Beta-Alanine

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Beta-alanine is a modified version of the amino acid Alanine. Once ingested, it turns into the molecule carnosine which acts as a potent acid buffer in the body.

Carnosine is stored in body cells and released in response to drops in pH. Increasing body stores of carnosine can both protect against diet induced drops in pH (such as occurs from ketone production in ketosis) and from exercise induced lactic acid production.

Via buffering lactic acid, beta-alanine has been shown to enhance performance in muscular endurance. Many people note being able to perform one or two additional reps in the gym when training in sets of 8-15 repetitions. Moderate to high intensity cardiovascular events that stress the muscular system highly such as rowing or sprinting also see performance increases with beta-alanine, although they are less significant.

Beta-alanine is a well-researched compound with good reliability and validity. Many studies note beneficial but minor benefits on exercise performance.

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Doses of 2-5g are normally used and may result in paresthesia (face tingling).

Doses of 800mg have been shown to not cause paresthesia, and using this amount in doses divided by 3 hours is also effective.

Beta-alanine supplementation capacity increases with the amount of muscle mass and acidosis the body experiences. Doses up to 20-30g a day have been used before and are well tolerated outside of the parasthesia.

• What beneficial compounds are primarily found in animal products?

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Beta-Alanine has in your body, and how strong these effects are.

Level of Evidence	Effect	Change	Magnitude of Effect Size	Scientific Consensus	Comments
A	Muscular Endurance		Minor	100% See all 8 studies	The data from the lone meta-analysis suggesting a 2.5% increase in muscular endurance during exercises between 60-240s (usually measured by time to exhaustion) seems to... show be a good summation. The benefit is present, but is pretty small in magnitude.
B	Power Output			100% See all 5 studies	No significant effects on acute power output
B	VO2 max			60% See all 5 studies	Highly unreliable effects on VO2 max and currently is thought to have no significant effect.
B	Anaerobic Running Capacity		Minor	50% See all 4 studies	Somewhat effective, may simply be secondary to enhancing muscular endurance and reducing fatigue rather than any cardiopulmonary interaction
B	Fatigue		Minor	71% See all 7 studies	Seems somewhat effective in reducing fatigue and secondary to that, improving time to exhaustion.
C	Fat Mass		Minor	100% See 2 studies	Mechanisms unknown, but some studies suggest a fat loss effect (possibly secondary to extra workout volume)
C	Lean Mass		Minor	100% See all 3 studies	Doesn't appear overly potent, but either inherently or through greater workload there appears to be a hypertrophic effect associated with beta-alanine.
C	Testosterone			100% See study
C	Cortisol			100% See study
C	Growth Hormone			100% See study

Studies Excluded from Consideration

• Excluded due to only Beta-Alanine group containing Creatine and thus being confounded^[1]

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Edit1. Sources and Structure

1.1. Sources

Carnosine, the active metabolite of beta-alanine, is present in muscle tissue and thus is found primarily in meat products, particularly deep water species of fish; It is thought that these deep sea animals maintain high carnosine levels to combat the state of metabolic acidosis induced from low oxygen levels in deep waters ^[2]. Levels of carnosine in the muscle tissues of animals directly relates to the metabolic acidosis stressors placed on that animal (with the highest levels being in horses, racing dogs, and the Balaenoptera acutorostrata whale), which suggests that farm-raised animal products may have lower levels of carnosine than wild animals. ^[3]

The most common food sources of Carnosine and Beta-Alanine are meat products, due to skeletal muscle being a storage of Carnosine. These foods tend to include:

• Beef, with 300mg Carnosine per 200g^[4] or 1745-1961mcg/g^[5]
• Pork at 2439+/-13mcg/g^[5]
• Chicken and poultry at around 666+/-9mcg/g, which tend to have thrice the Anserine as they do Carnosine^[5]
• Fish^[6]
• Chicken broth^[4]

Carnosine, as well as beta-alanine, appear to be meat-exclusive ingredients with higher levels in land animals relative to poultry and are correlated with the amount of metabolic activity the animal underwent during life

1.2. Synthesis de novo

Beta-alanine is converted into Carnosine (Beta-alanyl-L-histidine) via the addition of a histidine amino acid group via the enzyme carnosine synthetase which was later identified as ATP-grasp domain containing protein-1 (ATPGD1)^[7] which is expressed highly in skeletal muscle and to a lesser extent in the brain.^[8] Carnosine is a dipeptide found in high levels in skeletal muscle, but also exists in the brain and cardiac muscle. Carnosine's most prominent role is that of acid base equilibrium maintenance (buffering H⁺ ions), but it is also implicated in being neuroprotective, of potential use in treating autism^[9], protective against glycation^[10], anti-aging^[11], antioxidant^[12], and sensitizing contractile muscles to calcium.^[13]

