Rapamycin and risk of cardiovascular disease

Yes it is.

Yep yep. Might I add the anthocyanins in purple sweet potato are much more cost effective than supplements and blueberries :wink:

Is that actually purple yam? Not familiar with that one - but beware of confusion. Also, processing may change a lot - leading to possibly different results.

The package states organic purple sweet potato powder, the ad copy states pure natural premium purple yam powder.

Yep unfortunately the industry uses yam and sweet potatoes interchangeably.

I posted briefly here.

Basically, as we age, all of us will have a decline cerebral metabolic rate of glucose use, which is symptomatic with neurodegeneration. Being diabetic massively accelerates this curve.

As a way to ameliorate this loss, generating ketones via diet offer mitochondria an alternate fuel source to promote optimal function. Neurons, Astrocytes and Oligodendrocytes all metabolise ketone bodies

Ketones have all sorts of other pro-longevity signalling pathways.

The diet combined with fasting, of course, blunts glucose spike/AUC, already shown to promote longevity in mice, so that’s an additional freebie.

A ketogenic diet extends longevity and healthspan in adult mice

And by default, a ketogenic diet imposes protein restrictions, and we know quite conclusively in plethora of rodent studies, that protein restriction, most especially BCAA, and furthermore, leucine restriction promotes longevity.

Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice

Metabolomics Study of Isocaloric Different Dietary Patterns on the Life Span in Healthy Population

Promoting Health and Longevity through Diet: From Model Organisms to Humans
https://www.cell.com/action/showPdf?pii=S0092-8674(15)00186-5

Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

“We have determined that reduced dietary BCAAs improves metabolic health even in the absence of significant alterations in the dietary carbohydrate:protein ratio”

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

Caloric Restriction vs. Animal-Protein Restriction

“The lifespan extension associated with dietary restriction may be due less to a reduction in calories, and more to a reduction in animal protein (particularly the amino acid leucine, which may accelerate aging via the enzyme TOR).”

As for Okinawans/Sardinans, the long lived “islander” cohorts (yet vastly different diets), from all the literature I’ve read, their longevity signal is majority genetic (enriched lineages), but on the specific dietary side, what they do share in common and is pro longevity is…LOW animal protein and mild CR. This would be very consistent with all the rodent longevity literature.

New Horizons: Dietary protein, ageing and the Okinawan ratio

“Such studies in insects and mice indicate that animals with ad libitum access to low-protein, high-carbohydrate diets have longest lifespans. Remarkably, the optimum content and ratio of dietary protein to carbohydrates for ageing in experimental animals are almost identical to those in the traditional diets of the long-lived people on the island of Okinawa. The energy from their diets was derived from 9% protein and 85% carbohydrates”

Healthy aging diets other than the Mediterranean: A Focus on the Okinawan Diet

So being low carb/ketogenic and overlaying OMAD fasting, I get a combination of benefits and hedges, all associated with longevity:

  1. Low glucose spikes/AUC.
  2. Low animal protein (classic ket macros 20% protein, 75% plant fats, < 5% net carbs)
  3. Ketone bodies generation as alternate compensatory brain fuel for aging, lowers inflammation (NLRP3 inflammasome), HDAC inhibitor, lowers body fat, preserves muscle loss.
  4. Fasting and all the metabolic benefits, lowering fT3 and metabolic rate. Ghrelin spurs brain neurogenesis.

I feel amazing after 6 yrs on the switch, much leaner, no impediments to muscle build, excellent biomarkers. I have super high energy level. My wife tells me my memory and cognitive is amazing.

But a long way to go to a 100…the hill will only get steeper.

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I’ll add Okinawans + Westernization = about average Japanese life expectancy, thus not sure much is genetics

They already naturally blocked glucose spikes and relatively low protein.

I’ll also add traditionally Okinawans tend to skip dinner. That’s very close to TRF/Ketones when it adds up to 16 hours - especially for lean folks. :slight_smile:

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The Okinawan diet is amazing, super nutrient dense!

I am simply trying to translate the known longevity literature into a human protocol. I do eat a ton of nutrient dense whole foods ONLY, whether wild animal protein, plant fats, or above ground vegetables.

I tell anyone to just start with dumping sugar, simple carbs, and fasting…they confer huge metabolic benefits without doing a full diet reboot.

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Oh and btw I’d be careful with Greger at “NutritionFacts” he can get misleading. The previous name of “NutritionFacts” was “Vegan Research Institute” and he used to promote veganism as a cure for death.

He almost certainly reads “animal meat = bad” with cherry picking. Not saying all the cherries he picks are bad - but I would simply be wary of bias. If one is a pragmatic vegetarian - I don’t have any issues. But he is almost certainly of the ideological type.

Leucine I don’t think is particularly “bad” if you are already doing CR and rapa. There’s also mTOR tissue-specificity in liver, fat, and muscle for leucine while barely staying long enough in your system with an ultra-short half-life. I’m not eating tons of animal meat or taking BCAA supplements to sip Leucine all day (maybe will in very specific situations in the future), but I’ll happily eat some salmon roe and an egg after a workout.

