Amino acids

The Essential Amino Acids (EAA)

In the healthy adult, there are nine Essential Amino Acids: Leucine, Isoleucine, Valine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Histidine. Each performs specific functions that cannot be replicated by the others:

• Leucine — main activator of muscle protein synthesis through the mTOR (mammalian target of rapamycin) pathway. It is the most studied amino acid in the context of sports performance and muscle mass maintenance.
• Isoleucine — participates in protein synthesis and muscle energy metabolism. Together with Leucine and Valine, it forms the BCAA (Branched-Chain Amino Acids) group.
• Valine — third component of BCAAs. Involved in muscle energy metabolism and maintenance of nitrogen balance.
• Lysine — a structural component of Collagen and Keratin. Plays a role in calcium absorption and carnitine production, which is involved in lipid metabolism.
• Methionine — a precursor of cysteine, taurine, and S-adenosylmethionine (SAM), a universal donor of methyl groups involved in numerous biochemical processes including the synthesis of endogenous Creatine.
• Phenylalanine — precursor of tyrosine, dopamine, adrenaline, noradrenaline and melanin. Involved in the regulation of mood and neurological function.
• Threonine — structural component of collagen and elastin. Contributes to immune system function and intestinal mucosal health.
• Tryptophan — precursor of serotonin and melatonin. Plays a role in the regulation of sleep, mood and stress response. It is the Essential Amino Acid found in lower amounts in common protein sources.
• Histidine — precursor of histamine, involved in immune response. Considered essential in adults, while in children its essentiality is more pronounced due to its role in growth support.

The deficiency of even one Essential Amino Acid is sufficient to limit protein synthesis in the body-regardless of the availability of the others. This principle, known as the law of the minimum applied to protein nutrition, underlies the importance of assessing protein quality not just in terms of quantity but in terms of the completeness of the amino acid profile.

The BCAAs: leucine, isoleucine and valine

BCAAs (Branched-Chain Amino Acids) are a subgroup of three Essential Amino Acids-Leucine, Isoleucine, and Valine — that share a branched side-chain chemical structure. This structural feature distinguishes them from other EAAs by their metabolism: BCAAs are primarily oxidized in skeletal muscle, not in the liver, making them available as a direct energy substrate during exercise.

BCAAs were among the first amino acid supplements to become popular in the sports nutrition market, with an extensive research literature behind them. The strongest evidence concerns their anticatabolic role — reduction of muscle protein breakdown during prolonged exercise — and tryptophan-mediated reduction of central fatigue. Leucine in particular is the main molecular signal that activates post-exercise muscle protein synthesis.

The most common ratio in formulations is 2:1:1 (Leucine:Isoleucine:Valine), although formulations with a ratio of 4:1:1 or higher, which increase the Leucine portion to maximize mTOR stimulation, are also common. More recent research tends to prefer complete EAA formulations over BCAAs alone, as the supply of all Essential Amino Acids ensures a more complete protein synthetic response.

Conditionally Essential Amino Acids

Some amino acids that are normally synthesizable by the body become indispensable under specific conditions. The most relevant for nutraceutical formulation are:

• Glutamine — the most abundant amino acid in plasma and skeletal muscle. Under conditions of high metabolic stress (intense exercise, illness, surgery), endogenous synthesis is insufficient to meet requirements. Plays a role in supporting immune function and intestinal mucosal integrity.
• Arginine — nitric oxide (NO) precursor, an endogenous vasodilator involved in the regulation of muscle blood flow. Used in pre-workout formulations for vasodilation and recovery support. Precursor of endogenous Creatine along with Glycine and Methionine.
• Cysteine — component of Glutathione, the major endogenous antioxidant. Its synthesis depends on the availability of Methionine.
• Glycine — structural component of Collagen (about 33% of amino acid composition). Involved in Creatine and Glutathione synthesis. In some formulations it is combined with Magnesium (Magnesium Bisglycinate) as a carrier to increase bioavailability.

Protein quality: PDCAAS and DIAAS

The quality of a protein source is assessed not only by the amount of Protein per gram but by the profile and digestibility of the Amino Acids that make it up. The two most commonly used evaluation systems are:

• PDCAAS (Protein Digestibility Corrected Amino Acid Score) — FAO/WHO system introduced in 1993. Assesses protein quality based on Essential Amino Acid profile and fecal digestibility. The maximum value is 1.0 – achieved by whey, egg and soy proteins.
• DIAAS (Digestible Indispensable Amino Acid Score) — newer system (FAO/WHO 2013), considered more accurate because it measures ileal digestibility of each individual Amino Acid instead of total protein digestibility. It is EFSA’s recommended parameter for assessing protein quality in supplements.

The relevance for formulation is concrete: a protein source with high DIAAS ensures a higher net availability of Essential Amino Acids for protein synthesis, for the same grams of protein declared on the label. Whey protein and egg albumin achieve the highest values; plant-based proteins generally have lower DIAAS, but the combination of different sources (rice + pea, for example) allows for complete amino acid profiles even in plant-based formulations.

Creatine and Amino Acids: an endogenous synthesis

A concrete example of the interconnection between Amino Acids and other nutraceutical ingredients is Creatine: the body synthesizes it endogenously from three Amino Acids — Arginine, Glycine, and Methionine. Adequate intake of these precursors through diet or supplementation is the necessary condition for endogenous synthesis to occur efficiently. Those on a vegetarian or vegan diet, lacking the major dietary sources of Creatine (meat and fish), often have lower muscle reserves that can benefit from both direct Creatine supplementation and optimized supply of the precursor Amino Acids.

The forms available for formulation

Amino acids in supplements come in different forms, with implications for bioavailability, palatability, and application:

• Free Form (L-amino acids) — Amino acids in pure crystalline form, not bound to peptides or proteins. Rapidly absorbed, do not require protein digestion. Reference form for BCAAs and EAAs in sports nutrition supplements.
• Protein Hydrolysates — Protein partially enzymatically digested into di- and tri-peptides. Faster absorption than whole protein, complete amino acid profile. Used in hydrolyzed whey protein (whey hydrolysate).
• Whole Protein Powder — Whey concentrate/isolate, casein, vegetable protein (pea, rice, soy, hemp). The amino acid profile depends on the source. Plant-based formulations often require the combination of multiple sources to achieve a complete EAA profile.
• Chelate Forms — Amino acids bound to minerals as carriers to increase their bioavailability (Magnesium Bisglycinate, Zinc Bisglycinate). In this case the Amino Acid performs a transport function as well as a nutritional function.

Adequate protein intake through a varied diet is generally sufficient to meet the Essential Amino Acid requirement in the healthy adult population. Supplementation with Free Amino Acids or BCAAs is particularly designed in the context of sports performance, muscle recovery, and situations of increased requirements.

Always remember that it is important to consult a health care professional before starting any new supplement or treatment.