12 AAKG Benefits + Side Effects, Dosage

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12 AAKG Benefits + Side Effects,

Dosage
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Written by Joe Cohen, BS | Last updated: June 4, 2019
C ONT E NT S
Arginine alpha-ketoglutarate (AAKG) is a dietar supplement
used  athletes and oduilders to improve sports
performance, reduce muscle fatigue, and enhance recover.
However, AAKG supplementation ma also have added enefits for
various diseases. Read on to find out more aout how AAKG works,

and 12 was it can help improve our health.
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What is Arginine Alpha-Ketoglutarate (AAKG)?
Arginine alpha-ketoglutarate (AAKG) is a modified version of the
amino acid arginine [1].
Alpha-ketoglutarate is an intermediate compound in the series of
reactions that produce energ for the od. It is the source of the
amino acids glutamate and glutamine. Glutamate is the main
excitator neurotransmitter in the rain and can increase one
formation. Glutamine is the main source of energ for cell division
[2, 3].
To improve asorption in the stomach, alpha-
ketoglutarate supplements come in the form of various salts. The
most common comination is ornithine and alpha-ketoglutarate [4,
5].
Alpha-ketoglutarate also regulates amino acid snthesis, energ
production, and formation of free radicals. It functions as a
messenger molecule in man chemical reactions in the od [4].
Glutamine enhances protein, muscle development, and immune
function [4]. 
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Arginine, also known as L-arginine, apart from eing a component
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of proteins, stimulates the release of hormones such as insulin,
glucagon, prolactin, and growth hormone.
Arginine also plas a critical role in maintaining normal lood
pressure, heart function, and immunit. These functions are
mediated through the production of nitric oxide. Arginine is roken
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down into ornithine and creatine. Ornithine is essential for cell
growth and division, while creatine is important for muscle
contraction [6].
Arginine is otained from food and snthesized in the od. It is
therefore referred to as a semi-essential amino acid. In health
adults, food and snthesis in the od are sufficient to meet the
necessar demands for this amino acid. These demands include
tissue repair, snthesis of proteins, and maintenance of immune
function [7].
During periods of rapid growth, phsical stress, or injur, the suppl
of L-arginine ma e insufficient to meet the od’s needs. During
this time, L-arginine taken as a dietar supplement can help
maintain muscle mass and improve odil function [7].
ource: [8]

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upplementing L-arginine can improve the capacit for exercise.
This improvement can e seen immediatel after consuming
arginine. Additionall, long-term improvements are seen due to
increased protein snthesis in muscles [7].
In addition to its performance-enhancing effects, arginine has
proven to e a safe and effective therap for high lood pressure,
tpe 2 diaetes, and erectile dsfunction [9, 10, 11, 12].
Arginine reduces infection rates in conditions where the od is
prone to infection, such as surger or critical illness [9].
Arginine in comination with alpha-ketoglutarate (as arginine alpha-
ketoglutarate [AAKG]) has een mainl manufactured and marketed
to athletes for its performance-enhancing potential [13, 14, 15].
However, in clinical settings, L-arginine alone is used more often [16,
6].
Composition of AAKG
Arginine alpha-ketoglutarate is formed when two arginine
molecules comine with one molecule of alpha-ketoglutarate.

The comination of alpha-ketoglutarate and arginine improves the
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stailit of arginine. This is supposed to improve its performance-
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enhancing ailities and its role in energ production.

