IngredientesAlanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain, and is consequently classified as a non-polar, aliphatic α-amino acid. Its systematic chemical name is (S)-2-aminopropanoic acid, also called α-aminopropanoic acid. Its molecular formula is C₃H₇NO₂, abbreviated as Ala.
Alanine is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG). The L-isomer of alanine (left-handed) is the one that is incorporated into proteins, and L-alanine is second only to L-leucine in rate of occurrence, accounting for 7.8% of the primary structure in a sample of 1,150 proteins.
The distinction between the two naturally occurring stereoisomers is important. L-alanine, or alpha-alanine (α-alanine), is a constituent of proteins. The right-handed form, D-alanine, occurs in peptides in some bacterial cell walls (in peptidoglycan) and in some peptide antibiotics, and occurs in the tissues of many crustaceans and molluscs as an osmolyte. This article focuses specifically on L-alanine, the biologically active protein-building form.
Alanine is an aliphatic amino acid, because the side-chain connected to the α-carbon atom is a methyl group (–CH₃). It is the simplest α-amino acid after glycine. The methyl side-chain of alanine is non-reactive and is therefore hardly ever directly involved in protein function. Under biological conditions, alanine exists in its zwitterionic form with its amine group protonated (as −NH₃⁺) and its carboxyl group deprotonated (as −CO₂⁻).
Out of the twenty amino acids that occur naturally, alanine is the only one that can form a stable α-helix in water and has the strongest tendency to form helices.
Alanine is a nonessential amino acid, meaning it can be manufactured by the human body, and does not need to be obtained through the diet. It is described as "nonessential" because it is made by the body, but it is nonetheless necessary for the biosynthesis of proteins. However, all amino acids may become essential if the body is unable to produce them.
Alanine was first synthesized in 1850 when Adolph Strecker combined acetaldehyde and ammonia with hydrogen cyanide. The amino acid was named Alanin in German, in reference to aldehyde, with the interfix -an- for ease of pronunciation, the German ending -in used in chemical compounds being analogous to English -ine.
An especially rich source of L-alanine is silk fibroin, from which the amino acid was first isolated in 1879. L-alanine, along with L-serine, glycine, and L-proline, are the chief amino acids that make up spider silk proteins.
L-alanine is one of the smallest chiral compounds and has been widely used in food, pharmaceutical, and veterinary fields for a long history. For example, it is used as a pre- and postoperative nutrition therapy together with other L-amino acids in clinical medicine and as a sweetener for its sweet taste in the food industry.
Because L-alanine is not a botanical or herbal extract but a ubiquitous component of all protein-containing foods, its "traditional use" is inseparable from the historical consumption of protein-rich foods across all human cultures. There is no documented record of L-alanine being intentionally isolated and administered as a medicinal preparation in traditional herbal or folk medicine systems prior to the modern era of biochemistry. Its clinical and therapeutic use began in the 20th century following advances in amino acid chemistry and physiology.
In the modern industrial and clinical context, L-alanine is extensively used in the chemical, food, and medicine industries. Industrial production has been mainly based on the enzymatic process using petroleum-based L-aspartic acid as the substrate, though production from renewable biomass using microbial fermentation has emerged as an alternative route.
Alanine is found in a wide variety of foods, but is particularly concentrated in meats. Animal-derived sources provide especially high concentrations. Dietary sources rich in L-alanine include meat, poultry, fish, eggs, and dairy products. Plant-based sources also contribute; L-alanine is additionally present in legumes and whole grains.
Endogenously, alanine can be synthesized from pyruvate and branched-chain amino acids such as valine, leucine, and isoleucine. It is produced by direct β-decarboxylation of L-aspartate by L-aspartate β-decarboxylase or transamination of pyruvate in the glucose-alanine cycle, and is a precursor for gluconeogenesis.
L-Alanine is a nonessential amino acid which is highly concentrated in muscle.
L-Alanine is widely used as a nutritional supplement, as a sweetener and flavor enhancer in the food industry, as a flavor enhancer and preservative in the beverage industry, as an intermediate for medicine manufacturing in the pharmaceutical industry, and as a nutritional supplement and sour corrective agent in agriculture and animal feed.
