contrast with glucose and ethanol, presence of either carbon source promotes aging,  glycerol  not only does not shorten life span of DR-ed yeast, its uptake and utilization may contribute to long term survival (Wei et al., 2008).  Taken together, the data  suggest that genetically induced "carbon source substitution" of the pro-aging ethanol with the neutral glycerol in long-lived mutants creates a DR-like environment.

 

 

 

There are many articles to read!    I await you thorough review and analysis.

Edited by Sibiriak
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Good find Sibiriak, so from the above it would seem  that Valter Longo himself has been studying those carbon sources substitutes in his experiments on yeasts, extendign the use of some glycerol  to humans during the FMD.

We don't have a dose though, although probably not much can be added to a tea. Looking forward to read some of the articles you cited, although delving into the metabolism of yeasts sure sounds a pretty adventurous reading.

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Another Longo article making similar points about glycerol.

 

Fasting: Molecular Mechanisms and Clinical Applications

 

Adaptive responses to fasting in mammals

In most mammals, the liver serves as the main reservoir of glucose, which is stored in the form of glycogen. In humans, depending upon their level of physical activity, 12 to 24 hours of fasting typically results in a 20% or greater decrease in serum glucose and depletion of the hepatic glycogen, accompanied by a switch to a metabolic mode in which non-hepatic glucose, fat-derived ketone bodies and free fatty acids are used as energy sources (Figures 2 and and3).3). Whereas most tissues can utilize fatty acids for energy, during prolonged periods of fasting, the brain relies on the ketone bodies β-hydroxybutyrate and acetoacetate in addition to glucose for energy consumption (Figure 3B). Ketone bodies are produced in hepatocytes from the acetyl-CoA generated from β oxidation of fatty acids released into the bloodstream by adipocytes, and also by the conversion of ketogenic amino acids.

 

After hepatic glycogen depletion, ketone bodies, fat-derived glycerol, and amino acids account for the gluconeogenesis-dependent generation of approximately 80 grams/day of glucose, which is mostly utilized by the brain. Depending on body weight and composition, the ketone bodies, free fatty acids and gluconeogenesis allow the majority of human beings to survive 30 or more days in the absence of any food and allow certain species, such as king penguins, to survive for over 5 months without food (Eichhorn et al., 2011) (Figure 3C).

 

In humans, during prolonged fasting, the plasma levels of 3-β-hydroxybutyrate are about 5 times those of free fatty acids and acetoacetic acid (Figure 3A and 3B). The brain and other organs utilize ketone bodies in a process termed ketolysis, in which acetoacetic acid and 3-β-hydroxybutyrate are converted into acetoacetyl-CoA and then acetyl-CoA. These metabolic adaptations to fasting in mammals are reminiscent of those described earlier for E. coli and yeast, in which acetic acid accumulates in response to food deprivation (Gonidakis et al., 2010; Longo et al., 2012). In yeast, glucose, acetic acid and ethanol, but not glycerol which is also generated during fasting from the breakdown of fats, accelerate aging (Fabrizio et al., 2005; Wei et al., 2009).

 

Thus, glycerol functions as a carbon source that does not activate the pro-aging nutrient signaling pathways but can be catabolized by cells. It will be important to understand how the different carbon sources generated during fasting affect cellular protection and aging. and to determine whether glycerol, specific ketone bodies or fatty acids can provide nourishment while reducing cellular aging in mammals, a possibility suggested by beneficial effects of a dietary ketone precursor in a mouse model of Alzheimer’s disease (Kashiwaya et al., 2012). It will also be important to study, in various model organisms and humans, how high intake of specific types of fats (medium- vs. long-chain fatty acids, etc.) in substitution of carbohydrates and proteins influences gluconeogenesis and glucose levels as well as aging and diseases.

 

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This is an interesting practical article on glycerol supplementation. They used 1.2 g/kg bodyweight, which is a lot. seems to boost gluconeogenesis and is an hyperhydrating agent. Easy to understand now how it can minimize muscle loss during a FMD (lesser use of muscle glycogen, lesser dehydration).

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590833/

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Good work, Mccoy and Mechanism.   Interesting topic.  Lot's of different angles on dietary glycerol.

 

The Prolon FMD appears to contain a very modest amount of glycerol.  It's only in the "L-drinks",  which are 20 calories each (and it's listed in the algal oil DHA supplement).   You get one L-drink per day on days 2-5.

 

https://fastlifehacks.com/prolon-fast-mimicking-diet-box-contents-calories-macros/

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MMMmmm, 20 kcal in the L-drinks, with no other energy sources but teh glycerin.

 

As to content of glycerin, since it's a carbohydrate = 20/4= 5 grams

 

It's more or less in line with the reccomanded amount as a pre-workout supplement, about 3 grams, as underlined in these bodybuilder's sites

 

https://www.bestworkoutsupplementsblog.com/top-glycerol-supplements/

 

https://supplementsinreview.com/pre-workout/glycerol-pre-workout/

 

The L-drinks are part of days 2 to 5, so an intake of 5 grams of glycerol/glycerin after dinner should bring about the beneficial effects foreseen by Longo's FMD.

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Mccoy,  are you going to be drinking glycerol drinks regularly?     

 

That's an interesting question, to which I don't know the answer yet. I've drunk glycerol for the 1st time when starting today my 7th FMD cycle. Very sweet taste, probably it's not included among the sweeteners because of its caloric load.

 

I'll have to do some research and see if it might carry some undesired side effects. Sure some hyperhydration in the summertime won't hurt. But again, I'll have to do some search.

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  • 7 months later...
On 6/14/2018 at 9:07 AM, mccoy said:

MMMmmm, 20 kcal in the L-drinks, with no other energy sources but teh glycerin.