Natural Sources of L-arginine and Alpha-
ketoglutarate
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L-arginine is one of 20 amino acids. It is considered a semi-essential
amino acid ecause it can e otained from oth foods and uilt
within our odies.
L-arginine is found in high concentration in foods like watermelon,
nuts, seeds, algae, meats, seafood, eans, lentils, whole grains, rice
protein concentrate, and so protein isolate [17].
L-arginine is snthesized in the od from citrulline. Though this
snthesis can occur in man cell tpes, the majorit occurs in the
kidne [18, 19].
Alpha-ketoglutarate in an intermediate in the ccle to convert food
to energ. In this ccle, it is formed from isocitrate. It can also e
formed from glutamate [2].
Dietar supplements of L-arginine alpha-ketoglutarate (AAKG) are
sold in the form of talets, pills, or powder.
Alpha-ketoglutarate and L-arginine can also e purchased
separatel as individual supplements. These are availale as
capsules or powder. 
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It is unknown how the comination of arginine alpha-ketoglutarate
enhances performance ut is most likel caused  elevated levels
of nitric oxide [15]. help direct you to the right resources.
Alpha-ketoglutarate
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Alpha-ketoglutarate is a product of the mitochondria and plas a
vital role in the conversion of food into energ. It is also a source of
glutamine and glutamate. In muscles, glutamine and glutamate
inhiit protein reakdown and increase protein snthesis [2].
Alpha-ketoglutarate enhances one formation. It regulates the
snthesis of collagen possil  increasing the numer of
molecules availale for snthesis. Collagen is a significant
component of one tissue.
Alpha-ketoglutarate stimulates the production of insulin-like
growth factor-1 and growth hormone. These are oth hormones
that regulate one reccling and formation of new one tissue [4].
Alpha-ketoglutarate also has immune-enhancing properties and is
potentiall useful in delaing aging [2].
L-arginine
L-arginine is roken down into nitric oxide (NO) in various tissues.
Depending on where it’s produced, nitric oxide plas a critical role
in regulating diverse functions in the od [17, 20].
• In the rain, it is a messenger molecule etween nerves
• In the immune sstem, it mediates the activit of white lood cells
• In the cardiovascular sstem, it has protective effects  relaxing
lood vessels. This increases lood suppl and oxgen deliver
around the od, 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 snthesis and thus increases muscle
development [21].
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L-arginine is also involved in the removal of toxins  forming urea,
which is filtered out of the od through urine [22].
In the liver, L-arginine is converted to glucose and alpha-
ketoglutarate. Therefore, it acts as a potential source of energ
[23].
AAKG comines the potential enefits of oth molecules,
L-arginine, and alpha-ketoglutarate.
Health Benefits of Arginine Alpha-ketoglutarate
There is limited research regarding the comination of arginine and
alpha-ketoglutarate Most of the reported enefits of this
comination are anecdotal.
The effects of supplementing with arginine alpha-ketoglutarate for 7
das were studied in 24 phsicall active men after performing
resistance (D-RCT). Arginine alpha-ketoglutarate comined had no
effects on heart rate, lood pressure, lood flow, or nitric oxide
levels. However, the amount of L-arginine in the lood was
increased [24].

upplementing arginine alpha-ketoglutarate (300 mg) in 16 health
men did not provide an performance-enhancing enefit, regardless
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of their exercise training status (D-RCT) [1].
In a randomized controlled trial in 12 trained men, AAKG did not
improve muscle endurance or significantl affect the lood pressure
response to anaeroic work [25].
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In a randomized controlled trial in 35 resistance trained men,
arginine was safe and well tolerated and positivel influenced
muscular strength and peak power performance. AAKG did not
influence od composition or aeroic capacit [15].
Although there is limited evidence that the comination of arginine
alpha-ketoglutarate has health enefits, the individual molecules
L-arginine and alpha-ketoglutarate have een researched for their
health enefits.
Alpha-ketoglutarate
upplementing alpha-ketoglutarate ma e useful in treating
severe trauma, infections, surger, and wound healing [4].
1) Alpha-ketoglutarate Improves Wound Healing
upplementation of ornithine alpha-ketoglutarate in 54 urn
patients significantl improved wound healing (D-RCT) [26].
imilarl, a stud of 60 urn patients who were given ornithine
alpha-ketoglutarate for 21 das showed significant improvements in