As a dietary supplement, L-alanine is available in the following forms:
The most well-established mechanism of L-alanine action is its central role in the glucose-alanine cycle, a hepatic-muscle metabolic axis. The glucose-alanine cycle is a metabolic pathway in which extrahepatic tissues (mainly skeletal muscle) export nitrogen and the carbon skeleton of pyruvate, produced by glycolysis, to the liver in the form of alanine.
The physiological roles of the cycle are the transport of nitrogen in a non-toxic form and of the gluconeogenic substrate pyruvate to the liver, thereby shifting the metabolic burden associated with nitrogen disposal and glucose regeneration to the liver. The net energy cost to the liver is approximately 3–5 ATP per cycle, necessary to support gluconeogenesis and the urea cycle.
The cycle operates as follows: Alanine is synthesized in muscle by transamination of glucose-derived pyruvate and released into the bloodstream. In the liver, the carbon skeleton of alanine is reconverted to glucose. The glucose synthesized from alanine in the liver can then be used in muscles for alanine synthesis again, closing the loop known as the glucose-alanine cycle.
Alanine is quantitatively the primary amino acid released by muscle and extracted by the splanchnic bed in postabsorptive as well as prolonged fasted humans, and the hepatic capacity for conversion of alanine to glucose exceeds that of all other amino acids.
Insulin inhibits gluconeogenesis by reducing hepatic alanine uptake. In contrast, in diabetes, an increase in hepatic alanine extraction is observed in the face of diminished circulating substrate. In prolonged fasting, diminished alanine release is the mechanism whereby gluconeogenesis is reduced. In circumstances in which alanine is deficient, such as pregnancy and ketotic hypoglycemia of infancy, fasting hypoglycemia is accentuated.
It has been believed for many years that alanine is the primary glucogenic amino acid and that the liver has a central position in gluconeogenesis. The results of in vitro, animal, and human studies demonstrate that both alanine and glutamine play an essential role in gluconeogenesis in various physiological and pathological conditions; alanine is more important in gluconeogenesis in the liver, while glutamine is the primary precursor for gluconeogenesis in the kidneys and small intestine.
L-alanine is the amino acid with the largest concentration changes during prolonged starvation, and it acts as an intermediary metabolite in the transfer of pyruvate from the skeletal muscle to the liver, where it is particularly relevant for hepatic gluconeogenesis.
In addition to being a carbon source, L-alanine functions as a non-toxic carrier of nitrogen. When amino acids are oxidized for energy in extrahepatic tissues, pyruvate produced via glycolysis acts as an amino-group acceptor, leading to the formation of alanine. In hepatocytes, the amino group of alanine is transferred to α-ketoglutarate, producing pyruvate and glutamate. Most of the amino groups derived from glutamate enter the urea cycle, whereas a smaller fraction may serve as nitrogen donors in biosynthetic reactions. The pyruvate generated in the liver enters gluconeogenesis and is used for glucose synthesis.
L-alanine is necessary for the biosynthesis of proteins. Its abundance and its structural simplicity make it one of the most frequently incorporated amino acids in polypeptide chains, though its methyl side-chain is non-reactive and is therefore hardly ever directly involved in protein function. Its primary structural role is in determining protein shape and stability, particularly in helical conformations.
A systematic literature search of intervention studies identified that L-alanine is among the amino acids examined for effects on glucose and insulin concentrations. Oral ingestion of most individual amino acids induces an insulin response but does not alter glucose concentrations in healthy participants.
Human studies have demonstrated that L-alanine infusion stimulates glucagon secretion. With saline, glucagon increased in hypoglycemia in non-diabetic subjects but not in diabetic subjects. Alanine infusion augmented glucagon secretion further, indicating a distinct amino acid-mediated glucagon secretory pathway in the pancreas.
Evidence level: Moderate (human clinical studies exist, primarily in specific clinical populations; large-scale RCTs are lacking).
