Could alpha ketoglutarate (AKG) supplements be the closest thing to a fountain of youth?
The world of longevity medicine has focused primarily on powerful and natural NAD+ precursors and other body-protective ingredients.
For the most part, other classes of molecules have flown under the radar.
Yet the potential lifespan and healthspan-promoting properties of alpha-ketoglutarate are mind-blowing.
In this article, I will break down the latest science and benefits around alpha-ketoglutarate, and review all the best AKG supplements available.
What is Alpha Keto Glutarate
Alpha-ketoglutarate is a small molecule naturally abundant throughout the body. Although used for all kinds of bodily processes, AKG is famously used by mitochondria to generate energy. Supplementation has become popular to replenish the levels that naturally decline with age. Preliminary findings show significant lifespan-enhancing benefits, but compared to many other ingredients, research is still emerging.
One of the most important criteria to consider when evaluating Alpha Ketoglutarate supplements is the form of that AKG.
Types of AKG
Alpha-ketoglutarate supplements come in all different forms. Most are just ordinary alpha-ketoglutarate.
Unfortunately, as much as 80% of normal oral AKG never reaches the bloodstream.
Yet scientists have discovered that alpha-ketoglutarate is the most effective, stable, and longest-lasting when bound to something else.
The two most common bioavailable forms are:
- Arginine Alpha-Ketoglutarate (AAKG)
- Calcium Alpha-Ketoglutarate (CaAKG)
AAKG is L-arginine (an amino acid involved in nitric oxide synthesis) bound to AKG. This form is good for the blood and hormone-enhancing properties of AKG. Overall, it’s far superior to traditional alpha-ketoglutarate but not as good as the next option.
CaAKG is calcium (an excitatory mineral) bound to AKG. As you’ll see in the science section, this is the form most commonly used in clinical research. The same one shows longevity benefits and biological age reversal. This form lasts longer because it’s slowly absorbed in the gut and gradually enters the bloodstream. CaAKG is the clear winner for longevity biohackers seeking research-backed supplements.
There are three other interesting forms to mention.
Creatine AKG (C-AKG) is creatine bound to alpha-ketoglutarate. Since AKG is a Krebs cycle intermediate, it easily enters cells and can deliver creatine into muscle cells. Entering the cell without needing a transporter like most creatine. Plus, we wouldn’t need an excitatory calcium counter-ion which theoretically makes it better for the nervous system.
Ornithine AKG (OKG) is the amino acid L-Ornithine bound to alpha-ketoglutarate. What’s interesting is that neither ingredient is very bioavailable on its own. Ornithine HCL can increase sleep quality in two ways. By reducing the stress hormone cortisol and also levels of ammonia. Paradoxically, some people report finding OKG a bit stimulating.
Sodium AKG (Na-AKG) is another one popular in Polish studies. They claim it has a stronger effect than Ca-AKG, but I didn’t take the time to translate all the Polish research. Given the prevalence and necessity of sodium, this one seems like it warrants extra attention.
So far, the research on CaAKG and AAKG looks most promising.
The Best AKG Supplements & Products
Unlike many longevity supplements, there aren’t many quality alpha-ketoglutarate products available.
As indicated in the research, absorption matters. Liposomal encapsulation ensures you get the greatest bioavailability and longest effects, with the lowest dose necessary.
These are the top AKG capsules and powders you can buy online.
DoNotAge
Overview
Form: Normal
Dosage: 400mg
Servings: 366
Refund Policy: 14-day money-back guarantee
Serving Cost: $0.64
Do Not Age (appropriately abbreviated DNA) is one of the fastest-growing research-backed longevity supplement vendors. Founded by Alan Graves, DNA’s mission is to fight aging. This is one of the best shops for European bioharmonizers as they are based out of the UK.
Do Not Age’s Ca-AKG is exactly what you’d expect—pure AKG with nothing else added. Every product comes with their Do Not Age Quality Guarantee meaning that it’s guaranteed to arrive at your doorstep with full potency. Most supplements sit, decay, and degrade long before they reach you. DNA products do not, which has made them popular with researchers and scientists.
To get the therapeutic dose, you’ll need a much larger serving. This is a notable downside but for the price and everything you else you can get, it’s still a top-grade supplement.
I am a fan of Do Not Age’s CaAKG because the company is reputable and the product is affordable.
Use the exclusive Do Not Age code URBAN for 10% off
Novos Core Multi-Ingredient
Overview
Form: Normal
Dosage: 1,100mg
Servings: 30
Refund Policy: 30-day money-back guarantee
Serving Cost: $3.63
Created by Chris Mirabile, NOVOS is a company of longevity scientists and doctors formulating products to slow the aging process. Their science team has backgrounds from Harvard, MIT, and other top institutions. NOVOS Core, their flagship product, is one of few that targets all 10 known root causes of aging. This supplement also claims to improve appearance, brain function, and energy levels. How can they possibly target all known hallmarks of aging?
