EAA - Essential Knowledge

EAA – The Essential Knowledge

If you are somewhat familiar with supplements, chances are you’ve at least heard of essential amino acids, known more commonly as the abbreviated EAA. They have been a very popular supplement in the sports nutrition industry, especially for the last decade or so with their use going from occasional to nearly every company producing their own version of it for sale, especially in the further isolated trio of BCAA. So, the question remains, what exactly are they, what are the benefits of using them. In this article, we will examine all of these areas, discuss the research behind them and help you make an informed choice of whether or not you want to invest in supplementing with EAA.

EAA – What Are They?

 The building blocks from which all proteins are created are amino acids. There are 20 amino acids that are found in the body and of those, 9 are considered essential and in these, 3 of them are considered the ever popular Branched Chain Amino Acids (BCAA). In other words, essential amino acids mean that unlike the other 11, they can’t be synthesized in the body and must be ingested through diet or supplementation (1). Furthermore, they are all crucial for our survival and proper function, so this also plays a role in what makes them essential.

L-Leucine, formally known as 2-Amino-4-methylpentanoic acid, is an essential amino acid that falls into the branched chain amino acid (BCAA) class along with isoleucine and valine. It is considered the ‘king’ of the amino acids, being the most potent inducer of protein synthesis on the molecular level (2). Upon ingestion, it is metabolized into several metabolites that have distinct roles and interestingly are often standalone supplements such as hydroxyisocaproic acid (HICA) and hydroxymethlybutyrate (HMB) (3). The primary mechanism of action of leucine is activation of Target of Rapamycin (TOR) which is referred to as mTOR in mammals. Specifically, leucine activates mTORc1 which is one of two subsets of the complex (4). Another mechanism of action is signaling via the insulin receptors to stimulate mTOR activation as it is known to stimulate insulin secretion from the pancreas as well as initially promote glucose uptake into muscle cells for an approximately 45 minute window, however isoleucine appears to promote glucose uptake better and for a longer period (5). It is important to note that this effect appears to be synergistic with carbohydrate ingestion in both insulin secretion and muscle protein synthesis (6). Though higher concentrations of Leucine are required for attenuating atrophy, it has also been shown to promote muscle protein synthesis even at low concentrations, offering an anti-catabolic effect. This muscle preserving effect has been noted in disease states characterized by muscle wasting and the benefits appear to be dose dependent (7).

L-Isoleucine, known by the chemical name 2-amino-3-methylpentanoic acid is an essential amino acid that is among the 3 classified as branched chain amino acids (BCAA) along with leucine and valine. The primary mechanism for which isoleucine is responsible is increasing glucose uptake independent of AMPK activation as well as acting as a mild activator of mTOR (8). It is also important to note that this increase in glucose uptake is independent of the two classic pathways of insulin receptors or AMPK activation (9). Having the the primary benefit of increasing glucose uptake into the cell, this is crucial as it works synergistically with the amino acid leucine in this regard. Isoleucine is also regarded as an anti-catabolic catalyst as it appears to reduce rates of gluconeogenesis (the conversion of non-carbohydrate substrates such as amino acids into glucose) (10).

L-Valine is one of the three essential amino acids that falls into the branched chain amino acid (BCAA) category along with leucine and isoleucine. It is metabolized in the body upon ingestion into 2-ketoisovalerate via an enzyme and then irreversibly into isobutyryl-CoA (11). Valine is known as a glucogenic amino acid as it can be converted into glucose via the liver, appearing to be fueled by the methyl carbons it possesses (12). L-Valine is useful in a variety of research supported applications. Such including stimulation of muscle protein synthesis, and elimination of excess nitrogen from the liver. There is also supporting data that valine may be helpful in treating liver and gallbladder diseases or preventing muscle loss at high altitudes (13). Valine is also an important amino acid when it comes to cognitive function and is used in the treatment of brain trauma (14).