Carnosine is synthesized from beta-alanine via the ATPGD1 enzyme, which is locally expressed in skeletal muscle and the brain

Beta-alanine is synthesized in the liver^[14] and transported to muscle cells to later synthesize carnosine inside the muscle cell, of which type II muscle fibers show a greater storage capacity than type I muscle fibers. Muscle cells lack the ability to take up carnosine directly^[15] and thus it must take up the two substrate. Of the two, beta-alanine availability is the rate-limiting step in carnosine synthesis in vivo.^[16]

Due to the localized expression of ATPGD1 in the muscle tissue and availability of beta-alanine being the rate-limiting step, beta-alanine supplementation is highly effective in increasing muscle carnosine stores when orally ingested.^[17][18] When looking at the effects on muscle tissue, beta-alanine is more effective than carnosine itself at the same dose (with the difference becoming nonsignificant with increasing carnosine dose), possibly due to a greater percentage of oral intake being devoted to skeletal muscle.^[19]

Beta-Alanine is created in the liver and excreted into serum, where it can be taken up by tissues expressing the ATPGD1 enzyme to creatine carnosine. Its availability is the rate-limiting step of carnosine synthesis, and providing more beta-alanine increases carnosine synthesis in these tissues

Ingested Carnosine is hydrolyzed into its substrates via the carnosinase enzymes, which have two isomers (CN1 and CN2^[20]). CN1 mRNA (which is specific to Carnosine) is expressed in the brain and the liver mostly, with the protein being found in serum. It should be noted that interspecies differences exist, with CN1 existing in the aforementioned areas in humans (and thus a lack of circulating carnosine is the result) while in rodents it is localized to the kidneys.^[21] The CN2 is a non-specific dipeptidase and exists in the cytosol of cells, and is fairly prominent but only hydrolyzes Carnosine at a pH of 9.5 suggesting that it regulates excess Carnosine.^[20]

Carnosine is hydrolyzed into its two peptides by Carnosinase enzymes, one specific (and expressed in the liver and brain) and one non-specific that may regulate excess levels of carnosine

1.3. Carnosine Status (Deficiency, Surplus)

Some pseudo-vitamin compounds such as Creatine or L-Carnitine have relative deficiency states that are attenuated with supplementation of the molecule. Beta-Alanine does not appear to be similar in this regard.

Carnosine deficiencies exist, but are traced back and named according to a dietary L-Histidine deficiency with a lack of dietary L-histidine depressing serum and muscular levels of beta-alanine and carnosine (which are made from L-Histidine).^[22] Levels are restored when dietary L-Histidine is replaced, and dietary L-Histidine per se can increase muscular carnosine stores as well.^[23]

Whether or not a Carnosine relative deficiency exists that is independent of an L-Histidine deficiency has been observed when dietary carnosine is omitted (via a vegetarian diet^[24]) but not enough evidence exists to discuss the relevance of this deficiency state.

Any deficiency state related to Carnosine and Beta-Alanine could also be called a general 'protein deficiency' associated with the essential amino acid L-Histitine, and can be abolished merely by consuming more protein. Beta-Alanine and Carnosine per se do not have a pseudo-vitamin status

Muscular Carnosine stores may be slightly depressed when on a vegetarian diet, as one study using omnivorous subjects divided either to an omnivorous diet (control) or a vegatarian diet noted that the control experienced a nonsignificant 11% increase in storages while the vegetarian group experienced a nonsignificant 9% decrease; the difference between the two groups reaching significance.^[24] The vegetarian group expressed less carnosine synthase mRNA^[24] which tends to be upregulated in response to both Carnosine and Beta-Alanine ingestion.^[8] A relative lack of Carnosine in the diet has also been hypothesized to underlie aging and age-related pathologies^[25][26] and a decrease of carnosine has also been observed during the aging process by up to 35% in mice,^[27] but this relative deficiency state is more hypothetical and preliminary than the aforementioned pseudo-vitamins.

Beta-Alanine or Carnosine would probably be good ideas for vegetarian and vegans persons, people who do not eat meat or animal tissue

Trained individuals show a greater potential capacity for carnosine in muscles when compared to sedentary individuals^[28], and experienced bodybuilders show twice the capacity of untrained individuals.^[29] However, this is not always seen as one study in elite rowers noted that baseline carnosine was similar to a previously studied untrained control.^[30]

These effects, however, may not be due to the act of training. Although there have been some reports of increases of muscle carnosine content during short term resistance training^[31], most studies do not show acute changes in carnosine levels with training alone.^[32][33] The differences in carnosine stores between non-supplemented populations are either due to long term adaptations (possibly in hepatic beta-alanine synthesis), variations in food intake between the populations, or (in the case of some bodybuilders) the confounding effects of testosterone on carnosine levels in muscles being positively correlated.^[34]