NOVOS Core uses 12 ingredients, collectively backed by over 190 studies. NOVOS didn’t take any shortcuts, using clinical dosages of each. Every serving includes a full 1,100mg dose of calcium alpha-ketoglutarate.
Usually, a formula like this would require you to take a whole handful of capsules. NOVOS took a different approach and formulated this all-in-one product into a drink. Every serving comes in its own sachet, containing unsanitized powder.
I have three main criticisms against NOVOS. First, I couldn’t find a CoA or any evidence of third-party lab testing (a major issue). Without that, we don’t know purity or safety. Second, they included an unnecessary filler, Silicon Dioxide, in the formula. Third is the price. NOVOS Core is among the most expensive longevity formulas.
If you want the most comprehensive, clinically-dosed all-in-one longevity formula that includes Ca-AKG, and don’t mind the lack of third-party testing, NOVOS Core is worth considering.
Use the exclusive NOVOS code URBAN5 for $5 off
Affiliate Disclosure: This post contains affiliate links, which means Outliyr LLC gets a small commission if you buy (at no cost to you). Thanks for your support!
LIPO CaAKG
Overview
Form: Liposomal
Dosage: 300mg
Servings: 90
Refund Policy: 30-day money-back guarantee
Serving Cost: $0.54
Founded by Bryan Nettles, Renue By Science (formerly Alive by Science) offers longevity supplements with the goal of helping your healthspan and quality of life. So that you can do the things you love, for longer.
Renue By Science uses liposomal encapsulation technology, combined with third-party lab testing for potency and safety which can be found in the accompanying certificate of analysis (CoA).
Renue By Science’s CaAKG is a strong. Each serving contains 300mg of CaAKG, likely delivering the equivalent dosing of over 1,000mg but without the issues of consuming large supplement doses.
Between the potency and price, this can be a good pick-up.
NAD⁺ DEFENDER
Overview
Form: Liposomal
Dosage: 230mg
Servings: 60
Refund Policy: 30-day money-back guarantee
Serving Cost: $0.83
NAD Defender is designed to spare the body’s molecule of anti-aging—NAD+. It does so by reducing systemic inflammation, something beneficial to virtually all modern humans.
Aside from the lower dose, the calcium alpha-ketoglutarate inside this product is no different than their pure AKG. What sets it apart, however, is the stack of other longevity ingredients.
NAD Defender contains Berberine, HLA, and of course, Ca-AKG. I like this formula for hard-charging athletes and anyone that’s physically active. HLA improves connective tissue, while CaAKG acts as an ergogenic workout aid, and the berberine keeps blood sugar steady. Also making it a solid choice for those in their later years.
NAD Defender is an affordable longevity supplement stack that includes CaAKG.
AKG Supplement Health & Longevity Benefits
The ketoglutarate family is well-researched, with my current search yielding thousands of papers.
Initially, alpha-ketoglutarate was investigated and used in the treatment of various disease states.
Modern recent studies have focused on its use to improve the function of cells via a measurement called biological age.
Recent research suggests that AKG benefits at least two hallmarks of aging:
- Inflammation
- Epigenetic expression
Alpha ketoglutarate reduces inflammation caused by senescent cells. Indirectly improving NAD+ levels.
It seems to improve the expression of genes (called epigenetics) and helps cells express themselves in an optimal youthful state.
Finally, AKG stimulates the body’s protective mechanisms and pathways.
Now, let’s explore the most common uses and benefits of supplementing alpha ketoglutarate.
Muscle growth & athletic recovery
Decades ago, bodybuilders were among the first to take AKG supplements. They use it for several reasons. For one, muscle tissue contains a high concentration of mitochondria. Improving mitochondrial function results in better workouts, in turn increases muscle building. Additionally, alpha-ketoglutarate benefits muscle tissue in two other ways.
First, it inhibits muscle protein breakdown. Second, it stimulates protein synthesis. AKG can even stimulate the production of the nutrient-delivery molecule called Nitric Oxide (NO).
AKG shows promise to boost performance, muscle growth, and speed up recovery.
Energy & endurance
The process of creating new mitochondria, called mitochondrial biogenesis, directly improves sports performance. The more mitochondria you have (and the better they function), the higher your energy levels.
At the same time, optimized mitochondria translate into greater endurance capacity by delaying the onset of fatigue. Acute use seems better suited for longer efforts rather than power or strength athletes. Continual usage shows benefits to different forms of exercise. Although one poorly designed trial didn’t show much benefit in well-trained individuals.
Healthspan & longevity
Calcium alpha-ketoglutarate and arginine AKG have regained popularity due to their unparalleled anti-aging & healthspan-improving potential.
