The central nervous system (CNS) requires several amino acids obtained from dietary sources. Arginine, histidine, tryptophan, and tyrosine are amino acids that serve as precursors for neurotransmitter and neuromodulator synthesis essential for brain function. Research indicates that the peripheral concentration of specific amino acids help regulate cognitive performance, central neurotransmission, and mood state. For example, low levels of tryptophan are associated with reduced CSN serotonin synthesis, which may negatively impact mood, behavior, and memory.1
This post discusses the best amino acids for supporting brain health, highlighting the role of N-Acetyl-L-leucine (NALL), and why you should consider taking an advanced NALL supplement. Use the links below to jump ahead to different topics on the page.
What are Essential Amino Acids?
The body regularly degrades and resynthesizes proteins and other nitrogenous compounds from dietary sources. The body synthesizes several times more protein than it ordinarily consumes, indicating its reutilization of amino acids. The by-products of this amino acid metabolism, including urea, creatinine, uric acid, and other nitrogenous products, are excreted in the urine. As a result, a continuous supply of dietary amino acids is required to compensate for the loss of nitrogen from the body through the feces, sweat, other bodily secretions, and the growth of hair and skin.
Essential amino acids are dietary essential or indispensable nutrients that are not synthesized by the body. The nine essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. The body also produces non-essential amino acids, including alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine.
The following table highlights the top well-studied amino acids for supporting brain health that are often found as ingredients in nutritional supplements.
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Top Well-Studied Amino Acids for Brain Health |
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How Amino Acids are Transported to the Brain
The amino acid composition of the food you eat is of greater consequence to the brain than any other of the body’s organ systems. The brain cannot simply absorb the nutrients it needs from the general circulation; it only receives the needed nutrients that are transported across the blood-brain barrier (BBB). The BBB isolates the brain from the body’s general circulation. While lipid-soluble compounds can typically passively cross the BBB, water-soluble compounds, such as amino acids, require special mechanisms for selective transportation into the brain.
At least three active mechanisms transport amino acids into the brain. Separate mechanisms exist for the transport across the BBB of large neutral amino acids, basic amino acids, and acidic amino acids.
Amino Acid Derivatives
Amino acid derivatives are synthesized through various biological pathways and enzymatic processes. Chemically, amino acid derivatives are compounds formed by modifications to the amino acid structure through methylation, phosphorylation, hydroxylation, and acetylation. These modifications alter the properties and functions of amino acids, thereby making the amino acid derivatives crucial in cellular signaling and regulation.
For example, the phosphorylation of serine, threonine, and tyrosine residues is a key step in signal transduction pathways. The phosphorylated amino acids behave as molecular switches, turning on or off various cellular processes.
The complex derivatives of amino acids include:
- Peptides: These are short-chain amino acids linked by peptide bonds and function as hormones, neurotransmitters, or antibiotics.
- Proteins: These are large and more complex structures consisting of one or more polypeptide chains. They serve as enzymes, structural components, signaling molecules, and transporters.
- Non-protein derivatives: These include neurotransmitters and metabolic intermediates that play specialized roles in cellular functions.
Other examples of complex amino acid derivatives include glutathione, which is a tripeptide, and collagen (the structural protein that provides strength and elasticity to connective tissues). N-Acetyl-L-leucine (NALL) is also an amino acid derivative, a modified, acetylated derivative of the natural essential amino acid leucine.
Pharmacologic Effects of N-Acetyl-L-leucine (NALL)
N-Acetyl-L-leucine has been conventionally used to address the symptoms of acute vertigo — the sudden, severe spinning sensation that can last up to 24 hours. It has been in use in France to alleviate vertigo and vertiginous symptoms for more than 50 years.
The following table highlights the pharmacologic effects of NALL for promoting brain health.*
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Pharmacologic Effects of N-Acetyl-L-leucine |
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The neuroprotective mechanism of action of NALL remains unclear. Research indicates that it might involve the activation of autophagy, the cellular degradative process in which damaged, aged, or superfluous cells are enclosed within double membrane-bound organelles called autophagosomes and delivered to lysosomes for degradation.*
Autophagy is critical for removing unnecessary cellular components that might otherwise prove detrimental to the survival of neurons. Autophagy is a cytoprotective process, and the neuroprotective function of NALL in traumatic brain injury might be mediated through autophagic activation.*
Efficacy and Safety of N-Acetyl-L-leucine
Amino acid derivatives are widely used as nutritional supplements to support various health functions. Branched-chain-amino acids (BCAAs) are particularly popular supplements to promote brain health and muscle protein synthesis and recovery.*
The efficacy and safety of NALL have been investigated for several lysosomal disorders, and its positive effects are directly correlated with its pharmacological actions. The amino acid derivative was observed to be well-tolerated in all observational and clinical studies with no reports of serious adverse reactions.6
Including An Advanced NALL Supplement in Your Diet
The oral intake of NALL supplements is preferred because this route of administration is more clinically relevant and has been shown to be safe and effective. However, the bioavailability of NALL is low (10-15%) when taken orally.7
When considering the best amino acid supplements for brain health, you should consider a NALL supplement. You should look for a formulation that enhances the bioavailability of the amino acid derivative. N-Acetyl-L-leucine, developed by Tesseract Medical Research, enhances the absorption and bioavailability of the active nutrient through the proprietary CyLoc® – DexKey® nutrient delivery nanotechnology. Tesseract’s CyLoc® technology encases each NALL molecule in its own dextrin fiber delivery cage. Tesseract’s DexKey® technology accompanies each CyLoc® molecule and breaks the dextrin fiber cage at the desired point in the intestinal tract for the optimal absorption and bioavailability of the NALL molecules.
The power of Tesseract supplements lies in enhancing palatability, maximizing solubility, absorption and bioavailability, and micro-dosing a single or multiple nutrients in a single, highly effective capsule. Shop products on our website and learn more about how they support neurological health.*
References
1Jenkins TA, et al. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain aAxis. Nutrients vol. 8,1 56. 20 Jan. 2016, doi:10.3390/nu8010056
2,5Günther L, et al. N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus. PloS One vol. 10,3 e0120891. 24 Mar. 2015, doi:10.1371/journal.pone.0120891
3Kaya E, et al. Acetyl-leucine slows disease progression in lysosomal storage disorders. Brain Communications vol. 3,1 fcaa148. 20 Dec. 2020, doi:10.1093/braincomms/fcaa148
4Bremova-Ertl T, et al. Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C.” Journal of Neurology vol. 269,3 (2022):1651-1662. doi:10.1007/s00415-021-10717-0
6,7Hegdekar N, et al. N-Acetyl-L-leucine improves functional recovery and attenuates cortical cell death and neuroinflammation after traumatic brain injury in mice. Scientific Reports vol. 11,1 9249. 29 Apr. 2021, doi:10.1038/s41598-021-88693-8
