Arginine Alpha-Ketoglutarate

AAKG is a combination of the amino acid arginine and an alpha-ketoglutarate molecule. It can improve training endurance and performance while mitigating fatigue and enhancing recovery. It also benefits oxygen volume, blood flow, and protein synthesis.

So, if you’re considering supplementing your diet and exercise routine with AAKG, let’s look into what AAKG actually is, its functions, and why it will help you perform better.

What Is Arginine Alpha-Ketoglutarate?

Arginine Alpha-Ketoglutarate, or AAKG, is a supplement comprised of the amino acid arginine attached to an alpha-ketoglutarate molecule (1). The supplement is used by athletes who believe it improves endurance and performance while reducing muscle fatigue and enhancing recovery.

We can break down the AAKG supplement into two parts: L-Arginine and Alpha-Ketoglutarate. Both have different functions.

AAKG is also a popular supplement because it can increase nitric oxide production in muscles. This is because nitric oxide is involved in several cell processes, such as widening blood vessels or vasodilation. By having wider blood vessels, the body can deliver nutrients and oxygen to working muscles at a more efficient rate during exercise, and, therefore, exercise performance is enhanced (1).

In theory, this could increase the delivery of oxygen and nutrients to exercising muscles, but while L-arginine does increase nitric oxide production, there is no clear scientific evidence to demonstrate that AAKG supplements have the same effect.

The addition of Alpha-Ketoglutarate is assumed to help improve the delivery of L-arginine in metabolic pathways. Simply put, this helps L-Arginine to work more efficiently throughout the body and therefore achieve even better results (1).

Benefits of AAKG

AAKG has several benefits for your exercise performance, but we should break down those benefits into what L-Arginine and Alpha-Ketoglutarate will have on your performance individually. However, let’s look at what AAKG’s proven benefits are:

Increased Strength And Power

Double-blind trials of AAKG suggested that it improves some measures of strength and power during weight training (2, 3).

One study from the Institute for Applied Training Science found that resistance-trained men who took four grams (0.14oz) of AAKG three times a day (i.e., 12g per day) for eight weeks during standardized training improved their 1RM (resistance maximum) bench press, sprint peak power, and time-to-peak power at significantly better rates in comparison to the placebo group (2).

The results indicate that AAKG supplementation could be a positive catalyst for 1RM strength, along with sprint power in response to training. However, it appears to have no significant effects on body composition.

Another study found that AAKG supplementation seems to b safe to use. It is well-tolerated and influences 1RM bench presses and Wingate peak power performance positively. However, the study found that AAKG did not improve body composition or aerobic capacity (3).

Counter Argument

While there are studies that demonstrate the positive effects of AAKG, the one study also indicates that AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by standard barbell bench press and leg press, regardless of the subjects’ training status (3).

L-Arginine

L-Arginine is an amino acid, and amino acids are the building blocks of proteins. They’re divided into essential and non-essential categories. Non-essential amino acids are made in the body, but essential amino acids are not. Therefore, our dietary intake must provide essential amino acids.

L-arginine is considered semi-essential or conditionally essential, meaning that it becomes essential under certain conditions or circumstances. These conditions or circumstances include pregnancy, infancy, critical illness, and trauma.

Therefore, it is necessary to produce nitric oxide, a signaling molecule needed for a variety of the body’s processes and functions, such as blood flow regulation, mitochondrial function, and cellular communication.

Alpha-ketoglutarate

Alpha-ketoglutarate plays an important role in cellular energy production, and more energy means more productivity and less fatigue during workouts. Alpha-ketoglutarate also helps to preserve glutamate levels during exercise. Glutamate is another protein-building amino acid. Therefore, with more energy and more glutamate, the body can build more muscle.

Benefits Of L-Arginine

As part of figuring out the benefits of AAKG, we can now inspect the benefits of its components. So, let’s take a look at the benefits of L-Arginine:

Increases VO2 Max

From an athletic perspective, Nitric oxide’s primary role is to regulate the delivery of oxygen to the muscles, and it does this by opening the blood vessels, which, in turn, improves blood flow. And not only will better blood flow lower blood pressure, but it will also decrease the demand on your heart and skeletal muscles.

In addition to this, better blood flow will also support your muscles’ ability to contract and transport metabolic byproducts, such as lactic acid. Therefore, nitric oxide is considered a key physiological performance indicator because it delivers oxygen-rich blood to every cell, tissue, and organ system in the body.

One study found that sports performance (VO2 max) significantly increased in the L-Arginine supplementation group compared to the subjects supplemented with placebos. The increase also remained significant after adjusting baseline values, physical activity, and usual dietary intake (4).

Daily supplementation of 2g of L-Arginine per day could increase sports performance in male athletes, enhancing protein synthesis and tissue repair. And as a precursor of nitric oxide, it will increase muscular power, endurance, and improved blood flow.

Therefore, it is plausible to believe that the L-Arginine increasing nitric oxide levels were the cause of increased VO2 max.

Evidence of this is found in another study that concluded that L-Arginine supplementation had similar effects to increased dietary intake of NO3(-), which is that it reduced the O2 cost of moderate-intensity exercise, blunted the VO2 slow component, and extended the time to exhaustion during sever-intensity exercise (5). This ultimately means that L-Arginine supplementation improves exercise performance and allows individuals to last longer.

