Arginine alpha-ketoglutarate (AAKG) is a nutritional supplement used by athletes and bodybuilders to improve sports performance, reduce muscular fatigue, and enhance healing.
But, AAKG supplementation might also have additional benefits for a variety of diseases. Keep reading to discover more about how AAKG works, and 12 ways it’s claimed to help improve health.
What Is Arginine Alpha-Ketoglutarate (AAKG)?
Arginine alpha-ketoglutarate (AAKG) is a modified variant of the amino acid arginine.
Alpha-ketoglutarate is an intermediate chemical from the series of reactions that produce energy to the body. It’s the origin of the amino acids glutamate and glutamine. Glutamate is the main excitatory neurotransmitter in the brain and may improve bone formation. Glutamine is the main source of electricity for cell division.
To improve absorption in the stomach, alpha-ketoglutarate supplements include in the form of various salts. The most frequent combination is ornithine and alpha-ketoglutarate.
Alpha-ketoglutarate also regulates amino acid synthesis, energy generation, and the formation of free radicals. It functions as a messenger molecule in many chemical reactions within the body.
Glutamine enhances protein, muscle development, and immune function.
Arginine, also known as L-arginine, apart from being a part of proteins, stimulates the release of hormones such as insulin, glucagon, prolactin, and growth hormone.
Arginine also plays a critical role in maintaining normal blood pressure, heart function, and resistance. These functions are mediated via the production of nitric oxide. Arginine is broken down into ornithine and creatine. Ornithine is vital for cell growth and division, while nourishment is important for muscle contraction.
Arginine is obtained from food and synthesized in the body. It is thus referred to as a semi-essential amino acid. In healthy adults, food and synthesis in the body are adequate to satisfy the necessary demands for the amino acid. These demands include tissue repair, synthesis of proteins, and maintenance of immune function.
During periods of rapid growth, bodily anxiety, or injury, the supply of L-arginine may be insufficient to meet the body’s needs. In this time, L-arginine taken as a dietary supplement may help maintain muscle mass and enhance physiological function.
Supplementing L-arginine may improve the ability for exercise. This improvement may be viewed immediately after swallowing arginine. Furthermore, long-term improvements might be seen due to increased protein synthesis in muscles.
Along with its performance-enhancing effects, arginine appears to be a safe and effective therapy for hypertension, type 2 diabetes, and erectile dysfunction.
Arginine reduces disease rates in conditions where the body is prone to disease, for example, surgery or serious illness.
Arginine in combination with alpha-ketoglutarate (as arginine alpha-ketoglutarate [AAKG]) has been largely manufactured and marketed to athletes for its performance-enhancing potential.
However, in clinical settings, L-arginine alone is utilized more often.
Composition of AAKG
Arginine alpha-ketoglutarate is formed when two arginine molecules combine with one molecule of alpha-ketoglutarate.
The combination of both alpha-ketoglutarate and arginine enhances the stability of arginine. This is supposed to boost its performance-enhancing skills and their role in energy production.
Natural Resources of L-arginine and Alpha-ketoglutarate
L-arginine is one of those 20 amino acids. It’s regarded as a semi-essential amino acid as it can be gotten from both meals and built within our own bodies.
L-arginine is found in high concentrations in foods like watermelon, seeds, nuts, algae, meats, seafood, legumes, lentils, whole grains, rice protein concentrate, and soy protein isolate.
L-arginine is synthesized within the body from citrulline. Though this synthesis can occur in many cell types, most happen in the liver.
Alpha-ketoglutarate within an intermediate in the cycle to convert food to energy. In this cycle, it is formed from isocitrate. Additionally, it may be formed by glutamate.
Dietary supplements of L-arginine alpha-ketoglutarate (AAKG) are sold in the kind of tablets, pills, or powder.
Alpha-ketoglutarate and L-arginine may also be purchased individually as different supplements. All these are available as powder or capsules.
