Multiple Nutritional Effects of Essential Amino Acids

Protein and amino acids are the basic organic compounds of cells and the main undertaders of life activities. They have important physiological functions such as promoting muscle growth, improving immunity and relieving fatigue. Amino acids are the basic building blocks of proteins. There are 20 kinds of natural amino acids that make up proteins [1]. From the perspective of nutrition, these amino acids can be classified into essential amino acids, conditional essential amino acids and non-essential amino acids. Essential amino acids must be supplied from an exogenous diet because the body lacks the metabolic pathways needed to synthesize them [2,3]. Although variations are possible depending on the metabolic state of an individual,

the general held thought is that there are nine essential amino acids, including Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan and Valine. All nine essential amino acids have an important impact on human health. They’re involved in many processes, including tissue growth, energy production, immune function and nutrient absorption. The amount of essential amino acids in food intake will affect the balance of amino acids in the human body. Essential amino acids, in addition to their normal physiological functions, can also be used as nutritional supplements and play an important role in different populations. A large number of studies have shown that essential amino acids can promote the synthesis of muscle protein, inhibit its degradation [4], recovery after exercise [5] and enhance endurance during exercise [6]. Improves age-related muscle decay [7] and even has a positive effect on bone health [8].

Protein supplementation by athletes has a long history. Even in the ancient Greek Olympic Games, high-protein diets have been popular among athletes. Protein requirements increase with the intensity of exercise, and protein intake of power athletes is usually 50% to 100% higher than that of sedentary person [9]. During exercise, there is a decrease in the amount of muscle protein produced, and conversely, there is an increase in the amount of muscle protein breakdown resulting in a decrease in the total muscle protein. High intensity exercise can also damage muscles. This can lead to decreased muscle condition, which can lead to decreased athletic performance. To gain skeletal muscle mass, the rate of muscle protein synthesis must exceed the rate of breakdown. Protein synthesis can be stimulated by resistance exercise in combination with amino acids, and both factors mediate this effect by activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway [10].

Rapid aminoacidemia in the postexercise period enhances Muscle Protein Synthesis (MPS) and anabolic signaling to a greater extent, the intake of slowly digested proteins or the intake of large amounts of fat and/or carbohydrates, which would slow gastric empting and protein absorption and would also likely reduce the rates of MPS during post-exercise recovery [11]. Børsheim et al. [12] found a dose of 6 g of orally administered Essential Amino Acids (EAAs) stimulates net muscle protein balance in healthy volunteers when consumed 1 and 2h after resistance exercise. It is also concluded that non-essential amino acids are not necessary to stimulate muscle protein net balance (NB) and that there is a dosedependent effect of EAAs ingestion on muscle protein synthesis.

Evidence suggests that leucine plays a major role in stimulating muscle protein synthesis [13]. Muscle protein production rate depends on the amount of leucine in the essential amino acids. essential amino acids containing an high ratio of leucine increase the rate of muscle protein production compared to conventional essential amino acids. The research of Stefan MP et al. [14] indicated Muscle Protein Synthesis (MPS) was 33% (P<0.05) greater when increasing the concentration of leucine in an EAA supplement consumed during recovery of exercise [14]. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength and it is strictly correlated with physical disability, poor quality of life and death [15]. The weakened skeletal muscle protein synthesis response to food/nutrition in the elderly may be the cause of sarcopenia. Therefore, stimulating the synthesis of skeletal muscle protein is the most effective method to prevent and treat sarcopenia in the elderly. Studies have shown that oral administration of essential amino acids is an effective nutritional strategy to promote skeletal muscle protein synthesis in the elderly [16,17]. Dillon et al. [18] reported that the muscle protein synthesis rate was stimulated and the lean body mass was increased by the ingestion of 7.5g of essential amino acids twice a day for 3 months in elderly women. The muscle protein synthetic response is a saturable process, it seems apparent that there is an optimal dose of essential amino acids needed to maximally stimulate muscle protein synthesis in elderly; with too few essential amino acids potentially dampening the synthetic process, and too many essential amino acids saturating the synthetic system.

Another study demonstrated that the use of an essential amino acids mixture with an increased leucine more efficiently stimulated skeletal muscle protein synthesis in the elderly. Japanese women (aged >75 years) with sarcopenia who ingested 3g of leucineenriched essential amino acids twice daily and moderate intensity exercise for 3 months gained muscle mass and strength as well as increased walking speed [17]. Studies have shown that essential amino acids not only affect skeletal muscle protein synthesis in healthy people, but also have a positive effect on patients with disease. An eight-week intervention consisting of a leucineenriched amino acid supplementation and low-intensity resistance training increased muscle mass, strength, and physical function in post-stroke patients with sarcopenia [19].