Carnosine levels are observed to be increased in persons with a history of athleticism. This is not observed all the time, however, and may be more reflective of dietary carnosine (meat) than training status

1.4. Structure and Related Structures

Carnosine is beta-alanyl-L-histidine, a dipeptide of Beta-Alanine and L-Histidine. Other molecules that exist and are related to Carnosine are HomoCarnosine, which is a dipeptide where GABA replaces Beta-alanine (Gamma-aminobutryl-L-histidine) and localized to brain tissue, and Anserine which is Carnosine with an additional methyl group (beta-alanyl-l-methyl-L-histidine) and found in areas where Carnosine is also present such as Skeletal Muscle.^[35] All compounds share similar anti-oxidative properties and are collectively called 'Histidine containing dipeptides'.^[36][37]

A fourth and less studied histidine containing dipeptide is structurally related to Anserine, but just with the methyl group placed somewhere else on the nitrogen containing ring. This stucture, Balenine, contains the methyl group attached to the 3-carbon on the nitrogen containing ring rather than the 1-carbon.^[38][39] This appears to exist in similar places as Carnosine and Anserine.

Edit2. Pharmacology

2.1. Supplementation

When it comes to enhancement, Carnosine levels are determined primarily by the availability of extra-cellular beta-alanine^[16] and this primary determinant is overruled only by an outright L-Histidine deficiency.^[22] This is due to Carnosine being a dipeptide of both beta-alanine and histidine, with the formal name of beta-alanyl-l-histidine, and is a reason that L-Histidine is not used to enhance intracellular Carnosine stores routinely (although it has been implicated in doing so^[23]).

L-Histidine increases Carnosine stores only during periods of relative Carnosine deficiency, put for enhancing stores beyond this Beta-Alanine becomes the rate limiting step rather than L-Histidine, and thus Beta-Alanine would need to be supplemented

Carnosine is a dipeptide of Histidine and Beta-Alanine (beta-alanyl-L-histidine) and upon ingestion can be metabolized into free L-Histidine and Beta-Alanine in the liver tissue which expresses Carnosinase enzymes, meaning that Carnosine supplementation can provide Beta-Alanine to overcome the rate-limit of its own synthesis in muscle tissue.

Carnosine itself can still be absorbed, with 1.2-14% of the oral dose of 1, 2, or 4g in man being excreted in the urine as intact carnosine, despite one subject having a test meal of both 2g Beta-alanine and 2g L-Histidine without influencing Carnosine levels in the urine.^[40] It is thought that they can be absorbed from the intestinal tract^[41] via proton-coupled peptide transporters PEPT1 and PEPT2,^[42][43] despite not being found in the blood, which is thought to be from the plasma carnosinase enzyme metabolizing free Carnosine rapidly.^[40] A later study analyzing Carnosine kinetics has also noted that administration of Carnosine in either free (supplemental) form or via food products fails to lead to a detectable serum spike, although Anserine was increased with food and urinary Carnosine still increased.^[4]

Carnosine appears to be rapidly hydrolyzed into its constituents in humans, which differs from animals that can have elevated carnosine levels in serum. This limits the possible benefits associated with Carnosine somewhat, and renders supplemental carnosine to an inefficient form of beta-alanine

2.2. Muscle Carnosine Stores

When compared to Carnosine itself, beta-alanine appears to be more effective in the dose needed to reach similar levels of muscular carnosine and more likely to cause ergogenic benefits associated with carnosine.^[19]

In the Gastrocnemius muscle (mostly Type II fibers), studies that measure Muscle Carnosine stores note increases of 9.7+/-10.8% (2 weeks of 3.2g, increasing to 44.5+/-12.5% after 2 more weeks at 3.2g and 4 weeks at 1.6g) and 8.1 ± 11.5% (2 weeks of 1.6g, increasing to 35.5+/-13.3% after 8 weeks).^[44]

In the Tibialis muscle (mostly Type I) these increases are noted to be by 17.4+/-9.6% (2 weeks of 3.2g) and 11.8+/-7.4% (2 weeks of 1.6g) with lesser peak levels of 21.9+/-14.4% to 30.3 ± 14.8 after 8 weeks; the differences noted are in part due to dose, and in part due to lower baseline levels of beta-alanine in Type I muscles possible causing a greater increase acutely.^[44]

Muscle stores of beta-alanine and carnosine can be increased in as little as two weeks significantly, and a higher dose may exert more of a benefit when taken for a prolonged period of time

One study also simultaneously measured muscular Creatine stores, and found that beta-alanine had no influence on Muscular Creatine storages.^[44]

A study using a unilateral training program found that beta-alanine increased in both the trained and untrained leg to equal levels over 4 weeks, without increasing in either leg of the control group; suggesting that muscle contraction does not increase muscle storage of beta-alanine.^[45]

