However, AAKG supplementation may also have added benefits for various diseases. Read on to find out more about how AAKG works, and 12 ways it can help improve your health.
What is Arginine Alpha-Ketoglutarate (AAKG)?
Alpha-ketoglutarate is an intermediate compound in the series of reactions that produce energy for the body. It is the source of the amino acids glutamate and glutamine. Glutamate is the main excitatory neurotransmitter in the brain and can increase bone formation. Glutamine is the main source of energy for cell division [2, 3].
Alpha-ketoglutarate also regulates amino acid synthesis, energy production, and formation of free radicals. It functions as a messenger molecule in many chemical reactions in the body .
Glutamine enhances protein, muscle development, and immune function .
Arginine also plays a critical role in maintaining normal blood pressure, heart function, and immunity. These functions are mediated through the production of nitric oxide. Arginine is broken down into ornithine and creatine. Ornithine is essential for cell growth and division, while creatine is important for muscle contraction .
Arginine is obtained from food and synthesized in the body. It is therefore referred to as a semi-essential amino acid. In healthy adults, food and synthesis in the body are sufficient to meet the necessary demands for this amino acid. These demands include tissue repair, synthesis of proteins, and maintenance of immune function .
During periods of rapid growth, physical stress, or injury, the supply of L-arginine may be insufficient to meet the body’s needs. During this time, L-arginine taken as a dietary supplement can help maintain muscle mass and improve bodily function .
Supplementing L-arginine can improve the capacity for exercise. This improvement can be seen immediately after consuming arginine. Additionally, long-term improvements are seen due to increased protein synthesis in muscles .
Arginine reduces infection rates in conditions where the body is prone to infection, such as surgery or critical illness .
Composition of AAKG
Arginine alpha-ketoglutarate is formed when two arginine molecules combine with one molecule of alpha-ketoglutarate.
The combination of alpha-ketoglutarate and arginine improves the stability of arginine. This is supposed to improve its performance-enhancing abilities and its role in energy production.
Natural Sources of L-arginine and Alpha-ketoglutarate
L-arginine is one of 20 amino acids. It is considered a semi-essential amino acid because it can be obtained from both foods and built within our bodies.
L-arginine is found in high concentration in foods like watermelon, nuts, seeds, algae, meats, seafood, beans, lentils, whole grains, rice protein concentrate, and soy protein isolate .
Alpha-ketoglutarate in an intermediate in the cycle to convert food to energy. In this cycle, it is formed from isocitrate. It can also be formed from glutamate .
Dietary supplements of L-arginine alpha-ketoglutarate (AAKG) are sold in the form of tablets, pills, or powder.
Alpha-ketoglutarate and L-arginine can also be purchased separately as individual supplements. These are available as capsules or powder.
Mechanism of Action
It is unknown how the combination of arginine alpha-ketoglutarate enhances performance but is most likely caused by elevated levels of nitric oxide .
Alpha-ketoglutarate is a product of the mitochondria and plays a vital role in the conversion of food into energy. It is also a source of glutamine and glutamate. In muscles, glutamine and glutamate inhibit protein breakdown and increase protein synthesis .
Alpha-ketoglutarate enhances bone formation. It regulates the synthesis of collagen possibly by increasing the number of molecules available for synthesis. Collagen is a significant component of bone tissue.
Alpha-ketoglutarate also has immune-enhancing properties and is potentially useful in delaying aging .
- In the brain, it is a messenger molecule between nerves
- In the immune system, it mediates the activity of white blood cells
- In the cardiovascular system, it has protective effects by relaxing blood vessels. This increases blood supply and oxygen delivery around the body, and aids 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 thus increases muscle development .
AAKG combines the potential benefits of both molecules, L-arginine, and alpha-ketoglutarate.
Health 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 7 days were studied in 24 physically active men after performing resistance (DB-RCT). Arginine alpha-ketoglutarate combined had no effects on heart rate, blood pressure, blood flow, or nitric oxide levels. However, the amount of L-arginine in the blood was increased .
Supplementing arginine alpha-ketoglutarate (300 mg) in 16 healthy men did not provide any performance-enhancing benefit, regardless of their exercise training status (DB-RCT) .
In a randomized controlled trial in 12 trained men, AAKG did not improve muscle endurance or significantly affect the blood pressure response to anaerobic work .
In a randomized controlled trial in 35 resistance trained men, arginine was safe and well tolerated and positively influenced muscular strength and peak power performance. AAKG did not influence body composition or aerobic capacity .
Although there is limited evidence that the combination of arginine alpha-ketoglutarate has health benefits, the individual molecules L-arginine and alpha-ketoglutarate have been researched for their health benefits.