wound healing (D-RCT) [27].
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In rats suffering from urns, ornithine alpha-ketoglutarate SelfHacked CEO
supplementation increased glutamine levels, resulting in improved
wound healing [5, 28].
2) Alpha-ketoglutarate Prevents Muscle Loss
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In 21 people who underwent surgical trauma, supplementing alpha-
ketoglutarate in a controlled trial prevented muscle reakdown and
increased protein snthesis [29].
Adominal surger reduces muscle protein snthesis and increases
fatigue. In 22 adults who had stomach surger (RCT), supplementing
alpha-ketoglutarate improved glutamine suppl in the muscles and
prevented muscle loss [30].
3) Alpha-ketoglutarate Improves Bone Health
Alpha-ketoglutarate increases collagen production and iron
asorption, which increases one densit and strength [2].
In 76 menopausal women (D-RCT) with one weakness, intake of
alpha-ketoglutarate for 24 weeks prevented one loss and reduced
the smptoms of menopause. It also reconstructed the one tissue
[31].
A numer of animal studies have indicated that supplementing
alpha-ketoglutarate improved one densit [32, 33, 32].
4) Alpha-ketoglutarate and Immune Function
Alpha-ketoglutarate ma improve immune function. In the od, it is
converted into glutamine. Glutamine can increase levels of white
lood cells (macrophages and neutrophils) [34].
upplementing ornithine alpha-ketoglutarate in old patients that are
nutrient deficient successfull improved overall health. This was
seen  increasing appetite and improving motor skills. It also
shortened recover time from severe illnesses and surger [35].
In mice, alpha-ketoglutarate added to drinking water improved
immunit in the stomach and lowered od weight [36].

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5) Alpha-ketoglutarate May Benefit Cancer
In cell-ased studies, alpha-ketoglutarate prevented the
multiplication of cancerous cells [37, 38].
In multiple animal studies, supplementing alpha-ketoglutarate
reduced lood suppl to tumors, resulting in tumor death [39].
6) Alpha-ketoglutarate and Aging
upplementation with alpha-ketoglutarate delaed aging in the
worm Caenorhaditis elegans [40].
7) Alpha-ketoglutarate Cures Cyanide Poisoning
In rats, oral supplementation of alpha-ketoglutarate locked the
effects of canide, a toxic poison that can e fatal [41].
L-arginine
L-arginine has een proven to enefit a variet of conditions such
as diaetes, high lood pressure, and erectile dsfunction [9, 10,
11, 12].
1) Arginine Improves Muscle Health 
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A dail intake of L-arginine for 45 das reduced muscle fatigue and
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increased athletic performance in 56 male soccer plaers (D-RCT)
[42].
In 8 health sujects, L-arginine supplementation efore exercise
improved strength and exercise capacit  reducing lood levels
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of lactate and ammonia. oth are reakdown products associated
with muscle fatigue (D-RCT) [43].
Long-term (3-week) L-arginine supplementation in 16 health males
reduced lood lactate levels and oxgen consumption during
exercise (D-RCT) [44].
L-arginine supplementation for 6 months in 11 postmenopausal
women also improved muscle force and power (D-RCT) [45].
2) Arginine Is Beneficial for Diabetes
Diaetes is associated with low levels of arginine and lood vessel
dsfunction. everal animal studies indicate that supplementation
with L-arginine ma e an effective wa to improve lood vessel
function in diaetes [R].
Acute injection of L-arginine increases the levels of insulin in the
lood. This reduces the amount of glucose released from the liver
[46].
Long-term (21- to 31-da) oral intake of L-arginine in 26 patients
improved insulin sensitivit, lood vessel function, and reduced
lood glucose levels in patients with tpe 2 diaetes (D-RCT) [11,
10].
3) Arginine Improves Immune Function in Cancer
In a controlled trial of patients with advanced reast cancer,
L-arginine intake for 3 das (efore chemotherap) reduced the
suppression of the immune sstem caused  chemotherap [47].
Oral intake of L-arginine in 13 health individuals increased the
levels and activit of immune cells involved in comating tumor
growth (C56+, natural killer cells, lmphocte-activated killer cells)

