Amino Acids

Building blocks for key neurotransmitters and hormones, and agents that are part of the processes of cellular energy production, osmoregulation, signaling, antioxidation, neurogenesis, and neuroprotection.

N-Acetyl-L-Tyrosine

Scientific Name:
(2S)-2-(acetylamino)-3-(4-hydroxyphenyl)propanoic acid

Overview:
Acetyl-L-Tyrosine is an acetylated form of the amino acid L-Tyrosine with nootropic effects. It increases attention, motivation and concentration, and improves memory and learning.>

Scientific Name:
(2S)-2-(acetylamino)-3-(4-hydroxyphenyl)propanoic acid

Mechanisms:

  • Increases the bioavailability of Tyrosine[1]
  • Tyrosine is a Dopamine precursor – increases the synthesis of dopamine[2]
  • Increases the synthesis of noradrenaline from dopamine and balances the levels of Serotonin and GABA[1]
  • Anxiolytic activity[3]
  • Improves neuronal communication
  • Melanin precursor – can reduce neurotoxicity by removing quinones and toxic metals[4]
References

[1] Topall G & Laborit H (1989). Brain tyrosine increases after treating with prodrugs: comparison with tyrosine. J Pharm Pharmacol, 41(11):789-91. doi: 10.1111/j.2042-7158.1989.tb06368.x
[2] Fernstrom JD & Fernstrom MH (2007). Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr, 137(6 Suppl 1):1539S-1547S. PMID: 17513421
[3] Banderet LE & Lieberman HR (1989). Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull, 22(4):759-62. doi: 10.1016/0006-8993(84)91207-1
[4] Miyazaki I & Asanuma M (2009). Approaches to prevent dopamine quinone-induced neurotoxicity. Neurochem Res, 34(4):698-706. doi: 10.1007/s11064-008-9843-1

Taurine

Scientific Name:
2-aminoethanesulphonic acid

Overview:
Taurine is an organic amino sulfonic acid with nootropic and neuroprotective actions. It can improve memory and has anxiolytic effects.

Scientific Name:
2-aminoethanesulphonic acid

Mechanisms:

  • Neuroprotective through antioxidant and toxin removal activity[1]
  • May improve memory by increasing long-term synaptic potentiation[2]
  • Activates GABA and Glycine receptors – anxiolytic effect[3]
  • Decreases the affinity of NMDA glutamate receptors to Glycine, needed for their activation[4]
  • Central nervous system depressant – has a sedative effects and promotes sleep and relaxation
  • Cell membrane stabilizer
References

<[1] Aruoma OI, et al (1988). The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J. 1988 Nov 15;256(1):251-5. doi: 10.1042/bj2560251
[2] del Olmo N, et al (2004). Role of taurine uptake on the induction of long-term synaptic potentiation. Eur J Neurosci, 19(7):1875-86. doi: 10.1111/j.1460-9568.2004.03309.x
[3] Zhang CG & Kim SJ (2007). Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo. Ann Nutr Metab, 51(4):379-86. doi: 10.1159/000107687
[4] Chan CY, et al (2013). Direct interaction of taurine with the NMDA glutamate receptor subtype via multiple mechanisms. Adv Exp Med Biol, 775:45-52. doi: 10.1007/978-1-4614-6130-2_4
[5] Caletti G, et al (2015). Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats. Behav Brain Res, 283:11-5. doi: 10.1016/j.bbr.2015.01.018

L-Tryptophan

L-Tryptophan Common Name

Tryptophan

Top Benefits of L-Tryptophan

  • Supports cell energy generation*
  • Supports healthy aging*
  • Supports healthy sleep and body clock function*
  • Supports prosocial behaviors*

What is L-Tryptophan?

