4 Best AKG Supplements: Benefits, Dosage, & Review of Alpha-Ketoglutarate

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 that 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.

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:

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 increasing 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 we age. So, for example, with every one 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 benefit 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 parameters of arterial health.

Finally, a bunch of Polish University studies have 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. 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.

1. There’s longevity research backing its effects in both cells, animals, and humans
2. It improves multiple mechanisms of aging
3. 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!