Most of the animal research on AKG looks quite promising. In 2014, AKG improved the lifespan of a kind of worm called C. Elegans by 47.3%! Follow-up research in 2018 and 2019 found similarly impressive results in flys.
More recently in 2020, one of the world’s leading anti-aging research institutes fed mice alpha-ketoglutarate. The Buck Institute’s study found treatment with CaAKG resulted in a 9.6% to 12.8% median lifespan increase.
Healthspan is the measure of lifestyle that accounts for the quality of those years. After all, lifespan extension is only valuable if you’re able to enjoy those years.
Even more impressively, was the healthspan increase from that same study (emphasis mine),
“Our findings show that CaAKG treatment decreases the proportion of life in which the animal is frail and vulnerable to adverse health incomes (determined as the area under the frailty curve and calculated at a 46% reduction for females and 41% for males.”
Meaning the mice lived ~13% longer and with a ~43.5% greater quality of life during those years. Plus, they looked better — maintaining more strength and with fewer gray hairs.
Much of these effects are likely attributable to the normalization of inflammation levels, as well as the modulation of key longevity pathways.
Biological age reversal
All longevity enthusiasts seek supplements that can reverse biological age. Although we cannot yet directly “turn back the clock”, certain interventions can certainly slow the rate as we age. So, for example, with every calendar year we age only 0.5 biological years.
Biological age reversal often correlates closely with healthspan.
Indeed, several papers support Calcium alpha-ketoglutarate’s ability to slow biological aging.
The first was on Rejuvant, an alpha-ketoglutarate-based formulation. Just a short course reversed biological age by up to 8 years (emphasis mine),
“While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging.”
This is quite impressive. Few (if any) other formulations have shown even a fraction of these results.
Since I used tested and reviewed the TruDiagnostic Epigenetic Biological Age Testing service, Iearned firsthand the difficulty of biological age reversal. I’m considering recreating this experiment and re-testing it to see if I get similar results.
Regardless, the impact of Ca-AKG on biological age looks very promising.
Bone density & skin health
Calcium alpha-ketoglutarate seems to impact other areas that decline with age. Skin appearance and bone density are actually powerful biomarkers of longevity.
Damaged skin has higher levels of senescent cells, which causes all kinds of downstream aging issues (and senescent cell burden is a hallmark of aging). Ca-AKG seems to keep skin youthful and healthy. It also stimulates the synthesis of collagen and protein to support optimal detoxification and normal cellular function.
So far in mice, this supplement also appears to improve bone mass, reduce bone loss, and accelerate bone regeneration.
Fertility improved
Can α-ketoglutarate help those struggling with fertility?
As humans continue to postpone childbearing into later years, fertility issues have skyrocketed. One 2021 study investigated the role of alpha-ketoglutarate and age-related fertility.
They noticed significant fertility improvements from long-term supplementation, and the researchers used mice to tease out the mechanisms.
While certainly promising, I’d like to see clinical research in humans.
Detox & immunity
Detoxification is the natural process the body uses to rid itself of byproducts of metabolism, cellular waste, and other toxins. AKG can help rebalance the immune system and keep the body running optimally.
On the detoxification front, alpha-ketoglutarate helps the body remove excess ammonia and nitrogen from the blood. These result from the metabolism of dietary protein and can quickly accumulate. Ammonia in large quantities is toxic. By improving ammonia clearance, AKG supports optimal detoxification.
Alpha-ketoglutarate also positively modulates the immune system. It helps specialized immune cells called macrophages mount more appropriate immune responses. AKG provides hungry immune cells with an amino acid called glutamine and the neurotransmitter glutamate. Increasing the number and activity of immune cells like neutrophils, phagocytosis, lymphocytes, and macrophages.
Other immune benefits of AKG likely stem from its beneficial changes to the gut microbiome.
Stem cell rejuvenation
Another AKG benefits worth discussing is its impact on stem cells.
Stem cells are a form of generalized cells naturally present throughout the body that can take the form of any tissue. These “jack of all trades” cells are incredibly valuable and important to maintain health. They decline with age, and so does the body’s ability to repair and regenerate.
One 2020 study showed that AKG supplementation can protect a form of stem cells called mesenchymal stromal/stem cells (MSCs) from damage.
Although this study investigated bone stem cells specifically, I’d love to see it replicated for other tissue types.
Biomarker improvements
AKG improves various other biomarkers too.
First, it appears to improve phosphate metabolism. This in turn helps correct obesity.
Several mouse studies have found that it improves the parameters of arterial health.
Finally, a bunch of Polish University studies has uncovered some impressive anti-aging effects.
Optimally Using AKG Supplements
Using alpha ketoglutarate supplements is safe and straightforward.
There are a few things to note before getting started.