L-Tryptophan is an essential amino acid. The body cannot synthesize it: it must be obtained from the diet. It functions as a metabolic precursor (i.e., substrate) for the synthesis of nicotinamide adenine dinucleotide (NAD), an important coenzyme found in all living cells—NAD is used for mitochondrial energy production and activation of the important sirtuin healthspan pathways. NAD can be made by any molecule which contains a niacin or nicotinamide (vitamin B3) molecule. L-Tryptophan is unique because it’s the only other way to build NAD that doesn’t start from vitamin B3. L-Tryptophan is also the precursor for the synthesis of the neurotransmitter serotonin and the neurohormone melatonin, which regulates sleep-wake cycles and nighttime body clock functions. In addition to these three main molecules, L-tryptophan is involved in making many other important intermediate molecules. Giving extra L-tryptophan allows the body to use it where it is needed most … at that time and over the next 12-16 hours. In general, giving extra L-tryptophan with breakfast supports both daytime mood (presumably via supporting serotonin function) and nightly sleep (presumably via supporting melatonin function). Giving some extra L-tryptophan also helps support body clock, orienting many of it’s daytime functions earlier in the day. L-tryptophan supplementation may support prosocial behaviors. Low-to-modest doses of L-tryptophan prior to bed may support healthier sleep cycles.

Neurohacker’s L-Tryptophan Sourcing

L-Tryptophan is used as a precursor (i.e., substrate) by the body to make NAD, serotonin, and melatonin. Our main reason for including it in a formulation would be to support biosynthesis of one or more of these important molecules.

In general, L-tryptophan is additive with other strategies for making NAD (such as the non-flushing form (niacinamide) and flushing form (niacin) of vitamin B3, so it can be useful to stack the two together in formulations.

L-Tryptophan sourcing is focused on identifying and purchasing from a reputable supplier and ensuring it is NON-GMO, gluten-free and vegan.

L-Tryptophan Dosing Principles and Rationale

L-Tryptophan is generally considered to be dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed (between several hundred mg to several grams or more a day). It’s been estimated that an average adult diet provides about 800-1000 mg/day of L-tryptophan. In studies that have looked at augmenting the breakfast meal with L-tryptophan, amounts less than the amount in an average diet have been ufficient to produce positive subjective responses during the day, with sleep that night, and with overall body clock function. When taken prior to bed, a dose close to ¼ the daily average intake has been sufficient to support healthier deep sleep. These studies are consistent with L-tryptophan supplementation supporting healthier function when given in amounts that are less than what would be found in an average diet. 

L-Tryptophan Key Mechanisms

NAD(P) synthesis

  • L-tryptophan is a substrate in the de novo NAD+ synthesis pathway via the kynurenine pathway (KP) (1)
  • NAD+ can be converted to the coenzyme NADP+ by the enzyme NAD kinase (2)
  • NAD(H) and NADP(H) are key molecules in essential redox pathways of cellular metabolism and energy production (3)
  • NAD(H) is essential for the production of ATP through the citric acid cycle and oxidative phosphorylation (3)
  • NADP(H) is essential in many anabolic metabolic reactions, including DNA and RNA synthesis (3)
  • NADP(H) is a cofactor for some cytochrome P450 enzymes that detoxify xenobiotics (4)
  • NADPH also acts as a cofactor for glutathione reductase, the enzyme used to maintain reduced glutathione (GSH) levels (3)
  • NAD(H) and NADP(H) are essential for healthy aging (3)

Brain function

  • L-tryptophan is a precursor for serotonin (a neurotransmitter) and melatonin (a neurohormone) synthesis (5)
  • Upregulates the rate of serotonin synthesis (6, 7)
  • Promotes social behavior (8, 9)

Exercise performance (ergogenic effect)

  • Supports power output (10, 11)
  • Delays time to exertion (10, 11) 

Social Cognition

  • Supports healthier social interactions (12–14)
  • Promotes charitable behaviors (15)

Synergies

  • Nicotinic acid (niacin) and nicotinamide (niacinamide) as substrates for NAD synthesis. 