2.3. Elimination

One comparative study in healthy young athletes with one protocol of 1.6g beta-alanine daily for 8 weeks compared against double the dose (3.2g) for 4 weeks and 1.6g for the remaining four noted that the group that took 3.2g had twice the increase of muscular carnosine storages relative to the 1.6g group and that these differences persisted even after 4 weeks of using the same dose and slightly after 8 weeks of washout.^[44]

Beta-alanine supplementation appears to have a long wash-out period, with levels higher than baseline even after 8 weeks

Edit3. Longevity and Aging

Carnosine, the product that beta-alanine forms to buffer H⁺ ions, appears to exert rudimentary anti-aging properties.^[11] Its mechanisms are currently speculative for the most part, with some authors hypothesizing that it may act similar to Resveratrol due to their mechanisms being tied in to exercise.^[11] Currently, most known mechansims of Carnosine are related to protein metabolism.

Intracellular Carnosine stores have been noted to, in muscle cells, decline up to 35% in SAMP8 (senescence accelerated) mice during the aging process.^[27]

Carnosine and its depletion appear to be associated with aging, and bufferin carnosine stores may attenuate the aging process

3.1. Mechanisms

In cultured normal human fibroblasts, L-Carnosine has been found to reduce the rats of telomere shortening at 20mM^[46] and possibly secondary to this L-Carnosine can reduce the rates of cellular aging in cultured fibroblasts.^[47][48]

This may be an observed effect from Carnosine's possible ability to suppress post-synthetic errors in protein metabolism due to a mixture of its anti-oxidant, toxic metal-ion chelation, anti-glycating and aldehyde/carbonyl-binding activities,^[49] although at least one study has noted that Carnosine may be able to suppress mRNA translation initiation.^[50] Cellular accumulation of altered proteins and the subsequent proteotoxic stress is highly associated with the aging process.^[51][52] The causative role of altered proteins (damaged protein byproducts in the cytosol) in the aging process is strengthed by studies showing reduced aging rates associated with less protein synthesis, which produces less metabolic byproducts such as protein carbonyls and increase the relative count of chaperone proteins (from the endoplasmic reticulum) for proteolytic activity.^[53][54] A delay in aging associated with reduced protein synthesis has also been observed in methionine-deficienct mice.^[55][56]

Of important note is the general efficacy of Carnosine in reducing formation of altered proteins, as it has shown suppressive effects on protein modification induced by Reactive Oxygen Species (ROS),^[57] Reactive Nitrogen Species (RNS),^[58] glycating agents^[10][59] of which protein-AGEs are intimately linked with the aging process^[60] as well as aldehydes such as malondialdehyde (MDA)^[61] methylglyoxal (MG)^[62] and hydroxynoneal.^[63] These appear to be relevant in vivo as Carnosine-Aldehyde adducts have been detected in the urine, indicating they are formed in the body^[64][65] and at least once a carnosine-phosphatidylcholine adduct has been detected in living human leg tissue.^[66]

Additionally, Carnosine has been shown to induce Vimentin^[67] which is readily glycated and acts in a sacrificial manner to reduce reactivity of protein carbonyls and aldehydes.^[68]

Carnosine appears to have general protective (anti-oxidative, mostly) effects on a variety of proteins in cells, which may prevent their accumulation in the body. Carnosine may also act in a sacrificial manner to excrete some modified protein carbonyls from the body

Beyond acting in a reactive manner to protect cells from altered proteins, Carnosine may reduce the formation of these proteins by stimulating proteolysis (breakdown of proteins)^[69][70][71] which may be secondary to upregulation of cellular stress factors (Heat Shock Proteins) via Carnosine-Zinc complexes known as polaprezinc.^[72][73][74]

Carnosine may also theoretically act as a central point in different metabolic pathways that reduce formation of protein carbonyls and aldehydes initially

3.2. Interventions

Currently, Carnosine has shown anti-aging effects in both Drosophilia^[75][76] as well as sensecence-accelerated mice (mice who age prematurely).^[77] This latter study on mice noted that a 50% survival rates in these mice was increased by 20%, and that the increase in median lifespan was accompanied by less lipid peroxidation (oxidation of fatty acids), and this increase in mean lifespan has been replicated in another study usng 100mg/kg carnosine oral ingestion, although it failed to increase maximum lifespan; this dose correlates to 16mg/kg human ingestion or approximately 1.5g daily for a 200lb human.^[78]

Interestingly, Creatine supplementation may increase lifespan vicariously through Carnosine^[27] and Carnosine per se appears to be more effective at these anti-aging properties than an equi-molar combination of beta-alanine and L-histidine.^[78]

Has shown efficacy in insects for extending lifespan, and in mice it appears to extend median lifespan without significantly influencing maximal lifespan. Carnosine may be more effective than Beta-Alanine

