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Optimal calories, protein, muscle and fat for longevity? Its really complicated...

Oliver Zolman MD

· Longevity

This guy goes briefly through a load of decent studies on PubMed in each video + is really easy to watch

From my knowledge of the evidence base, everything on this guys channels seems very consistent with the correct interpretation of the evidence.

But... is high total protein intake and high intake of all types of amino acids best for longevity?

Taking high 1) methionine 2) or leucine amino acids *long term* (e.g. several times the recommended daily allowance dose for decades) may not be good for longevity, IF you already have good muscle mass and are not in certain situations e.g. some acute or emergency medical scenarios

Why? There is evidence such intakes can boost "IGF-1", a growth protein, and stop the lifespan boosting effects of calorie restriction in mice / total lifespan can be lengthened in methionine restricted mice versus normal diet mice / and is associated with poorer clinical outcomes in humans that have markers of high protein and methionine intake etc such as people with higher IGF-1 or higher urea or blood urea nitrogen (BUN) having higher risks of various age-related diseases.

Note that if you are old, have low muscle mass (e.g. sarcopenia/frailty) or low IGF-1, increasing methionine, leucine and total protein intake may be very important for improving health outcomes; also in many acute or emergency medical situations and select conditions higher protein intake can be useful; so these situations it may not apply.

Also IGF-1 is related to growth hormone, and growth hormone therapies may be useful for e.g. a 3 - 12 month period in regenerating certain organs, such as the heart or thymus. But I am not sure by how much IGF-1 is raised by this.

Also I am not sure if total protein intake matters, as this can be confounded by methionine and leucine intake in studies.

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How to maybe get around the potential risks of longterm high methionine and leucine intake.

1) This may not even matter if you are under age 30, 35 or 40, it may have negligible health benefits (as there are no studies to show it matters a lot at these ages to my knowledge)

2) Having periods (e.g. 3 months?) of higher methionine and leucine intake and then changing your protein intake to move them down to 1 to 2x recommended daily allowance (RDA) levels: this is untested to my knowledge, but may help you get the potential benefits of higher IGF-1 and of lower IGF-1. But how long is each up and downward cycle? And how high? Based on what biomarkers? Should it be based on e.g. thymic fat mass on MRI or just chronological age, cancer risk or diagnoses etc? Are there even benefits, or does everyone/do some people need growth hormone injected rather than just more dietary methionine and leucine to get the best benefits?

3) Keeping methionine and leucine to around 2 x RDA levels (as this hedges against the risk that only longterm lower methionine levels would provide this benefit), but then you have the risk that you are not gaining any benefits of periods of higher IGF-1

Methionine and leucine rich foods are mostly from animal protein - including eggs and dairy - with the exception of collagen protein powder.

And then there are total calories and fat to look into too.

What I want to know is

1) Confirm an optimal range (is it 100 - 150 at all ages? or is it different for younger people?)

2) Is there evidence as someone at age 20/30/40/50/60 can still gain just as much muscle mass with a 1 - 2 x RDA methione/leucine diet and IGF-1 of 100 - 150 (assuming this range is "optimal") (there are good trials showing collagen powder which is low methionine leucine does improve muscle mass a lot in elderly/older age people, but younger I am not sure on evidence), as if so then this helps justify the benefits of a lower methionine/leucine diet as people may be concerned about muscle loss

2) What else controls IGF-1 levels other than methionine and leucine (and that other amino acid i'm forgetting) intake

3) What is a summary of the evidence of all the benefits of having an IGF-1 above 150, and when would you want this

3) What is the evidence that high total protein intake adjusted for methionine, leucine and that other amino acid that may be anti-longevity may be unhealthy, e.g. over 1 - 1.5 g/kgbw/d when RDA for total protein is 0.6 g/kgbw/d, to see if other amino acids may need to be reduced

4) What are the risks AND benefits of lowering IGF-1 to e.g. 100 - 150 at each adult decade of age, if IGF-1 is already already higher

5) what age do they start methionine restriction in mouse /monkey studies and whats the human equivalent age

6) What's all the clinical evidence for methionine increased or methionine reduction interventions

7) Is IGF-1 the only marker that needs to be measured as a good surrogate of protein intake clinical outcome risks

8) How long would you want to increase IGF-1 for if cycling, and how high, and what are the benefits of this

9) How much, if at all, does thymic rejuvenation dose growth hormone increase IGF-1, as may be useful in understanding a rejuvenation threshold level, i.e. effects that only activate at certain levels

10) What is optimal total body muscle mass in kg for different health outcomes at different decades of age, as measured by dexa, volume MRI or water impedence or other validated 95% accurate methods of muscle mass measurement ; and likewise for total body muscle function tests

11) what does 5 mg rapamycin a week, and standard immunosuppresion dose, do to IGF-1 levels, as this may add some more info

12) What about all the lifespan studies on glycine and huge drop in intracellular glycine levels in umol/L at old versus young and the effects of glutathione etc... maybe one could systematically review every amino acid for optimal intake and to see whether its worth measuring all of them in their umol/L RBC or WBC or buccal cell range, and their surrogate markers like GSH:total Glutathione for glycine and cysteine and then doing amino acid therapies to change all these back to 20 year old healthy control levels

13) Surely its impossible, without maybe follistatin or similar gene therapy, to maintain a large amount of muscle if reducing calories; how much do you lose at 2000kcal/d and 1800kcal/d for men and similar numbers for women, if doing calorie restriction optimal nutrition

14) Is there evidence you can still have higher total body muscle mass than you would expect from a calorie restricted diet and still have the benefits of calorie restriction? E.g. through high total protein intake but under 2x methionine leucine RDA. What % of the different types of benefits of CRON get removed from having a high total muscle mass?

15) What BMI to aim for? Is a BMI of 17 really optimal for some people? Is BMI^2 or BMI^1.7something or WHR better for assessing risk of low BMI in people over 175 cm?

16) How many calories to consume?

17) Markers of calorie restriction efficacy and safety?

18) Getting around side effects of calorie restriction? E.g. lightheadedness, psychiatric effects, exercise intolerance (osteoporosis and osteopenia can be got around via exercise, strontium (if no cardiovascular disease), calcium, vitamin D, vitamin K2 MK4 15 mg)

19) Optimal ranges of different types of visceral and subcutaneous white fat, beige fat and brown fat, as relevant

20) What age to start calorie restriction

From this I might be able to create a health guideline for each decade of life for optimal 1) total protein intake, 2) amino acid profile intake 3) IGF-1 pattern, 4) total body muscle mass 5) muscle group functionality 6) calorie intake 7) body weight target or BMI 8) visceral and subcutaneous fat ranges and subtypes; as I feel it is more complex than just (for men) eat 1800 calories a day from age 30 onwards, keep methionine and leucine to 2x RDA, total protein around 1.6g /kgbw/d and IGF-1 always at 100 - 150, ovo-lacto vegetarian and I'd like to get around the frail appearance of full CRON.

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