Exhaustion, as well as fatigue, will sooner or later occur depending on different forms of exercise. It is characterized by a decreased performance linked with an increase in real or perceived difficulty to overcome a task or exercise [20,21]. Although studies related to exhaustion are common, etiology has not been fully elucidated. It may be related to the dysfunction of the immune and endocrine system, inflammatory response, and antioxidant defense system [20,22]. It is worth emphasizing that restoring fatigue and exhaustion caused by exercise requires repairing the damage that has occurred in the body and removing the metabolites accumulated during exercise [20,23]. Blood Urea Nitrogen (BUN) is one of the blood biochemical parameters related to exhaustion and a metabolite of protein and amino acids [24]. Blood Lactic Acid (BLA) is produced by anaerobic glycolysis, which can be further degraded through the tricarboxylic acid cycle to produce ATP or transferred to other tissues for oxidation or gluconeogenesis. It is an important parameter of exhaustion [20,25]. Glutathione (GSH) is one of the most important biomarkers of antioxidant capacity. It is closely related to the recovery of exercise-induced exhaustion [20, 22,26]. The study [6] showed Leucine enriched essential amino acids exerted better exhaustion amelioration effects by increasing exhaustion time of rats, reducing the accumulation of BLA and BUN caused by exercise, and increasing the GSH content to quickly restore the antioxidant capacity. The result suggested that leucine-enriched essential amino acid supplementary after exercise may play a more important role in improving recovery of exhaustion in endurance exercise. Repeated performance of highforce, eccentric muscle contractions or unaccustomed exercise can cause tissue damage in the affected muscles [27]. Muscle tissue damage is accompanied by the leakage of proteins such as Creatine Phosphokinase (CPK) and myoglobin, from the muscle tissue into the bloodstream [28]. Since muscle tissue

damage deceases muscle strength and range of motion, it can have a profound effect on the ability to perform subsequent bouts of exercise [29]. Thus, alleviating muscle damage and aiding recovery from muscle damage is necessary for athletes to maximize their performance. In a randomized, double-blind, placebo controlled crossover study, researchers demonstrated that the relative increase of the peak serum CPK activity was significantly lower in Leucine-enriched essential amino acids ingestion than in placebo ingestion Thus, the findings indicate that Leucine-enriched essential amino acids intake decreases the level of muscle damage and promotes recovery after exercise in humans [5].

The aging process is characterized by changes in body composition, such as an increase in body fat, and a reduction in lean mass and bone density (osteopenia) [30]. Osteopenia, which increases the incidence of fractures, is one of the largest musculoskeletal disorders and a leading cause of death in the elderly. Muscle and bone are two interconnected tissues [31]. Essential amino acids supplement has been shown to improve muscle function in the elderly with normal activity [18] and during bed rest [19,32].

A Chinese study found that in older community-dwelling adults of 1424 men and 1573 women with a mean age of 72 years, serum valine, leucine, isoleucine, phenylalanine, tryptophan, and tyrosine were significantly lower in osteoporosis subjects [33]. Another study in monozygotic twins demonstrated the genetic independent benefit of several specific amino acids (leucine in particular) intakes for bone health [34]. Serum essential amino acid levels in subjects with osteoporosis are not always consistent across studies; Therefore, there is no accepted conclusion on the correlation between serum essential amino acids and bone mass. Although in people who receive additional essential amino acid supplements, most studies have shown that essential amino acids are beneficial to bone mineral density [8]. With the possibility of more research in the future, the correlation between essential amino acids and aging bone metabolism should become clearer.

Essential amino acids play an important role in maintaining normal metabolism, homeostasis and health. They have a wide range of physiological and biological functions. Currently, Essential amino acids are known to have a beneficial effect on the anabolic reaction of muscle protein, protecting and repairing the damage of skeletal muscle and myocardium caused by exercise stress, and improving exercise endurance. Furthermore, Essential amino acids have a positive effect on age-related muscle decay and disease-induced sarcopenia and bone health. The optimal ratio of essential amino acids needs to contain the correct amount of leucine. The anti-aging gene Sirtuin 1 is critical for the function of various tissues, sarcopenia and bone health. Leucine is a Sirtuin 1 activator and with other Sirtuin 1 activators is connected to reversal of age-related muscle decay, sarcopenia and bone health [35-40]. However, the body also has differences in the absorption and utilization of different essential amino acids. Only further research and exploration of the interaction, regulation mechanism, optimal ratio and other functions among essential amino acids can provide a more favorable basis for rational use and make them play a greater role.

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