LaraPo
#802
What is a reliable brand of ALG on Amazon? I tried Prohealth longevity brand in the past but didn’t notice any changes and stopped. Rejuvant of course is good but too expensive.
I have taken some forms of AKG off and on in the past. I have never subjectively felt any difference. Based on more recent studies, I have started taking the timed-release form that was used in the study. Right now, I am taking it five days a week, right before workouts. So far, I haven’t noticed anything.
This is the brand from Amazon that I am using. “Third Party Tested.” Their certificate is outdated. They are ~75% cheaper than Rejuvant. They claim to have piperine and enteric-coated capsules. They are a small company, so I don’t know how reliable they are.
“LongJuvity Calcium Alpha-Ketoglutarate” Time Release AKG Supplement
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Siim Land’s Supplement Tier List
I agree with his Junk and God lists. However, there are some in the other tiers I would move around.
Surprisingly he includes Rapamycin and Metformin in here.
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Curious
#805
In my case I would remove Mag-threonate from the very good and put it as Okay. I can’t find human research that can convince me that it is a top supplement.
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LukeMV
#806
Did we ever find out what the human equivalent dosage of AKG was used in the ITP that failed?
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I have not found any trials that did not use a sustained-release form. A mouse study that used AKG in the feed, and it failed.
“no peer-reviewed SR vs IR comparisons yet.”
A human study is underway, and it uses the Rejuvant brand.
“Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)—intervention study protocol - PMC”
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What makes you believe that AKG works in humans despite failing in mice whose diet was very high in AKG? If AKG decreased frailty or increased mitochondrial efficiacy, would that not result in a cancer-delaying effect? Anything that decreases biological age should realistically also delay cancer and other age-related diseases such as AD. Are there any animal models for AD where AKG showed an effect?
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LukeMV
#809
I asked Vera AI and this is what it said
In the NIA Interventions Testing Program (ITP), **calcium α-ketoglutarate (Ca-AKG)**was tested at 2% of the diet (w/w) in genetically heterogeneous mice. This intervention failed to extend lifespan in either sex.
To translate this to a human equivalent dose (HED), the FDA-recommended body surface area conversion was applied:
-
Mouse dose: 2% dietary supplementation ≈ 2.0–2.5 g/kg/day (depending on food intake).
-
HED calculation: Mouse dose ÷ 12.3 (conversion factor) ≈ 160–200 mg/kg/day in humans.
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For a 70 kg human: ≈ 11–14 g/day of Ca-AKG.
Thus, the equivalent human dose tested in the ITP was approximately 11–14 g/day, which did not show lifespan extension in mice 1.
| Study (Model) |
AKG Dose Used |
Human Equivalent Dose (HED) |
Outcome |
Clinical Evidence |
| ITP (mice, genetically heterogeneous) |
2% Ca-AKG in diet (~2–2.5 g/kg/day) |
~160–200 mg/kg/day → 11–14 g/day for 70 kg adult |
No lifespan extension |
NIA ITP report in EBioMedicine I1
|
Conclusion: The ITP tested an AKG dose equivalent to ~11–14 g/day in humans, and this regimen did not extend lifespan in mice. This suggests that either the intervention window, formulation, or biological context may be critical for any potential longevity effects.
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One could ask the same questions about Omega-3. The ITP did not show any lifespan extension when fish oil was given to mice, so why even bother considering it as a “longevity drug” in humans? Then there’s the case of aspirin, where ITP ran different studies. In one study they got a life extension benefit with one dosing level, but then in another study they did not see a benefit.
Lithium is another drug (not yet tested by ITP) that shows no lifespan extending effect in mice, but might very well in humans if the anti-Alzheimer’s effects are to be believed; and vitamin D does not appear to extend mouse lifespan, either.
Mice are different from humans in several respects. Here are just a few: (1) They don’t naturally get heart attacks; (2) they don’t naturally get Alzheimer’s; (3) they have high telomerase activity in many cells types (in humans telomerase is mainly restricted to certain specific tissues), and their telomeres are longer; (4) they produce their own vitamin C. And there are dozens more.
What about Brian Kennedy’s group findings contrasting with ITP, isn’t that just fraud? No. Those studies were carried out by people at the Buck Institute, including Gordon Lithgow. They’re not trying to fake you out:
The parameters of the study were just different from ITP.
