9 ms·

Bodybuilding supplement promotes healthy aging and extends life span in mice

124 points by pella 6y ago

cmendel 6y ago
Alpha-ketoglutarate for those who don't want to read the article. Here's the Wikipedia page: https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid I don't expect it to be terribly helpful though, it's a bit dense to the layperson.
- SenorTibbs 6y ago
  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.
OneGuy123 6y ago
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.
- qeternity 6y ago
  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).
  - GordonS 6y ago
    Can it? I haven't read on the specifics for a while, but I thought most people had to stay lower than 20g of carbs per day to stay in ketosis?
  - ISaIF73 6y ago
    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.
    - pizza234 6y ago
      > 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.
      - ISaIF73 6y ago
        > 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)
rvanlaar 6y ago
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. https://www.youtube.com/watch?v=JLb5hZLw44s https://www.youtube.com/watch?v=JLb5hZLw44s
- nabla9 6y ago
  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.
  - smoyer 6y ago
    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/ http://wormshack.ua.edu/).
  - dcolkitt 6y ago
    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. [1] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000432 https://journals.plos.org/plosbiology/article?id=10.1371/jou... [2] https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-and-life-expectancy/ https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-...
throwaway4good 6y ago
Why do we need to mouse experiments when a large number of bodybuilders have moved straight to human trails?
- mahesh_rm 6y ago
  Because they are not in their natural death age range yet, and because of the huge amount of confounding variables.
  - nabla9 6y ago
    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.
    - ben_w 6y ago
      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?
      - victorbstan 6y ago
        They also take a lot of other supplements. So you can’t narrow it down to anything.
- globular-toast 6y ago
  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.
koolhead17 6y ago
Sample Size? Who financed this?
- swebs 6y ago
  Here's the paper. https://www.biorxiv.org/content/10.1101/779157v1.full.pdf https://www.biorxiv.org/content/10.1101/779157v1.full.pdf
Lio 6y ago
This is a really interesting article. 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. 1. https://www.nih.gov/news-events/news-releases/drugs-against-alpha-ketoglutarate-may-combat-deadly-childhood-brain-tumor https://www.nih.gov/news-events/news-releases/drugs-against-...
ovi256 6y ago
This is great news if you're lab mice! https://twitter.com/justsaysinmice?lang=en https://twitter.com/justsaysinmice?lang=en This is a parody twitter account that reminds us that all these new health breakthroughs are, indeed, applicable to mice only. It's a horribly narrow funnel that filters these to what is applicable to humans, outside a lab.
sradman 6y ago
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. [1] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30417-4 https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)... [2] https://en.wikipedia.org/wiki/C57BL/6 https://en.wikipedia.org/wiki/C57BL/6 [3] https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid
ykevinator 6y ago
It's the chemical, not the weightlifting
xwdv 6y ago
There’s only three supplements worth taking: Creatine - to top off your bodies ATP stores and maximize power output. Beta Alanine - to maximize your carnosine stores and decreasing the burning pain that comes from lactic acid, letting you push harder for longer. Citrulline - to relax blood vessels and boost nitric oxide in your body, giving your muscles more oxygen for more work and powerful erections. When their powers combine, you can reach your max potentials, with correct dosing.
- RankingMember 6y ago
  Re: beta-alanine, anecdotally all it ever seemed to give me were strong tingling feelings. Maybe I'll give it a go again sometime. > giving your muscles more oxygen for more work and powerful erections. hopefully not both at once ;)
  - xwdv 6y ago
    You have to take them for quite some time. The tingling should stop happening after some times.
davidu 6y ago
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. ;-)
- 0134340 6y ago
  Really? I don't think either are known for their long lives.
  - Scoundreller 6y ago
    It’s a grim looking future...
  - nscalf 6y ago
    The idea isn’t that they have long lives, it’s that they’re pushing the edge of possibilities for the human body and things are discovered there.
- hyko 6y ago
  The future of human health is shooting people in the head to cure a broken leg?
  - davidu 6y ago
    lol, no, that's the future of democracy.
- dennyabraham 6y ago
  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.
- ideals 6y ago
  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.
mrfusion 6y ago
So why is this a body building supplement?
- m0llusk 6y ago
  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.