L-Threonine is an essential amino acid that is one of the 20 common proteinogenic amino acids for humans and is used as a ‘building block’ for other amino acids in the body. It is naturally occurring through the diet or it can be synthetically produced in the laboratory setting via reaction on mercury acetate and crotonic acid, yielding a mixture of D-threonine and L-threonine, though only L-threonine is biologically active for humans (15). L-Threonine is used for a variety of functions in the body including supporting the connection of connective tissue, bone health, liver health and supporting the immune system. L-threonine has also been used as a part of treatment for various nervous system disorders including spinal spasticity (16), multiple sclerosis (17), and amyotrophic lateral sclerosis (18). The proposed mechanism for how l-threonine works in the body for aiding with these disorders is that it is chemically altered in the body to glycine which works with the brain to reduce constant, unwanted muscle contractions (19).

L-Phenylalanine, known by the chemical name 2-amino-3-phenyl-propanoic acid, is an essential amino acid that is found in 3 forms, including D-phenylalanine, L-phenylalanine, and the mix made in the laboratory called DL-phenylalanine. D-phenylalanine is considered a non-essential form of the amino acid and its role in humans isn’t understood. One the other hand l-phenylalanine is the one found in proteins and used as a building block of proteins (20). Phenylalanine is a precursor to multiple things including melanin, dopamine, noradrenalin, thyroxine and tyrosine (21). L-Phenylalanine has a wide array of benefits for use from both diet and supplementation. One interesting example is that it may be a pain reliever or work to enhance the effects of other pain relief medications (22). There is also supporting evidence that phenylalanine may when use in premenstrual syndrome and Parkinson's, enhance the effects of acupuncture and electric transcutaneous nerve stimulation (TENS) (23). Lastly, much like tyrosine, phenylalanine can have a catecholamine like effect, and help mediate a variety of the central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation (24).

L-Lysine is a naturally occurring, essential amino acid that is required for growth and repair tissue. It is found in a variety of foods including but limited to red meats, fish and dairy. The daily recommended amount for lysine intake is roughly 8g per day or 12mg/kg in adults, 44mg/kg for children and 97mg/kg for three to six-month olds (25). Interestingly, lysine was first used as a food additive rather than a supplement and it should be noted that vegetarian diets high in grains but low in legumes are particularly at risk for lysine deficiency (26). It also is important to note that lysine appears to interact with some trace minerals to allow them easier access into intestinal cells, however there is not conclusive evidence as to whether the inclusion of lysine with these minerals increases absorption (27). L-Lysine has been shown to have vital role in a variety of aspects. Research has shown that it is concentrated in muscle tissue and helps in the absorption of calcium from the intestinal tract (28), the promotion of bone growth (29), and the formation of collagen which is an important body protein that is the basic matrix of the connective tissues, skin, cartilage, and bone (30). A deficiency in lysine has been shown to contribute to reduced growth and immunity along with an increase in urinary calcium (31). This latter fact suggests that adequate lysine may help prevent osteoporosis through better absorption and utilization of calcium (32).

L-Histidine is one of the 23 proteinogenic amino acids that has an imidazole functional group. It is produced in small amounts by the body so it must be predominantly sourced from diet and is considered an essential amino acid for this reason. L-histidine is found in a variety of protein rich foods, produced exclusively by young plant tissues and passed to animals via the food chain. The natural L-histidine content in foods will vary depending on storage conditions and preparation methods and may differ from the standard value (33). L-Histidine plays a vital role in numerous functions within the human body. First and foremost, L-histidine has the important characteristic that it can be converted into various substances including but not limited to histamine, glutamate and hemoglobin (34). It also has a role in various aspects of metabolism and ensures oxygen supply to all the tissues and organs of the body (35). Research has also indicated it to be a building block for iron containing molecules which is vital as it ensures a sufficient energy supply in the cells and can detoxify the body of heavy metals through its ability to combine with them (36). It has also been observed that L-histidine is necessary for the formation of the myelin sheath and can be used to prevent degenerative conditions such as Alzheimer’s (37). Lastly it has also been suggested that L-Histidine can have a therapeutic effect for inflammation and can therefore be used in the treatment of arthritis and allergies (38).

L- Methionine is a sulpher containing amino acid that is required for growth and tissue repair. Additionally, it is a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals (39). There are also A number of studies report beneficial effects of methionine dietary supplementation on gut function, including improvement of the mucosal villus architecture, as well as methionine intake-associated decreased risk of colon cancer (40).