REFERENCES

1. A. A.-B. Badawy, Int. J. Tryptophan Res. 10, 1178646917691938 (2017).
2. G. Magni et al., Cell. Mol. Life Sci. 61, 19–34 (2004).
3. W. Ying, Antioxid. Redox Signal. 10, 179–206 (2008).
4. D. S. Riddick et al., Drug Metab. Dispos. 41, 12–23 (2013).
5. L. Palego, L. Betti, A. Rossi, G. Giannaccini, J. Amino Acids. 2016, 8952520 (2016).
6. J. D. Fernstrom, Physiol. Rev. 63, 484–546 (1983).
7. J. D. Fernstrom, J. Nutr. Biochem. 1, 508–517 (1990).
8. L. Steenbergen, B. J. Jongkees, R. Sellaro, L. S. Colzato, Neurosci. Biobehav. Rev. 64, 346–358 (2016).
9. S. N. Young, Philos. Trans. R. Soc. Lond. B Biol. Sci. 368, 20110375 (2013).
10. C. Javierre, R. Segura, J. L. Ventura, A. Suárez, J. M. Rosés, Int. J. Neurosci. 120, 319–327 (2010).
11. R. Segura, J. L. Ventura, Int. J. Sports Med. 9, 301–305 (1988).
12. D.S. Moskowitz, G. Pinard, D.C. Zuroff, L. Annable, S.N. Young, Neuropsychopharmacology. 25, 277–289 (2001).
13. A. Nantel-Vivier, R.O. Pihl, S.N. Young, S. Parent, S.A. Bélanger, R. Sutton, M.-E. Dubois, R.E. Tremblay, J.R. Séguin, PLoS One. 6 (2011) e20304.
14. K. Hogenelst, R.A. Schoevers, M. Aan Het Rot, Int. J. Neuropsychopharmacol. 18 (2015).
15. L. Steenbergen, R. Sellaro, L.S. Colzato, Front. Psychol. 5, 1451 (2014).

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Calcium β-Hydroxy-β-Methylbutyrate (CaHMB)

Calcium β-Hydroxy-β-Methylbutyrate (CaHMB) Common Name

β-hydroxy-β-methylbutyric acid

Top Benefits of HMB

  • Supports exercise performance*
  • Supports muscle structure and function*
  • Supports healthy metabolic pathways*
  • Supports healthy aging*

What is HMB?

β-Hydroxy-β-Methylbutyric acid (HMB) is a metabolite of the essential amino acid L-leucine, with roughly 5% of dietary l-leucine converted into HMB. HMB is best known for supporting skeletal muscle function, particularly in supporting recovery from muscle damage, mitigating muscle protein breakdown, and sountering age-related muscle loss. 

Neurohacker’s HMB Sourcing

There are two main forms of HMB used as a dietary supplement. One is a calcium salt (Calcium HMB or CaHMB). The other is a free fatty acid form. We decided to use CaHMB, because it has been the most-studied form of HMB. 

HMB Dosing Principles and Rationale

For ergogenic purposes (i.e., to enhance sports performance) and to counter muscle wasting syndromes HMB is usually dosed at either 1.5 or 3 grams a day (3 grams is the more common dosage). This is a much larger dose of HMB than what’s made in the body. The capacity to make HMB is influenced by diet. It’s estimated that a healthy adult produces about 0.3 grams (i.e., 300 mg) of HMB per day. A person with a high dietary intake of leucine might make two or three times more, while a diet lower in leucine would result in less. HMB is also affected by age: Our body makes less HMB from leucine as we get older. We selected a dose of HMB intended to support this more physiological HMB range.

HMB Key Mechanisms 

Exercise performance (ergogenic effects)

  • Protects from muscle damage and muscle protein degradation (muscle loss / sarcopenia) (1–12)
  • Supports muscle strength and mass (9–14)
  • Supports muscle structure and function (14)
  • Supports endurance performance (15)
  • Supports post-exercise recovery (6)
  • Supports mitochondrial function in muscles (16)

Metabolism

  • Supports healthy insulin sensitivity (17)
  • Downregulates fat accumulation and blood/liver lipid levels (17)
  • Upregulates adiponectin levels (18)

Signaling pathways

  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) (18)
  • Upregulates nuclear transcription factors of mitochondrial biogenesis (nuclear respiratory factor 1 [NRF1]) (18)
  • Downregulates proliferator-activated receptor gamma (PPARγ) (18)
  • Upregulates AMP-activated protein kinase (AMPK) signaling (18, 19)
  • Upregulates SIRT1 signaling 19,20

