Forcing The Heart To Burn Glucose Instead Of Fat May Cure Heart Failure

[maillol]

Maybe it doesn’t, at least in any significant way. I can see why they would put the manufacturers would put that in. Keep in mind “nitric oxide” is basically buzzword in athletic circles. It implies improved blood flow, better oxygenation, more nutrients, etc. Most athletes don’t have a clue to its negative consequences, only that it gives you sick pumps.

Yes I was thinking that too.
After writing that post I found this post The Nitric Oxide (NO) Theory Of Aging
which explains mildronate's affect on NO in more detail. Basically it lowers iNOS (the bad one) and normalises eNOS (the good one).

 

[haidut]

@haidut ....good one man but there Is one thing I dont understand, I know about masai tribe that consume Milk and meat only and dont have diseases, do you have any idea why? Thank you.

The fat in milk has a good balance between MCT of SFA and LCT of SFA. The MCT get metabolized similar to sugar and saturated fat such as palmitic acid actually activate PDH and promote glucose oxidation. Calcium also activates PDH. So, drinking milk provides mostly sugars, protein, and some fat with such a composition that not much inhibition of glucose is seen and in fact even increase in glucose oxidation likely results.

 

[zarrin77]

Mildronate will increase eNOS, which is good. The negatives of nitric oxide depend where the nitric oxide is and where it was produced from.

Produced inside of nerve cells via nNOS? Inflammatory
Produced from macrophages as iNOS? Inflammatory
Produced into the vasculature via eNOS? Anti-inflammatory. Why? Well one reason is that when NO from eNOS drops, it usually means that eNOS has been “uncoupled” from NO, which is bad because then eNOS makes superoxide instead of NO, stiffening the vascular system.

 

[MetabolicTrash]

Simple dietary and/or supplemental means are alluded to, but the study's main point of focus is on a drug to help do this?

You need a "specialized drug" to eat less fat and more carbs so that heart cells can use more glucose?

Or is this process not easily reversible? I mean if you are eating high-fat diets that makes sense, but why would a complete 180 by itself not be enough over time, along with additional and fitting supplements/drugs already known to help glucose oxidation? Do the cells get accustomed to, say, fats somehow and won't switch over to glucose easily, even adding in things like aspirin, niacinamide, thyroid, progesterone, very low fat diets, lowering stress in all ways possible, etc.?

I would have guessed that aspirin, preg, thyroid, etc. with low fat (especially PUFA) ought to be pretty powerful alone without any concerns for some new drug, unless maybe it is trying to be more direct in how it would affect the mitochondria/lipid membrane/etc. somehow?

In other words, what would this new drug theoretically do that many a great bits of what Peat alone has written/spoken of would not (without any serious negatives)?

Would it not just be another "shot" at something like Mildronate?

 

[lvysaur]

@haidut ....good one man but there Is one thing I dont understand, I know about masai tribe that consume Milk and meat only and dont have diseases, do you have any idea why? Thank you.

Maasai don't eat much meat, it's for special occasions. They mostly drink milk, soured milk, and grain porridge. Supplemented with a bit of blood and meat from time to time.

Regarding the blood, I think it's due to calcium's natural inhibition of iron absorption. And is also the reason Northwest Europeans have hemochromatosis/high iron problems (highly lactase persistent, and I would expect Maasai, Punjabis, Saudis etc to have similar problems).

Regarding the "why don't Maasai have diseases", maybe physical activity is a big factor.
Back when I was in college (only a few years ago), I drank 3 pints of whole milk a day, plus a meat/seafood dinner. But I also had to walk 1 mile to/from campus. You'll find that maybe 98% of Americans get nowhere near this much exercise. And I firmly believe the effects of low intensity high duration exercise (aka walking) can't be replicated in the gym. Unless you live in a city you won't get this exercise unless you actively try to every day--it's too easy to get in your car and drive.

