Amino Acid

The Amino Plus Blend appears to refer to a multi-amino acid formulation, potentially designed for use in metabolic disorders such as phenylketonuria (PKU) or for supporting protein metabolism in malnutrition or aging. In PKU, phenylalanine-free amino acid mixtures are essential to meet protein requirements while restricting natural protein intake, and tablet-based formulations have been shown to be a practical and acceptable alternative to liquid protein substitutes, improving adherence in some patients (PMID 12651759). Aromatic amino acid (AAA) supplementation, including phenylalanine and tyrosine, has demonstrated benefits in enhancing whole-body protein synthesis in children with severe acute malnutrition during recovery, suggesting a potential role in catabolic or undernourished states (PMID 24647391). However, evidence for additional leucine co-ingestion in elderly adults shows no further augmentation of post-exercise muscle protein synthesis beyond protein and carbohydrate intake alone, challenging the benefit of isolated branched-chain amino acid supplementation in aging muscle (PMID 17697406). Overall, amino acid blends are most effective when tailored to specific metabolic needs, such as in inborn errors of metabolism or malnutrition, rather than as general supplements in healthy individuals.

Beta-Hydroxy-Beta-Methylbutyrate (HMB) is a metabolite of the branched-chain amino acid leucine that plays a role in promoting muscle protein synthesis and reducing muscle protein breakdown. It is commonly used as a supplement to support muscle mass, strength, and recovery, particularly in populations experiencing muscle loss or undergoing physical stress. Research shows HMB supplementation can significantly improve muscle mass, strength, and physical performance in older adults with sarcopenia (PMID 39999663) and reduce muscle loss in aging populations (PMID 26169182). In critically ill patients, such as those with COPD in intensive care, short-term HMB supplementation demonstrates anti-inflammatory and anticatabolic effects, improving protein metabolism and clinical outcomes (PMID 17077073). However, evidence for ergogenic benefits in healthy, trained individuals is less consistent, with no significant improvements in strength or body composition observed in resistance-trained men (PMID 11599506) or collegiate athletes (PMID 12580653). A recent meta-analysis found limited evidence for HMB improving endurance performance or VO₂ max in healthy individuals (PMID 38090973). Overall, the most consistent benefits are seen in clinical or aging populations with muscle wasting conditions.

Betaine (N-trimethylglycine) is a naturally occurring compound that functions as a methyl donor and osmolyte, playing key roles in homocysteine metabolism, cellular hydration, and antioxidant defense. It remethylates homocysteine to methionine via the betaine-homocysteine methyltransferase (BHMT) pathway, independent of folate and vitamin B12, making it particularly relevant in managing elevated homocysteine levels (PMID 12730412, 14699020). Supplementation has been shown to significantly lower fasting and post-methionine-load plasma homocysteine in individuals with mildly elevated levels, suggesting a potential role in cardiovascular risk reduction. Additionally, betaine supports metabolic health by improving insulin sensitivity and hepatic metabolism in prediabetic individuals (PMID 29860335), and exhibits anti-inflammatory and antioxidant effects, particularly in chronic kidney disease models (PMID 35792998). It also enhances anabolic signaling, increasing growth hormone and insulin-like growth factor-1 responses to acute exercise, indicating potential ergogenic benefits (PMID 22976217).

Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide primarily found in skeletal muscle and brain tissue, with multifunctional roles including antioxidant activity, anti-inflammatory effects, pH buffering, and protection against glycation and oxidative damage. Supplementation with carnosine or its precursor β-alanine has been shown to increase muscle carnosine concentrations, which may improve high-intensity exercise performance by buffering intracellular acidosis (PMID 24389513, PMID 38086332). Emerging evidence also supports broader health benefits: carnosine supplementation (2g/day) improved cognitive performance in younger adults in a placebo-controlled trial (PMID 39919936), reduced markers of inflammation and oxidative stress such as CRP and malondialdehyde (PMID 38086332), improved lipid profiles in individuals with dyslipidemia (PMID 37686787), and showed potential in improving glycemic control in prediabetes and type 2 diabetes (PMID 40999397). Its mechanisms include scavenging reactive oxygen species, modulating immune cell function, and inhibiting advanced glycation end-products (PMID 35630780).

Creatine monohydrate is a well-researched dietary supplement that enhances short-duration, high-intensity exercise performance by increasing intramuscular phosphocreatine stores, thereby supporting rapid ATP regeneration during anaerobic activity (PMID 23851411, 34234088). It has been shown to improve muscle strength, power output, and lean mass gains when combined with resistance training, with benefits observed in both males and females (PMID 11099372, 32549301). Additional potential benefits include improved post-exercise recovery, injury prevention, and neuroprotective effects. Creatine monohydrate is the most bioavailable and cost-effective form of creatine, with no evidence supporting superior efficacy of alternative forms such as creatine ethyl ester (PMID 35268011). Short- and long-term use is considered safe in healthy individuals, with minimal adverse effects (PMID 34234088, 18652082).

