AAKG supplement dosage, safety, risks, side effects and benefits
How to best use these natural pills
August 27 2017 by Ray Sahelian, M.D.

AAKG contains arginine, a conditionally essential amino acid that has a number of vital roles in human biochemistry. Arginine plays an important role in the urea cycle, helping to rid the body of excess ammonia. This amino acid is also important in protein synthesis as well as for the support of healthy immune function. AAKG has arginine with alpha-ketoglutarate, another key player in amino acid metabolism, as well as in energy production.

What are the benefits of supplementation?

Physical and athletic performance influence
Creatine, arginine alpha-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance.
Int J Sport Nutrition Exercise Metab. 2008.
This study compared a commercial dietary supplement of creatine, AAKG, glutamine, taurine, branched-chain amino acids, and medium-chain triglycerides with creatine alone or placebo on exercise performance and body composition. Thirty-five young men were randomized to Creatine + AAKG, Creatine, or placebo for 10 days. Body composition, muscle endurance (bench press), and peak and average power were measured before and after supplementation. Creatine alone and in combination with AAKG improves upper body muscle endurance, and creatine + AAKG supplementation improves peak power output.

Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate AAKG in trained adult men.
Nutrition. 2006. Exercise and Sport Nutrition Laboratory at the Center for Exercise, Nutrition, and Preventative Health Research, Department of Health, Human Performance, Baylor University, Waco, Texas, USA.
Healthy middle aged men fasted for 8 hours and then ingested 4 grams of time-released or non-timed-released l-arginine alpha-ketoglutarate. After 1 wk the alternative supplement was ingested. In study 2, resistance-trained adult men were randomly assigned to ingest 4 g of AAKG (three times a day) or placebo. Participants performed 4 d of periodized resistance training per week for 8 wk. The following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. In study 1, significant differences were observed in plasma arginine levels in subjects taking non-timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group for 1RM bench press, Wingate peak power, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity. Supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. It did not influence body composition or aerobic capacity.

Int J Sport Nutr Exerc Metabolism. 2011. Effects of 7 days of arginine-alpha-ketoglutarate supplementation on blood flow, plasma L-arginine, nitric oxide metabolites, and asymmetric dimethyl arginine after resistance exercise. Arginine-alpha-ketoglutarate (AAKG) supplements are alleged to increase nitric oxide production, thereby resulting in vasodilation during resistance exercise. This study sought to determine the effects of AAKG supplementation on hemodynamics and brachial-artery blood flow and the circulating levels of L-arginine, nitric oxide metabolites (NOx; nitrate/nitrite), asymmetric dimethyl arginine (ADMA), and L-arginine:ADMA ratio after resistance exercise. Twenty-four physically active men underwent 7 days of AAKG supplementation with 12 g/day of either NO(2) Platinum or placebo. Before and after supplementation, a resistance-exercise session involving the elbow flexors was performed involving 3 sets of 15 repetitions with 70% of 1-repetition maximum. Data were collected immediately before, immediately after (PST), and 30 min after (30PST) each exercise session. Data were analyzed with factorial ANOVA. Heart rate, blood pressure, and blood flow were increased in both groups at PST but not different between groups. Plasma L-arginine was increased in the NO(2) group. NOx was shown to increase in both groups at PST) and at 30PST but was not different between groups. ADMA was not affected between tests or time points; however, the L-arginine:ADMA ratio was increased in the NO(2) group. NO(2) Platinum increased plasma L-arginine levels; however, the effects observed in hemodynamics, brachial-artery blood flow, and NOx can only be attributed to the resistance exercise.

I have read information from different websites. One site says, "Dramatically Increases Nitric Oxide Production For Increased Muscle Pump! AAKG is arginine alpha-ketoglutarate in a sustained release formula which is pH buffered to ensure maximum absorption. Arginine released into the bloodstream will dramatically increase nitric oxide production. An increase in nitric oxide may lead to the following benefits: extended and enhanced "muscle pump" after training, improved endurance and recovery time, improved workout capacity, and increased sexual vigor." Is this statement true?
    A review of Medline revealed two human studies with AAKG supplements and the results appear promising, I await results of a couple of more studies to have a better idea of the benefits and side effects.

Q. I read a study which says, "In fact, participants that took AAKG prior to exercise had compromised endurance and strength. Because AAKG supplementation may hinder muscular endurance, the use of these supplements before resistance training should be questioned."
   A. I am not sure which study you are referring to, but, as of 2016, I am still awaiting more data on this supplement before recommending it wholeheartedly.

ALS, amyotrophic lateral sclerosis
PLoS One. 2014. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model. ALS mice were fed standard rodent diet, KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.

