#60

So to be clear and summarizing this multi year thread thus far:

  1. Over the past several years many of us here have tried AKG in the 1-3g per day dose, over 1 month to greater than this (I believe I saw six months)

  2. it sounds like one person saw “greater energy over the first week” and another saw “gray hair darken” but then all noticeable impacts became unnoticeable. No one else noticed any impact of AKG

  3. no-one had any tests done to show there were any impacts?

  4. @John_Hemming has concerns about IL-10, and my initial literature reading this morning on this topic trying to understand what the risks are led me down such a deep dark rabbit hole of immune response being both positive and negative that I’m not sure what to make of it now: reducing inflammaging? — good. Reducing immune response against threats (probably including cancer) — bad. And articles on both sides suggesting reducing IL-10 fights aging, and enhancing it fights aging. So I’m now more confused than when I started.

  5. no-one continued it?

Is anyone still taking it?

Did anyone else see their hair darken?

For those that stopped, was it simply “no noticeable effects”? Or was there a noticeable negative effect? Or was it just not worth potential risks given no noticeable effects?

I’m very curious if it is a replacement to rapamycin. It sounds like no one wants to take it WITH rapamycin. Also if “hair darkened” is a normal response to taking it, obviously an aesthetic benefit but far more importantly it may be an indication of actual biological age — this is what I think many interventions are solely lacking. For instance, has anyone’s hair darkened on rapamycin? — this concerns me that this isn’t happening (even though life extension is well documented) as it suggests biological aging is not being reduced, only slowed (hypothesis).

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#61

This is the paper I found. It was not in a journal.

https://repositorium.sdum.uminho.pt/handle/1822/54794

Chronic inflammation is present in several diseases from autoimmunity to cancer, neurodegenerative diseases and others. A chronic state of low-grade inflammation, known as inflammaging, has also been linked to aging. To counteract this chronic inflammation, the anti- inflammatory cytokine interleukin (IL)-10 appears as a potential candidate. IL-10 has a broad role in regulating the immune system and has several distinct actions in different cells. Due to its great therapeutic potential in inflammatory and autoimmune diseases, understanding the impact of IL-10 in the organism homeostasis is fundamental. Our group has been investigating this issue, by resorting to a novel mouse model of inducible IL-10 over-expression (pMT-10). Previous results indicated that pMT-10 mice over-expressing IL-10 for 30 days develop a myeloproliferative phenotype, which is similar to that of animal models and patients with myeloproliferative neoplasms and is compatible with an aged hematopoietic system. The main aim of this thesis was to extensively characterize at the organism level the effects of 75 days of sustained IL-10 over-expression. Interestingly, we found that pMT-10 mice die prematurely and present hair depigmentation, along with an histological phenotype suggestive of an aged skin. This skin phenotype is marked by a reduction of dermal and skin fat thickness, wound healing delay and alterations at the hair follicle (HF) level, including the frequency, length and melanin content. Resorting to an ex vivo model, we found the cellular phenotype of fibroblasts retrieved from pMT-10 mice that over-expressed IL-10 for 75 days to be compatible to that of elderly fibroblasts. Finally, using an in vitro system, we gained evidence that IL-10 triggers cellular senescence in mouse adult fibroblasts. Together, these data disclosed IL-10 over- expression to induce multiple phenotypes that parallel premature aging and age-related diseases. In all, this thesis brings novel insight on the biology of IL-10, which might shed light into novel targets involved in aging and into the importance of immune-driven aging, showing that immune balances, rather than inflammaging play a role in this process.

Finally, using an in vitro system, we gained evidence that IL-10 triggers cellular senescence in mouse adult fibroblasts.

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#62

I think I have some AKG on back order at the moment, but to be honest I have inteventions that I know work. On my list of things to try sits Urolithin A which seems to have a lot more potential than AKG.

I am not myself sure how AKG works, but it is one of the Krebs/TCA/Citric Acid metabolites and they all seem to have some interest although citrate seems to be the most significant (not surprising given that it is the citric acid cycle).

Malate and Citrate swap via the citrate carrier, but that still requires the function of the citrate carrier which is inhibited by IL-10 (via the Janus Kinase and NF kappa B).

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#63

To keep the number of supplements I take from getting completely out of hand and the fact that new “wonder” supplements appear daily, I take a new supplement for ~ 30 - 60 days, unless there are good studies that show benefits only after long use.
I took AKG for 30 days each morning before I went to the gym. I felt absolutely no subjective effects and decided to stop taking it. I still have a couple of bottles on the shelf.

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#64

I’m with you: fewer are better. Plus I want to add taurine with creatine midday before the gym (which I stopped but want to restart from all the benefits I keep reading about). And I’m still not on rapa although plan to, and thinking about Nattokinase (seasonally) and NMN (although reading about the lack of NMN in samples continues to prevent me from bothering).

