Why You Need Essential Amino Acids

If you are like most people, you have probably heard of “essential amino acids”, and that you need a certain amount of each. Amino acids are the basic building blocks that make up the larger proteins in our body. What you probably don’t know though is who decided that 9 amino acids are essential, or why. I dug into the research a little out of curiosity, and here is what I found.

There are nine essential amino acids, and they are the following:

  1. Histidine
  2. Isoleucine
  3. Leucine
  4. Lysine
  5. Methionine
  6. Phenylalanine
  7. Threonine
  8. Tryptophan
  9. Valine

The story all starts with rats. Early on in the 1900’s researchers attempted to keep rats alive by feeding it a protein powder derived from corn which contained only a single protein called zein. Turns out the rats died. Then they added some of the protein casein from cow’s milk and tada — they survived. This led them to wonder what the exact amino acids were which were required for the rat’s survival and general happiness. At 1931, Of the twenty amino acids known to be present in proteins, only lysine tryptophan, cystine and histidine were definitely established as essential dietary components [15].

One researcher which took a keen interest in figuring out the others was William Cumming Rose. In 1949, Rose got busy in his lab and created some wafers (which provided most of the rats calories) and liquid solutions containing varying amino acids (AAs). He kept the vitamin and calorie intakes of the rats constant, and most things the same. In biochemistry, there are 22 amino acids of special importance which are called “proteinogenic” amino acids which means protein-building. They are the known basic building blocks which are used to form a vast array of proteins used by animals.

William C. Rose

Although many amino acids were known to scientists then, and about 500 known today [1], Rose constructed the rat diets by varying them in the 20 proteinogenic AAs. What he determined by doing this was that he could eliminate some amino acids and the rats would keep growing fine with no symptoms of deficiency. In his first series of experiments, he one by one eliminated 10 of the amino acids and claimed that they were dispensable for rats [2]. He then went on to do the same in Humans and concluded that they are also dispensable for us, but that valine and methionine are indispensable. He observed that a deficiency in valine or methione is followed by “a pronounced negative nitrogen balance, a marked failure in appetite, a sensation of extreme fatigue, and a distinct increase in irritability. These symptoms manifest themselves even when the subjects are unaware that a dietary alteration has been made, and disappear when the missing amino acid is returned to the food.” Therefore establishing valine and methionine as being essential nutrients to man.

In 1951, with a sample of only two men as subjects, he went on to determine that threonine and histidine were also nonessential. He did this by using the method of measuring nitrogen balance. Nitrogen is a component of protein, and so by measuring nitrogen you can indirectly measure protein intake and loss. Nitrogen balance is a measurement of the input of nitrogen (via eating nitrogen containing protein) and how much is lost to urine, feces, sweat, hair, skin etc [3]. If you intake more nitrogen than you lose, you are said to have a positive nitrogen balance and this is considered a good thing as it is associated with growth, tissue repair, pregnancy, and health. If you lose more nitrogen than you intake, you are said to have a negative nitrogen balance, and this is considered a bad thing because it is associated with waste, tissue injury, burns, fevers, fasting, and lack of health [3]. What he noted was that you could eliminate threonine and histidine from their diets and their nitrogen balance would essentially be the same.

Again in ’51, he did another elimination experiment with isoleucine and determined that it had a larger effect on nitrogen balance than any other amino acid [4]. After the subjects reached negative nitrogen balance via isoleucine deficiency, he went on to eliminate histidine as well, which didn’t affect their balance as he expected. He then re-added isoleucine and their balance returned to normal, as he expected, even though histidine was still absent. Due to it’s significance on nitrogen balance, isoleucine was proclaimed to be an essential amino acid to man [4].