Supplementing alpha-ketoglutarate may be useful in treating severe trauma, infections, surgery, and wound healing .
1) Alpha-ketoglutarate Improves Wound Healing
Supplementation of ornithine alpha-ketoglutarate in 54 burn patients significantly improved wound healing (DB-RCT) .
Similarly, a study of 60 burn patients who were given ornithine alpha-ketoglutarate for 21 days showed significant improvements in wound healing (DB-RCT) .
2) Alpha-ketoglutarate Prevents Muscle Loss
In 21 people who underwent surgical trauma, supplementing alpha-ketoglutarate in a controlled trial prevented muscle breakdown and increased protein synthesis .
Abdominal surgery reduces muscle protein synthesis and increases fatigue. In 22 adults who had stomach surgery (RCT), supplementing alpha-ketoglutarate improved glutamine supply in the muscles and prevented muscle loss .
3) Alpha-ketoglutarate Improves Bone Health
In 76 menopausal women (DB-RCT) with bone weakness, intake of alpha-ketoglutarate for 24 weeks prevented bone loss and reduced the symptoms of menopause. It also reconstructed the bone tissue .
4) Alpha-ketoglutarate and Immune Function
Alpha-ketoglutarate may improve immune function. In the body, it is converted into glutamine. Glutamine can increase levels of white blood cells (macrophages and neutrophils) .
Supplementing ornithine alpha-ketoglutarate in old patients that are nutrient deficient successfully improved overall health. This was seen by increasing appetite and improving motor skills. It also shortened recovery time from severe illnesses and surgery .
In mice, alpha-ketoglutarate added to drinking water improved immunity in the stomach and lowered body weight .
5) Alpha-ketoglutarate May Benefit Cancer
In multiple animal studies, supplementing alpha-ketoglutarate reduced blood supply to tumors, resulting in tumor death .
6) Alpha-ketoglutarate and Aging
Supplementation with alpha-ketoglutarate delayed aging in the worm Caenorhabditis elegans .
7) Alpha-ketoglutarate Cures Cyanide Poisoning
In rats, oral supplementation of alpha-ketoglutarate blocked the effects of cyanide, a toxic poison that can be fatal .
1) Arginine Improves Muscle Health
A daily intake of L-arginine for 45 days reduced muscle fatigue and increased athletic performance in 56 male soccer players (DB-RCT) .
In 8 healthy subjects, L-arginine supplementation before exercise improved strength and exercise capacity by reducing blood levels of lactate and ammonia. Both are breakdown products associated with muscle fatigue (DB-RCT) .
Long-term (3-week) L-arginine supplementation in 16 healthy males reduced blood lactate levels and oxygen consumption during exercise (DB-RCT) .
L-arginine supplementation for 6 months in 11 postmenopausal women also improved muscle force and power (DB-RCT) .
2) Arginine Is Beneficial for Diabetes
Diabetes is associated with low levels of arginine and blood vessel dysfunction. Several animal studies indicate that supplementation with L-arginine may be an effective way to improve blood vessel function in diabetes [R].
Acute injection of L-arginine increases the levels 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 in 26 patients improved insulin sensitivity, blood vessel function, and reduced blood glucose levels in patients with type 2 diabetes (DB-RCT) [11, 10].
3) Arginine Improves Immune Function in Cancer
Oral intake of L-arginine in 13 healthy individuals increased the levels and activity of immune cells involved in combating tumor growth (C56+, natural killer cells, lymphocyte-activated killer cells) .
In human cells and mice, L-arginine supplementation increased survival and anti-tumor activity of immune cells .
4) Arginine Increases Exercise Capacity in Patients with Heart Disease
L-arginine supplementation improved the capacity for exercise in 16 elderly individuals with heart disease (DB-RCT) .
In 22 individuals with stable angina pectoris and healed heart attack, oral L-arginine taken for 3 days improved exercise workload by increasing oxygen availability during physical activity (DB-RCT) .
5) Arginine Accelerates Recovery from Wound Injuries
In 36 healthy humans, arginine supplementation for 2 weeks enhanced wound healing and improved immune responses (DB-RCT) .
In guinea pigs, L-arginine ingestion improved immunity and survival from burn injuries .
In mice models, L-arginine reduced injury to the airway passage caused due to allergic inflammation .
7) Arginine May Improve Blood Vessel Health
A meta-analysis showed that L-arginine can reduce blood pressure in adults with high blood pressure .
Arginine supplementation reduced the increased reactivity of blood cells involved in clotting (platelets) in adults with high cholesterol levels. It also reduced blood clotting (DB-RCT) .
Arginine supplementation in 28 healthy men for 45 days reduced blood sugar and fat levels (DB-RCT) .