[48].
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In human cells and mice, L-arginine supplementation increased
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survival and anti-tumor activit of immune cells [49].
4) Arginine Increases Exercise Capacity in Patients with
Heart Disease
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L-arginine supplementation improved the capacit for exercise in 16
elderl individuals with heart disease (D-RCT) [50].
In 22 individuals with stale angina pectoris and healed heart
attack, oral L-arginine taken for 3 das improved exercise workload
 increasing oxgen availailit during phsical activit (D-RCT)
[51].
5) Arginine Accelerates Recovery from Wound Injuries
In 36 health humans, arginine supplementation for 2 weeks
enhanced wound healing and improved immune responses (D-
RCT) [52].
In guinea pigs, L-arginine ingestion improved immunit and survival
from urn injuries [53].
In mice models, L-arginine reduced injur to the airwa passage
caused due to allergic inflammation [54].
7) Arginine May Improve Blood Vessel Health
A meta-analsis showed that L-arginine can reduce lood pressure
in adults with high lood pressure [16].
Arginine supplementation reduced the increased reactivit of lood
cells involved in clotting (platelets) in adults with high cholesterol
levels. It also reduced lood clotting (D-RCT) [55].
In raits, supplementing with arginine enefits atherosclerotic
conditions  widening lood vessels, thinning vessel walls, and
inhiiting the uildup of fat [56, 57, 58].
Arginine supplementation in 28 health men for 45 das reduced
lood sugar and fat levels (D-RCT) [59].

However, a meta-analsis of 927 showed no effect of arginine
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supplementation (9 g/da for 30 das to 3 months) in patients with
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acute heart attacks [60].
Also, arginine did not improve nitric oxide availailit in patients with
heart disease [61]. help direct you to the right resources.
8) Arginine Reduces Fat

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Long-term use of L-arginine in addition to diet and exercise
improved glucose and insulin levels. It also decreased ell fat in
overweight adults with tpe 2 diaetes [10].
In pigs, dietar supplementation with L-arginine reduced fat
deposits and promoted muscle gain throughout the od [62].
9) Arginine Reduces Pain in Disorders of the Digestive

Tract
Oral L-arginine supplementation consideral reduces the
frequenc and intensit of chest pain attacks and the use of
painkillers in 8 patients with movement disorders of the gut (D-
RCT) [63].
In rats, L-arginine accelerated ulcer healing  increasing lood flow
and forming new lood vessels [64].
10) Arginine Helps Infertility and Sexual Dysfunction
L-arginine given for 6 weeks to 29 men improved erectile
dsfunction in 31% of them (D-RCT) [65].
upplementation with oral L-arginine in 34 women unresponsive to
in vitro fertilization (IVF) increased pregnanc rates. This effect
occurred  improving ovarian response and the environment of the
uterus [66].
In goat sperm cells, L-arginine increased sperm vitalit through
increased production of nitric oxide. This effect ma e eneficial
for increasing fertilit [67].
11) Arginine Improves Cognitive Function in Dementia
L-arginine (1.6 g/da) intake increased intellectual function in elderl
patients with dementia [68].

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12) Arginine Fights Aging
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Aging is associated with reduced nitric oxide levels. Arginine
supplementation ma help to maintain normal nitric oxide levels to
counteralance the aging process [69].
Side Effects of Arginine Alpha-ketoglutarate

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upplementing arginine alpha-ketoglutarate (AAKG) for 8 weeks
had no significant adverse effects in 45 health men (D-RCT) [15].
There have een 3 reported hospitalizations associated with
arginine alpha-ketoglutarate supplementations. Patients presented
with dizziness, vomiting, palpitations, and sncope [70].
Side Effects of Alpha-ketoglutarate
No significant side effects caused  alpha-ketoglutarate have een
reported in humans [71].
However, there is potential for toxicit with repeated intake ased
on studies in rats. Adverse effects oserved were diarrhea and a
decrease in od weight. Anemia was also seen in female rats, ut
this was resolved after stopping supplementation [72].
Side Effects of Arginine
Arginine has not een associated with serious adverse effects [6].
Doses up to 30 grams per da are usuall well tolerated.
The most frequent adverse effects are nausea and diarrhea
reported occasionall at doses etween 15 to 30 grams [18].
No effect on liver function, lood glucose, or concentration of lood
electroltes has een reported [18].
A meta-analsis of 11 studies (D-RCT) including 387 health
participants indicates that it can significantl lower lood pressure
[73].
At higher doses, arginine has een reported to give a itter taste in
the mouth.