Edit4. Neurology

4.1. Mechanisms

Beta-alanine moderates many neurological actions via its actions as a taurine-channel blocker, inhibiting tissue uptake of dietary Taurine; the mechanism appears to be competitive inhibition, as both compounds use the taurine transporter to get into the brain due to possessing a beta-amino group.^[79][80] In vitro studies that incubate a cell with beta-alanine note decreases of cellular taurine stores due to this inhibition^[81] and may sometimes deplete cells.^[82]

Beta-alanine also appears to act via glycine and GABA(A) receptors (both inhibitory neurotransmitters) with comparable efficacy to glycine and GABA themselves.^[83] These mechansims of action are similar to taurine, which also acts upon glycine and GABA(A) receptors.^[84]

A possible final mechanism in the brain is beta-alanine antagonism of the System A transporter, which facilitates glycine uptake.^[85]

May have inhibitory actions in the brain itself by sharing similar structres to sedatory neurotransmitters like glycine and GABA, but at the same time may compete with these molecules; overall effects unclear

Beta-alanine, via carnosine, may also exert indirect anti-oxidative effects. Carnosine can support the structure of the anti-oxidant enzyme Cu/Zn-Superoxide dismutase^[37] which has been noted in vivo in rats^[86] and may be the mechansim behind increased SOD activity in humans,^[87] which would enhance the already basic anti-oxidant properties of Carnosine via SOD's own anti-oxidant activity, and is similar to how L-Carnitine can stabilize SOD to enhance its actions.^[88] Carnosine itself is implicated in reducing oxidative damage to lipids^[89] as well as proteins,^[90] which can reduce their aggregation in neural tissue.^[91][92] Possibly via these actions, Carnosine has been hypothesized to aid in Alzheimer's Disease^[90] and has shown benefit to motor function in persons with Parkinson's Disease.^[87]

Beta-alanine, via Carnosine, may be a neurological anti-oxidant

4.2. Neurotransmitters

Beta-alanine, when fed to mice over a month, did not appear to significantly influence serotonin nor adrenaline levels in the cortex or hypothalamus but reduced levels of serotonin's main metabolite, 5-HIAA, in the hypothalamus.^[80] A significant increase in brain carnosine and brain BDNF levels were also noted.^[80]

An increase in dopamine levels has been noted in the nuclear accumbens due to beta-alanine in a concentration dependent manner up to 1omM, although concentrations of 0.1mM were active; this mechanism is vicariously through the glycine receptor and similar to glycine, Taurine, and Alcohol.^[93]

4.3. Interventions

One comparative study has been conducted using similar doses of each compound (22.5mmol/kg) in mice, and as assessed by Forced Swim Test (model of anti-depression) Taurine was more effective at reducing periods of immobility (suggesting more anti-depressive actions) while beta-alanine significantly improved performance on an Elevated Plus Maze (suggestive of more anxiolytic actions).^[80]

In human studies that evaluate mood, it is found that 1.6g and 3.2g beta-alanine for 8 weeks is associated with a non-significant trend for increased mood relative to placebo, with no difference between groups.^[94]

Lack of evidence on mood, but may possess anxiety reducing (anxiolytic properties)

One pilot study using preformed carnosine (beta-alanyl-L-histidine) in 36 Parkinsons patients noted that when basic therapy (personalized L-DOPA or dopaminergic medication) was paired with 1.5g Carnosine for 30 days, that the Carnosine group improved 32-53% on motor parameters of the Unified Parkinson's Disease Rating Scale including hand tremors, muscle stiffness, and mobility issues.^[87] MAO-B activity was unaffected in this study, and the activity of Cu/Zn-SuperOxide Dismutase was increased 26% which may have caused the decrease in serum protein carbonyls noted.^[87]

4.4. Chronic Fatigue

Beta-Alanine in the urine (elevated concentrations) is the second best predictor of Chronic Fatigue Syndrome, second only to amino-hydroxy-N-methyl-pyrrolidine (CFSUM1).^[95] In further analysis, urinary beta-alanine was the best predictor of the Chronic Fatigue Syndrome symptoms of dizziness, Hyperesthesia including light (photophobia), Myalgia and muscle cramps, as well as abdominal pain and gastric reflux.^[96] The symptoms of chronic fatigue (notably persistent lethargy, somnolence, and altered pain responses) have been noted in the rare disorder of hyper-beta-alanemia, which is an inborn error of metabolism that results in elevated beta-alanine levels in serum.^[97] A later study noted that in another group of persons with Chronic Fatigue that only a subgroup investigated exhibited elevated urinary beta-alanine levels, and that the group as a whole was not significantly different than control.^[98]

Some correlative evidence suggestive that beta-alanine might play a role in Chronic Fatigue, but no conclusions can be made at this point in time

