Calum Gore is an expert in medical biochemistry and health and the founder of biochemical diagnostic testing services company Gore BioScience. He is based in Leicester, Leicestershire.
The essential amino acids leucine, isoleucine and valine together make up the branched chain amino acids (BCAAs). In total they comprise 30% of the body’s total muscle protein.
The fitness industry, athletes and bodybuilders have long used BCAAs for many of the following perceived benefits: increased protein synthesis; increased muscular hypertrophy; improved exercise recovery; increased muscle endurance; improved glucose disposal; increased energy; and increased gluconeogenesis, which is the metabolic process in which glucose is derived from non-carbohydrate sources.
These claims are supported by a significant amount of research, although some more than others. Consequently, there have been some extreme recommendations of BCAAs usage because of the potential benefits. But one aspect that is rarely discussed or even acknowledged is how the overuse of BCAAs can result in other important nutrients being depleted.
When you consume any substance it requires the action of specific enzymes to metabolise them, and these enzymes are all nutrient dependent. So the more of a substance you put into the body, the more you will deplete specific nutrients. To understand these potential side-effects we need to examine the biochemistry behind BCAAs.
In skeletal muscle BCAAs are converted to branched chain keto acids, which requires an enzyme called branched chain keto acid dehydrogenase. This enzyme requires the presence of the active form of vitamin B, or cofactor Pyridoxal 5 Phosphate (P5P).
This is the primary reason why vitamin B6 is critical for amino acid metabolism. High levels of BCAAs in the urine can indicate a depletion of B6. On a side note, the presence of xanthurenate and kynurenate will also be a high in the urine and are consequently definitive markers for B6 deficiency. We have an organic urine acid test, which measure xanthurenate, kynurenate and BCAA levels as part of our toxicology profile.
The keto acids are catabolised by another enzyme called branched chain a-ketoacid dehydrogenase complex. This is a multi-nutrient dependant enzyme, requiring thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5) and lipoate from lipoic acid. Again, high levels of BCAAs in the urine can indicate a depletion of these important nutrients.
The brain connection
In the brain BCAAs also play a key role in the control of serotonin, a neurotransmitter that regulates mood and relaxes you, by competing with tryptophan (which is converted into serotonin in the brain) for entry past the blood-brain barrier (BBB).
BCAAs will also compete with tyrosine to cross the BBB, which is converted into dopamine, the neurotransmitter that is associated with being happy. As already discussed, you can see that BCAAs can block the absorption of tryptophan into the brain and also deplete vitamin B6. So BCAAs in my opinion can have a severe effect on your serotonin output, which can drastically change your mood, even potentially leading to depression.
The importance of vitamin B6 to the body is an article in itself and the importance of this vital vitamin cannot be stressed enough. It is a cofactor for more than 60 amino acid conversions, with some enzymes playing a role in BCAAs conversions, as detailed above, and also the important conversions of neurotransmitters in the brain. These include the enzyme GAD, which converts glutamate to GABA, the very important neurotransmitter regulating mood, and the conversion of tryptophan to serotonin.
A deficiency in vitamin B6 leads to a slow conversion process or no conversion process at all. General deficiency problems include neurotransmitter problems; decreased haemoglobin production, leading to certain anemias, and seborrheic dermatitis, an inflammatory skin disorder affecting the scalp, face and torso.
While BCAAs do provide many benefits it should be clear by now that their consumption can result in certain nutrients being depleted that will lead to unwanted side effects, including depression. So when using BCAAs you must consider the nutrients needed to convert them for use and make sure to supplement these as well.
We recommend that when taking BCAAs you must also take a good vitamin complex at the same time, and not just straight vitamin B6 because of the cofactors needed. Taking 5-Hydroxytryptophan (5-HTP), a metabolic intermediate in the biosynthesis of serotonin and melatonin from tryptophan, two hours after your BCAAs will help restore serotonin levels, and 5-HTP converts to serotonin very easily with little nutrient dependent enzymes. Taking tyrosine one hour before BCAAs will also help your dopamine levels.
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