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#65

Hi Eric, I also am preparing to start rapamycin but want to do a full set of testing first and beyond the standard blood tests that have been recommended here, I’m researching what other tests or biomarkers would best represent the positive changes that I expect to see from taking rapamycin. I’m putting together a list of relatively simple and inexpensive tests (all short of the epigenetic clock tests) to add to the standard blood tests and the Levine Phenotypic Age. They would include functional tests (like sit-to stand, grip strength), blood pressure, heart rate measures (resting heart rate, maximum heart rate, heart rate variation), maybe a mental acuity test (MoCA test?), maybe a sleep score, maybe eyesight, hearing, olfactory tests. But anyway as many factors that could possibly be improved by taking rapamycin.
And on AKG, I am taking it but my research says that it might be the closest OTC supplement to rapamycin (another Caloric restriction mimetic) so that there is probably a lot of overlap. So I may stop when I start rapamycin. Hard to say because Metformin (another Caloric restriction mimetic) shows some synergies when taken with rapamycin and AKG may also. Here’s a great recent article on AKG.
“As discussed above, aging is physiological changes that occur in the body, leading to senescence, the decline of biological functions, and reduction of the capacity for regulation of metabolic stress. It is very clear that the number and proportion of elderly people are increasing in all countries. In recent years, anti-aging related researches have become one of the most interesting and promising research fields focused on finding new or already existing medicines that could tackle aging. To this end, several compounds such as rapamycin, metformin and AKG have been proposed as anti-aging drug. It is important to note that AKG has some advantages over other drugs associated with longevity. First, AKG is a compound found naturally in the body. Second, AKG has a high solubility in aqueous solutions. Third, AKG is completely consumed by the organism; in other words, there is no excretion of it either in the form of urine or feces. Forth, AKG derivatives (e.g. Ca-AKG) have the capacity to cross the cell membrane.
Interestingly, AKG increases food intake, leading to an increase in muscle and bone growth in animal models. We still know little about the mechanisms involved in aging in human and AKG effects on it, but this multi-purpose metabolite might significantly improve longevity and healthspan in human.”

https://www.sciencedirect.com/science/article/pii/S053155652300075X

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If you could only take 10 supplements a day, what would they be?
#66

Where did you get potassium AKG?

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#67

Sorry, my mistake. I was going by my faulty memory. The potassium supplement I am taking:
Nutricost Potassium BHB Salts, Exogenous Ketone Supplement.

The AKG supplement I was taking was:
Double Wood AKG Supplement (Alpha Ketoglutaric Acid)

Both are from Amazon.

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#68

Drat! Thanks. (Post must be at least 20 characters )

#69

Thanks for that. How long have you been taking AKG? Any noticeable effects, or just taking it because of your literature interpretation?

#70

I’ve only been taking AKG for about 3 weeks and I take a number of other supplements so I can’t be sure of any changes. Be sure to get it from a reputable company with third party testing certification (for all supplements) or you may not be getting what you pay for. I do think (from my reading) that AKG is particularly valuable if you are not taking rapamycin. I’m trying to maximize my biomarkers of aging with non pharmaceutical supplements first and then add rapamycin and see what changes. The challenge is to set up the right testing protocol (not Bryan Johnson level) that can be done every 3 months so that you can add or drop an intervention (like AKG or rapamycin) and see if it makes a difference (shows a result in your tests). Often you might not feel anything subjectively but it may show up in a test (blood or otherwise).

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#71

“On the assumption that the average mouse weighs 30 gm and consumes 5 gm of food/day of food/day”

So 2% w/w on 5gm/day food = 0.1g/day CaAKG for mouse

Converting 0.1g/day consumption for a 30 g mouse to an equivalent consumption for a 70kg human = 0.1/30 * 70,000g = 233g/day of CaAKG

Someone please check, but is human supplementation ORDERS of magnitude lower?

100mg food/0.03kg weight=3,333mg/kg

Human equivalent dose conversion factor=12.3

(3,333/12.3)mg/kg=271mg/kg

271mg/kg*70kg=18,970mg CaAKG/day for a 70kg human.

Let’s call it 19grams, which is also about 3.75g supplemental calcium per day. That’s quite a bit of supplemental calcium, see for example below.

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#72

Just ordered CA-AKG from DoNotAge. It’s time for me to give it a go. I used the 10% off code BRAD.

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#73

I have been taking calc-AKG for just over a week. From what I have read it is quite promising as an health span extender. Even though they consumed a huge amount in the mice research from what I have read in the human research benefits have been seen with around 1500 to 2000mgs. One must realise that people have been taking AKG Long Before the latest research and have been claiming benefits. Even though I have been taking it a week I am not expecting many benefits until after 4 to 6 months of usage

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#74

How much AKG are you taking?

AKG is interesting because it is another Krebs metabolite. I have been looking at the Krebs metabolites more generally and some seem to have positive effects in the cytosol and others negative.

AKG is odd because it metabolises very quickly, but I think it probably creates the right precursors to enable an increase in AKG in cells.

I would say, however, that AKG appears to be anabolic in nature and hence if being cycled it might be best to cycle it at a different time to Rapamycin (or other catabolic molecules).

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#75

I am taking 1600 mgs shared between 2 does dally.

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#76

The molecular weight of AKG is about 144 as an ion, about 146 as an acid. Calcium is about 40. Arginine is about 174. AAKG is about 320. Hence if people take 1.6 g of CaAKG that is about 1.25g of AKH. With Arginine it would be less than 0.8.

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#77

Can Ca-AKG be split between morning and evening doses or is it something to avoid before bed? I’ve been taking the full 1g at breakfast

#78

If it inhibits autophagy i would suggest only taking it with breakfast

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#79

I took it for about three years and have to say that I didn’t feel any different at all. But I’m not sure you will feel anything. It’s the long term effect that is beneficial

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