Counter Argument

However, some studies find that L-Arginine has no benefits on exercise performance.

One study found that the information available does not support L-Arginine use on its own or with creatine or caffeine. It doesn’t enhance performance or recovery from exhaustion (6).

Another study found that the plasma nitrate concentrations indicate greater nitric oxide availability following acute L-Arginine supplementation with nitrate, as well as with nitrate alone, in comparison to a placebo. However, there was no additional effect when L-Arginine was added to nitrate (7).

Therefore, there were no effects of supplementation on exercise performance and endurance.

Then, a different study found that running times did not differ in two tests in either ARG or PLA. Four weeks of L-Arginine supplementation didn’t cause any beneficial changes to metabolic or hormonal parameters beyond those achieved with exercise without supplementation (8).

Finally, a study on L-Arginine or placebo supplementation during strength training exercises found that plasma nitrate levels did not change significantly. The results did not support L-Arginine supplementation as an ergogenic aid for strength performance (9).

Improved Blood Flow

A study was conducted to determine whether supplementation with L-Arginine improves endothelial function in micro vessels. This occurs when nitric oxide production is increased. After L-Arginine ingestion, endothelium-dependent vasodilation in the young, trained subjects increased (10).

However, it remained the same with other groups, and there were no differences in the endothelium-independent vasodilation. With aging subjects, endothelium-independent vasodilation decreased, and endothelium-dependent vasodilation remained largely unchanged.

This demonstrates that a single dose of L-Arginine has an influence on endothelium-dependent vasodilation. This occurs mostly in observations of young, trained subjects.

A different study found that L-Arginine supplementation could be used as an essential tool in treating complications in diabetic subjects – or at least in patients with non-complicated diabetes (11).

However, the data did not produce enough evidence to conclude the mechanisms by which L-Arginine therapy induces improvements in cardiovascular function.

Alpha-Ketoglutarate Benefits

Along with L-Arginine’s benefits, AAKG benefits from its second component, Alpha-ketoglutarate.

Stimulates Protein Synthesis and Inhibits Protein Degradation In Muscles

Alpha-ketoglutarate is a nitrogen scavenger and a source of glutamate and glutamine, stimulating protein synthesis and inhibiting muscle protein degradation. Alpha-ketoglutarate is a precursor of glutamate and glutamine in central metabolic fuel for gastrointestinal tract cells as well (12).

Therefore, Alpha-ketoglutarate can decrease protein catabolism and increase protein synthesis, enhancing bone tissue formation in skeletal muscles and being used in clinical applications (12).

A different study found that Alpha-ketoglutarate helped prevent muscle breakdown in trauma patients. On a postoperative day, nitrogen balance was negative in the control group but not the Alpha-ketoglutarate group (13).

This suggests that if precursors for glutamine synthesis in skeletal muscle are available, it could be crucial for the degree of muscle protein catabolism following surgical trauma.

More research suggests that Alpha-ketoglutarate can effectively inhibit skeletal muscle atrophy from excessive protein degradation. It also helps prevent muscle dysfunction, fatigue, and weakening athletic ability (14). Research also demonstrated that Alpha-ketoglutarate could attenuate corticosterone-induced protein degradation.

It also rescued muscle atrophy and dysfunction in a Duchenne muscular dystrophy model and inhibited the expression of protein hydroxylase 3 (PHD3).

The findings provide a molecular base for the potential use of exercise-generated metabolite Alpha-ketoglutarate in muscle atrophy treatment and identify PHD3 as a potential target for the development of therapies to alleviate muscle wasting (14).

Athletic Performance, Muscular Hypertrophy, and Fat Loss

Alpha-ketoglutarate has also been found to be a metabolic signature of resistance exercise performance, with studies showing that supplementation led to a substantial accumulation of the tricarboxylic acid cycle intermediate (15).

Human plasma Alpha-ketoglutarate is also negatively correlated with BMI. The pharmacological elevation of Alpha-ketoglutarate induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo (15).

This reveals an unappreciated mechanism for the beneficial effects of resistance exercise, using Alpha-ketoglutarate as a systemically derived molecule for the stimulation of muscle hypertrophy and fat loss (15).

A separate study demonstrated that Alpha-ketoglutarate promoted skeletal muscle hypertrophy via the Akt/mTOR signaling pathway. The G-protein receptor, GPR91, may also be partially attributed to Alpha-ketoglutarate skeletal muscle protein synthesis (16).

Is AAKG Safe?

With all of these benefits in mind, one important question remains. Is AAKG safe to use?

In a study on the effects of arginine alpha-ketoglutarate supplementation on quality of life, it was found that weight lifters in a double-blind trial that to four grams of AAKG three times a day reported no significant side effects such as changes in blood pressure or heart rate, and showed no abnormalities in standard blood tests for general health (17).

They also reported no undesirable changes in general health, mental health, or other quality-of-life measures.

Conclusion

So, there is plenty of research available to suggest that athletes, bodybuilders, and other individuals that engage in regular exercise will yield significant results in terms of improvements to exercise performance. The research shows that AAKG has yielded some measurable improvements in strength and power output.

The supplement is considered safe, but take note that there isn’t enough scientific research available to unequivocally prove these findings, so always consult with a medical professional before deciding to use the supplement. Although, it appears that it may be worth trying if you’re looking to enhance athletic performance.