Edit5. Exercise and Performance

5.1. Mechanisms

Out of the multiple mechanisms of systemic buffering (including bicarbonate, phosphates, and proteins/amino acids) carnosine contributes to intracellular buffering due to its imidazole structure in its histidine residue.^[3] Large stores of histidine dipeptides can be stored in cells with no apparent adverse effects, and due to this storage the effects of beta-alanine are not time-dependent. The benefits of beta-alanine are highly associated with how much beta-alanine and carnosine (buffering agents) are present in a muscle cell prior to contraction.^[99]

Due to this buffering, beta-alanine can reduce acidosis without influencing oxygen uptake.^[100] Although lactate (lactic acid) does not appear to inhibit muscular contraction per se, it is correlated. It is argued that this may be due to accumulation of H+ ions which may eventually inhibit muscle contraction and glycolysis.^[101] Many studies pinpoint that buffering acidity in vivo leads to subsequent increases in performance in short-term high-intensity exercise via either direct or indirect mechanisms.^[102]

5.2. Neural

Beta-alanine does appears to partly show increased time to volitional exhaustion by reducing the perception of fatigue,^[103] which has been replicated in college-level footballers^[104] as well as older individuals with 2.4g (55-92)^[105] and shows some additive effects with Creatine supplementation.^[106] The aforementioned study on college-level athletes noted a discord between subjective ratings of fatigue (which reached significance) and fatigue as measured by a Wingate anaerobic test, which merely trended towards anti-fatigue.^[104]

May reduce the perception of fatigue during near-exhaustive exercise, and at least one study in elderly persons suggests improve neural function and possibly less falls secondary to that

5.3. Power Output

Beta-alanine supplementation, when administered to strength athletes, does not seem to enhance 1 rep maximal strength nor isometric strength in isolation^[32] although this is somewhat contested, as the improvements in power over time in resistance trained males have been noted to have their rate increased with beta-alanine at 4.8g daily over 30 days.^[107] Creatine supplementation may have its efficacy at improving peak power output enhanced by beta-alanine slightly.^[1] Another study in Sprinters noted that while beta-alanine (4.8g for 4 weeks) was able to improve muscular endurance during repeated maximal contractions, it failed to exert improvements in power during a 400m sprint test.^[108]

When power-related studies are subject to meta-analysis,^[109] they have an effect size larger than placebo but this effect size fails to reach statistical significance. When these studies are pooled upon the basis of being less than 60 seconds (which excludes events like rowing^[30]) the effect size fails to be different from placebo.

Improvements in acute power output have been noted but are much less reliable than longer duration exercise, and beta-alanine does not appear to significantly increase acute power output. It may enhance the accrual of power of a period of time secondary to enhanced exercise volume, however

5.4. Anaerobic Exercise

In studies using beta-alanine against placebo in conjunction with a fitness routine, beta-alanine at four does of 1.5g over 6 weeks in athletic women failed to be significant better than placebo (dextrose) at increasing VO2 max, although it improved lean mass accrual (increased body mass without influencing fat mass) and trended to increase performance.^[110] Beta-alanine also failed to improve sprint performance in this study^[111] with 4g beta-alanine for a week followed by 6g intake for 3 weeks, but this may have been influenced by the testing protcol (maximal sprints on non-motorized treadmill).^[111]

This increased performance during intense non-maximal exercise has been seen in elite rowers, where 5g daily (1g taken every other hour) for 7 weeks (with an average of 9.5 weekly training sessions) noted that even in this population beta-alanine could improve performance (2.7+/-4.8s improvement) relative to placebo (1.7+/-6.8s) and that improvements were highly correlated with muscular carnosine levels both pre and post supplementation.^[30] Most improvement in this study was seen during the 500m-1500m range, the slowest of the tested 2k,^[30] although another study in elite rowers measuring 2k performance after 28 days of 80 mg/kg Beta-Alanine supplementation failed to replicated this observed benefit by barely missing statistical significance.^[112] Improvements in performance have also been seen with collegiate level American footballers and Wrestlers, where performance on a 300 yard shuttle run and flexed arm hang improved.^[44]

The benefits of beta-alanine on exercise performance appear to be nonspecific when considering the demographics, and could be of benefit to novice athletes as well as advanced with nonsignificant differences between sexes

Beta-alanine shows the most promise in exercises which stress intracellular acidosis (usually exericse over 30 seconds, as failure from H⁺ ions is minimal under this time frame^[113]), or short term and high intensity (but not necessarily 1 rep maximal) exercise such as sprinting, rowing, and weight-lifting. Benefit has been shown in these activities with beta-alanine supplementation.^{[17][114] [115][116]} In studies using resistance training as a means of measuring performance, an increase in workload volume is sometimes observed.^[104]

