KarlT
#13
There are clearly multiple good methods to get and be healthy. And multiple ways to extend life span as we’ve seen in mice. There may not be a “best” way. And likely the best methods change by age and other individual criteria. How many ways can you impact mtorc?
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If the only reason you are using a restrictive diet is to lower MTOR, why not just use Rapamycin and eat what you like? I guarantee that Rapamycin will lower your MTOR more than any diet!
And, if that’s not enough, throw in some Metformin to help.
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Neo
#15
I’m not sure but there may also be a bit of what people are optimizing for. Simplified
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if you are optimizing to avoid frailty, sarcopenia, osteoporosis then more resistance training and accompanied higher protein intake may be helpful
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if you are optimizing for chance of longest longevity per say, then in my view the evidence is for not overdoing protein as it is pro-growth and in many ways pro-growth seems to be anti longevity
Given how the risk of eg a hipfracture in old age often leads to early death or at least decreased healthspan, etc, one might want to weigh the first path above more.
If one is instead is optimizing for longevity escape velocity and/or think one either has less risks of sarcopenia/osteoporosis and/or think that one is young enough that good interventions for frailty will come online in time before becoming frail (eg myostatin gene therapy type of things) then one may want to lean more towards the second path.
While also a simplification, most of the value of higher protein seems to be connected to building/retaining muscle (and hence avoiding frailty and perhaps in the interim also having better glucose control, etc). If one does not spend time on the resistance training part of the first path or if one has good muscle outcomes with less protein then it seems like one may want to increase the percentage one follows the second path and more protein is not “being used”/“needed” and hence while increase the cost of the negative pro growth signaling.
Personally I cycle periods of building muscle and higher protein with periods with lower protein and in both cases monitor my muscle mass and aim to ensure that I have the minimum (and no more) of protein where I personally still achieve those muscle goals and while longer term I am also monitoring my bone health via annual bone density dexa scans.
I also time the protein intake to be higher around the days when I am focused on resistance training and proteins intake to be lower on days that are way from resistance training days (either more cardio focused or rest day)
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De Strider，Thank you for your valuable advice. I am indeed considering starting to take Rapamycin. However, my main concern now is that I have seen many people on forums reporting elevated blood sugar and triglyceride levels after taking Rapamycin, eventually leading to discontinuation of the medication. How do you view this issue, and do you have any effective solutions? Additionally, what is the appropriate weekly dosage for a typical 40-year-old male? Thank you, and I hope to receive your further response.
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Neo
#17
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I can only tell you what I do, so please take it with a grain of salt as no one knows for sure what the best dose is.
I have also added ezetimibe daily to lower LDL cholesterol and provide an energy boost.
I have slightly higher HBA1C at 5.7 (5.6 is the normal cutoff)
I have high LDL at 122 (99 is the cutoff)
These are the only two parameters that are abnormal. And since then I have added ezetimibe for the LDL and more Metformin for the HBA1C. I am confident these will help.
Prior to my last bloodwork, all my parameters were normal.
Personally, I feel the benefits of Rapamycin outweigh the negatives listed above. I will be checking my blood work shortly after Christmas and let all of you know the results.
(I am also switching to a very high dosage for the following two months as a trial. I am not recommending it until I get the results)
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Neo
#19
Dr. Dudley Lamming, a aging and rapamycin scientist people seem to generally like a lot on this forum, is the senior author of that new study and said:
“We know that many people deliberately consuming high-protein diets or consuming protein supplements to support their exercise regimen are not metabolically unhealthy, despite the body of evidence showing that high-protein levels can have detrimental metabolic effects,” says senior author Dudley Lamming, Associate Professor of Medicine (Endocrinology) at the Department of Medicine, School of Medicine and Public Health, University of Wisconsin.
“Our research may explain this conundrum, by showing that resistance exercise protects from high-protein-induced fat gain in mice. This suggests that metabolically unhealthy, sedentary individuals with a high-protein diet or protein supplements might benefit from either reducing their protein intake or more resistance exercise.”
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Neo
#20
Might be worth looking into what optimal ranges are vs just “normal”. Even if close to “normal” they may be far from optimal.
Both of these are among the most important ones anyone optimizing for health and life extension probably wants to nail.
So while “the only two” they really are “two crucial ones”.
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I completely agree, which is why I have increased my dosage of Metformin to 500 mg daily (1 g on the day of Rapamycin dosing) and have added 10 mg of Ezetimibe daily.
I tried to add Rosuvastatin, but the side effects were too horrible. If the LDL cholesterol is still an issue, I will consider adding Bempedoic Acid. But, I want to give the Ezetimibe by itself a shot first.
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swsl
#22
I was going to ask if you had tried Rosuvastatin. Did you go low dosage? I just started on 5mg every other day about a month ago and zero issues so far. That’s only 15-20 mg per week. Many people are dosing at 20 mg daily which is dramatically larger load at 140 mg in a week.
There is some evidence for Rosuva effectiveness at low levels. I will do a lipid panel in a month or so to check. My LDL was low last test but ApoB and particle count have ranged a bit high in the past and am not only looking for long term particle damage control but for the other less measurable effects of statins as well .
