#90

Agetron, if I may can I ask how much did that 60ml bottle of TRT cost you and how long does it last?

1 Like
#91

That container is not TRT cypionate… it is rapamycin/siriolimus skin lotion .2% It requires a prescription and is componded… costs $180. Lasts about 2 months. I use it on neck and face after showering in the morning. Been using 3 years… seems to work according to my dermatologist.

My TRT cypionate is free through insurance per my General Practioner GP prescription. I use 200 mg 1 ml vial by injection in thigh weekly with 1 pill of Anastrozole (prevent gynecomastia… man boobs).

Hope that helps.

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#92

OK, got it I thought you were using acronym TRT for Topical Rapamycin Treatment :rofl:

1 Like
#93

I am somewhat disappointed with Stanfield’s response to this. The study in question focused not only on high protein diet, but also high leucine content diet. He countered this with a study of high plant protein diet, which is low in leucine, giving better health outcomes. He is completely ignoring the leucine; thus he’s comparing apples to oranges. It seems like the high protein is not the problem, but rather high leucine which ACTIVATES M-tor and that might be the problem. He should know better but maybe he is purposely misleading to save face. What we need is a high protein diet low BCAA vs high BCAA comparison.

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#94

I don’t think he is deliberately misleading but he has been banging the high protein drum for a while now and it is difficult to change entrenched opinions.

There are real concerns about high BCAA consumption and metabolic health but I’m not fully convinced leucine in the amounts most people eat it is a significant contributor to CVD.

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#95

New email from Brad Stanfield…

Debunking the High Protein Diet Panic

Recently, a headline from the New York Post caused quite a stir: “You might be eating an artery-damaging amount of protein, new study warns.”

This statement, based on a study in Nature Metabolism, set off alarms across social media platforms, including among my YouTube channel viewers, where I’ve shared my adherence to a high-protein diet.

Let’s dissect the facts to understand the real implications of this study.

The research began by referencing animal studies that associate high-protein diets with atherosclerosis development, potentially due to the overstimulation of a specific enzyme known as mTORC1.

The authors posited a human protein intake threshold that might trigger mTORC1 overactivation, leading to heart disease.

Their investigation unfolded across two experiments:

  1. Liquid Meal Test with 14 Participants: This test compared the effects of a 10% protein meal versus a 50% protein meal after an overnight fast.
  2. Real-Food Scenario Study: Mimicking everyday meals, this study used liquified real foods, contrasting a standard 15% protein meal against a high-protein meal containing 22%.

The findings confirmed that high-protein diets do indeed activate mTORC1, aligning with initial hypotheses, whereas lower protein intakes did not. They pinpointed that dietary protein intakes exceeding roughly 25g per meal (or ≥22% of energy requirement) activate mTOR signalling in monocytes/macrophages.

From these observations, the authors concluded that:

  1. mTORC1 overactivation in mice is linked to vascular blockages.
  2. High-protein meals activate mTORC1.
  3. Thus, high-protein diets may cause vascular blockages.

Why These Conclusions Are Misleading

The narrative spun by the study and subsequently by the media is misleading for several reasons.

We possess substantial real-world evidence contradicting the notion that high-protein diets harm cardiovascular health.

For instance, a 2023 meta-analysis encompassing 6 studies with 221,583 participants found no association between high-protein diets, cardiovascular disease, or strokes. Moreover, a 2020 BMJ meta-analysis indicated that higher protein intakes correlate with reduced all-cause mortality rates.

This existing, robust data overshadows the new study’s reliance on animal models and biomarkers for its conclusions.

In light of this, here’s my guidance to my patients:

  • Engage in resistance training.
  • Amplify the benefits of your workouts with a high-protein diet, targeting 1.6 grams per kg of body weight.
  • View the new study with skepticism—it’s more sensationalism than science.
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#96

Yeah, let’s actually read the study… just the abstract.

Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies

Sina Naghshi 1 2, Omid Sadeghi 3, Walter C Willett 4 5, Ahmad Esmaillzadeh 6 7 8

Affiliations expand

Free PMC article

Abstract

Objective: To examine and quantify the potential dose-response relation between intake of total, animal, and plant protein and the risk of mortality from all causes, cardiovascular disease, and cancer.

Design: Systematic review and meta-analysis of prospective cohort studies.

Data sources: PubMed, Scopus, and ISI Web of Science until December 2019, and references of retrieved relevant articles.

Study selection: Prospective cohort studies that reported the risk estimates for all cause, cardiovascular, and cancer mortality in adults aged 18 or older.

Data synthesis: Random effects models were used to calculate pooled effect sizes and 95% confidence intervals for the highest versus lowest categories of protein intake and to incorporate variation between studies. Linear and non-linear dose-response analyses were done to evaluate the dose-response relations between protein intake and mortality.