Mechanism of Action
It is unknown how the combination of arginine alpha-ketoglutarate enhances performance but it’s probably caused by elevated levels of nitric oxide.
Alpha-ketoglutarate is a product of these mitochondria and plays a very important part in the conversion of food into energy. It is also a supply of glutamine and glutamate. In muscles, glutamine and glutamate inhibit protein breakdown and increase protein synthesis.
Alpha-ketoglutarate enhances bone formation. It modulates the synthesis of collagen possibly by raising the amount of molecules available for synthesis. Collagen is a significant part of bone tissue.
Alpha-ketoglutarate stimulates the production of insulin-like growth factor-1 and growth hormone. All these are both hormones that modulate bone recycling and the creation of new bone tissue.
Alpha-ketoglutarate also has immune-enhancing properties and is potentially useful in delaying aging.
L-arginine is broken down into nitric oxide (NO) in a variety of tissues. Based on where it’s generated, nitric oxide plays a critical part in controlling diverse roles from your system.
- From the brain, it’s a messenger molecule between nerves
- In the immune system, it mediates the action of white blood cells
- From the cardiovascular system, it has protective effects by relaxing blood vessels. This increases circulation and oxygen consumption round the entire body and assists in the removal of waste.
L-arginine also stimulates the secretion of growth hormone. This results in the production of insulin-like growth factor 1 (IGF-1). IGF-1 enhances protein synthesis and so raises muscle development.
L-arginine can also be involved in the removal of toxins by forming urea, which is filtered from the body through urine.
In the liver, L-arginine is switched to glucose and alpha-ketoglutarate. For that reason, it acts as a potential supply of energy.
AAKG is claimed to combine the prospective advantages of both molecules, L-arginine, and alpha-ketoglutarate.
Insufficient Evidence for the Benefits of Arginine Alpha-ketoglutarate
There is limited research regarding the combination of arginine and alpha-ketoglutarate Most of the reported benefits of this combination are anecdotal.
The effects of supplementing with arginine alpha-ketoglutarate for seven days have been analyzed in 24 physically active guys following performing resistance training. Arginine alpha-ketoglutarate combined had no consequences on heart speed, blood pressure, blood circulation, or nitric oxide levels. On the other hand, the amount of L-arginine in the blood was raised.
Supplementing arginine alpha-ketoglutarate (300 mg) in 16 healthy men did not provide any performance-enhancing advantage, irrespective of their exercise status.
At a clinical trial on 12 trained guys, AAKG did not improve muscle endurance or substantially affect the blood pressure response to anaerobic work.
In a second trial on 35 resistance-trained men, arginine was safe and well-tolerated and favorably affected muscular strength and peak strength efficiency. AAKG didn’t affect body composition or aerobic capability.
Although there’s limited evidence that the combination of arginine alpha-ketoglutarate has health advantages, the individual molecules L-arginine and alpha-ketoglutarate are researched for their health benefits.
Health Benefits of Alpha-ketoglutarate
Supplementing alpha-ketoglutarate may be useful in improving severe trauma, ailments, surgery, and wound healing, even though the evidence is very limited.
Insufficient Evidence for:
1) Wound Healing
Supplementation of ornithine alpha-ketoglutarate in 54 burn patients significantly enhanced wound healing.
Similarly, a study of 60 burn patients who were granted ornithine alpha-ketoglutarate for 21 days showed significant improvements in wound healing.
In rats suffering from burns, ornithine alpha-ketoglutarate supplementation increased glutamine levels, leading to improved wound healing.
Even though the results are promising, the evidence to back the usage of alpha-ketoglutarate in wound healing comes from 2 clinical trials and a few animal research. Further clinical research is required to confirm these preliminary results.
2) Muscle Loss
In 21 people who underwent surgical injury, supplementing alpha-ketoglutarate at a controlled trial prevented muscle breakdown and increased protein synthesis.
Preventive operation reduces muscle protein synthesis and increases exhaustion. In 22 adults who had stomach operation, supplementing alpha-ketoglutarate improved glutamine supply in the muscles and prevented muscle reduction.