Synergies

  • Synergistic with resveratrol in upregulating AMPK and SIRT1 (19)
  • May be additive with creatine for muscle performance (9)

REFERENCES 

1. A. P. Rossi et al., Drugs Aging. 34, 833–840 (2017).
2. H. Wu et al., Arch. Gerontol. Geriatr. 61, 168–175 (2015).
3. K. A. van Someren, A. J. Edwards, G. Howatson, Int. J. Sport Nutr. Exerc. Metab. 15, 413–424 (2005).
4. A. E. Knitter, L. Panton, J. A. Rathmacher, A. Petersen, R. Sharp, J. Appl. Physiol. 89, 1340–1344 (2000).
5. P. Ostaszewski et al., J. Anim. Physiol. Anim. Nutr. . 84, 1–8 (2000).
6. J. M. Wilson et al., Br. J. Nutr. 110, 538–544 (2013).
7. M. H. Rahimi, H. Mohammadi, H. Eshaghi, G. Askari, M. Miraghajani, J. Am. Coll. Nutr. 37, 640–649 (2018).
8. D. J. Wilkinson et al., Clin. Nutr. (2017), doi:10.1016/j.clnu.2017.09.024.
9. E. Jówko et al., Nutrition. 17, 558–566 (2001).
10. S. Nissen et al., J. Appl. Physiol. 81, 2095–2104 (1996).
11. L. B. Panton, J. A. Rathmacher, S. Baier, S. Nissen, Nutrition. 16, 734–739 (2000).
12. J. M. Wilson et al., Eur. J. Appl. Physiol. 114, 1217–1227 (2014).
13. S. L. Nissen, R. L. Sharp, J. Appl. Physiol. 94, 651–659 (2003).
14. J. R. Stout et al., Exp. Gerontol. 48, 1303–1310 (2013).
15. M. D. Vukovich, G. D. Dreifort, J. Strength Cond. Res. 15, 491–497 (2001).
16. R. A. Standley et al., J. Appl. Physiol. 123, 1092–1100 (2017).
17. M. H. Sharawy, M. S. El-Awady, N. Megahed, N. M. Gameil, Can. J. Physiol. Pharmacol. 94, 488–497 (2016).
18. Y. Duan et al., Food Funct. 9, 4836–4846 (2018).
19. A. Bruckbauer et al., Nutr. Metab. . 9, 77 (2012).

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Tri-creatine Malate

Tricreatine Malate Common Names

Creatine | Malate | Malic Acid

Top Benefits of Tricreatine Malate

  • Supports mitochondrial efficiency*
  • Supports muscle performance*
  • Supports cardiac function*
  • Supports cognition*

What is Tricreatine Malate?

Tricreatine malate is made up of three creatines bound to one malate. Both molecules are involved in supporting efficient cellular energy production. Creatine is named from the Greek word from meat (kreas), because it was originally discovered in skeletal muscle. It plays a key role in tissues, like muscles and the brain, that use high amounts of energy. Because it concentrates in muscles, the best food sources are red meat, pork, lamb, poultry, and fish. While we can make some creatine in the body, persons not eating meat might not make sufficient creatine to optimize tissue status. So creatine as a dietary supplement may be more important to take as a supplement for vegans and vegetarians. Creatine is used in the phosphocreatine (phosphagen) system. This system regenerates ATP from ADP in tissues, and is especially important in circumstances with high energy demand. Because of this role, creatine is often described as an ATP “buffer.” Malate is a salt of malic acid, a compound that was first identified in apple juice, leading to it being named for the Latin word for apple (mālum). Malate is an intermediate in the citric acid cycle, a circular pathway that helps turn food into energy (i.e., ATP) and build important biomolecules. Adding intermediates like malate into this cycle helps upregulate the flux (i.e., the cycle can essentially spin faster).

Neurohacker’s Tricreatine Malate Sourcing

We opt to use creatine as tricreatine malate, instead of a creatine monohydrate or other form of creatine, when both creatine and malate play a role supporting pathways or processes in a formulation.