124 points by pella 6y ago

Alpha-ketoglutarate for those who don't want to read the article. Here's the Wikipedia page: https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid I don't expect it to be terribly helpful though, it's a bit dense to the layperson.

SenorTibbs 6y ago
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.

OneGuy123 6y ago

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.

qeternity 6y ago
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).
- GordonS 6y ago
  Can it? I haven't read on the specifics for a while, but I thought most people had to stay lower than 20g of carbs per day to stay in ketosis?
- ISaIF73 6y ago
  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.
  - pizza234 6y ago
    > 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.
    - ISaIF73 6y ago
      > 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)

rvanlaar 6y ago

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. https://www.youtube.com/watch?v=JLb5hZLw44s https://www.youtube.com/watch?v=JLb5hZLw44s

nabla9 6y ago
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.
- smoyer 6y ago
  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/ http://wormshack.ua.edu/).
- dcolkitt 6y ago
  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. [1] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000432 https://journals.plos.org/plosbiology/article?id=10.1371/jou... [2] https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-and-life-expectancy/ https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-...

throwaway4good 6y ago

Why do we need to mouse experiments when a large number of bodybuilders have moved straight to human trails?

mahesh_rm 6y ago
Because they are not in their natural death age range yet, and because of the huge amount of confounding variables.
- nabla9 6y ago
  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.
  - ben_w 6y ago
    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?
    - victorbstan 6y ago
      They also take a lot of other supplements. So you can’t narrow it down to anything.
globular-toast 6y ago
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.

koolhead17 6y ago

Sample Size? Who financed this?

swebs 6y ago
Here's the paper. https://www.biorxiv.org/content/10.1101/779157v1.full.pdf https://www.biorxiv.org/content/10.1101/779157v1.full.pdf

Lio 6y ago

This is a really interesting article. 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. 1. https://www.nih.gov/news-events/news-releases/drugs-against-alpha-ketoglutarate-may-combat-deadly-childhood-brain-tumor https://www.nih.gov/news-events/news-releases/drugs-against-...

ovi256 6y ago

This is great news if you're lab mice! https://twitter.com/justsaysinmice?lang=en https://twitter.com/justsaysinmice?lang=en This is a parody twitter account that reminds us that all these new health breakthroughs are, indeed, applicable to mice only. It's a horribly narrow funnel that filters these to what is applicable to humans, outside a lab.

sradman 6y ago

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. [1] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30417-4 https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)... [2] https://en.wikipedia.org/wiki/C57BL/6 https://en.wikipedia.org/wiki/C57BL/6 [3] https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid

ykevinator 6y ago

It's the chemical, not the weightlifting

xwdv 6y ago

There’s only three supplements worth taking: Creatine - to top off your bodies ATP stores and maximize power output. Beta Alanine - to maximize your carnosine stores and decreasing the burning pain that comes from lactic acid, letting you push harder for longer. Citrulline - to relax blood vessels and boost nitric oxide in your body, giving your muscles more oxygen for more work and powerful erections. When their powers combine, you can reach your max potentials, with correct dosing.

RankingMember 6y ago
Re: beta-alanine, anecdotally all it ever seemed to give me were strong tingling feelings. Maybe I'll give it a go again sometime. > giving your muscles more oxygen for more work and powerful erections. hopefully not both at once ;)
- xwdv 6y ago
  You have to take them for quite some time. The tingling should stop happening after some times.

davidu 6y ago

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. ;-)

0134340 6y ago
Really? I don't think either are known for their long lives.
- Scoundreller 6y ago
  It’s a grim looking future...
- nscalf 6y ago
  The idea isn’t that they have long lives, it’s that they’re pushing the edge of possibilities for the human body and things are discovered there.
hyko 6y ago
The future of human health is shooting people in the head to cure a broken leg?
- davidu 6y ago
  lol, no, that's the future of democracy.
dennyabraham 6y ago
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.
ideals 6y ago
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.

mrfusion 6y ago

So why is this a body building supplement?

m0llusk 6y ago
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.