 

[GelatinGoblin]

Interesting thread.
Glucose Oxidation and Mitochondrial function is good.. who woulda guessed

 

[aliml]

Castration of Male Mice Induces Metabolic Remodeling of the Heart

Abstract. Androgen deprivation therapy of prostate cancer, which suppresses serum testosterone to castrate levels, is associated with increased risk of heart fa

academic.oup.com

Androgen deprivation therapy of prostate cancer, which suppresses serum testosterone to castrate levels, is associated with increased risk of heart failure. Here we tested the hypothesis that castration alters cardiac energy substrate uptake, which is tightly coupled to the regulation of cardiac structure and function. Short-term (3-4 weeks) surgical castration of male mice reduced the relative heart weight. While castration did not affect cardiac function in unstressed conditions, we observed reductions in heart rate, stroke volume, cardiac output and cardiac index during pharmacological stress with dobutamine in castrated versus sham-operated mice. Experiments using radiolabeled lipoproteins and glucose showed that castration shifted energy substrate uptake in the heart from lipids towards glucose, while testosterone replacement had the opposite effect. There was increased expression of fetal genes in the heart of castrated mice, including a strong increase in mRNA and protein levels of β-myosin heavy chain (MHC), the fetal isoform of MHC. In conclusion, castration of male mice induces metabolic remodeling and expression of the fetal gene program in the heart, in association with a reduced cardiac performance during pharmacological stress. These findings may be relevant for the selection of treatment strategies for heart failure in the setting of testosterone deficiency.

 

[cs3000]

One of the blockbuster studies I have seen over the last 12 months. It reads as if written by Peat himself and discusses tissue regeneration, Randle cycle, dietary control of metabolism, etc. AFAIK this is the first study brave enough to demonstrate that simply switching fuel types in an organism can have profound structural effects, and reverse pathological changes (e.g. heart fibrosis / failure) officially considered irreversible. Another important finding of the study was that the beneficial effects on heart failure could be elicited both by pharmacologically inhibiting fatty acid oxidation (FAO), as well as by simply lowering dietary fat intake and increasing carbohydrates. The pharmacological intervention that decreased FAO and increased glucose oxidation was aimed at inhibiting the enzyme PDK (PDK4 specifically). That enzyme is the master brake of another crucial respiratory enzyme known as pyruvate dehydrogenase (PDH). PDH is the rate-limiting step in glucose oxidation. Anything that activates PDK results in PDH inhibition and thus glucose oxidation. Increased FAO just so happens to be one of the most powerful activators of PDK (PDK4 specifically) and as such (due to the Randle cycle) an inhibitor of glucose oxidation

While the study above does not mention specific doses for B1, in-vivo studies with both animals and humans have demonstrated that a HED of 100mg-300mg daily is sufficient to elicit a potent PDK inhibition and PDH activation effect. Adding 300mg-500mg niacinamide (vitamin B3) will likely potentiate the effects of B1 as a result of the anti-lipolytic effects of niacinamide as well as its direct FAO inhibition effects due to SIRT blockade. So, as hard as it is to believe that an "irreversible" condition such as heart failure may be curable it looks like the solution may not only be simple but cheap, safe, and widely available as well. Now, the only thing remaining to demonstrate so that the picture is complete is that not only does increased FAO (probably due to estrogen) prevent proper heart regeneration beyond infancy, it may be THE actual cause of heart failure to start with (at any age).

Mitochondrial substrate utilization regulates cardiomyocyte cell-cycle progression | Nature Metabolism

Changing what heart cells eat could help them regenerate: New study suggests that encouraging cardiomyocytes to consume glucose instead of fatty acids could help treat heart failure

Amazing info

so they deleted PDK4 for the regeneration effect, i wonder what the threshold is for inhibiting to regain the cardiomyocyte proliferation ability, would it have to be near 100%? how far of an inhibition can you get with oral thiamine + niacinimide?

ray said in his heart article thyroid hormone is involved in hearts functionally enlarging which allows for more powerful contraction, and it wasnt due to cell size increase.
heres 1 in its favor in mammals @haidut -> Thyroid hormone induces cyclin D1 nuclear translocation and DNA synthesis in adult rat cardiomyocytes - PubMed
and here its shown a short lasting thyroid hormone burst is what creates "final" major burst of +40% heart cells in young pre-adolescent mice A proliferative burst during preadolescence establishes the final cardiomyocyte number - PubMed (the t3 rises before proliferation, it sets up the conditions)

If human CMs, like those of the mouse, continue to divide efficiently during preadolescence, this may provide a basis for stimulating cardiomyogenesis in young patients by the administration of T3

A prospective randomized clinical study of thyroid hormone treatment after operations for complex congenital heart disease

T3 treatment of the overall study group did not significantly alter postoperative outcome measures, including the TISS, days of mechanical ventilation, or overall length of hospital stay. In contrast, newborn patients showed the tendency for a positive therapeutic response to T3 treatment

now it seems t3 can stimulate the response in adults when regained through the FAO inhibition glucose oxidation increasing approach. re-activate capacity and stimulate