Results: 32 prospective cohort studies were included in the systematic review and 31 in the meta-analysis. During the follow-up period of 3.5 to 32 years, 113 039 deaths (16 429‬ from cardiovascular disease and 22 303‬ from cancer) occurred among 715 128 participants. Intake of total protein was associated with a lower risk of all cause mortality (pooled effect size 0.94, 95% confidence interval 0.89 to 0.99, I2=58.4%, P<0.001). Intake of plant protein was significantly associated with a lower risk of all cause mortality (pooled effect size 0.92, 95% confidence interval 0.87 to 0.97, I2=57.5%, P=0.003) and cardiovascular disease mortality (pooled hazard ratio 0.88, 95% confidence interval 0.80 to 0.96, I2=63.7%, P=0.001), but not with cancer mortality. Intake of total and animal protein was not significantly associated with risk of cardiovascular disease and cancer mortality. A dose-response analysis showed a significant inverse dose-response association between intake of plant protein and all cause mortality (P=0.05 for non-linearity). An additional 3% energy from plant proteins a day was associated with a 5% lower risk of death from all causes.

Conclusions: Higher intake of total protein was associated with a lower risk of all cause mortality, and intake of plant protein was associated with a lower risk of all cause and cardiovascular disease mortality. Replacement of foods high in animal protein with plant protein sources could be associated with longevity.

:thinking:

For the record: I am not a vegan, I am mainly a pescetarian and bovine collagen user with occasional high quality animal meat.

5 Likes
#97

I heard on a podcast discussing muscle and longevity that glycine supplementation could offset methionine in animal protein (but no impact on leucine, which is the focus of this thread). Here are some sources for what was said (but not from that specific reference):

Glycine may reduce homocysteine levels following high-protein meals ((Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats - PubMed)).

After eating a high-protein meal — or taking methionine supplements — circulating homocysteine increases within hours. The level of increase depends on the dose (9Trusted Source).

However, this increase only occurs temporarily after meals and is perfectly normal. On the other hand, an increase in your base level of homocysteine is more of a concern.

To increase base levels of homocysteine, a high dose of pure methionine is needed. This dose has been estimated to be equivalent to about five times the normal daily intake of methionine, which is about 1 gram per day (6Trusted Source, 28Trusted Source, 29Trusted Source, 30Trusted Source).

Conversely, lower doses do not increase base levels of homocysteine ([(The effect of excess daily methionine intake on plasma homocysteine after a methionine loading test in humans - PubMed)).

Simply put, evidence is lacking to suggest that a diet high in muscle meat increases base levels of homocysteine in healthy people.

Though homocysteine is a product of methionine metabolism, dietary methionine intake is generally not the cause of elevated base homocysteine levels.

Muscle meat is relatively high in methionine, which can be turned into another amino acid: homocysteine.

Unlike methionine, homocysteine is not found in food. It’s formed in your body when dietary methionine is metabolized, mainly in your liver (5Trusted Source).

Excessive consumption of methionine may lead to elevated blood levels of homocysteine — especially if you’re deficient in certain nutrients, such as folate (6Trusted Source).

Homocysteine is highly reactive within your body. High intake of methionine from supplements or animal protein may have adverse effects on the function of blood vessels (9Trusted Source).

High blood levels of homocysteine have been associated with several chronic conditions, such as heart disease (7Trusted Source, 8Trusted Source).

However, evidence that elevated homocysteine, in itself, causes heart disease is weak.

In fact, studies show that reducing homocysteine levels with folate or other B vitamins after a heart attack does not decrease the frequency of recurrent events in the heart or circulatory system (10Trusted Source, 11Trusted Source, 12Trusted Source).

Additionally, other studies suggest that strategies to reduce homocysteine levels have little or no effects on heart disease events or your risk of death (13Trusted Source, 14Trusted Source).

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#98

Wow, I didn’t think about homocysteine. So not only animal has lots of leucine that causes M-tor activation but may raise homocysteine via methionine pathway.
Another reason to use more collagen and bone broth (glycine rich) but less meat. That’s definitely a big part of my diet approach.

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#99

Since homocysteine levels are easily checked by a blood test, maybe test to see if one has concerningly high levels before altering one’s diet? Most meat is such a rich source of nutrition that to tell people to eat less of it may be doing them a disservice.

1 Like
#100

I am not giving anyone any recommendations here. One definitely has to understand and dial in their nutrition before making major changes, especially with something like a vegan diet. With a proper pescetarian diet, I am not really missing out on much and according to the studies actually may be better off.

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#101

Very true, good point. Personally I am eating more fish in place of meat for my lunches and enjoying it. I shouldn’t have suggested you were recommending anything.