The role of L-alanine in blood glucose homeostasis has been studied in human subjects, especially in the context of hypoglycemia in insulin-dependent (type 1) diabetes mellitus (IDDM). Several studies published in peer-reviewed journals have examined this area:
A study referenced by Wiethop and Cryer, published in Diabetes Care (1993), examined glycemic actions of alanine and terbutaline in IDDM, and a companion paper examined their use in treatment of hypoglycemia in IDDM. Saleh and Cryer also published a study in Diabetes Care (1997) on alanine and terbutaline in the prevention of nocturnal hypoglycemia in IDDM.
An important human study examined oral alanine in normal and diabetic subjects. Blood beta-hydroxybutyrate and plasma free fatty acids, glucose, insulin, and growth hormone responses were measured following oral L-alanine in doses of 0.5 or 0.1 g/kg. In normal and untreated adult diabetic subjects, beta-hydroxybutyrate decreased 59%–84% (high dose) and 34%–47% (low dose). This reduction occurred in two phases, the first corresponding to a rise in plasma insulin and the second corresponding to a fall in free fatty acids (with high dose only). However, plasma glucose remained stable in normal and untreated diabetics, but rose significantly in insulin-dependent diabetics.
Animal evidence is also available. A study in alloxan-induced diabetic rats found that the antidiabetic effect of L-alanine was tested in alloxan-induced diabetic rats, divided into groups receiving 150 and 300 mg/kg body weight L-alanine. The outcomes indicate that 300 mg/kg L-alanine resulted in a significant decrease (p < .05) in weight and blood glucose. L-alanine also restored tissue antioxidants, kidney, and liver functions, and histopathological studies showed the potential of L-alanine in regeneration of the islets of Langerhans. These findings are preclinical and cannot be directly extrapolated to humans.
A subsequent animal study found that co-administration of L-alanine and L-glutamine restored important tissue antioxidants, liver and kidney functions, and rescued islets cells degeneration, with these amino acids potentially serving as nutraceuticals for the management and treatment of diabetes. Again, this evidence is limited to rodent models.
Summary: Human clinical data support a role for L-alanine in raising blood glucose in hypoglycemia and stimulating glucagon secretion, particularly in IDDM. Animal data suggest antidiabetic and islet-protective properties. Confirmatory large-scale human RCTs are lacking.
Evidence level: Preliminary (single small human clinical study, infusion route, partial positive results).
A human clinical study investigated the potential of L-alanine to support brain function during glucose deprivation. The aim was to investigate the potential for the non-glucose metabolic substrate alanine to support brain function during glucose deprivation in man. Seven healthy men were studied on two occasions using a hyperinsulinaemic glucose clamp to lower arterialized plasma glucose to 2.5 mmol/l, in the presence of either 2 mmol/kg/h alanine infusion or saline, measuring counter-regulatory hormonal responses, symptoms, and cognitive function with a mini-battery of tests sensitive to hypoglycaemia.
Alanine infusion elevated plasma alanine and lactate. Cognitive function assessed by the Stroop word and colour subtests deteriorated less with alanine than saline (P < 0.01 for both). However, other cognitive function tests deteriorated equally, and counter-regulatory hormones rose equally during hypoglycemia in both studies except for increased glucagon with alanine. There was no significant effect of alanine on either autonomic or neuroglycopenic symptom scores. The researchers concluded that some, but not all, aspects of cognitive performance may be supported by an alanine infusion during hypoglycemia, and it is not clear whether alanine supports brain function directly or via increased availability of lactate.
Summary: A single, small (n=7), proof-of-concept clinical study showed partial cognitive benefits during hypoglycemia with intravenous alanine. The route of administration (infusion, not oral) and small sample size limit generalizability.
Evidence level: Low-to-moderate (small clinical series and case reports; no large RCTs).
L-Alanine has been explored as a nutritional adjunct in glycogen storage disease type II (GSD-II), also known as Pompe disease, in which muscle catabolism is pronounced.
A study published in Neurology (2000) by Bodamer, Halliday, and Leonard examined the effects of L-alanine supplementation in late-onset GSD-II. Five subjects with the late-onset form of GSD-II (age range 15 to 47 years) and seven healthy control subjects (age range 28 to 55 years) were studied. Following alanine supplementation, resting energy expenditure decreased in patients with GSD-II, leucine flux decreased significantly, as did leucine oxidation. The study concluded that L-alanine reduces protein turnover and catabolism in GSD-II.