Tricreatine malate sourcing is focused on ensuring it is non-GMO, gluten-free and vegan.

Tricreatine Malate Dosing Principles and Rationale

Creatine  is dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed (up to about 5 grams a day). Dosage of creatine will vary depending on the purpose of a formulation. If the goal is to quickly saturate muscle stores for sports performance uses, higher doses (3-5 grams) are recommended. If the goal is to augment the diet, a lower dose taken consistently over time is recommended. It’s been estimated that an omnivore diet provides about 1 gram of creatine a day(1, 2) and that young adults make about 1 gram a day.(1, 3) This combination of what we get in the diet and make (i.e., biosynthesis) is needed to offset the approximately 2 grams of creatine we lose everyday. A low dose of creatine can contribute a significant degree to offsetting this daily loss. 

Tricreatine Malate Key Mechanisms

Creatine

Mitochondrial biogenesis

  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) (4)
  • Upregulates transcription factors of mitochondrial biogenesis (mitochondrial transcription factor A [TFAM]) (4)
  • Upregulates mitochondrial DNA (mtDNA) (4)

Mitochondrial structure and function

  • Protects mitochondrial structure and function (4–6)
  • Supports mitochondrial membrane potential (4, 5)

Signaling pathways

  • Upregulates AMP-activated protein kinase (AMPK) signaling (4, 7–10)

Exercise performance (ergogenic effects)

  • Upregulates the muscle pool of phosphocreatine to be used for ATP regeneration (10–15)
  • Supports strength performance (12–14, 16–21)
  • Upregulates lean mass (14, 16–21)
  • Supports muscle structure and function (12–14, 16)
  • Upregulates the skeletal muscle glucose transporter GLUT-4 (8, 9, 12, 22)

Cardiovascular function

  • Supports energy generation in cardiac muscle (23)
  • Protects cardiac muscle against ischemia/hypoxia (24)

Neuroprotective effects

  • Protects neurons from cell damage and toxicity (5, 6, 25–28)

Synergies

  • CoQ10 and lipoic acid – support mitochondrial function (29)
  • L-carnitine and L-leucine – support muscle mass and strength (30)

Malate

Krebs cyle (citric acid cycle) function

  • Supports energy metabolism through the citric acid cycle (31)
  • Supports energy metabolism through the malate-aspartate shuttle (31)
  • Upregulates the NAD+/NAPH ratio (32)

Mitochondrial function

  • Supports mitochondrial membrane potential (32, 33)
  • Supports mitochondrial complex I-V performance (33)

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]) (34–36)
  • Downregulates oxidative stress and the generation of reactive oxygen species (ROS) (36)
  • Replenishes glutathione (GSH) levels (36)

Cellular signaling

  • Downregulates the expression of proinflammatory molecules (tumor necrosis factor alpha [TNFα]) (34)

Cardiovascular function

  • Protects cardiac muscle from ischemic injury (34)

Longevity

  • Increases lifespan (Caenorhabditis elegans) (32)

