#74

@John_Hemming On the topic of the importance of mitochondrial health, here’s a thought experiment that just occurred to me to see the energy expenditure of the body for doing nothing (i.e., just maintenance). This is simplistic, but how would you make it better?

Okay, to drive home the point that the body is doing a lot just to stay alive and repair stuff. And, any problem with ATP production by the mitochondria would interfere with this demand for energy even if enough food was consumed or enough fuel storage was in place or if autophagy was functioning well. The issue at hand is the mitochondria’s capacity to turn non-ATP fuel (fatty acids, glucose, lactate, ketone bodies, etc.) into ATP needed by the cells… cells die without a continuous flow of ATP, and cells (and organs) have the ability to down regulate processes that can’t be fueled. If i designed the system, I would prioritize surviving for the next few seconds or minutes over surviving for the next decade or two (especially for a 60 year old).

For context:
1000 kcal per hour is an all out, kick your butt level of intensity that can only be done by very fit people. I am not confident I could do this today. Most exercise I do is between 200 - 700 kcal over 45 min to 90 minutes. This is the energy my body needs to move my 200 lbs body around vigorously for around an hour. Call it 400 kcal per hour. That is what 400 kcals buys

Let’s see what the body needs every 24 hours just to do regular maintenance (including the stuff needed for healthspan and lifespan). For simplicity, let’s ignore the energy cost of digesting food. I’m also going to ignore the low energy usage of fidgeting and using the toilet, for simplicity sake. I’m also going to ignore the energy needed to do extra repair and adaptation from exercise.

25 kcal per KG body weight is a rough estimate of BMR…energy cost for keeping the body alive. Let’s say that amount includes the commonly referred to 30% used by the brain for thinking. An 80kg person would need 2000 kcal x (1-30%)= 1400 kcal to power all the body “stay alive” processes.

1400 kcal just to stay alive. Call it 60 kcals per hour every hour every day. Yes, 60<400, but that is a comparison of how hard I can exercise in an hour vs. doing nothing. I would have guessed a 100x difference, not a 7x.

Eating more won’t help. I need to keep vast hoards of healthy mitochondria powering my repair and maintenance processes to have a healthy body for a long time.

What did this rough sketch leave out or get wrong?

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#75

It is a good perspective, but we need to work out the dimensions.

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#76

I don’t have time to look into this in deetail, but in short, I think the problem with these studies you linked to on CoQ10, melatonin and quercetin is basically similar in that in all cases the doses you get from supplementing them is not high enough to have a significant effect on mTOR in vivo. The CoQ10 study was in vitro, the melatonin study used a very high dose given intraperitoneally and quercetin is metabolized to a large extent in the intestines and liver so all these are unlikely to reach concentrations as high as those found to effect mTOR after ingesting them at reasonable doses.

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#77

My uninformed guess is that eating a moderate to higher protein diet and reducing mToR using Rapa and possibly other means is the best of both worlds. My reasoning: the best guess as to why low protein diets correlate/cause longevity is via mToR per se. So we want lower mToR. But we also know protein has a lot of benefits, eg satiety/caloric control (from meat per se) and promoting higher muscle mass and strength, which is why Attia and Stanfield are so stoked on it. You might argue that the mechanism by which that happens is protein causing elevated mToR per se. However, mToR being the sine que non for muscle mass/strength is refuted by the clinical evidence of Rapamycin for prevention of sarcopenia and the large amount of anecdotal evidence of people on Rapamycin who have been gaining more muscle since they started it. I’ve yet to see a single anecdote of anyone reporting that they believe Rapa is inhibiting their muscle or strength building efforts.

The reason I’m posting this in this thread is bc we have been discussing combo therapies, and I’m treating the amount of protein consumption and Rapa as a combo therapy.

Would love to hear opposing ideas.

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#78

These are timing issues. When you eat food it is processed and the impact on different cells varies. The Rapamycin cycle depends upon its half life that varies between people, but is thought to be about 60 hours.