L-Tryptophan is an essential amino acid that was first discovered in the 1900s from casein protein. Interestingly, in humans, tryptophan has relatively low tissue storage and the overall tryptophan concentration in the body is the lowest among all amino acids, although only small amounts are necessary for general healthy nutrition (41). Dietary sources include oats, bananas, dried prunes, milk, tuna fish, cheese, bread, chicken, turkey, peanuts, and chocolate and the average intake for individuals is around ~1000mg a day (42).

What Makes BCAA Different Than The Other EAA?

Now, of these essential amino acids, three are regarded as BCAA and these include leucine, isoleucine and valine. They are quite different than the other amino acids as they are transported directly to the blood stream through the liver, whereas other amino acids are broken down and degraded. Instead, the liver takes the BCAAs and oxidizes them rather than metabolizing them directly and instead they are metabolized in the muscle tissue of the body (43). This is the biggest differentiating factor between BCAA versus the other essential amino acids.

In the muscle tissue, the specific enzymes needed to break down BCAA are mitochondrial dehydrogenase and branched-chain keto acid dehydrogenase BCKADH (44). After they are broken down into keto acids, they can be used as a fuel source in the muscle via the Krebs cycle or returned to the liver to be oxidized. Since muscle is designed in a way to use BCAA as fuel, in recent years, some companies have incorporated ketone versions of BCAA products to prevent the use of BCAAs as an energy source by the liver and instead utilized preferably for muscle. This is a promising concept considering roughly 35% of all muscle tissue is composed of BCAA and it is estimated that 3-18% of all skeletal muscle energy during training is provided by BCAA (45).

Now, with each of the three BCAA, there are notable, specific benefits associated with each. Often considered the ‘king’ of all the amino acids, Leucine is one of the most beneficial amino acids all around, By itself it can stimulate muscle protein synthesis which is the process responsible for muscle growth and recovery (46). 

Isoleucine is much like leucine and can stimulate protein synthesis as well; however it is to a lesser extent when it isn’t combined with the other BCAA. One main benefit that isoleucine does have, however, is that it can significantly increase glucose uptake and the usage of glucose during exercise, leading to greater energy production (47). Interestingly, it has also been observed that isoleucine may prevent fat storage by stimulating the receptors that inhibit fat storage and increase fat burning, though this has yet to be studied further in humans (48).

The third and final BCAA, valine, is known for its effects in promoting muscular endurance and decreasing fatigue during exercise. The mechanism of action is through valine competing with and winning against tryptophan for entry into the brain. Tryptophan converts to serotonin which signals to the body that it is fatigued, therefore leading to decreases in muscle endurance and strength, so by preventing tryptophan from entering the brain, valine prevents fatigue (49).

In regards to the ratio for how these amino acids should be consumed for maximal benefit, the scientifically supported ratio is 2:1:1, meaning 2 parts leucine to 1 part isoleucine and valine respectively. A majority of the supporting data for BCAA supplementation was conducted using this 2:1:1 ratio, though there is emerging, promising data that has shown benefits to a few other various ratios.

Benefits – Backing BCAA With Science

There are some very notable benefits of EAA supplementation. From the compilation of the research conducted, the most notable areas which we will expand on include their role in interacting with glucose metabolism, muscle building, fat loss and neurology.

On the neurological level, this is dealing with factors of perceived exertion and fatigue, looking specifically at the central hypothesis of fatigue which assumes that elevated serotonin concentrations in the brain are associated with induction of fatigue (50). As we mentioned briefly before, tryptophan converts to serotonin which in turn is responsible for signaling fatigue in the brain. This is brought on and exaggerated by exercise as it has been observed that exercise can increase tryptophan uptake by the brain in 30 minutes or less (51). So, in theory, since EAAs, specifically valine utilize the same transport to the brain, it is believed that supplementation can reduce the uptake of serotonin translating to a hindrance of fatigue (49).

In regards to glucose management, first and foremost is the role they appear to play in muscle glycogen. Research suggests that the supplementation of EAA (specifically the BCAA) during exercise can preserve both muscle and hepatic glycogen stores during and following training (52). This proposed mechanism is a result of the increased fat oxidation which may attenuate the decline in glucose seen during prolonged exercise.

