Uh oh, mice in labs are not like humans in this regard at all.
Lab Mice have extraordinary cell repair capabilities. My guess is that the AKG slows down cell division.
This podcast delves into the problem with lab mice and explains the trade offs that happen on an evolutionary and cellular level in mice with regards to longevity.
As a rule, all anti-aging studies and experiments lose effectiveness as the size and the natural life span of the animal used increases.
It's relatively easy to dramatically increase the natural lifespan of C. elegans with gene editing, drugs or even caffeine. Mice lifespan is little harder but doable. Anything that extends healthy human lifespan more than 5% is not in the radar.
My cursory understanding is that actuarial senescence (the increase in mortality rates for older populations) is not the primary driver of life span in most mammals.[1] Particularly small mammals, like lab rats. Whereas for first-world humans, it's the primary driver.
Actuarial senescence makes it devilishly difficult to achieve significant life expectancy gains. Because mortality rates increase with age, life expectancy gains only scale O(sqrt(N)) with mortality reductions. Paradoxically a 40% reduction in all-cause mortality across all ages only adds 5 years of life expectancy.[2]
The problem with life extension studies is small animals is that we may be measuring the wrong thing. A true breakthrough in human life spans will require slowing the rate of actuarial senescence. A wonder drug that only targets base rate mortality might double the mouse life span, but only add a few years to human life.
There's an organism I have seen referenced in a while ... in the first half of the last decade, my daughter who's now a doctoral candidate in human genetics at JHU did research in a lab right next door to the famous "worm shack" at UofA ( http://wormshack.ua.edu/).
Bret Weinstein's doctoral thesis Evolutionary Trade-Offs: Emergent Constraints and Their Adaptive Consequences [1] describes the hypothesis. Telomere length limits the number of times a cell can replicate so longer telomeres hold the potential for longer life. The trade-off is that long telomeres also allow pre-cancerous tumors to grow much larger and increase the probability of a cancer promoting mutation occurring in younger animals.
The paper Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice [1]:
> We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines.
Judging from the image of black mice in the article, the C57BL/6 strain of lab mice [2] are used in the study. This strain has long telomeres which should be taken into consideration with all the other caveats associated with longevity studies in mouse models.
If you are an optimist, then the hypothesis that AKG [3] supplementation safely reduces age related systemic inflammation is a positive outcome.
It's a metabolic intermediate of the citric acid cycle - the cycle is needed to reduce electron carriers (NAD+/FAD) which are then used to drive the electron transport chain for making ATP. In simplest terms: it's an important part of aerobic respiration.
That being said, it can be synthesized de novo very easily so long as your cells have enough glucose/fatty acids and enzymes are functioning properly. It's even formed directly by deamination of glutamate. I'm not sure these results would be very transferrable to humans.
Tim Ferriss had this amazing comment once in one of his books that if you want to know what the future of human health is in 5 years, look to what bodybuilders are doing today, and if you want to look at the future of human health 10-15 years out, look to what race horse breeders are doing. Something to that effect. ;-)
From someone who participates in this I would disagree. Bodybuilding at the highest level isn't really pushing any new boundaries. It's pretty well known 'how much' you can take (Dallas McCarver being a good example of that), and the compounds being taken aren't cutting edge or novel.
It's Novolog, Chinese HGH (because holy fuck is HGH expensive), several grams of Test and a rotating cycle of various compounds depending on which part of prep you're at, (ie wet compounds when you're putting on weight and dry compounds when you're cutting and in show prep to summarize roughly). There isn't really anything going on that isn't covered by the r/steroids wiki.
Perhaps Olympic level athletes are a better target, because bodybuilders aren't using any novel compounds, they buy what Chinese markets have available for purchase to synthesize.
I'm curious what his examples of horse breeding and bodybuilding technologies were that have made it into mainline human health. I know early HRT used mare estrogen, but that seems less a technology than a means of manufacture.
1) The mice are genetically rather similar to one another; the bodybuilders are not.
2) The mice are under identical diets; the bodybuilders are not.
3) The mice are all on the same amount of the substance; the bodybuilders are not.