Dose & form
First, you’ll quickly notice that dosage varies based on several factors.
The primary being:
- Delivery technology
- Goal
- Form
Normal capsules and powders will require much larger doses to get the same effects as low-dose liposomal encapsulated products.
Also, your ideal use depends on your goals.
For muscle growth, endurance, recovery, and sports performance, athletes prefer either arginine alpha-ketoglutarate (AAKG) or creatine alpha-ketoglutarate (CAG). These two are most favorable to muscle tissue and hormones. Most take 1 to 12 grams taken either pre-exercise or post-exercise.
For longevity, anti-aging, and biohacking, the exact protocol is less clear. Most of the research has used CaAKG, so I prefer that form. Especially to reduce biological age. The ideal dose of a normal powder would be 500mg – 1,200mg. The liposomal dose will depend on the preparation, so you’ll want to follow the label’s recommendations.
Safety
Overall, AKG is well tolerated and considered safe in typical dosages. I recommend following the dosage instructions on the product’s label.
So far there are no documented side effects attributed to alpha-ketoglutarate alone.
Upgrade Your Ca-AKG
There are several things you can combine/stack together with AKG to get far better, biosynergistic effects.
After all, the trial that showed an 8-year biological age reversal contained other ingredients that amplified the benefits of AKG.
Vitamin B6
The cheapest and simplest addition to a Ca-AKG stack would be vitamin B6 or a vitamin B complex. Since we’re commonly deficient in B vitamins, it’s a good idea on its own. B vitamins improve the energy generation process and also work to increase the absorption of AKG.
Whey protein stack
As explained in my guide to grass-fed whey protein powder, this one is a godsend for health optimizers. It’s ultra-pure, nicely combats anabolic resistance, and ameliorates one of the primary risks of aging — frailty. High-quality whey, specifically grass-fed, contains all kinds of beneficial peptides, growth factors, and regenerative molecules. This is key for the elderly and athletes alike.
NAD+ precursor
You’ve probably heard of NMN or NR, thanks to the work of Dr. David Sinclair. Both of these boost levels of the body’s master energy reservoir called NAD+. NAD+ is like gasoline in the body and powers vital longevity pathways and proteins like SIRTUINS. Levels drop swiftly after the age of 40-50, and people often report massive quality-of-life enhancements from supplementing these or living an NAD+ optimized lifestyle.
Spermidine
The most exciting longevity supplement I began using in 2022, spermidine is the only known agent that improves six of the nine hallmarks of aging. It’s notable for its hair, skin, and nail regenerative effects. As well as slight cognitive benefits. Most relevantly, spermidine promotes the cellular cleanup process of autophagy and protects the human genome (and epigenome). To learn more about this longevity superstar, read my research-backed guide and review of the best spermidine supplements.
Adding Alpha Ketoglutarate To The Optimized Longevity Stack?
Alpha-ketoglutarate is one of those molecules that hasn’t gotten the attention it deserves. That seems to be changing, as major anti-aging institutes are now beginning to explore its potential.
Although it’s no panacea, it does meet the criteria of an ideal longevity product.
- There’s longevity research backing its effects in both cells, animals, and humans
- It improves multiple mechanisms of aging
- It appears quite safe as it’s naturally occurring within the body, its decline coincides closely with the normal aging process, and it has a multi-decade history of use
Supplementing alpha-ketoglutarate makes sense for athletes or those looking to fully optimize their mitochondria and energy reserves, or more advanced longevity biohackers.
Overall AKG would not be the only longevity ingredient I’d use. But it’s a good addition to a balanced longevity supplement stack.
For these reasons, I will give alpha-ketoglutarate a…
Bioharmony Score: 4.1/5
My favorite AKG vendors are Renue by Science for highly bioavailable and pure alpha-ketoglutarate, and then NOVOS Core for an all-in-one formulation.
What do you think? Do you use AKG? Let me know why or why not in the comments below!
Ask Nick a Podcast Question
Howdy, Nick,
Really an inspiring article on the benefits of taking AKG. I am 84, have been training with weights for 63 years. I’m talking lifting heavy, muscle-building workouts, leaving the gym bone-tired. A couple years ago I started reading about NMN and it’s supposed benefits (lots of healthy mice out there). At the same time I found a biological age test using the results of blood lab markers. I tested out to 20 years younger than my chrono age at the time, 82. This is with no NMN or NR, only resistance training (hard training, no “muscle-toning” workouts).
My recent bio-age test, using minimal dose nmn, at 62 vs 84 chrono age.
I have ordered CaAKG Lipo from Renue by Science. Will see how that goes.
Thank you for the informative wordsmithing.
Hey Max,
Wow! That’s quite impressive. Any secrets you can share that you’ve used to slow your biological aging? Which BioAge test did you take? I’m also curious how your AKG experiment went.