According to a Meta-Analysis on Beta-Alanine, the benefits associated with Beta-Alanine tend to occur with activities lasting 60-240s, with some benefits to longer lasting activity; benefits in activities lasting less than 60s were not significant in this meta-analysis.^[109] This meta-analysis also pooled the collective benefit at 2.85% greater than placebo when the median dose was 179g (total, so something along the lines of 60 days of 3.2g or 30 days of 6.4g), suggesting a statistically significant but practically minor benefit.^[109] The relatively lacklustre but present benefit has also been replicated in a study using elite swimmers as a 'real world' model rather than controlled laboratory model, and noted that 4 weeks of beta-alanine loading at 4.8g daily was associated with a 1.3+/-1% improvement in performance parameters, and statistical significance was lost at 10 weeks when the dose was decreased to 3.2g.^[117]

This meta-analysis also noted that 5/15 studies (33%) acknowledge an element of financial support from a supplement company in the manuscript, which are cited here.^{[18][118][106][119][120]}

Appears to benefit exercise lasting over 60s and between the 60-240s timeframe most significantly, with mixed benefit on exercise lasting less time than that. Within these parameters, beta-alanine appears to be a reliable performance enhancing supplement on a variety of exericse parameters

Edit6. Interactions with Body Composition

6.1. Interactions with Exercise

One study conducted on collegiate American football players and wrestlers given 4g beta-alanine daily for 8 weeks found that, when paired with a high-workload, that the football players did not have significant differences in body weight changes yet fat mass gain was attenuated from 0.88% to 0.1% and lean mass was increased by 2.1+/-3.6lbs rather than 1.1+/-2.3lbs; wrestlers failed to lose weight with the beta-alanine supplementation (3.2+/-4.9lb weight loss in placebo, 0.43+/-4.6 in beta-alanine) and this was due to reversing a loss of 0.98+/-2.6lbs lean mass into a 1.1+/-4.3lb gain.^[44] This was a poster presentation, and full text can not be found online.

A study conducted in athletic women using 6g beta-alanine daily (alongisde 60g glucose) and compared to placebo (66g glucose) noted that the beta-alanine group increased body weight while placebo did not have their weight changed; this was due to an increase in lean mass, as fat mass remained unchanged.^[110] This study used a 6 week HIIT training protocol, and dietary recall suggested no significant differences in diet.^[110]

Finally, a study on 46 healthy men using Beta-Alanine with 4 divided doses of 1.5g daily (each dose paired with 15g dextrose) subject to three weeks of HIIT on an erg bike noted that despite no changes in the diet that the beta-alanine group had a significant increase of 67.6+/-8.9lbs lean mass to 68.6+/-8.6, with no influence on fat mass.^[118]

At the moment, three studies suggest a beneficial trend of body composition towards more lean mass and less fat mass. Mechanisms unknown, and the notion that these benefits are dependent on exercise cannot be refuted since all studies used beta-alanine paired with an exercise regimen

Edit7. Interactions with Hormones

7.1. Testosterone

30 days of beta-alanine supplementation at 4.8g daily, which was able to increase workout capacity, did so without influencing the testosterone response to exercise in healthy males^[107] and this lack of effect has been obsered with preformed carnosine.^[121] Another study assessing Creatine, beta-alanine, and their combination noted that the 22% increase in testosterone that occurred with creatine did not occur with the combination.^[1] This study did not suggest any possible mechanisms.

7.2. Cortisol

30 days of beta-alanine supplementation at 4.8g daily, which was able to increase workout capacity, did so without influencing the cortisol response to exercise in healthy males.^[107]

7.3. Growth Hormone

30 days of beta-alanine supplementation at 4.8g daily, which was able to increase workout capacity, did so without influencing the growth hormone response to exercise in healthy males.^[107]

Edit8. Nutrient-Nutrient Interactions

8.1. Taurine

Taurine and beta-alanine have their metabolism intimately linked, as they (as well as the neurotransmitter GABA) share similar structures and the former two are both beta amino acids. They both share the same transporter, the taurine transporter SLC6a6; competition may occur at this transporter and in experimental conditions beta-alanine can incude a transient taurine deficiency.^[122] These deficiency states have questionable relevance to in vivo models, and have not yet been established as being a concern (most studies using beta-alanine under 6.4g daily fail to note any side-effects associated with taurine deficiency).

Theoretically antagonistic to each other, but practical relevance of their interactions is not known

8.2. Creatine

Creatine supplementation and Beta-Alanine are commonly seen as sister supplements due to both having an extensive body of evidence for their efficacy in trained athletes. Several trials have been conducted with their combination.