“Preventing hyperphagia by calorie restriction or pair-feeding averts the health costs of a high-BCAA diet.”

https://www.nature.com/articles/s42255-019-0059-2

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I have zero use for him, don’t subscribe. He just happened to have a page on MTOR and proteins with a great list of references. It was a lazy page grab.

Yes leucine on CR/fasting/rapa is certainly not bad…I eat a good bolus of leucine daily! But it’s a very muted amount. I have never taken a BCAA supplement…my muscle build has exploded on 50g/day animal protein and chronic daily resistance exercise.

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Association is not causation.

Isn’t it equally plausible (my opinion more than plausible but causative), especially if you look at the mountain of research literature on protein, that the underlying longevity signal is LOW protein AUC? That would tie in a diversity of longevity diet cohorts…the central regulator is the protein signal, of course, intimately linked to mTOR?

Hard to tease it out. Could be low protein or perhaps the benefits conferred by fruits, vegetables, nuts, and beans.
Could also have nothing to do with diet but rather low stress, physically active, and good sleep. Who knows.

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Yep, it isn’t. I’m not implying that it must be causative, but we have some evidence - we have plausible mechanisms - mTOR inhibition from calorie restriction and low protein + alpha glucosidase/amylase inhibitors - despite a high carb diet with significant amounts of simple sugars. (Note I also have a wide array of other sub explanations) We also have subgroups that underwent the forces of Westernization after WWII that pushed those subgroups back to about average Japanese life expectancy, which is some evidence for primarily environmental factors and geographical based data.

Could there be some other confounder? Absolutely! And we should look for them (the Japanese researchers have been trying for quite a few decades as they deal with their aging population - I’ve taken enough time to go through research - as well as reviewing commercial claims to sell “Okinawan” based health products which haven’t seem to directly pan out). But in the absence of a better explanation, I think there’s enough to explore further empirically, despite the retrospective nature of the data

Let me understand your logic here.

You will blindly accept that rapmycin will translate to humans, on mice data: NO human data. Yet you won’t accept the thousands of papers on rodents and humans (directly associating with mTOR/IGF-1), showing high protein and reduced longevity, regardless of other dietary macros?

What ties rapamcyin to longevity…mTOR. What drives mTOR in mammals…protein.

Sounds like cherry picking confirmation bias.

I am agnostic a singular longevity pathway in humans.

I too don’t know the answer of course! So why not stack THE best science that is “easily human doable” together and hedge at min 2 interventions, low protein and Rapamycin?

The effects of CR (best longevity in mice) are partly theorized as low protein AUC.

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I see your point but I’m not sure that it’s all that conclusive. There’s evidence that low protein is better under the age of 65 , but higher protein may be better over 65. We’re on rapamycin so we don’t need the extra TOR inhibition.
That being said, all of my protein is from nuts, legumes and salmon. Some chicken thrown in occasionally. Fairly low.
But I don’t think the evidence is conclusive.

As far as my faith in rapamycin is concerned, I’m not married to it, but as of now it’s the best , and most studied, that we’ve got. If sometimes better comes along, I’ll jump on it.

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There is a basic problem with diets. Can you stay on the diet?

If you don’t like the diet, you probably won’t stay on it very long.

There are some basic problems because of cultural differences.

I am of northern European descent. I was born in 1941 during WWII.

I won’t bother you with details, but we ate a lot of deer, pheasant, duck, and a few other wild game types, so I was raised as a carnivore. Fresh vegetables were in short supply and we mostly ate canned vegetables.

The Okinawan diet may be great, but is not one I could enjoy.

Foods I don’t particularly like:

Salmon and most fish

Salads

Vegetables.

Fortunately or unfortunately this is the diet I can live with.

I mostly eat:

Chicken, beef, and shrimp

Broccoli, carrots, asparagus

Pineapple, cantaloupe

Lactaid whole milk,

Oat bran meal, with walnuts and blueberries (I eat a lot of blueberries and walnuts)

Protein shakes

Dark chocolate

Lots of coffee

Of course, there are other foods, but in small quantities.

Foods I would love to eat but don’t, except during the holiday, season, birthday parties, etc:

Cheesecake, ice cream, pies, croissants, freshly, baked bread, blueberry muffins, etc.

So, I use supplements to try to compensate for my dietary shortcomings

I have enjoyed a healthy life so far and have never spent a night in a hospital, I was born in a farmhouse, so not even then.

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I think your diet is very good actually. You could add some flax to your oat bran like I do for additional omega3’s since you don’t like salmon.

To be clear, I’m not saying everyone should eat like Okinawans - frankly, your diet doesn’t seem to have much shortcomings at all, when compared to Standard American Diet - it’s much better. I suppose you could talk to your doc about acarbose or the like for seasonal events - but that’s more of risk tolerance when it comes to classic desserts.

The main reason I was fascinated with Okinawan diets many years ago were they seemed to be the odd one out - very high carb with significant simple sugars intake - until I really dug deep upon closer inspection. That’s also on top of the use of so many different possible nutraceuticals with pharmaceutical effects demonstrated in vitro and in vivo. Particularly when already tested for such a long time over so many people.

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What are their simple sugars?

Curious - is ALA omega 3 intake really worth to modify a diet when it comes to bioavailability issues?