As to content of glycerin, since it's a carbohydrate = 20/4= 5 grams

The L-drinks are part of days 2 to 5, so an intake of 5 grams of glycerol/glycerin after dinner should bring about the beneficial effects foreseen by Longo's FMD

Thanks mccoy, Mechanism & Sibiriak for sharing great info/papers - pleasure to read through. Particularly want to dig into the linked chemotherapy paper more, as it dicusses glycerol a lot.

Just to add to what mccoy said about the dose used by Valter Longo in their Prolon fast mimicking diet. Whilst the nutritional info mentions 20 calories per serving, on the actual bottles (which I've only seen recently) the serving size varies based on bodyweight. Essentially they have drawn little notches on the bottle, with the weight next to them. So you'd use as much of the bottle as gets it down to the applicable notch. For a 240lb person it's over 75% of the 118ml bottle.

Fortunately, we can reverse engineer the glycerol quantity because the bottle also says "formulated to provide 50 calories per 100 lb body weight". As mccoy says, there's 4 calories per gram of carbohydrates, so that's 50/4 = 12.5g of glycerol per 100lbs body weight. I made a simple calculator on this page, where you can type your weight and it outputs the amount of glycerine for each of days 2-5.

Then, and its nit picking, there's potentially an extra ~1g to 1.5g of glycerol per 6 calorie algae oil packet (which has glycerine added), added on days 1 & 5.

Side note, thought it was interesting to see "inulin", a plant based fiber source, as a primary ingredient on their choco crisp bar. Presumably to increase satiety and (possibly) decrease glucose spike? Will be curious to learn what other "tricks" they've used when formulating the diet.

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Those packets all look so gross that I'd prefer to eat nothing.  And I have.

Prolon is not for picky eaters, I guess.

So I listened to the podcast. I can only assume that because glycerol is part of a triglyceride the body doesn’t recognize it as being fed at low levels? But he didn’t say. 

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alex2, good job on the amoutn of determining the glycerol content and nice website indeed.

I'd be a little reluctant now to ingest glycerol if not in minimal amounts, because of its known laxative effects which I felt in one of the latest FMDs I led.

I didn't ingest any of it for bodybuilding purposes, since the same and better effect of muscle hydration is probably achieved by use of creatine.

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On 2/4/2019 at 9:19 PM, Genny said:

So I listened to the podcast. I can only assume that because glycerol is part of a triglyceride the body doesn’t recognize it as being fed at low levels? But he didn’t say. 

Hi Genny!

No; triglycerides are very different from glycerol; glycerol is an alcohol; triglycerides are a lipid, that shouldn't be in large amounts in your blood.

You can "eat" (drink?) all the glycerol (or glycerine) that you want; it isn't digested.

  --  Saul

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  • 2 months later...

A question for glycerol experts Alex or Mccoy (or anyone else):  In the video clip at Alex's site "Role of Glycerol in Prolon Fast Mimicking Diet - Muscle Sparing" (https://fastlifehacks.com/valter-longo-diy-fast-mimicking-diet-plan/)  Longo says:

 

Quote

[0:56] We have glycerol in the fast mimicking diet, and glycerol turns out to be a byproduct of fat, but also is what you use in gluconeogenesis  to make sugar to feed the brain. Now, if you don't have glycerol, the body breaks down muscle, right?  So one of the observations in the clinical trial-- there was no or minimal loss of lean body mass after three cycles of the FMD, and we suspect that for example glycerol is playing that part...

 

But  glycerol is released during fasting via lipolysis--so why would the body preferentially "break down muscle" to produce it, rather than simply burn more fat?

(See  Longo quoted above, " glycerol which is also generated during fasting from the breakdown of fats ",  and the paper cited by Alex at his site, Glycerol gluconeogenesis in fasting humans https://europepmc.org/abstract/med/7647479):  "These findings confirm that the contribution of glycerol to glucose production is directly correlated to its release as a consequence of lipolysis and support the notion that the central physiological role of accelerated lipolysis in fasting is the provision of gluconeogenic precursor. "

 

 

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Sibiriak, this time I didn't use glycerol, nor any other supplements. The lost muscle mass will probably come back in a couple of weeks. Longo seems to believe that when the glycerol signal is high, the body will switch to more fat utilization than muscle utilization for nutrients. But muscle has amminoacids, whereas fat has not. Also, to make sure that Longo's hunch is exact, they should carry out a RCT with an arm using clycerol and the other arm not using it. 

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A couple more podcast from Valter Longo, probably the most interviewed man in the field of nutrition...

At about 21:10, the interviewer asks him about preserving muscle tissue and strength for longevity and for the athletic crowd.

There is an ongoing trial in Italy, so it's early to tell. Anyway, he goes on buy supporting the idea of assuming more protein but not very much, since it's probably making the receptors inactive. So the lowest amount which allows muscle growth is best. He says 30 grams after a workout; to me if it is not additional to the daily quota, it seems little, but it also depends on the kind of exercise, intense bodybuilding or a lighter training session.

He also seems to clear up the issue of the optimum IGF1 level which in another podcast he affirmed to be 140 mg/dL.  He implies here that IGF1 should be higher in old people to make up for anabolic resistance, so it should be higher than average for the age class. So, keeping the IGF at that value, as we discussed in another thread, really means to keep it low, relative to age, when young, average when 50-55 and higher when over 55

 

 

 

 

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This is another I listened to during my commutes. By the way, can you guys pick the lady's accent? Where is she from, a little different from the American I'm familiar with.

There are some interesting points especially after the middle of the podcast. Why he believes FMD is superior to water only fasting, why he believes that a keto-FMD is not advised, although it may be 20% more effective than the traditional FMD.

 

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