Nitrogen equilibrium remained significant in Roses investigations of the individual amino acids. By 1953 he had shown that Valine, Methionine, Threonine, Isoleucine, Leucine, and Phenylalanine were essential, and that the removal of these amino acids from the diet produced deficiency symptoms — “inducing a pronounced negative balance and is accompanied by a failure in appetite, a sensation of extreme fatigue, and an increase in nervous irritability. With the return to the diet of the missing amino acid, nitrogen equilibrium is reestablished promptly, and the subjective symptoms disappear.”[5]. In 1953, he proceeded to demonstrate the similar importance of Lysine and Tryptophan[6], and the unimportance of arginine [6], thus bringing us to a total of 8 essential amino acids. Lowering the intake of any of his 8 amino acids results in a lower nitrogen balance, indicating that the body is using more protein than it requires, which will soon result in deficiency symptoms. In summary: “Adult human subjects may be brought into nitrogen equilibrium upon diets in which 94 per cent of the total nitrogen is furnished by a mixture of the [eight] amino acids, other than histidine [and arginine], which were previously found to be essential for the growing rat.” [5].

Rose went about his business of conducting similar experiments as above, but now attempting to discover what the minimum requirements of each amino acid which is permits nitrogen balance when the diet gives sufficient quantities of the other seven amino acids. [7] He began with tryptophan, and noted that his subjects required differing amounts, and had no correlation with their bodyweight. But given that some people will need more than others, he recommended the requirement be whatever the person who needs the most needs, just to cover the contingency of being that person [7]. With positive nitrogen balance being the criterion of dietary adequacy, along with covering the people on the upper bound, he arrived at the first universal requirements of the 8 essential amino acids. Though note that he largely did these studies and arrived at his conclusions with a sample as little as 2–26 men. Anyhow, his requirements ended up being 250mg/day for tryptophan [6]; 1.10g/day phenylalanine [8]; 800mg/day lysine [9]; 500mg/day threonine [10]; 1.1g methionine/day [10]; 1.1g leucine/day [11]; 700mg isoleucine/day [11]; and finally 800mg valine [12]. Though two slight exceptions were made: the more tyrosine you consume, the less phenylalanine you need [13]; and the more Cystine you consume, the less Methionine you need [14].

But wait, isn’t Histidine an essential amino acid? In 1975, another exclusion study was done with the amino and proved Rose wrong, showing that although it doesn’t result in an immediately negative nitrogen balance like the others, it gradually does and subjects begin feeling ‘unwell’, develop skin lesions (like fine scales, dry skin) and high iron in their blood [16]. The deficient diet contained 60mg/day histidine, and the sufficient diet contained 1.2g/day. They added the Histidine back to their diets and it fixed the symptoms, thus establishing histidine as the ninth essential amino acid.

You can see the trend at this point that certain amino acids have been determined to be essential because nitrogen is a component of amino acids, and you can measure a human body’s use of nitrogen based on its output in urine, hair, skin, etc. When the nitrogen output exceeds the nitrogen input, the subject usually experiences ‘deficiency symptoms’ (or is expected to) such as low appetite, a sensation of extreme fatigue, and increased irritability. When the nitrogen balance is returned, the symptoms dissipate. In conclusion, an amino acid is determined to be essential or not based on whether it knocks us out of nitrogen-equilibrium. Ofcourse this is just the nitrogen-criterion, and a theoretical argument could be made the an amino acid is essential based on whether it causes any deficiency symptoms by itself.

Hope you enjoyed.

References

[1]https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.198308161#references-section

[2]http://www.jbc.org/content/188/1/49.long

[3]https://en.wikipedia.org/wiki/Nitrogen_balance

[4]http://www.jbc.org/content/193/2/605.long

[5]http://www.jbc.org/content/193/2/613.long

[6]http://www.jbc.org/content/206/1/421.long

[7]www.jbc.org/content/211/2/815.long

[8]http://www.jbc.org/content/213/2/913.long

[9]http://www.jbc.org/content/214/2/579.long

[10]http://www.jbc.org/content/215/1/101.long

[11]www.jbc.org/content/216/1/225.long

[12]www.jbc.org/cgi/pmidlookup?view=long&pmid=13271458

[13] www.jbc.org/content/217/1/95.long

[14]http://www.jbc.org/content/216/2/763.long

[15]www.jbc.org/content/94/1/155.full.pdf

[16]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC301830/