4) The mice aren't all on anything else; the bodybuilders are likely each on a highly individualized regimen of supplements, particular foods, medicines (prescribed or not).
5) The mice are near a critical age when you can see the effects of aging take place; the bodybuilders are not.
6) The mice can be sacrificed and autopsied at whim; the bodybuilders cannot.
Another obvious confound is that body builders engage in regular resistance exercise which is proven to promote skeletal, muscular, and neural health.
Anecdotally I know a man who is in his 90s and still lifts and cycles regularly and has for the past 40 years. He is definitely suffering the effects of aging, but when, for example, he falls his bones don't break and he's able to continue on. He's dealt with other medical conditions that normally wouldn't be treated in a man his age. But because of his good health, the doctors have gone ahead and gotten good outcomes. He also hasn't drank or smoked in the past 40 years either though, so there's another confound.
It's possible to use life span as a biomarker and not to follow the whole natural life cycle (when you know know the natural rate of death in all age-groups, deviations from it give information that allows to extrapolate).
Unfortunately it's near impossible for humans because we don't live in controlled environment and expected lifespan changes. Additionally bodybuilders and athletes have food, drug and lifestyle that is very different from others.
I can understand the value of controlling for confounding variables for small-scale tests, and I can totally accept that bodybuilders may be a specific abnormal group different from the general population, but surely the one thing we don’t have to care about in this particular case is a controlled environment, because we would want it to work in general and on almost everyone?
The drugs bodybuilders and other athletes take are often illegal and they are highly secretive about it. It's a big problem when trying to do any kind of science on these drugs.
Not sure why you're getting down voted, you're definitely right. Bodybuilders are often taking steroids, and the more serious ones are taking HGH and insulin (not illegal, but not a standard supplement either). From the article linked below "we estimated that among Americans currently age 13 to 50 years, 2.9–4.0 million have used AAS (anabolic androgenic steriods)." They are secretive about it with most not wanting to bust that "I'm natural" myth about them. Instagram guys are notorious for that. Watch a YouTube video by Seth Feroce, a body builder who is very open about his steroid use, and you'll see just how many illegal drugs these guys use.
A lot of people don't want it to be true and this is a standard reaction to that. The truth is performance enhancing drugs (PEDs) in general are a dirty little secret that are used widely in some of the top echelons of society. Top sportsmen, movie stars, bodybuilders, models, you name it, they're all on PEDs to some extent.
This article is not about drugs though, it's about supplements. The vast majority of supplements that body builders take (proteins of various kinds, creatine, AKG, etc.) are perfectly legal, even in competitions. Whether it's safe to take them long term is another matter, but it's a far cry from illegal steroid use.
Legal or illegal, they are still secretive about it. And, in any case, you can't do science on a supplement using people on a cocktail of various substances.
I know quite a few body builders, and let me tell you, they are not even a tiny by secretive about taking supplements. Why on earth would they be?
It's NOT drugs. It's supplements. Think vitamin C, not cocaine. Most of them beyond protein don't do anything much at all, there's a lot of marketing hype.
I'm not talking about supplements, I'm talking about drugs. Many of them are on drugs and they are notoriously secretive about it. It's difficult to study supplements on bodybuilders because they are on stuff they won't tell you about.
They are secretive about taking drugs though, because they're things like unsafe doses of anabolic or 'not for human consumption' experimental or substances intended for animals.
> often illegal and they are highly secretive about it.
Nope. Primarily insulin is used to help digest 10,000 to 20,000 calories per day, and TRT (testosterone) from doctors.
Most of the Mr. Olympias have interviews on Youtube. They usually don't give the dose so that amateurs don't emulate them, but otherwise are pretty open about it.
(I was one of the strongest and biggest Gold's Gym members in the Bay Area just by sleeping 8 hours a day and going to the gym every 3 days in my 20's and 30's, so you can get results naturally if that's your #1 priority for a few years. For example, I maxed out all of the machines.
Note that if you're an engineer, make sure you have a sensible goal beforehand, since nobody needs a super-heavyweight engineer.)
I don't usually come on HN to say "you're wrong", but in this case you are.