References

1. J. T. Brosnan, R. P. da Silva, M. E. Brosnan, Amino Acids. 40, 1325–1331 (2011).
2. M. E. Brosnan, J. T. Brosnan, Amino Acids. 48, 1785–1791 (2016).
3. R. Cooper, F. Naclerio, J. Allgrove, A. Jimenez, J. Int. Soc. Sports Nutr. 9, 33 (2012).
4. E. Barbieri et al., Oxid. Med. Cell. Longev. 2016, 5152029 (2016).
5. L. M. Rambo et al., Amino Acids. 44, 857–868 (2013).
6. P. Klivenyi et al., Nat. Med. 5, 347–350 (1999).
7. L. Zhang et al., J. Agric. Food Chem. 65, 6991–6999 (2017).
8. C. R. R. Alves et al., Amino Acids. 43, 1803–1807 (2012).
9. J.-S. Ju, J. L. Smith, P. J. Oppelt, J. S. Fisher, Am. J. Physiol. Endocrinol. Metab. 288, E347–52 (2005).
10. R. B. Ceddia, G. Sweeney, J. Physiol. 555, 409–421 (2004).
11. B. Banerjee et al., Magn. Reson. Imaging. 28, 698–707 (2010).
12. B. Gualano et al., Med. Sci. Sports Exerc. 43, 770–778 (2011).
13. C. R. R. Alves et al., Arthritis Care Res. . 65, 1449–1459 (2013).
14. D. G. Burke et al., Med. Sci. Sports Exerc. 35, 1946–1955 (2003).
15. J. T. Brosnan, M. E. Brosnan, Annu. Rev. Nutr. 27, 241–261 (2007).
16. J. S. Volek et al., Med. Sci. Sports Exerc. 31, 1147–1156 (1999).
17. S. L. Nissen, R. L. Sharp, J. Appl. Physiol. 94, 651–659 (2003).
18. R. B. Kreider, Mol. Cell. Biochem. 244, 89–94 (2003).
19. L. A. Gotshalk et al., Eur. J. Appl. Physiol. 102, 223–231 (2008).
20. L. A. Gotshalk et al., Med. Sci. Sports Exerc. 34, 537–543 (2002).
21. J. D. Branch, Int. J. Sport Nutr. Exerc. Metab. 13, 198–226 (2003).
22. B. Op ’t Eijnde, B. Ursø, E. A. Richter, P. L. Greenhaff, P. Hespel, Diabetes. 50, 18–23 (2001).
23. V. Saks et al., J. Physiol. 571, 253–273 (2006).
24. C. A. Lygate et al., Cardiovasc. Res. 96, 466–475 (2012).
25. G. J. Brewer, T. W. Wallimann, J. Neurochem. 74, 1968–1978 (2000).
26. B. Valastro, A. Dekundy, W. Danysz, G. Quack, Behav. Brain Res. 197, 90–96 (2009).
27. R. T. Matthews et al., J. Neurosci. 18, 156–163 (1998).
28. P. G. Sullivan, J. D. Geiger, M. P. Mattson, S. W. Scheff, Ann. Neurol. 48, 723–729 (2000).
29. M. C. Rodriguez et al., Muscle Nerve. 35, 235–242 (2007).
30. M. Evans et al., Nutr. Metab. . 14, 7 (2017).
31. J. M. Berg, J. L. Tymoczko, G. J. Gatto, L. Stryer, Eds., Biochemistry (W.H. Freeman and Company, 8th ed., 2015).
32. C. B. Edwards, N. Copes, A. G. Brito, J. Canfield, P. C. Bradshaw, PLoS One. 8, e58345 (2013).
33. J.-L. Wu, Q.-P. Wu, Y.-P. Peng, J.-M. Zhang, Physiol. Res. 60, 329–336 (2011).
34. S. Ding, Y. Yang, J. Mei, Evid. Based. Complement. Alternat. Med. 2016, 3803657 (2016).
35. X. Zeng, J. Wu, Q. Wu, J. Zhang, Physiol. Res. 64, 71–78 (2015).
36. J.-L. Wu et al., Physiol. Res. 57, 261–268 (2008).

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

L-carnitine

L-carnitine Common Name

Levocarnitine

Top Benefits of L-carnitine

  • Supports mitochondrial function*
  • Supports healthy metabolism of fats*
  • Supports healthy heart function*
  • Supports healthy aging*

What is L-carnitine?

L-carnitine is an important molecule because it’s needed to convert fat into energy. The name carnitine is derived from Latin “carnus” (flesh), because it was originally found in meat extracts. Animal products such as meat, poultry, fish, and milk are the best food sources, with redder meats tending to have higher levels of L-carnitine. Adults eating animal products consume about 60–180 milligrams of carnitine per day.(1) The human body can make carnitine from lysine using other micronutrients as cofactors. Adults eating a variety of animal products get about 75% of the daily carnitine needs filled from the diet, so only need to make about 25% of what they use.(2) Vegans get noticeably less (about 10–12 milligrams),(1) with vegetarians getting a bit more than vegans because of eating dairy products. In both cases, because the diet is limited in L-carnitine, they may need to make as much as 90% of their daily needs.(2) While the human body can make carnitine from lysine, it may not always be able to make sufficient amounts to meet demands. This has led to it being thought of as a “conditionally essential” nutrient. L-carnitine’s most important role is in mitochondrial fat metabolism—it is used to transport long-chain fatty acids across the mitochondrial membrane for breakdown by mitochondrial β-oxidation. This transportation function allows fats and oils from our diet to be used for energy production and enhances mitochondria potential to burn fat. This function is especially important in tissues and organs that use a lot of fat as an energy source, including the heart and skeletal muscles. 