Weren’t those “7 year decrease in epigenetic age” numbers just pure hype, Kennedy trying to fake us out again? No. Even though his name is on the paper, he didn’t have a lot to do with that study. They came to him with the results, I think.
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Omega 3 and aspirin have a role in treating/preventing cardiovascular disease and AD. Neither will delay cancer formation and growth. Nor do they have an effect on biological aging.
If something supposedly lowers your biological age, I do expect to see some effect on lifespan. If you have two groups of people (both on statins/PCSK9i/BE/EZE, SGLT2i, … to prevent cardiovascular disease and diabetes) and treat one with AKG (or any other substance that lowers your biological age/slows your biological aging) and the other with placebo and neither have a statistically significant difference in all-cause mortality nor in AD rates despite being biologically “younger” according to the test… is the test really useful or even measuring the right metrics? No it isn’t.
Epigenetic aging tests appear like a huge scam at the moment. Maybe they will be useful in the future.
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I can totally believe some epigenetic testing companies are running a scam, but don’t think Horvath or Morgan Levine are running ones. Sure, they might slip up and say “aging” when they mean “Grimage” or “epigenetic age”; but they’re not trying to con people about what it measures.
Some of these tests (like Phenoage, as I recall) were designed to predict “morbities” (e.g. risk of cardiovascular disease and cancer) and mortality risk. However, there’s no guarantee they will continue to be useful once you start making interventions – if you do an intervention to hack some clock (e.g. make the Phenoage number go down), there’s no guarantee that you’ll reduce the risk of contracting these morbities. The predictive power of these methods is limited to “situation normal” (no hacking) in the population as a whole.
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Are those tests more predictive than merely looking at LDL-C and HbA1c? Do interventions that cause a reduction in epigenetic aging have a statistically significant impact on cardiovascular event rates or new onset of diabetes rates?
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I answered that in the last sentence. There is a difference between these two probability measures:
(1) Pick a random person in the population from the past (before knowledge of the test), measure their Phenoage. Given that they are such and so age and their Phenoage is high, what is the probability that they will develop a morbidity?
(2) Pick a random person from the population with a high phenoage, do some interventions to lower it, how does that affect their risk of a morbidity?
And, by the way, the same is true of hbA1C – you can artificially lower it, without affecting your risk of diabetes.
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Fair question.
As I stated before, “Based on more recent studies, I have started taking the timed-release form that was used in the study. Right now, I am taking it five days a week, right before workouts. So far, I haven’t noticed anything.”
I only decided to revisit it because I wasn’t using a timed-release form.
I am sure it will just end up as another failed supplement that I have tried.
There is no compelling evidence for using it as a supplement, but many bodybuilders use it.
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Speaking of sustained release… I discovered today that Nature Made puts out a slow-release vitamin C pill. I bought some just today (they are cheap). It’s hard to find info about just how long they continuously release vitamin C, but following a few searches with Perplexity, it seems it ought to take about 5 to 6 hours until blood plasma peaks, and then plasma vitamin C levels should be elevated for several hours after that. Plain vitamin C pills will only keep plasma C levels elevated for about half the duration.
I might also look into buying niacinamide slow-release (not sure Nature Made sells such a product).
Addendum: They have a B 100 time-release pill that includes niacin (100 mg).
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Small 2022 study about the combined effect of Magnesium and Vitamin D:
The effect of combined magnesium and vitamin D supplementation on vitamin D status, systemic inflammation, and blood pressure: A randomized double-blinded controlled trial
https://www.sciencedirect.com/science/article/pii/S0899900722000867
Participants who received magnesium and vitamin D had a greater increase in serum 25-hydroxyvitamin D [the usable form of vitamin D produced in the liver] compared with participants in the vitamin D only group.
Magnesium helps the body to “activate” vitamin D / produce the active form.
Addendum: I wrote earlier that this is the “active” form of Vtiamin D that they measured. That form actually takes one more step. The form they measured was 25-hydroxyvitamin D, then that ultimately gets converted in the kidneys to the active form 1,25-dihydroxyvitamin D, or calcitrol. So, it goes
vitamin D → 25-hydroxyvitamin D (liver) → 1,25-dihydroxyvitamin D (kidneys)
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Yes Magnesium helps your body absorb vitamin D3. Since most people are deficient in magnesium and vitamin D3, both should be taken if you are vitamin D3 deficient, like myself.