A case report published in Pediatric Neurology described a male with late infantile GSD-II who presented at 12 months of age with muscular hypotonia and developmental delay. Oral supplementation with L-alanine was administered for 5 years. Progression of skeletal myopathy was slow, and cardiomyopathy resolved almost completely. The authors suggested that L-alanine may be a valuable supplement for infants with glycogen storage disease type II.
A 2022 case report published in Italian Journal of Pediatrics (PMC) explored L-alanine supplementation in a patient with infantile-onset Pompe disease (IOPD) on enzyme replacement therapy (ERT). The patient showed physical signs of inability to accumulate energy when exclusively on ERT, while fat mass increase and resting energy expenditure reduction occurred when supplemented with L-alanine oral supplementation (LAOS), likely reflecting anabolic pathways' implementation. The authors noted that this was the first case reporting potential LAOS benefits in PD-on ERT patients, and that longitudinal case control studies are yet needed to evaluate possible efficacy of combined LAOS and ERT treatment.
A single adult case study, published in J Inherit Metab Dis (2006) by Mundy, Williams, Cousins, and Lee, assessed the effect of L-alanine therapy in a patient with adult onset GSD-II. L-alanine, described as a simple and relatively cheap therapy, has been shown to reduce protein degradation in GSD-II patients but had not previously been assessed for clinical benefit in a controlled study.
Summary: Small human studies and case reports consistently show that L-alanine supplementation reduces muscle protein catabolism in GSD-II. This is a physiologically coherent effect. The evidence base is small, consisting of case reports and a single controlled study of five patients. Larger controlled trials are needed.
Evidence level: Preliminary (murine preclinical study; limited human data specific to L-alanine alone).
A published preclinical study (murine model) investigated the ergogenic effect of BCAAs and L-alanine supplementation. The study corroborated the use of BCAAs combined with L-alanine (ALA) to support muscle health during physiological exercise, underlining how the relative BCAAs/ALA ratio is important to control BCAAs distribution. This study was conducted in a murine model and is explicitly described as a preclinical, proof-of-concept study, limiting direct translation to humans.
Alanine synthesis is preferred during increased breakdown of glycogen stores in muscles and subsequent pyruvate supply from glycolysis. The glucose synthesized from alanine in the liver can be used in muscles for alanine synthesis again. As a result of the gradual depletion of muscle glycogen stores and subsequent decrease in glycolysis and pyruvate supply, alanine release from muscles decreases, and glutamine production and its potential use for gluconeogenesis increases.
Summary: The role of L-alanine in exercise physiology is mechanistically well-understood through the glucose-alanine cycle, but direct evidence from controlled human studies that L-alanine supplementation improves exercise performance as an isolated intervention is lacking. Preclinical data are supportive but not conclusive.
Evidence level: Weak (single small RCT using a multi-amino acid combination, industry-sponsored, exploratory).
A randomized, double-blind, placebo-controlled exploratory trial assessed a combination of five amino acids — serine, alanine, glutamate, aspartate, and tyrosine (SAGAT) — for effects on mental health and fatigue in healthy office workers. The RCT was conducted in participants aged between 20 and 65 years with fatigue sensation, randomized to receive either SAGAT or placebo, ingested for four weeks. A transient mental work was loaded at day 0 and after four weeks of intervention. Fatigue sensation was the primary outcome; mood status, cognitive function, work efficiency, and blood markers were secondary outcomes. The number of participants analyzed for efficacy evaluation was 20 in SAGAT and 22 in placebo.
There were no significant differences in the primary outcomes (fatigue sensation). However, as secondary outcomes, the SAGAT group showed a significant improvement in motivation and cognitive function in the recovery period after mental work loaded in a four-week intervention compared to the placebo. The authors concluded that the current findings suggest SAGAT contributes to maintaining proper motivation and cognitive function.