Steroid use is extremely common in body builders. It's pretty much a requirement since steroids JUST WORK. If you're not doing them, and the competitors are doing them, then you have no shot of winning. Yes, they have "natural bodybuilding", but look at those guys against the pros in the open divisions or the men's physique divisions - there's no comparison.
They are not on TRT. They are taking testosterone doses 4-8x higher than a 20 year old male.
So, steroids, all the serious bodybuilders are using it. The next level to get big is to combine HGH and insulin together. They have a massive synergistic effect. HGH in the morning with insulin around meals and it triggers the cells in the body to pull in vast amounts of energy (insulin) with tons of growth signals from the HGH. Steroids trigger muscle growth and rapid recovery, and the 3 of these drugs together allow body builders to train longer & harder, recover quicker, and convert food to growth much easier.
> "One of the biggest members" - "maxed out all the machines"
Call me very skeptical. Yes, you definitely can get results naturally. If you have great genes, you can get very good results. But, you'll never be a body builder level huge without the cocktail I just outlined.
Because the op stated his gym specifically I have credence for this comment.
Good gyms for your build come with the all essential all pervading membrane osmosis crossing competitive atmosphere written by generations (gym generations of cohorts joining and competing really is a interesting subject and I think non builder scientists won't get any results from studying builders till one if them gets into the scene. It's not too hard I nearly did and back pedalled deliberately to later frequent regrets because the community just blows away any other uncontrolled self select non vocational grouping of ambitious men I have even heard about: I have even thought about fictionalizing a extrapolation of my experience how a depressive won't-dignify-brogrammer-hegemony nerd got his balls back thanks to the downright amazing decent people who inhabited my local gym. This was before gyms hardly existed in London and the nearest was called MuscleWorks. Nice pics of Sly and Arnie above the reception counter I thought, learning only years later both worked out there for Mr Universe... Not anybody said anything about those pictures but I soon noticed that same reverent upward gaze and nod like the Catholic genuflect, by the one time it wasn't observed by a visiting engineer... At any rate. I got the best wake up to life in human terms and the subsequent 14 years simply rocked...
Second confidence I take from the op that's being downplayed here is the idea that the op couldn't have built naturally
Well if my pair didn't already clang like bowling balls of solid steel just from meeting some of the regular guys who clearly had enough of my insecurities within ten seconds of observing me and put that Bs straight out the nearest window in the least painful major bsectomy of my life, I have to put the rest down to something about the sheer ts you create after spending time with a bunch of real sound alpha guys carrying less attitude than they let on fat competition days. Immense ts boost. All natural. 5 stone differencs for this otherwise unhappy skinny 6'4" nerd..
If you think they're only using insulin and test I have a bridge to sell you.
All the pros use a variety of drugs illegally, including steroids, HGH, diuretics for show prep, etc. At least Ronnie had the sense to become a cop considering half of the force are already on steroids anyway.
Before anyone jumps to conclusions about what I'm saying, I think it should all be legal.
In a lot of countries HGH, Testosterone are sold without a doctor prescription. However when this topic comes up on HN it always seems that it's highly illegal to buy and to use it.
Plus the cocktails of SARMS and other experimental / unapproved drugs that are circulating currently. And bodybuilder test doses are nothing close to HRT Testosterone from doctors.
Does anyone with a medical background have an opinion on how we should balance this against studies[1] that indicate reducing the bodies natural production of alpha ketoglutarate may reduce the likelihood of in operable brain tumours?
It's not like I would rush out and act on either report because as a layman I can't really assess the findings.
L-Arginine Alpha Ketoglutarate (AAKG) is advertised as a Nitric Oxide increasing agent to improve results of exercise on muscles, improve protein synthesis generally, and growth hormone secretion. All of these assertions are rather vague and have at best limited scientific support, but it is considered a diet supplement and is known to be safe even at high doses so there is little regulation that applies.
Ketones kick in a no-carb diet/fasting: so this can be connected to the knowledge that calorie restriction extends lifespan: both this supplement and calorie restrictions have ketone production/supplementation in common, so perhaps life "extension" has ketons at its root.
The human body can actually consume a fair number of carbs and still be in ketosis. I think of the big marketing problems that ketogenic diets have is the perception that it’s “no carb” which makes it almost impossible in modern life (oh no, I have a work lunch and everything has some small amount of carbs).