Neurohacker’s L-carnitine Sourcing

L-Carnitine is used by the body to transport long-chain fatty acids (fats) so they can be broken down and used to make cellular energy (ATP).

In general, L-carnitine is additive with other strategies used for supporting mitochondrial function (i.e., mitochondrial nutrients like CoQ10 and lipoic acid).

Carnitine can also be supplemented as acetyl-L-carnitine (ALCAR). While both ALCAR and L-carnitine support the same functions, in general, the ALCAR form tends to be used in research more for brain and nervous system support, while the L-carnitine form has been researched more for supporting heart and skeletal muscles. But both forms support all tissues.

L-carnitine sourcing is focused on ensuring it is NON-GMO, gluten-free and vegan.

L-carnitine Dosing Principles and Rationale

L-carnitine is generally considered to be dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed (between 500 mg to several grams a day). These higher supplemental doses are pharmacological (i.e., substantially higher than what the body gets from the diet and makes daily), while a lower dose would be more physiological. We opted for a dose slightly higher than the daily physiological amount, because, like most nutrients, L-carnitine isn’t perfectly absorbed. 

L-carnitine Key Mechanisms

Mitochondrial function and structure

  • Supports fatty acid β-oxidation (3)
  • Protects from mitochondrial dysfunction (4)
  • Promotes the production of ATP (5)
  • Supports mitochondrial structure (5)

Metabolism

  • Supports healthy insulin sensitivity  (6–8)
  • Downregulates fat accumulation and blood / liver lipid levels (5)

Healthy aging and protective effects

  • Downregulates oxidative stress and reactive oxygen species production (4, 9)
  • Protects against neurotoxic agents (4)
  • Supports cardiovascular function (10–12)
  • Supports liver function (5)
  • Upregulates telomerase activity and telomere length (13, 14)
  • Delays aging of mesenchymal stem cells (13–15)

Synergies

  • Lipoic acid – support  mitochondrial function (16)
  • Creatine and L-leucine – support muscle function and structure (17)

REFERENCES

1. C. J. Rebouche, Ann. N. Y. Acad. Sci. 1033, 30–41 (2004).
2. C. J. Rebouche, The FASEB Journal. 6, 3379–3386 (1992).
3. D. W. Foster, Ann. N. Y. Acad. Sci. 1033, 1–16 (2004).
4. D. Elinos-Calderón et al., Exp. Brain Res. 197, 287–296 (2009).
5. K. Kon et al., Hepatol. Res. 47, E44–E54 (2017).
6. M. Malaguarnera et al., Am. J. Gastroenterol. 105, 1338–1345 (2010).
7. A. Molfino et al., JPEN J. Parenter. Enteral Nutr. 34, 295–299 (2010).
8. B. Capaldo, R. Napoli, P. Di Bonito, G. Albano, L. Saccà, Diabetes Res. Clin. Pract. 14, 191–195 (1991).
9. G. Guerreiro et al., J. Cell. Biochem. (2018), doi:10.1002/jcb.27332.
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 *These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

L-Theanine

Scientific Name:
L-gamma-glutamylethylamide

Overview:
L-Theanine is an amino acid analog of glutamate and glutamine found in green tea from Camellia sinensis with neuroprotective effects. L-Theanine has anxiolytic activity and studies suggest that it may improve memory.