Two little clinical trials cannot be considered sufficient evidence to assert that alpha-ketoglutarate prevents muscle development. Larger, more robust clinical results are required.
3) Bone Health
Alpha-ketoglutarate increases collagen production and iron absorption, which might improve bone density and strength.
In 76 menopausal women with bone weakness, the ingestion of alpha-ketoglutarate for 24 weeks prevented bone loss and decreased the symptoms of menopause. Additionally, it rebuilt the bone tissue.
A variety of animal studies have suggested that supplementing alpha-ketoglutarate improved bone density.
Again, just a single clinical trial and a couple of animal studies support the use of the amino acid to promote bone health. Their preliminary findings should be replicated in more clinical trials on larger populations.
4) Immune Function
Alpha-ketoglutarate may enhance immune function. In the body, it is converted to glutamine. Glutamine can increase the levels of white blood cells (macrophages and neutrophils).
Supplementing ornithine alpha-ketoglutarate in old, nutrient-deficient patients successfully enhanced overall wellbeing. This was seen by increasing appetite and enhancing motor skills. Additionally, it shortened the recovery period from severe illnesses and surgery.
In mice, alpha-ketoglutarate added to drinking water improved immunity in the gut and lowered body weight.
Yet more, the amount of research supporting the use of alpha-ketoglutarate to stimulate immune function is insufficient. Additional clinical studies are necessary.
Animal and Cell Research (Lack of Proof)
No clinical evidence supports using alpha-ketoglutarate for some of the conditions listed in this section. Below is a list of the existing animal and cell-based research, which should guide additional investigational efforts. On the other hand, the research recorded should not be interpreted as encouraging of any health benefit.
Supplementation with alpha-ketoglutarate delayed aging from the worm Caenorhabditis elegans.
In rats, oral supplementation of alpha-ketoglutarate blocked the effects of cyanide, a toxic poison that can be deadly.
Below, we’ll discuss some preliminary research on alpha-ketoglutarate’s potential anticancer effects. It is still in the animal and mobile stage and further clinical studies have yet to determine if this amino acid may be useful in cancer therapies.
Don’t under any conditions attempt to replace traditional cancer treatments with alpha-ketoglutarate or any other nutritional supplements. If you want to use it as a supportive step, speak with your physician to prevent any unexpected interactions.
In multiple animal research, supplementing alpha-ketoglutarate reduced blood supply to tumors, leading to tumor death.
During cell-based studies, alpha-ketoglutarate prevented the multiplication of cancerous cells.
Health Benefits of L-arginine
L-arginine was investigated regarding its possible health benefits for a number of conditions such as diabetes, high blood pressure, and erectile dysfunction.
Possibly Successful for:
1) Muscle Health
The daily intake of L-arginine for 45 days decreased muscle fatigue and increased athletic performance in 56 male soccer players.
In 8 healthy folks, L-arginine supplementation before exercise enhanced strength and exercise capacity by reducing blood levels of lactate and ammonia. These two are breakdown products associated with muscle fatigue.
Long-term (3-week) L-arginine supplementation in 16 healthy males reduced blood lactate levels and oxygen intake during exercise.
L-arginine supplementation for 2 weeks in 11 postmenopausal women also improved muscle force and power.
Even though a bit limited, the existing evidence indicates that L-arginine may encourage muscle health. You might discuss with your physician how supplementing this amino acid might help in your situation.
2) Blood Vessel Health
A meta-analysis of 7 research concluded that L-arginine can decrease blood pressure in adults with high blood pressure.
Arginine supplementation reduced the platelet reactivity at a clinical trial on 14 adults with higher cholesterol levels. Subsequently, this reduced blood clotting.
In rabbits, supplementing with arginine benefited atherosclerotic conditions by widening blood vessels, thinning vessel walls, and preventing the accumulation of fat.