Was there any reason that keto diets became popular? In my personal experience a diet high in proteins with overall calorific deficit works the best. Carbs seem to keep me more energetic, workouts are better and I have much more options on what I can eat.
I have seen it being quoted that Keto's effectiveness has been proved but is it any better than a balanced high protein diet.
Keto, in any of its multiple incarnations, works. That's why it became popular. I just lost 20 kg if you like anecdotes. I first heard about it in the 70's when it became popular in Spain. That time it was called Atkins.
It has always been controversial and there has been a lot of disinformation about it. If you want to see an example look in Wikipedia the difference in tone between articles about Atkins or ketogenic diets and ketosis itself. While ketosis seems like a regular metabolic process as any other, anything about the diets is pictured as controversial and pseudoscientific, even if it's just based on ketosis.
I just stopped caring. The diet itself is much easier to follow now than it seems. There are tons of information in the web, a lot of products and carbs tables. In particular, what I do now different is using a lot more of vegetal food: avocados, broccoli, salads and less protein, but still some unprocessed beef, poultry or fish every day. Erytritol is nicer to my guts than other sweeteners, too. Oh, and don't forget vitamins supplements, specially B1 to accelerate metabolism, but the more complete the better.
I exercise regularly with no problems, gaining some muscle at the same time that I lost fat. And my last blood analysis gave some superb numbers.
Edit: protein shakes that I bought for the gym are also a nice trick.
Keto “works” (which I assume you mean for weight loss) because it helps people get into a caloric deficit easier. High fat and moderate protein is highly satiating and helps people to eat fewer calories without needing to track calories closely. Of course, it’s also possible to gain weight if you eat at caloric surplus in Keto.
Also, since carbs are virtually eliminated, most of the weight loss in the beginning is water and glycogen.
Gaining muscle while losing fat is possible in a regular diet. That’s called newbie gains. And since you lost weight, your blood numbers improved.
Since keto works for you, it’s great. But I wanted to clarify that your result is not specially because of the keto diet. It can be achieved with just about any diet.
Ketosis exists. You didn’t just lose 20kg of water and glycogen. In the beginning you probably did though.
My point is that everything you did is possible with a regular diet. You can lose weight, improve blood numbers, gain muscle/lose fat at same time, etc. with a regular diet.
> My point is that everything you did is possible with a regular diet. You can lose weight, improve blood numbers, gain muscle/lose fat at same time, etc. with a regular diet.
True, but keto (or at least "low carb") makes it much, much easier to manage your hunger/appetite/satiety signals.
You'd really have to go to a lot of effort to overeat on meat and vegetables.
This is a topic I find mildly entertaining. Most high-performance athletes don't follow these kinds of special diets [keto, or other fads] and instead focus on balance. Sure, some take to custom-tailored macro nutrient balances and all that, but for the most part the equation is pretty similar. And very often there's a major emphasis on lean proteins and vegetables. I don't know why there's an effort to look elsewhere for answers, beyond looking for shortcuts.
That sounds good but I think it's what you weigh in, say, 5 years time that really counts. Your brain will by then have fully learnt the new diet and it may not satisfy to the extent that it currently does. The glamour will have worn off and you'll have been tempted many times to rejoin the prevailing carbohydrate culture, if only to appease a cake-baking relative.
No, that's not what happens. I have a long story fighting my metabolism. It's just not possible for me to eat like people around me and not get fat, except in periods where I've been very physically active, as in heavy exercise dayly.
In my twenties I did the diet three times, alternating with sports, last time for two years. Later the problem was eating in restaurants for work. Eventually I regained control without the need of a diet... until a couple of years ago. Nothing worked and it seemed like I was going to lose the final battle. A relentless weight gain, even with very limited calories intake. So I decided to try again keto in March, that I had not done in a decade.
For me it's not a problem to keep relatives or acquitances from tempting me. I did learn the key phrases to shut the allegedly well meaning people that offers sugar. It's funny how the most frequent question is: why a diet? You're not fat. People are used to diets that don't work.
Now the only trick is to prepare meals at home. In any case, I don't plan to be doing a diet forever. Just some months more to lose a little more, then exercising more often to keep the weight.