Asthma testimonial
Email - I had chronic bronchial asthma caused by histamine, because I'm allergic to the same substance. Bodybuilding train, and takes some supplements, but noticed a significant improvement when I take arginine alpha-ketoglutarate.

High blood pressure
Q. I am taking L-Arginine AAKG powder, 6 grams/day, plus 1600 mg of L-Citrulline/day. I read that one should not consume Arginine AAKG for continuous, high level use for more than 60 days. Would I be in danger if I took AAKG on a continuous basis? If so, what would be my symptoms? And if so, what would be my alternative, since I take it to lower my blood pressure, only. Would free-form L-arginine be better for long term use ?
   A. Long term studies are not available to determine the full safety or side effect profile of these supplements.

Immune system effect
Does an increase in NO in the body product damaging free radicals if one takes AAKG. I have taken this supplement before and if too much is taken by me I get a cold sore.
   A. It's difficult to say since I have not seen research regarding its influence on the immune system.

Safety, risks, side effects, danger
AAKG side effects have been reported as case studies in medical journals.

Adverse effects associated with arginine alpha-ketoglutarate containing supplements.
Hum Exp Toxicol. 2009; Department of Emergency Medicine, New York City Poison Center, New York University School of Medicine, New York, New York. "A 33-year-old man presented with palpitations, dizziness, vomiting, and syncope, after the use of NO(2) platinum. A 21-year-old man with palpitations and near syncope had used a "nitric oxide" supplement. He was tachycardic to 115 bpm with otherwise normal examination. Laboratory values including methemoglobin, and ECG were unremarkable. A 24-year-old man presented after taking NO-Xplode with palpitations and a headache. His examination, laboratory values, and ECG were normal. He was discharged. The purported active ingredient in these products is arginine alpha-ketoglutarate. The symptoms could be due to vasodilation from increased levels of nitric oxide, though other etiologies cannot be excluded. AAKG containing supplements may be associated with adverse effects requiring hospital admission."
   Note by Dr. Sahelian: One should not attribute these reactions solely to AAKG since many of these products contain a number of other ingredients. For instance, NO-Xplode has Vitamin B-6 (as pyridoxine HCl) 25 mg Vitamin B-12 (as Cyanocobalamin) 120 mcg Folic Acid 400 mcg  Magnesium 360mg Phosphorus 500 mg Calcium 75 mg NO-XPLODE's Proprietary Blend 20.50 g NO Meta-Fusion Ener-Tropic Xplosion Taurine Glucuronolactone MCT Oil (Medium Chain Triglycerides) L-tyrosine AKG Methylxanthines (caffeine) Vincamine Vinburnine (whole plant) L-Tyrosine Common Periwinkle Vinpocetine Phospho-Electrolyte Replacers Di-Calcium Phosphate Di-Sodium Phosphate Di-Potassium Phosphate Glycerol Hydrating Polymers Glyceryl Stearate Magnesium Glycerol Phosphate Potassium Glycerol Phosphate AVPT (Advanced Volumizing and Performance Technology) Sodium Bicarbonate Cinnulin PF (Aqueous Cinnamon Extract) Glycocyamine Trimethylglycine Di-Creatine Malate Modified Glucose Polymer (Maltodextrin) RC-NOS (Rutaecarpine 95%) Sodium Creatine Phosphate Matrix Creatine Ethyl Ester-Beta-Alanine Dual Action Composite (CarnoSyn) Creatinol-O-phosphate-Malic Acid Interfusion  Creatine AAB (Creatine Alpha-Amino-N-Butyrate)  Guanidino Propionic Acid  and Ketoisocaproate Potassium.

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Supplement Facts
Serving Size: 3 Tablets
Servings Per Container: 60
  Amount Per Serving % Daily Value
AAKG (L-Arginine-Alpha-Ketoglutarate) 3.5 g (3,500 mg) *

Suggested Use: As a dietary supplement, take 2 or 3 tablets once or twice daily on an empty stomach, preferably in the morning and one hour before workouts. Not recommended for continuous, high-level use for more than 60 days.
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NOW Foods AAKG dosage
3500 mg per 3 tablets
Vegetarian Formula
A Dietary Supplement
L-Arginine-alpha-ketoglutarate 3.5 g (3,500 mg)

NOW AAKG has paired arginine amino acid with alpha-ketoglutarate, another key player in amino acid metabolism, as well as in energy production. Consumers will find that NOW AAKG compares favorably to similar products on the market, but with the additional benefit of a 3500 mg dose and value pricing.

What is the differences in L-Arginine Alpha-Keto Glutarate 1:1 and 2:1?
    AAKG 2:1 consists of two parts-L-Arginine and one part Alpha Keto Glutarate acid, and AAKG 1:1 consists of one part L-Arginine and one part Alpha Keto Glutarate acid. There probably is little difference in these two forms in terms of their physiological effect.