Another area that EAA supplementation has shown benefits is that of their effects on muscle building and fat loss. During training, the contraction of skeletal muscle causes normal and necessary breakdown of the tissues. EAA supplementation has been shown to have a muscle sparing effect largely as a result of leucine, due to its ability to stimulate the mammalian target of rapamycin, more commonly known as mTOR which plays a critical role in stimulating protein synthesis (the rebuilding process of muscle) (53).

Furthermore, aside from being able to stimulate mTOR directly, leucine also appears to be able to promote protein synthesis via the increase of insulin secretion (54). This is important as insulin is one of the most anabolic hormones in the body and signals anabolic (building) response.

Last but not least, there is promising data that EAA can aid in fat loss while sparing muscle. As we covered earlier, isoleucine may prevent fat storage by stimulating the receptors that inhibit fat storage and increase fat burning (48). On top of this, research has indicated that leucine increases the release of fat cells (adipocytes) to be used as fuel rather than other energy sources (55). Combined with the characteristics of EAA to help spare muscle, this helps create the ideal scenario to preventing the loss of muscle while dieting to reduce body fat.

Do I need just BCAA or all EAA?

             This is one of the hottest topics of the last few years and many have gone as far as saying that BCAA by themselves are worthless or even counterproductive to building muscle. This stems from the fact of how muscle is built. Keeping it in a simplified version, muscles are made up of amino acids and synthesizes new protein (muscle) from the amino acids you ingest. The issue is that muscle protein synthesis (creation) only occurs when all 9 essential amino acids are present, and without all of them, it doesn’t happen.

Some say that in theory that if you’re ingesting BCAA and sparking the illicit response that they have without all of the essential amino acids available, it will have no positive effect. The thing is, that if proper nutrition is in place, having a diet rich in protein the body will be perfectly fine. You see, the body is an amazing machine and can use amino acids ingested as needed, so even if you aren’t consuming all EAA with your BCAA, so long as your diet is on point, you’ll still have amino acids available to work toward muscle protein synthesis upon the trigger that leucine provides. It never hurts to use a full spectrum formula to optimize your muscle growth potential, but saying that BCAA alone are pointless is ridiculous.

EAAs Consumption – Supplements vs. Whole Foods/Protein Powder

Now the next topic that arises quite a bit is in regards to the consumption of EAA in pure, supplement form compared to ingesting them via protein powder or whole foods. Yes, there are definitely adequate amounts of essential amino acids in protein powder and whole foods that will allow you to reach the daily requirement, however the supplement version does have advantages and makes it the optimal choice.

First off, the EAAs in whole food and protein powders are peptide bound to other amino acids, meaning they must be broken down and freed through the digestive process before being able to enter the blood stream. Even though it is regarded as the fastest digesting protein available, whey protein still takes several hours to be broken down and digested before the amino acids are unbound and whole foods require an even longer time.

With this in mind, the supplement form of EAA are already free-form, meaning that they don’t required this same digestion and are rapidly absorbed into the blood stream to be shuttled to the muscles. Furthermore, this rapid absorption will spike amino acid levels to a greater extend and much more rapid rate than the peptide bound aminos in whole food and protein powders, having a much more immediate impact on kick starting protein synthesis and promoting anabolism (building/muscle sparing).

Another positive of this is that with the unique nature of EAA bypassing the liver, they provide an immediate source of energy for the muscle during workouts with no digestion required. This is due to the nature of muscle to use EAA as energy, especially for the isoleucine and valine which are considered glucogenic amino acids as they can be an immediate energy source after converting to glucose (56).

The last advantage that EAA have over whole food sources is that they are ideal to be used during and immediately before your workout. The reason for this is that both digestion and training require increased blood flow from the body. If you ingest food too close to training, this can cause issues as the blood needed for the digestive system is diverted to the working skeletal muscle and away from the digestive system and this can cause cramping and other gastric distress.

Essentially the End

             We’ve covered a lot of material in this article, specifically the characteristics of each of the EAA and some of their effects in the body. I hope that this helps you have a firmer grasp of the specifics of why each amino acid is important and make an informed choice on why you may or may not want to supplement with EAA (including BCAA). There is much to be discussed on the topic, but that is for a later day. Pre, intra or post workout, EAA supplementation is growing exponentially and is here to stay.

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