Glycine is a non-essential amino acid involved in multiple physiological processes, including protein synthesis, antioxidant defense, and purine metabolism. It serves as a precursor for glutathione, creatine, and heme synthesis, and has anti-inflammatory and cytoprotective properties. Clinical evidence suggests that glycine supplementation, particularly in combination with tryptophan, can significantly reduce serum uric acid levels in individuals with mild hyperuricemia, likely through enhanced uric acid metabolism or excretion (PMID 30845731). Additionally, glycine is a key substrate in the endogenous production of guanidinoacetic acid (GAA), which is further converted to creatine, highlighting its role in energy metabolism (PMID 36571614, PMID 25680689). Dietary sources of glycine include protein-rich foods such as meat, dairy, and legumes, with higher concentrations found in collagen-containing tissues.

L-arginine is a semi-essential amino acid involved in protein synthesis, nitric oxide (NO) production, immune function, and cardiovascular regulation. It serves as the primary substrate for nitric oxide synthase (NOS), promoting vasodilation and endothelial function, which underpins its potential benefits in cardiovascular health, exercise performance, and pregnancy-related complications such as preeclampsia (PMID 36040377, PMID 38644716, PMID 31652143). Supplementation may improve insulin sensitivity, reduce cardiometabolic risk, and support gut integrity, particularly in conditions involving impaired endogenous synthesis, such as after intestinal resection or in inflammatory bowel disease (IBD) (PMID 36040377, PMID 5, PMID 31652143). While endogenous production typically meets needs in healthy adults, dietary or supplemental arginine may be beneficial in specific clinical contexts, including metabolic dysfunction, pregnancy, and critical illness.

L-Glutamine is a conditionally essential amino acid that plays a critical role in immune function, gut barrier integrity, and cellular metabolism, particularly during catabolic states such as critical illness, trauma, or intense exercise (PMID 11533315, 15090905). It serves as a primary fuel source for enterocytes and immune cells, supporting gut-associated lymphoid tissue and reducing intestinal permeability (PMID 15090905, 39397201). Glutamine enhances antioxidant defenses via glutathione synthesis and may modulate stress responses through heat shock proteins (PMID 15090905). While early studies suggested benefits in critically ill patients, recent meta-analyses indicate that intravenous glutamine may be associated with increased harm in intensive care settings, particularly in multiorgan failure (PMID 26252319, 26283217). However, enteral glutamine appears safer and may support gut barrier function in adults, with emerging evidence showing reduced intestinal permeability (PMID 39397201). In non-critical populations, glutamine supplementation increases plasma IL-6 during exercise, suggesting an immunomodulatory role (PMID 12611772), but shows no benefit in pediatric persistent diarrhea (PMID 23340559).

L-Isoleucine is one of the three branched-chain amino acids (BCAAs), alongside leucine and valine, and plays a key role in protein synthesis, energy metabolism, and glucose regulation. Emerging evidence suggests that isoleucine may improve glucose tolerance and reduce postprandial glucose levels, with acute administration shown to enhance insulin sensitivity in both rodents and humans (PMID 32823899). Chronic supplementation in rodent models prevents diet-induced weight gain and improves metabolic markers, particularly in the context of high-fat diets (PMID 32823899). Unlike leucine, which is the primary activator of mTORC1 and muscle protein synthesis, isoleucine appears to exert more metabolic than anabolic effects, with limited direct evidence for stimulating muscle growth in humans (PMID 27934654, PMID 28852372). While BCAA supplementation, including isoleucine, has been studied in clinical populations such as those with liver disease or cancer cachexia, the specific role of isoleucine alone remains less defined, and most benefits are observed in combination with other BCAAs (PMID 17414498, PMID 24572834).

L-Leucine is a branched-chain essential amino acid that plays a central role in regulating muscle protein synthesis (MPS) by activating the mTOR signaling pathway. It functions both as a substrate for protein synthesis and as a signaling molecule that stimulates anabolic pathways, making it a key target for interventions aimed at sarcopenia, malnutrition, and muscle wasting conditions. Evidence suggests that leucine supplementation may improve muscle mass, strength, and physical performance in older adults with sarcopenia, particularly when combined with resistance training (PMID 40805998, 31627427). In older populations, leucine enhances the anabolic response to protein intake, especially in low-protein meals, and may help counteract anabolic resistance associated with aging (PMID 24284442, 25234223). While some studies show benefits in lean mass and strength, results on functional outcomes like insulin sensitivity are mixed, with no additional improvement beyond resistance training alone in prefrail and frail older women (PMID 31149709). In chronic liver disease, leucine and other branched-chain amino acids may help mitigate sarcopenia and malnutrition due to impaired protein metabolism (PMID 32993404). Preliminary evidence also indicates potential for leucine to support protein anabolism in patients with advanced cancer before refractory cachexia develops (PMID 24572834). However, effects are most pronounced when baseline nutrition or muscle mass is suboptimal.