However, a meta-analysis of 927 showed no effect of arginine supplementation (9 g/day for 30 days to 3 months) in patients with acute heart attacks .
Also, arginine did not improve nitric oxide availability in patients with heart disease .
8) Arginine Reduces Fat
Long-term use of L-arginine in addition to diet and exercise improved glucose and insulin levels. It also decreased belly fat in overweight adults with type 2 diabetes .
In pigs, dietary supplementation with L-arginine reduced fat deposits and promoted muscle gain throughout the body .
9) Arginine Reduces Pain in Disorders of the Digestive Tract
10) Arginine Helps Infertility and Sexual Dysfunction
L-arginine given for 6 weeks to 29 men improved erectile dysfunction in 31% of them (DB-RCT) .
Supplementation with oral L-arginine in 34 women unresponsive to in vitro fertilization (IVF) increased pregnancy rates. This effect occurred by improving ovarian response and the environment of the uterus .
In goat sperm cells, L-arginine increased sperm vitality through increased production of nitric oxide. This effect may be beneficial for increasing fertility .
11) Arginine Improves Cognitive Function in Dementia
12) Arginine Fights Aging
Aging is associated with reduced nitric oxide levels. Arginine supplementation may help to maintain normal nitric oxide levels to counterbalance the aging process .
Side Effects of Arginine Alpha-ketoglutarate
Supplementing arginine alpha-ketoglutarate (AAKG) for 8 weeks had no significant adverse effects in 45 healthy men (DB-RCT) .
There have been 3 reported hospitalizations associated with arginine alpha-ketoglutarate supplementations. Patients presented with dizziness, vomiting, palpitations, and syncope .
Side Effects of Alpha-ketoglutarate
No significant side effects caused by alpha-ketoglutarate have been reported in humans .
However, there is potential for toxicity with repeated intake based on studies in rats. Adverse effects observed were diarrhea and a decrease in body weight. Anemia was also seen in female rats, but this was resolved after stopping supplementation .
Side Effects of Arginine
Arginine has not been associated with serious adverse effects .
Doses up to 30 grams per day are usually well tolerated.
No effect on liver function, blood glucose, or concentration of blood electrolytes has been reported .
A meta-analysis of 11 studies (DB-RCT) including 387 healthy participants indicates that it can significantly lower blood pressure .
At higher doses, arginine has been reported to give a bitter taste in the mouth.
Arginine alpha-ketoglutarate supplement should not be used by individuals who have had a heart attack .
Not enough is known about the use of AAKG or alpha-ketoglutarate during pregnancy and breastfeeding. Therefore, use in these conditions is not recommended.
Arginine supplementation should be used with caution in infants, pregnant or lactating women, and in individuals with viral infections or serious kidney or liver malfunction, asthma, or cancer [18, 13].
Patients with herpes infections should take L-arginine with caution, as it may aggravate the virus and increase symptoms. However, this caution has not been validated in clinical trials .
Patients with electrolyte imbalances are at a higher risk of developing metabolic acidosis, a condition in which the amount 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 preparations) .
Limitations and Caveats
Research-based evidence to support the use of arginine alpha-ketoglutarate to increase strength and improve exercise performance is limited and not conclusive. More studies are needed to demonstrate the beneficial effects of arginine alpha-ketoglutarate supplementation in various disease conditions [1, 24].
Although L-arginine and alpha-ketoglutarate have demonstrated health benefits when studied individually, there is no research indicating that taking them together will enhance these benefits.
Drug interactions with arginine alpha-ketoglutarate are not known.
No drug or food interactions have been reported with alpha-ketoglutarate.
L-arginine may interact with insulin and cholesterol-lowering agents.
L-arginine is broken down into nitric oxide in the body, and thus patients taking nitric oxide donors should supplement with caution. These include isosorbide mononitrate, sodium nitroprusside, and glyceryl trinitrate.
The suggested dosage of arginine alpha-ketoglutarate ranges from 1.2 to 3.5 grams per tablet, taken 2 or 3 times a day on an empty stomach.
The tablets should be taken preferably in the morning and at least 30 minutes before workouts.
Up to 20 grams of L-arginine per day is considered safe and non-toxic .
The user recommended dose of the powdered form ranges from 1.5 to 3.5 grams per day.
People doing weight training reported relief from muscle pain when taking arginine alpha-ketoglutarate. Many found that intake made them feel mentally and physically active. People also found that it increased their muscle strength and energy output.
L-arginine supplements seemed great for people with sensitive stomachs and they experienced no side-effects. People recommended it for a great pump at affordable pricing.
Due to the mild taste associated with it, people recommend it be consumed with a juice or smoothie.