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It makes me wonder if the recent study on vitamin D maintaining telomere length would see an even greater effect if they also supplemented with magnesium.
Given that this vitamin D result (the one on telomere lengths) was a bit of a shock to many (assuming it holds up with further testing), it also makes one wonder what other simple interventions could protect cells, maybe even increasing DNA repair efficiency. It could be that a combination of some very common supplements in a high enough dose (but not too high) will do the trick, possibly cutting the rate of DNA damage in half.
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2013 study:
Specialty Supplement Use and Biologic Measures of Oxidative Stress and DNA Damage
https://aacrjournals.org/cebp/article/22/12/2312/69717/Specialty-Supplement-Use-and-Biologic-Measures-of
Methods: In the VITamins And Lifestyle (VITAL) biomarker study of 209 persons living in the Seattle area, we examined the association between current use of several specialty supplements and oxidative stress, DNA damage, and DNA repair capacity. Use of glucosamine, chondroitin, fish oil, methylsulfonylmethane (MSM), coenzyme Q10 (CoQ10), ginseng, ginkgo, and saw palmetto was ascertained by a supplement inventory/interview, whereas the use of fiber supplements was ascertained by questionnaire. Supplements used by more than 30 persons (glucosamine and chondroitin) were evaluated as the trend across number of pills/week (non-use, <14 pills/week, 14+ pills/week), whereas less commonly used supplements were evaluated as use/non-use. Oxidative stress was measured by urinary 8-isoprostane and PGF2α concentrations using enzyme immunoassays (EIA), whereas lymphocyte DNA damage and DNA repair capacity were measured using the Comet assay. Multivariate-adjusted linear regression was used to model the associations between supplement use and oxidative stress/DNA damage.
Results: Use of glucosamine (P trend: 0.01), chondroitin (P trend: 0.003), and fiber supplements (P: 0.01) was associated with reduced PGF2α concentrations, whereas CoQ10 supplementation was associated with reduced baseline DNA damage (P: 0.003).
Hmm… why is CoQ10 use associated with reduced baseline DNA damage, but not the others?
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One of my favorite supplements is anti-inflammatory and anti-pyretic, reducing knee pain and lowering hs-CRP. It is Boswellia serrata, otherwise known as frankincense. For me, using it was a life-changer; it (plus rapamycin?) has left me almost entirely pain-free except for some minor lower back pain.
My latest results:
Evidence supports the use of Boswellia serrata extract for knee and joint pain and much more:
- Boswellia Serrata Extract offers several health benefits, including:
- Reduction of Inflammation and Pain:
- Contains boswellic acids with anti-inflammatory properties.
- Clinical studies indicate effectiveness in reducing pain and improving symptoms in osteoarthritis and rheumatoid arthritis patients.
- Reduces knee and joint pain.
- Comparable efficacy to NSAID pain medications but with fewer side effects.
- Potential Treatment for Autoimmune Diseases:
- Helps regulate the immune system and inhibits the production of pro-inflammatory cytokines.
- Shows potential benefits in small studies for conditions like rheumatoid arthritis, Crohn’s disease, and ulcerative colitis.
- Exhibits anti-proliferative and anti-tumor effects in lab and animal studies, with early indications of anti-cancer benefits.
- Improvement of Digestive Health:
- Increases bile flow and may assist in treating digestive conditions such as IBD, IBS, and liver disease.
- Used for treating gastric ulcers and alleviating acid reflux symptoms.
Provides neuroprotective effects by reducing inflammation in the brain.Small studies suggest benefits for memory, cognition, and mood in patients with brain injuries.
Based on the current evidence, pain, stiffness and joints’ function start to improve after 4 weeks of continuous Boswellia and its extract (at least 100–250 mg).
"a significant decrease in the activity of hs‐CRP in the BSE‐treated group was observed in contrast to that from the placebo receiving group (p < 0.01; Figure 2f). These findings are clearly suggesting that BSE is a powerful inhibitor of hs‐CRP induced by local inflammation in patients
with OA."
Boswellia serrata has Beneficial Anti-Inflammatory and Antioxidant Properties in a Model of Experimental Colitis
https://onlinelibrary.wiley.com/doi/10.1002/ptr.5142
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