Contraindications
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Arginine alpha-ketoglutarate supplement should not e used 
individuals who have had a heart attack [70].
Not enough is known aout the use of AAKG or alpha-ketoglutarate
during pregnanc and reastfeeding. Therefore, use in these
conditions is not recommended.
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Arginine
Arginine supplementation should e used with caution in infants,
pregnant or lactating women, and in individuals with viral infections
or serious kidne or liver malfunction, asthma, or cancer [18, 13].
Patients with herpes infections should take L-arginine with caution,
as it ma aggravate the virus and increase smptoms. However, this
caution has not een validated in clinical trials [6].
Patients with electrolte imalances are at a higher risk of
developing metaolic acidosis, a condition in which the amount of
acid in the lood increases to dangerous levels. This occurs with
injectale forms of arginine (due to the high chloride content found
in these preparations) [74].
imilarl, in patients with kidne and/or liver impairment, low
potassium and high lood urea nitrogen levels ma occur with
L-arginine supplements [75].
Limitations and Caveats
Research-ased 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 eneficial effects of arginine alpha-ketoglutarate
supplementation in various disease conditions [1, 24].
Although L-arginine and alpha-ketoglutarate have demonstrated
health enefits when studied individuall, there is no research
indicating that taking them together will enhance these enefits.
Drug Interactions
Drug interactions with arginine alpha-ketoglutarate are not known.

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ketoglutarate.
L-arginine ma interact with insulin and cholesterol-lowering agents.
L-arginine is roken down into nitric oxide in the od, and thus
patients taking nitric oxide donors should supplement with caution.
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These include isosoride mononitrate, sodium nitroprusside, and
glcerl trinitrate.
Dosage
The suggested dosage of arginine alpha-ketoglutarate ranges from
1.2 to 3.5 grams per talet, taken 2 or 3 times a da on an empt
stomach.
The talets should e taken preferal in the morning and at least
30 minutes efore workouts.
Up to 20 grams of L-arginine per da is considered safe and non-
toxic [71].
The user recommended dose of the powdered form ranges from 1.5
to 3.5 grams per da.
User Experiences
People doing weight training reported relief from muscle pain when
taking arginine alpha-ketoglutarate. Man found that intake made
them feel mentall and phsicall active. People also found that it
increased their muscle strength and energ output.
L-arginine supplements seemed great for people with sensitive
stomachs and the experienced no side-effects. People
recommended it for a great pump at affordale pricing.
Due to the mild taste associated with it, people recommend it e
consumed with a juice or smoothie.
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12 AAKG Benefits + Side Effects, Dosage - SelfHacked Page 1 of 18

Evidence Based  4.3

12 AAKG Benefits + Side Effects,

Written by Joe Cohen, BS | Last updated: June 4, 2019

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Health Benefits of Arginine Alpha-ketoglutarate

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1) Alpha-ketoglutarate Improves Wound Healing

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3) Alpha-ketoglutarate Improves Bone Health

4) Alpha-ketoglutarate and Immune Function

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5) Alpha-ketoglutarate May Benefit Cancer

6) Alpha-ketoglutarate and Aging

7) Alpha-ketoglutarate Cures Cyanide Poisoning

1) Arginine Improves Muscle Health 

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2) Arginine Is Beneficial for Diabetes

3) Arginine Improves Immune Function in Cancer

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5) Arginine Accelerates Recovery from Wound Injuries

7) Arginine May Improve Blood Vessel Health

8) Arginine Reduces Fat

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9) Arginine Reduces Pain in Disorders of the Digestive

10) Arginine Helps Infertility and Sexual Dysfunction

11) Arginine Improves Cognitive Function in Dementia

Side Effects of Arginine Alpha-ketoglutarate

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Side Effects of Alpha-ketoglutarate

Side Effects of Arginine

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Limitations and Caveats

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