Importantly, this study was supported by Ajinomoto Co., Inc., and all authors are employees of Ajinomoto Co., Inc., introducing significant industry bias. Furthermore, alanine was tested as part of a combination, not in isolation, meaning the specific contribution of L-alanine cannot be determined. An independent summary of this study characterized it as showing that supplemental amino acids including alanine did not reduce feelings of fatigue in exhausted office workers.
Summary: The evidence for L-alanine's effect on mental health in healthy individuals is very weak. The sole available RCT used a five-amino-acid combination, was exploratory, was industry-funded, showed no effect on the primary outcome, and reported only modest secondary-outcome findings.
Evidence level: Moderate (multiple small RCTs in pediatric populations; mixed results).
L-alanine has been studied as an additive to oral rehydration solutions (ORS), based on its capacity to enhance co-transport of sodium and water across intestinal epithelium via sodium-coupled amino acid transporters.
A randomized, double-blind trial published in J Pediatr Gastroenterol Nutr (1991) determined whether adding 90 mmol/L of alanine with a reduction in glucose to 90 mmol/L (alanine ORS) improved the efficacy of the standard WHO-ORS. One hundred twenty-nine males aged 3–48 months with mild to moderate dehydration were randomly allocated to either treatment group. In the 0–6 hour period, median urine output was significantly greater in the alanine ORS group (p < 0.05). Between 0 hours and recovery, median values for duration of diarrhea, ORS consumption, and stool output were lower in the alanine ORS group, but these differences with the WHO-ORS group were not statistically significant.
A separate controlled trial published in Acta Paediatrica (1995) evaluated a hypo-osmolar ORS containing L-alanine and glucose vs. standard WHO-ORS in 55 children with persistent diarrhea. Stool outputs were significantly less in infants receiving hypo-osmolar ORS than in those receiving WHO-ORS for 0–24 h (p = 0.04), 0–48 h (p = 0.01), 0–72 h (p = 0.04), and 0–96 h (p = 0.03). Furthermore, a hypo-osmolar ORS containing L-alanine and glucose was found to be as efficacious as an intravenous solution and more effective than WHO-ORS for replacement of ongoing stool loss in persistent diarrhea.
A blind trial in infants with acute diarrhea (published in J Pediatr 1991) examined 20 male infants less than one year of age. The study assessed the efficacy of the addition of 30 mmol/L alanine to the standard WHO oral rehydration solution. Rehydration was satisfactory in both groups, but ORS that contained alanine did not reduce the purging rates of the infants compared with those who received standard ORS.
Summary: Studies of alanine-supplemented ORS in pediatric populations show some improvements in stool output and rehydration efficiency in specific trials, particularly for persistent diarrhea, but results are not uniformly positive. Sample sizes are small and results are mixed across studies.
The following dosages reflect those specifically reported in the scientific literature. They should not be interpreted as recommended doses.
L-alanine is a naturally occurring amino acid present in all protein-containing foods and is endogenously synthesized. As such, it has a broadly favorable safety profile at dietary levels. It is used as a pre- and postoperative nutrition therapy together with other L-amino acids in clinical medicine.
L-alpha-alanine can increase blood sugar levels in people with diabetes. This can be helpful if blood sugar levels are too low, but it can be harmful if blood sugar levels are normal or too high. Blood sugar should be monitored carefully in individuals with diabetes who use alanine.
This bidirectional glucose effect is pharmacologically significant: while L-alanine is studied as a treatment for hypoglycemia, its gluconeogenic activity may be counterproductive in normoglycemic or hyperglycemic diabetic states. In insulin-dependent diabetics, oral alanine produced a significant rise in plasma glucose.
A published study in Endocrinology, Diabetes & Metabolism (2022) demonstrated that exogenous d-β-hydroxybutyrate lowers blood glucose in part by decreasing the availability of L-alanine for gluconeogenesis. L-alanine is the amino acid with the largest concentration changes during prolonged starvation, and the infusion of ketone bodies lowers L-alanine blood levels more than any other amino acid. Individuals supplementing with exogenous ketones may therefore experience altered L-alanine levels and gluconeogenic dynamics, a mechanistically relevant but clinically unconfirmed interaction.