L-methionine is an essential sulfur-containing amino acid that plays a central role in protein synthesis, methylation reactions, and antioxidant defense. It serves as the precursor to S-adenosylmethionine (SAMe), the primary methyl donor in numerous biochemical pathways, including DNA and histone methylation, which are critical for epigenetic regulation and neuronal development (PMID 24445402, PMID 39519500). Methionine residues in proteins also act as endogenous antioxidants by scavenging reactive oxygen species through reversible oxidation to methionine sulfoxide, a process regulated by methionine sulfoxide reductases (PMID 11327324). Adequate methionine intake is vital for liver health, lipid metabolism, and homocysteine regulation, although excessive levels may contribute to hyperhomocysteinemia if cofactors such as vitamins B6, B12, and folic acid are insufficient (PMID 24445402, PMID 32845472). While direct supplementation of L-methionine is not commonly used in clinical practice, its metabolic derivatives like SAMe are studied for liver support and neurological function.

L-Theanine (γ-glutamylethylamide) is a non-proteinogenic amino acid primarily found in tea leaves, particularly green tea, and is recognized for its calming and cognitive-enhancing effects. It promotes relaxation without sedation by increasing alpha brain wave activity, which is associated with a state of wakeful relaxation and reduced anxiety (PMID 23155618, 29289576, 25759004). Research indicates that L-theanine may improve sleep quality by reducing sleep onset latency and daytime dysfunction, likely through its anxiolytic properties rather than direct sedation (PMID 33144101). It also supports cognitive function, especially attention and focus, particularly when combined with caffeine, due to synergistic effects on alertness and calmness (PMID 24946991). Proposed mechanisms include modulation of neurotransmitters such as GABA, dopamine, and serotonin, and potential neuroprotective effects via antioxidant and anti-inflammatory pathways (PMID 23155618, 29289576).

L-Valine is an essential branched-chain amino acid (BCAA) that plays a critical role in protein synthesis, energy production, and metabolic regulation. It is one of the three BCAAs—along with leucine and isoleucine—that are preferentially metabolized in skeletal muscle and contribute to muscle maintenance and recovery. BCAA supplementation, including valine, has been studied in clinical populations such as those with liver disease, where it may help correct the imbalanced ratio of BCAAs to aromatic amino acids (Fischer's ratio), potentially improving nutritional status and hepatic encephalopathy (PMID 17414498, 36184601). In patients with phenylketonuria (PKU), supplementation with large neutral amino acids like valine may competitively inhibit phenylalanine transport across the blood-brain barrier, reducing neurotoxic effects (PMID 23096009). However, in certain inborn errors of metabolism such as methylmalonic acidemia (MMA), valine intake must be carefully restricted due to its catabolic pathway producing propionyl-CoA, which exacerbates metabolic instability (PMID 26270765). No toxic effects of BCAA supplementation have been reported in clinical trials, suggesting a favorable safety profile in appropriate populations (PMID 17414498, 36184601).

N-acetyl-L-cysteine (NAC) is a modified form of the amino acid cysteine and serves as a precursor to glutathione, the body's primary intracellular antioxidant. It exerts multiple biological effects, including potent mucolytic, antioxidant, and anti-inflammatory actions. NAC has well-established use in acetaminophen (paracetamol) overdose by replenishing hepatic glutathione stores and detoxifying reactive metabolites (PMID 24080471). Beyond this, emerging evidence supports its role in modulating oxidative stress and inflammation in respiratory conditions such as chronic obstructive pulmonary disease, acute lung injury, and even in viral infections like COVID-19, where redox imbalance contributes to tissue damage (PMID 40141299, 32758904). NAC also shows promise in psychiatric and neurological conditions, including obsessive-compulsive disorder (OCD), where it modulates glutamatergic neurotransmission via the cystine-glutamate antiporter (PMID 26374743). Additionally, preclinical and clinical studies suggest protective effects against pesticide-induced toxicity and endometriosis by reducing cellular proliferation and promoting a less inflammatory phenotype, without adverse effects on fertility (PMID 20655527, 26946308). Despite its widespread use, the natural occurrence of NAC in dietary sources such as Allium species remains controversial and unproven (PMID 40931599).

PepForm Leucine peptides are bioactive peptide forms of the essential branched-chain amino acid (BCAA) leucine, potentially offering enhanced bioavailability and targeted physiological effects compared to free leucine. Research suggests that specific leucine-containing peptides, such as the tripeptide Leu-Ile-Lys, may exert protective effects in experimental nephrolithiasis by reducing oxidative stress and preserving renal tubular function, as demonstrated in a rat model of oxalate kidney stones (PMID 31655988). While free leucine supplementation has been studied for roles in muscle protein synthesis, metabolic regulation, and liver health, results are mixed. Leucine supplementation did not prevent weight gain or improve glycemic control in high-fat-fed rats (PMID 27544228), though systematic review data indicate potential benefits on glucose homeostasis in rodent models of glucose intolerance when administered at 90–140 mg/day during metabolic disease development (PMID 30264171). Leucine also supports protein metabolism and may benefit liver disease patients with BCAA deficiencies, commonly seen in advanced liver disease (PMID 24282351). However, evidence for PepForm specifically remains limited to preclinical models, and human data are lacking.