A study in untrained men assessing performance at the neuromuscular fatigue threshold (which beta-alanine has been shown to benefit in isolation^[103]) noted that 5.25g creatine and 1.6g beta-alanine with 34g dextrose (four times daily for 6 days, twice daily for 22 days) was able to increase performance at neuromuscular fatigue but was almost solely due to beta-alanine, with no additive effects with the ingestion of creatine and creatine not outperforming placebo in isolation.^[119]

When assessing the hormonal responses to exercise, something that beta-alanine has failed to accomplish in isolation,^[107] beta-alanine failed to influence the endocrine response and may have prevented the testosterone spike from Creatine supplementation, as creatine increased testosterone by 22% while beta-alanine alongside creatine did not alter testosterone.^[1] This study also noted that the combination was able to improve the average lean mass gain and fat mass loss during an exercise regimen better than creatine in isolation, and the combination improved average weekly training intensity yet failed to improve strength more than creatine in isolation.^[1]

One study has assessed their combination during aerobic exercise, and noted that the same doses of creatine and beta-alanine used in the neuromuscular fatigue study that the combination showed additive benefits on parameters of cardiopulmonary fitness (VO2 max, lactate and ventilatory thresholds, time to exhaustion).^[103] Creatine appeared to benefit ventilatory thresholds more on average and beta-alanine improved lactate thresholds more on average, and the combination slightly benefitted both (while still failing to influence VO2 max significantly).^[103]

Additive benefits in regards to body composition, where they both increase lean mass and decrease fat mass when combined with a resistance training regimen. No apparent synergism between the two, and the combination may not increase performance any more than the individual components

The noted suppression of testosterone (induced by creatine, suppressed by beta-alanine back to baseline) is probably not too relevant as the combination still increases lean mass and to a greater degree than Creatine in isolation

8.3. Sodium Bicarbonate

Sodium Bicarbonate (Baking Soda) has also been investigated for its ability to improve performance via an H⁺ buffering mechanism similar to beta-alanine.

Some studies look at their combination, and in a study on High Intensity Intermittent Cycling it was found that while beta-alanine significantly improved performance at 6.4g daily and Sodium Bicarbonate (0.3g/kg, two thirds taken with breakfast and the last bit 2 hours before testing) also improved performance in isolation; the combination appears to be additive, but this additive effect failed to reach statistical significance.^[123]

The two are most likely additive towards the same anti-fatigue purposes

Edit9. Safety, Toxicity, and Side-effects

9.1. Parasthesia

Beta-alanine supplementation can cause paresthesia, which is a potentially uncomfortable but ultimately harmless tingling of the skin; most commonly the face but also reported in the abdomen, chest, and extremities.

Paresthesia typically occurs when too great a dose of beta-alanine is taken acutely. It can be avoided by taking multiple doses throughout the day in minimum intervals of 3 hours (based on the time to peak serum levels, compound half-life, and return to baseline) with a dosage below the amount that causes paresthesia (which has been suspected of being 800mg averaged, or 10mg/kg BW in sedentary individuals).^[99]

Controlled release capsules can eliminate the side-effect of paresthesia, and remove the reported effects of skin tingling.^[124][94]

Additionally, some studies avoid parasthesia by dividing doses into smaller multiple doses; such as this study using 5g daily but in five divided doses of 1g taken every other hour.^[30]

9.2. Taurine Deficiency

Due to Taurine and Beta-alanine sharing the same transporter, a taurine deficiency can be experimentally induced by beta-alanine overfeeding, and this relative taurine deficiency may be coupled with some risks such as more susceptability to Alcohol-induced liver fat buildup^[125] (something taurine normally protects against).^[126] The aforementioned liver study used a fairly small dose of beta-alanine for rats (3% drinking water) but coupled it with a moderately large alcohol intake (36% of caloric intake)^[125] although this dose of beta-alanine has also been noted to induce cardiac effects in mice including remodelling^[122] and lipid peroxidation.^[127]

In animals, this 3% intake of beta-alanine in water may reduce circulating taurine levels by 50%^[128] to 77%^[122] and may reduce cardiac levels of taurine by 16.6-22.7%.^[127]

Beta-alanine appears to quite reliably induce taurine deficiencies in cellular studies where it is incubated (prolonged cellular exposure) and in animal studies cellular taurine can be reduced up to 50% with continual administration of beta-alanine via the drinking water

Of the studies indexed on Examine, no studies suggest that the parameters they have used beta-alanine (doses ranging from 2.6-6.4g daily with up to three dosing periods; taking 1g every other hour for 5g total in rowers) exposes humans to Taurine deficiency, although no human studies have assessed this directly.

Taurine deficiency may not be a practical concern with conserved beta-alanine supplementation (with breaks, for cells to accumulate taurine), but excessive usage of beta-alanine and full-day dosing has not been studied in humans and has plausiblity for inducing a taurine deficiency assuming the animal studies using beta-alanine spiked water

If you suffer from severe muscle cramps when you overdose on beta-alanine, that is a minor symptom of taurine deficiency and could be used as indicator

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