Arginine supplementation for 45 days decreased blood glucose and fat levels within a clinical trial on 28 healthy men.
However, a meta-analysis of 927 people showed no effect of arginine supplementation (9 g/day for 30 days to 3 months) in patients with acute heart attacks.
Additionally, arginine didn’t enhance nitric oxide availability in people with heart disease.
Insufficient Evidence for:
The subsequent purported benefits are just backed by restricted, low carb clinical trials and animal research. There’s inadequate evidence to support the use of L-arginine for any of these below-listed uses. Remember to speak with a doctor prior to taking L-arginine nutritional supplements. This amino acid should not be used as a substitute for accepted medical treatments.
1) Infertility and Sexual Dysfunction
L-arginine given for 6 months to 29 men improved erectile dysfunction in 31% of them.
Supplementation with oral L-arginine at 34 women unresponsive to in vitro fertilization (IVF) increased pregnancy rates. This impact occurred by enhancing ovarian response and the surroundings of the uterus.
In goat semen cells, L-arginine increased semen vitality through enhanced production of nitric oxide. This effect may be good for raising fertility.
Diabetes is associated with low levels of both arginine and blood vessel malfunction. Several animal studies suggest that supplementation with L-arginine may be an efficient means to improve blood vessel function in diabetes.
Acute injection of L-arginine increases the degree of insulin in the blood. This reduces the amount of glucose released from the liver.
Long-term (21- to 31-day) oral intake of L-arginine enhanced insulin sensitivity, blood vessel function, and reduced blood sugar levels in 26 patients with type 2 diabetes.
3) Immune Function in Cancer
At a clinical trial of patients with advanced breast cancer, L-arginine ingestion 3 times (before chemotherapy) reduced the suppression of the immune system caused by chemotherapy.
Oral consumption of L-arginine increased the levels and activity of immune cells involved in combating tumor development (C56+, natural killer cells, lymphocyte-activated killer cells) in a study on 13 healthy individuals.
In individual cells and mice, L-arginine supplementation increased the survival and anti-tumor activity of immune cells.
4) Exercise Capacity in People with Heart Disease
L-arginine supplementation improved the capability for exercise in 16 older people with heart disease.
In 22 people with constant chest pain (angina pectoris) and recovering from a heart attack, oral L-arginine required for 3 days improved exercise workload by increasing oxygen availability during physical activity.
5) Wound Injuries
In 36 healthy people, arginine supplementation for two weeks enhanced wound healing and enhanced immune reactions.
In guinea pigs, L-arginine intake improved immunity and survival from burn injuries.
In mice, L-arginine decreased injury to the airway passing brought on by allergic inflammation.
6) Fat Burning
Long-term use of L-arginine, as well as diet and exercise, enhanced glucose and insulin levels. Additionally, it decreased belly fat in 33 obese adults with type 2 diabetes.
In beans, dietary supplementation using L-arginine reduced fat deposits and encouraged muscle increase through the entire body.
7) Digestive Pain
Oral L-arginine supplementation considerably decreased the frequency and intensity of chest pain attacks and the use of painkillers in 8 patients with movement disorders of the intestine.
In rats, L-arginine accelerated ulcer healing by increasing circulation and forming new blood vessels.
8) Cognitive Function in Dementia
L-arginine (1.6 g/day) intake increased intellectual function in 16 elderly patients with dementia.
Aging has been associated with decreased nitric oxide levels in observational research on over 200 people. Arginine supplementation may help to maintain normal nitric oxide amounts to counterbalance the aging process.
Side Effects, Precautions & Dosage
Supplementing arginine alpha-ketoglutarate (AAKG) for 8 weeks had no substantial adverse effects in 45 healthy men.
There were 3 reported hospitalizations associated with arginine alpha-ketoglutarate supplementations. Patients presented with dizziness, vomiting, palpitations, and syncope.
No substantial side effects brought on by alpha-ketoglutarate have been reported in humans.