Scientific Name:
L-gamma-glutamylethylamide

Mechanisms:

  • Increases alpha brain waves – promotes attention and relaxation without sedation[1, 2]
  • Synergistic with caffeine in promoting concentration, motivation and memory
  • Can modulate the release of Dopamine, improving mood[3]
  • Weak antagonist of NMDA Glutamate receptors
  • Antioxidant effects and protects neurons from damage and hypoxia[4]
  • May upregulate the production of proteins associated with neuronal growth[5]
References

[1] Gomez-Ramirez M, et al (2007). The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine. Clin Neuropharmacol, 30(1):25-38. doi: 10.1097/01.WNF.0000240940.13876.17
[2] Rao TP1, et al (2015). In Search of a Safe Natural Sleep Aid. J Am Coll Nutr, 34(5):436-47. doi: 10.1080/07315724.2014.926153
[3] Yokogoshi H, et al (1998). Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res, 23(5):667-73. doi: 10.1023/A:1022490806093
[4] Sumathi T, et al (2016). l-Theanine alleviates the neuropathological changes induced by PCB (Aroclor 1254) via inhibiting upregulation of inflammatory cytokines and oxidative stress in rat brain. Environ Toxicol Pharmacol, 42:99-117. doi: 10.1016/j.etap.2016.01.008
[5] Takeda A, et al (2011). Facilitated neurogenesis in the developing hippocampus after intake of theanine, an amino acid in tea leaves, and object recognition memory. Cell Mol Neurobiol, 31(7):1079-88. doi: 10.1007/s10571-011-9707-0

Acetyl-L-Carnitine

Scientific Name:
(R)-3-Acetyloxy-4-trimethylammonio-butanoate/p>

Overview:
Acetyl-L-Carnitine is an acetylated form of L-carnitine with anti-aging, neuroprotective and nootropic effects. It decreases fatigue and improves attention, memory, learning and executive function.

Scientific Name:
(R)-3-Acetyloxy-4-trimethylammonio-butanoate/p>

Mechanisms:

  • The acetylated version of L-Carnitine can cross the blood brain barrier thereby providing better cognitive benefits[1]
  • In the brain, it originates Acetyl-CoA that can bind to choline to increase the production of Acetylcholine[1]
  • Synergistic with choline donors
  • Can increase the release of Noradrenaline and Serotonin[2]
  • Increases synaptic plasticity[3]
  • Potent cerebral antioxidant activity – can prevent and repair oxidative damage to neurons[4]
  • Increases energy production by mitochondria[5]
  • Can decrease toxicity associated with excessive excitatory neurotransmitter release and cellular waste accumulation[4]
References

[1] Nałecz KA, et al (2004). Carnitine: transport and physiological functions in the brain. Mol Aspects Med, 25(5-6):551-67.
[2] Smeland OB, et al (2012). Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. Neurochem Int, 61(1):100-7.
[3] Laschi R, et al (1990). Ultrastructural aspects of aging rat hippocampus after long-term administration of acetyl-L-carnitine. Int J Clin Pharmacol Res, 10(1-2):59-63.
[4] Zanelli SA, et al (2005). Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann N Y Acad Sci, 1053:153-61.
[5] Reuter SE & Evans AM (2012). Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet, 51(9):553-72.

DL-Phenylalanine

Scientific Name:
DL-Phenylalanine

Overview:
DLPA is a mixture of two forms of the essential amino acid phenylalanine, the naturally occurring L-phenylalanine and the synthetic D-phenylalanine with nootropic effects. DLPA enhances mood and can increases alertness and improve memory and learning.

Scientific Name:
DL-Phenylalanine

Mechanisms:

  • DL-Phenylalanine crosses the blood-brain barrier easily
  • Increases the production of dopamine and noradrenalin – mood enhancer
  • Decreases chronic pain by blocking the action of enkephalinase[1]
  • Binds to Glutamate AMPA receptors improving synaptic communication –memory and learning enhancement[2]
References

[1] Russell AL & McCarty MF (2000). DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system. Med Hypotheses, 55(4):283-8. doi: 10.1054/mehy.1999.1031
[2] Hill RA, et al (1997). Structure–activity studies for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid receptors: acidic hydroxyphenylalanines. J Med Chem, 40(20):3182-91. doi: 10.1021/jm950028z