But aren't fats calorie dense as well. Just 10g of Pecan is about 7g of fat and 70 calories. So even though you are consuming less in weight, it is more calorie dense.
Cookies are not even a good carb source and I doubt any diet will have it as a part. If you really want to not feel hungry, it is the fibre rich foods that seem to work best and don't even add to your caloric intake significantly.
I think there’s some research on Ketogenic diet’s effectiveness on epilepsy. But for general diet/health/weight loss, most of keto’s benefits sound like pseudoscience. That goes for many diet fads, not just keto.
What do you consider a fair amount of carbs? From what I remember, endurance athletes could stay in ketosis with around 100g of carbs daily, however this is not relatable for an average person. Another important fact is that on zero-carb diet with protein intake on athletic level (2-2.5g/bw_kg) you are in a moderate ketosis because of gluconeogenesis, which is a good thing according to Paul Saladino.
On the impossibility of zero-carb in modern life I have to say that it is completely false. I am on a carnivore diet myself now and eat close to none carbohydrates and I find it much more easy and sustainable than doing clean omnivore diet. I just got into habit of preparing my food based on muscle and organ meat at home and bring it with myself to work or wherever I'm going. Even if I didn't I can get cheese or some nuts from the shop sporadically. Dramatically lowered hunger cravings and stable levels of energy help a lot.
> On the impossibility of zero-carb in modern life I have to say that it is completely false
It's not impossible in a strict sense of course. One essentially removes food (in the enjoyment sense) from life; meat/nuts only (or "pretty much only") is appealing in the short term, then it becomes limiting/disgusting. I did keto for a short term.
If it works for you good, certainly, but it puts a lot of pressure, and it become the "fighting gravity" class of pressure. At some point one will stop, and balloon. I'm curious also, how old are you and how long have you been following this diet.
> One essentially removes food (in the enjoyment sense) from life
Absolutely false for me. Personally I enjoy no food more than a big
steak. Definitely there is more of the satiation factor than in
plant based meal, especially in something like steak with liver
mincemeat. Ton of nutriets.
> I'm curious also, how old are you and how long have you been following this diet.
6 month carnivorish keto with some nuts, 4 months pretty strict carnivore (garlic
and onion added to meat, sometimes coffee, that's it)
> 6 month carnivorish keto with some nuts, 4 months pretty strict carnivore (garlic and onion added to meat, sometimes coffee, that's it)
To be pedantic, including onions, nuts, or garlic isn’t the carnivore diet. Onion especially has a ton of sugar. So by your case, you kinda proved OP’s point about the difficulty of eliminating carbs in everyday life.
Onion has 9.3g carbs per 100g [1]. I add few small slices, no more than 1/4 average onion, so that ~30g of onion and 3g of carbs. Absolutely meaningless. I add that just for the taste and it is an amount that does not have any serious effect. I ate small but significant amount of nuts before, but not now so that's also not a factor now.
You may consider that 99% carnivore diet and that's absolutely ok. Another thing is that carnivore diet is not vegan-like in its choice of food products. It's all about health benefits and adding minimal amounts of vegetables that someone has no problem with isn't a big deal.
On carbs on carnivore: Honey is also considered as an animal product by most carnivore people and it has a lot of carbs obviosly.
That is a sporadic thing when I have no other food available. It's not pure zero-carb then and that's carnivorish not strict carnivore diet, however the impact of such very sporadic deviation is unsignificant.
>I think of the big marketing problems that ketogenic diets have is the perception that it’s “no carb”
Which is odd, because I don't know any that market themselves as "no carb". Ketogenic usually means "low-carb, high-fat", with low-carb being anything from 20-50g of carbs a day, to alternating none on some days vs normal other days.
I think the truly shocking thing to most people is just how many carbs they consume in a day when they measure their intake. I'm sure it feels like "no carb".
Lab Mice have extraordinary cell repair capabilities. My guess is that the AKG slows down cell division.
This podcast delves into the problem with lab mice and explains the trade offs that happen on an evolutionary and cellular level in mice with regards to longevity.
https://www.youtube.com/watch?v=JLb5hZLw44s