However, there’s potential for toxicity with recurrent ingestion based on studies in rats. Side effects observed were diarrhea and a decrease in body fat. Anemia was also seen in female athletes, but that was solved after stopping supplementation.
Arginine has not yet been associated with serious adverse effects.
Doses up to 30 g daily is often well tolerated.
The most frequent adverse effects are nausea and diarrhea reported occasionally at dosages between 15 to 30 g.
No effect on liver function, blood glucose, or concentration of blood electrolytes has been reported.
A meta-analysis of all 11 studies including 387 healthy participants suggested that it can significantly lower blood pressure.
At higher dosages, arginine has been reported to provide a sour taste in the mouth.
Arginine alpha-ketoglutarate supplements shouldn’t be used by men and women with a history of a heart attack.
Not enough is known about the usage of AAKG or alpha-ketoglutarate during pregnancy and breastfeeding. Consequently, their use in these conditions isn’t recommended.
Arginine supplementation should be used with care in babies, pregnant or lactating women, and in people who have viral infections or serious kidney or liver malfunction, asthma, or cancer.
Patients who have herpes diseases should take L-arginine with care, as it may aggravate the virus and increase symptoms. However, this caution hasn’t been validated in clinical trials.
Patients who have electrolyte imbalances are at a higher risk of developing metabolic acidosis, a condition in which the quantity of acid in the blood increases to dangerous levels. This occurs with injectable forms of arginine (due to the high chloride content found in these training).
Similarly, in patients with kidney and/or liver injury, low potassium and higher blood urea nitrogen amounts might happen with L-arginine nutritional supplements.
Limitations and Caveats
Research-based evidence to support using arginine alpha-ketoglutarate to increase strength and enhance exercise performance is limited and not conclusive. More studies are needed to show the beneficial effects of arginine alpha-ketoglutarate supplementation in various health states.
Even though L-arginine and alpha-ketoglutarate have shown health benefits when analyzed individually, there’s absolutely no research indicating that carrying them together will enhance these benefits.
To help avoid interactions, your physician should manage all your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you are taking. Talk to your healthcare provider to find out how metformin may interact with something else you’re taking.
Drug interactions with arginine alpha-ketoglutarate aren’t known.
No drug or food interactions have been reported with alpha-ketoglutarate.
L-arginine might interact with insulin and cholesterol-lowering agents.
L-arginine is broken down into nitric oxide in the body, and consequently, patients carrying nitric oxide donors must supplement with caution. These include isosorbide mononitrate, sodium nitroprusside, and glyceryl trinitrate.
Since none of these amino acids is accepted by the FDA for any ailments, there are no official doses. Users and nutritional supplement manufacturers have established unofficial doses based on trial and error. Speak with your physician before supplementing with AAKG.
The recommended dosage of arginine alpha-ketoglutarate ranges from 1.2 to 3.5 grams per tablet, taken 2 or 3 times per day on an empty stomach.
The pills should be taken preferably in the morning and at least 30 minutes before workouts.
Up to 20 g of L-arginine per day is deemed safe and non-toxic.
Users recommended dose of the powdered form ranges from 1.5 to 3.5 grams per day.
The opinions expressed in this section are solely those of AAKG consumers, that might or might not have scientific or medical training. Their testimonials do not reflect the opinions of us. We do not endorse any specific solution, service, or therapy.
Do not believe in user adventures as medical advice. Never delay or disregard seeking professional medical advice from your health care provider or other qualified health care providers because of something you’ve read on this article. We know that studying person, real-life encounters can be a very helpful resource, but it is not a replacement for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
People doing weight training reported relief from muscle strain when taking arginine alpha-ketoglutarate. Many found the supplement made them feel mentally and emotionally active. People also found that it increased their muscle strength and energy output.
L-arginine supplements appeared great for people with sensitive stomachs and they experienced no side-effects. Individuals recommended it for a fantastic pump at affordable prices.
As a result of its mild taste, people advocate consuming AAKG with a juice or smoothie.