Several human studies examined alanine in the context of insulin-induced hypoglycemia. Responses of glucagon to hypoglycemia were measured in eight patients with type 1 diabetes and six non-diabetic subjects during hyperinsulinaemic clamp studies. Subjects were studied on three randomized occasions with infusion of low- or high-dose alanine, or saline. With saline, glucagon increased in hypoglycemia in non-diabetic subjects but not in diabetic subjects. This implies that alanine's ability to stimulate glucagon is preserved in type 1 diabetics even when basal glucagon response to hypoglycemia is impaired — a clinically relevant interaction for those on insulin therapy.
L-alanine is used as a pre- and postoperative nutrition therapy together with other L-amino acids in clinical medicine. When used intravenously, it is administered under medical supervision in controlled clinical settings.
Because L-alanine is the primary substrate for hepatic gluconeogenesis and is extensively metabolized by the liver, alanine aminotransferase (ALT) is the key enzyme involved. Alanine supplementation has not been documented to cause hepatotoxicity at dietary or supplemental doses, though individuals with significant hepatic dysfunction would have altered alanine metabolism.
It is important to distinguish L-alanine from beta-alanine (β-alanine), which is a structurally different compound with different pharmacological properties. Beta-alanine is well known for producing transient paresthesia (skin tingling) at typical supplemental doses, an effect not attributed to L-alanine in published literature. D-alanine, or beta-alanine, is not found in proteins but occurs naturally in two peptides, carnosine and anserine, found in mammalian muscle. The confusion between these compounds in commercial supplement contexts is common, and their mechanisms and evidence bases are distinct.
Condiciones de salud que L-alanina puede ayudar a apoyar.
L-Alanine supplementation has been shown in animal studies to restore tissue antioxidant enzymes depleted by diabetes. It also contributes indirectly to antioxidant defense through its role in glutathione metabolism and as a substrate for alanyl-glutamine dipeptides used clinically to support redox homeostasis.
L-Alanine is the primary gluconeogenic amino acid and a central regulator of blood glucose via the glucose-alanine (Cahill) cycle. Human clinical data show it can raise blood glucose during hypoglycemia in insulin-dependent diabetes. Animal studies also demonstrate significant blood glucose lowering in diabetic models, possibly via hepatic AMPK activation.
L-Alanine supports cellular energy production by feeding pyruvate into the TCA cycle and by providing gluconeogenic substrate to the liver, which then supplies glucose for cellular ATP synthesis in peripheral tissues. The glucose-alanine cycle is a direct mechanism of inter-cellular energy support during periods of low carbohydrate availability.
L-Alanine participates directly in energy metabolism by shuttling carbon skeletons from skeletal muscle to the liver, where they are converted to glucose via gluconeogenesis to sustain ATP production. This inter-organ energy transfer, known as the Cahill cycle, is well established in human physiology. Intravenous alanine infusion in 60-hour fasted humans was shown to markedly stimulate hepatic gluconeogenesis and oxidative flux.
L-Alanine has been clinically tested as a treatment for iatrogenic hypoglycemia in insulin-dependent diabetic patients. A controlled clinical trial demonstrated that oral L-alanine produces sustained glucose recovery from hypoglycemia, superior in duration to oral glucose alone. Its mechanism relies on hepatic gluconeogenesis.
L-Alanine is a central metabolic hub linking muscle catabolism, hepatic gluconeogenesis, nitrogen disposal, and the urea cycle. It is the most important single amino acid for inter-organ carbon and nitrogen trafficking. Hepatic AMPK activation by L-alanine has also been demonstrated, linking it to broader metabolic regulation.
During sustained or intense exercise, L-alanine release from skeletal muscle increases as the glucose-alanine cycle is activated to maintain blood glucose and remove ammonia. Human studies confirm elevated circulating alanine with exercise and the cycle's role in prolonging glucose availability to working muscle. This biochemical function directly supports endurance capacity.
A combination of glycine, L-alanine, and glutamic acid was studied as a treatment for benign prostatic hyperplasia (BPH) symptoms as early as 1958. Clinical studies found the amino acid mixture reduced urinary symptoms and prostate size. L-alanine is one of three amino acids in this historically documented combination.
Sistemas corporales que L-alanina puede ayudar a apoyar.
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