Not on Metformin anymore (no good reason other than muscle studies) nor have I tried Rapa yet. Doing large doses of Omega 3 (3 grams daily) and long term Resveratrol (1 gram daily) user since being “prescribed” for Lyme disease ten years ago by herbalist.
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swsl
#23
It seems that the great majority of diet/health/longevity opinion leaders choose managing sarcopenia as a priority over the theoretical dangers of protein as favored by Dr. Longo.
Even those (most!) who greatly respect his fasting centric approach do not seem to concur (in practice) with this aspect of his approach.
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I tried Rosuvastatin 5 mg every other day and it was still horrible. It took me weeks after stopping to get back to normal. The muscle soreness and weakness was unbearable.
It just doesn’t work for some people. I can accept that and move on to other things. At least the ezetimibe also comes with an energy boost.
I also take 2 g of Omega-3 daily and 1 g of Resveratrol 3x a week.
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swsl
#25
Ah, ok. I am on the alert myself. I am taking CoQ. It’s interesting how much more that effect seems to happen in real life vs studies.
It seems that you are far more aware and engaged on these fronts than me. I only mentioned the Omega 3 and Res as a reference but I do think that my low triglyceride numbers may be helped by the O-3. I eat a fairly high saturated fat diet and have one APOE4 allele.
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For me, the muscle soreness happened in an instant. It didn’t gradually build up. It was more like getting hit by a truck. I was also taking CoQ10 and that didn’t seem to help.
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LaraPo
#27
Rosuvastatin didn’t work for me too. I was on 5 mg/day. Trying ezetimibe, 10mg, and Pantethine, 500 mg, now.
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Let me interject some ideas in here that I am not so far seeing represented in this discussion,
The first is that Mother Nature (evolution) is not profligate of biologic energy reserves and has conserved the system of cholesterol production for good reason. It is a component of every cell membrane in the body and a precursor of many vital hormones. (All classes of steroid hormones, glucocorticoids, mineralocorticoids, and sex hormones are derivatives of cholesterol.) This system is important enough that it includes a cholesterol making mechanism if we don’t get enough in our diet. To suppose that system in an error is woefully short sighted. Cynics claim the fear of cholesterol is only a result of labs finally having a test to measuire cholesterol.
Gary Taubes book, “Good Calorie Bad Calorie” includes the fact that Dwight Eisenhower’s 1955 heart attack occurred when his cholesterol was 156.
The second. Plaque build up in arteries is a complex process to protect damaged endotheliel cells. The damage is probably just another function of chronic inflammation, but for whatever reason, the damage is repaired with a clotting process (like a scab on the damaged knee) that is essentially an internal scab which eventually incorporates cholesterol. The damage causes the plaque. Cholesterol doesn’t cause the plaque.
But Third–is the kicker. Here is the Summary from The Journal “Annals of Nutrition and Metabolism,” 2015:66 “Cholesterol and Mortality.”
“Overall, an inverse trend is found between all-cause mortality and total (or low density lipoprotein [LDL]) cholesterol levels: mortality is highest in the lowest cholesterol group without exception. If limited to elderly people, this trend is universal. As discussed in Section 2, elderly people with the
highest cholesterol levels have the highest survival rates irrespective of where they live in the world.”
Let us factor in these pieces of information in this discussion of ;longevity and health.
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If nature is good, why aren’t we immortal with an indefinite youth and healthspan?
Cholesterol doesn’t cause the plaque.
With low enough cholesterol levels, plaque never even forms and we have evidence of soft plaque decreasing with low levels of LDL cholesterol.
“Overall, an inverse trend is found between all-cause mortality and total
This is an observational study that doesn’t take cofounding factors into account, like all the others. Why do you ignore the intervention studies where statins do indeed decrease all cause mortality?
“The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66−0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66−0.76) and non-CVD studies (0.70, 0.67−0.79).”
Effect of Statins on All-Cause Mortality in Adults: A Systematic Review and Meta-Analysis of Propensity Score-Matched Studies - PubMed (nih.gov)
Systematic reviews trump observational trials by the way, as indicated by this picture below.
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LaraPo
#30
My mother, 91, has high cholesterol for at least 30 years (before it was not measured). She refuses to take any statins. Amazingly, her heart is very healthy, she has normal BP, etc. She’s pretty active and lives independently. Her doctor, who’s at least 30 years younger, said he envies her bloodwork results. And I do too 
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jakexb
#31
For me, the muscle soreness happened in an instant. It didn’t gradually build up. It was more like getting hit by a truck. I was also taking CoQ10 and that didn’t seem to help.
I really wish we could know why statins do this with some people and not others. I feel like I’m notorious for getting side effects but somehow taking 20mg rosuvastatin is like eating m&ms. No issues even in the sluggtes.
But then I try to take finasteride for hair loss and it makes me feel like complete garbage.
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Finasteride also negatively affects me as well, but I guess not as bad as you. But I am glad you can handle Rosuvastatin. I wish I could.