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#79

I think there are multiple other reasons - skim some of the papers about protein or amino acid restriction and you can get a sense.

For instance another growth vs repair signaling aspect of protein is its impact via insulin increases. See eg the first two posts here

Insulin and aging – a disappointing relationship (Paper)?

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#80

Thanks! Although I don’t have the knowledge to fully follow through on your reasoning, what you say seems reasonable. I will continue with several of those supplements, but to be safe will discard some, going more for intermittent dosing.

I won’t burden you with studies on the remaining supplements, except if I find an indication of high enough effects on mTOR concentration in vivo at reasonable doses.

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#81

Related to this topic: Peter Attia’s supplements he takes.

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#82

Thanks @RapAdmin .

Has anyone tried the probiotic blend he says he takes and that is formulated to modulate glucose control?

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#83

For that price I can buy canagliflozin, acarbose and metformin. The price seems high to me, but for some it might be worth it.

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#84

Could be that it is enough to take it for a while to change one’s microbiome vs the drugs that have to be taken continuously

#85

yes - and more generally I’d prefer to take a probiotic if it achieves the same thing, as it would seem to offer much lower risk of side effects.

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#86

I’m surprised that Attia needs help with his blood sugar control. Now that he doesn’t do fasting, perhaps his blood sugar is not where he wants it.

#87

I think he said that he is testing it. And he is all about optimal markers and poorer glucose control seems is inevitable connected with aging… I myself also think that this is the most important part of metabolic health and I am not happy my HbA1c went from 4.8 to 4.9 on rapamycin for sure. And I am using acarbose. :sweat_smile:

ps. I find this probiotic just ridiculously priced… WTF is this?

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#88

My HbA1c goes all over the place on a weekly basis. I really do not think a movement from 4.8-4.9 or vice versa can be seen as being significant. It would have to move perhaps 0.5 to be a reliable movement.

HbA1c changes with metabolism and there are different versions of the test and I think probably daily movements as well.

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#89

@scta123 It’s hard to see if blood sugar will improve if blood sugar is already low (too low is unpleasant). As a counter point, I have higher blood sugar. I am currently testing a number of interventions to get it lower: metformin / berberine (I rotate them), ALA, SGLT2. Blood test soon to see results.
Last test: fasted glucose 87. HbA1c 5.7.

I will not be paying $150/month for probiotics.

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#90

I believe this probiotic should be flattening the spikes after meal. This could be detected via CGM I guess…

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#91

Here’s an example. On 11/10/23 using Randox my HbA1c was 24.9 mmol/l which I estimate to be around 4.4%, on 16/10/23 using Medichecks it was 30 mmol/l which I estimate to be 4.9%. I am not sure there was a material change in the underlying biomarker. I hazard a guess that the time metabolising with Medichecks is longer than Randox. Creatinine with Randox was 82.3 and 98 with Medichecks which underpins the metabolism hypothesis - because Creatinine also metabolises (goes up in untested blood already drawn). Cystatin-C with Randox was 0.73 which gives an eGFR of 95.

AFAIK the metabolism error with Cystatin-C is less than with Creatinine also having more muscles is less of an issue with Creatinine. However, I know a nephrologist whose view was that Cystatin-C was too variable.

Oddly enough, however, MCV which was 94.9 with Randox was 94.7 with with Medichecks. When I stick to my only one drinking day a week routine (which I don’t do when there are parties to go to) I think MCV comes down, however. MCV also metabolises.

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#92

@scta123 thanks. I’m still wondering about “flattening” the glucose curve. I don’t think a flat glucose level is a reasonable goal. Less AUC is measured by HbA1c. But there is some predictive information contained in the shape of glucose curves for sure. But does a short spike matter for health now? I don’t know. Not $150 per month worth, anyway.

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#93

Best to keep glucose below 8mmol/L. It shifts into a worse pathway when it goes over that I think the US value is 140 (rather than 144).

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