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#102

Pescatarian (or whatever you’d call your diet) seems like a terrific balance of all the positive dietary recommendations.

How are you thinking about heavy metals in fish? Is this an overblown issue? Or are you eating more of selective fish to avoid this issue? Some people have recommended not eating as much fish because of this.

Same question on microplastics. Overblown or strategy? (Maybe this is not as much a fish issue, bit more for sea salt)

I eat a lot of beef, probably more than most on this forum. But we also eat fish (primarily salmon) 1-2x per week. And when we’re somewhere where the seafood is particularly good (such as Portugal) we’ll eat it 5-7x per week.

Thank you.

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#103

I eat fish about 3 times a week. I try to stick to easily available wild caught, high Omega 3 and tasty fish in Costco.
Canned Sardines, Canned Tuna (tested for heavy metals), Salmon, Cod and Seabass… and shellfish - shrimp.

My diet has been constantly evolving based on new information and it’s not static. I feel like after 25 years I am very close to balancing a relatively tasty and maximally longevity increasing combo… I couldn’t do Bryan Johnson raw broccolli, cauliflower, etc. plate . YUCK. I am not that committed.

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#104

Agree! No way I’m lowering protein either…. Lol

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#105

Is protein discussion based on flawed reviews? See the summation of non-stat sig result to a significant one(A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults - PMC):

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The protein research is using FFM as endpoint, which according to Greger could just be water weight, liver or kidney swelling from extra protein, .49 correlation with muscle mass measured on MRI.

1 Like
#106

Dr. Attia debunks the theory of protein negatively affecting your arteries unless you are a transgenic mouse.

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#107

I see his points, but I still think he’s biased and in denial about dietary protein and aging. Even “acute” spikes of mTOR after protein-rich meals becomes “chronic” when you take into account multiple meals per day along with supplemental protein to meet a 1 gram per pound of body weight target. Compare this repeated stimulation of mTOR throughout each day, every day, with the (hopeful) anti-aging effects of suppressing mTOR for a couple of days per/week with a once weekly dose of rapa.

He competely ignores the large body of animal research showing anti-aging effects of protein restriction and individual amino acid restriction (i.e. methionine) because it’s “only animal research” (and inconvenient to his protein fetish), yet he relies exclusively on animal research to tout the likely anti-aging benefits of rapamycin. It just seems like he wants it both ways with mTOR and protein (to “have his venison jerky and eat it too”, if you will).

It’s fairly straightforward IMO, albeit more nuanced, to see that chronic mTOR stimulation via high protein intake is likely bad for aging on a molecular level while having some benefit for muscle growth when combined w/exercise (but even then, how important is all that extra protein when compared to the exercise stimulus itself along with adequate caloric intake?), while suppressing mTOR to some degree is likely very good for aging on a molecular level.

Can we get the benefits of both by doing cycles of high-protein w/exercise followed by low-protein/low-methionine/fasting/fasting-mimicking with or w/out rapamycin?

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Lifting weights "too much" might increase risk of death -- could rapamycin help?
#108

Ha ha, I like the word play, and, although I think Attia’s interpretation of the study adds useful insight, point taken about his study selection bias on the topic of protein.

I think animal research showing anti-aging effects of protein restriction is reasonably robust, interesting, and should not be ignored as a research direction. Unfortunately, for those middle aged and older, we can’t wait until the issue is resolved definitively if we want to extend our lifespan/health span. So, for me, when I weigh animal research that suggests a longevity advantage to low protein that MAY translate to humans against the human research that shows reductions in sarcopenia/osteoporosis, which DO impact lifespan and healthspan, I’m choosing a higher protein diet for now. Although, I’m not sure that one gram per pound lean mass is needed, I do find it increases my satiety which keeps my fat mass low, which strongly correlates with health span, so there’s that. And I do think protein RDA is way too low.

For the record I don’t find blue zone correlations helpful in resolving this issue. Blues zones research basically finds that if you compare a population that follows a non-process food diet, gets daily exercise or physical activity, is socially connected, and has low stress (blue zoners) they will live longer than a population that eats SAD, does not exercise, is socially isolated, and has high stress (typical developed populations), the blue zone population lives longer healthier lives. However, there are so many confounding factors contributing to blue-zone longevity, not to mention interactions between those factors, that teasing out the impact of a single variable like protein consumption is not possible.

I suspect that by making this a binary issue of high vs low protein or high mTor is bad and low mTor is good, we are missing the nuances in the conversation that would be helpful in resolving the question.

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#109

I think you missed the whole discussion on this thread where we discussed specific amino acids and their effects on m-tor and homocysteine levels, because I agree, reducing the diet to simplistic macro manipulation of low vs high protein is as asinine as low fat vs high fat or low carb vs high carb.

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