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

N-ACETYL-L-TYROSINE COMMON NAME

N-Acetyl-L-Tyrosine | NALT

TOP BENEFITS OF N-ACETYL-L-TYROSINE 

Supports working memory, mental flexibility, and information processing*

Supports adaptation to stressful circumstances*

WHAT IS N-ACETYL-L-TYROSINE?

N-acetyl-L-tyrosine (NALT) is an acetylated form of the amino acid L-tyrosine. NALT (as well as L-tyrosine) is used as a nootropic because it acts as a precursor for the important brain neurotransmitter dopamine. Dopamine has a large role in brain activities linked to reward, motivation, and pleasure, and plays a crucial part in modulating focus, motivation, cognitive flexibility, and emotional resilience. In addition to these creative-productive capacities and states, dopamine is one of the main regulators of motor control and coordination of body movements, so is also important for exercise and muscle performance. Supplying NALT (or other sources of L-tyrosine) for cognitive support may be especially useful when participating in more demanding or stressful tasks.[1] Oral NALT has increased brain levels of L-tyrosine.[2]

NEUROHACKER’S N-ACETYL-L-TYROSINE SOURCING

N-acetyl-L-tyrosine (NALT) is an acetylated form of the amino acid L-tyrosine; it has better solubility in water, so is a more functional form than L-tyrosine for use in liquids.

N of 1 (i.e., individual response) subjective feedback in the nootropic community suggests that NALT is experienced somewhat differently, and often at much lower doses than the more commonly used L-tyrosine.

Neurohacker uses a NALT that is sourced to be non-GMO, gluten-free, and vegan.

N-ACETYL-L-TYROSINE DOSING PRINCIPLES AND RATIONALE

N-acetyl-l-tyrosine (NALT) seems to be experienced somewhat differently (and often at lower doses) than L-tyrosine. NALT is interesting because real world experience of people taking it in the nootropic community does not match up with the bioavailability data. Neurohacker believes it's important to consider bioavailability data, but not place too much weight on it. Especially, with ingredients like NALT, where almost all of the bioavailability studies have been either in animals, non-oral dosing (i.v, i.p. etc.), and usually both. During our formulation and testing process, the NALT form has been additive in the context of an overall nootropic formula at doses that are typically much lower than would be expected based on bioavailability data and research on L-tyrosine. We also believe that supplementation of tyrosine, no matter which form is used, is subject to threshold responses (see Neurohacker Dosing Principles) because tyrosine-induced increase in dopamine synthesis is regulated by end-product inhibition (i.e., once the optimal level is reached, higher levels of tyrosine will no longer increase dopamine synthesis).[3] 

N-ACETYL-L-TYROSINE KEY MECHANISMS

Brain function

Supports working memory[13–19]

Supports cognitive flexibility[20] 

Supports logical reasoning[14]

Supports mathematical processing[14]

Supports convergent ("deep") thinking—a component of creativity[21] 

Supports perceptual-motor task performance[15,22]

Supports inhibition of behavioral responses—a cognitive control function[23]

Precursor for catecholamine synthesis [dopamine, noradrenaline, and adrenaline][4] 

Supports the rate of dopamine synthesis and release upon neuronal activation[5–10]

Supports norepinephrine synthesis and release upon neuronal activation[10–12]

Protects from neurotransmitter (DA, NE) depletion due to increased brain activity[1]

Protects from performance decline during cognitively demanding tasks[1]

Stress

Protects from the negative effects of stress on cognitive performance[15–18,22]

Protects from adverse behavioral responses to environmental stress[24]

Protects from stress-induced decreases in norepinephrine levels[25]

Protects from stress-induced increases in blood pressure[15,22] 

Supports global mood[26]

Synergies

Mucuna Pruriens, Phenylalanine, Phenylethylamine, Hordenine, Phosphatidylserine, Rhodiola Rosea, Vitamin C

 

REFERENCES 

[1] B.J. Jongkees, B. Hommel, S. Kühn, L.S. Colzato, J. Psychiatr. Res. 70 (2015) 50–57.
[2] G. Topall, H. Laborit, J. Pharm. Pharmacol. 41 (1989) 789–791.
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Acetyl-L-Carnitine

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

COMMON NAME 

Acetyl-L-Carnitine, Acetylcarnitine, ALCAR, ALC

TOP BENEFITS OF ACETYL-L-CARNITINE

  • Supports cholinergic neurotransmission *
  • Supports energy metabolism *
  • Supports brain function and cognitive performance *
  • Supports mood *
  • Supports neuroprotection *
  • Supports healthy aging *

WHAT IS ACETYL-L-CARNITINE?

Acetyl-L-Carnitine (ALCAR) is an acetylated form of L-carnitine. The major difference between ALCAR and L-carnitine is that ALCAR more readily crosses the blood-brain barrier, which is why it tends to be the preferred form for use in brain and nervous system support. The bioavailability of ALCAR is thought to be higher than that of L-carnitine. The name carnitine is derived from Latin “carnus” (flesh) because it was originally found in meat extracts. Adults eating animal products consume about 60–180 milligrams of carnitine per day [1]. Vegans get noticeably less (about 10–12 milligrams) [1], with vegetarians getting a bit more than vegans because of eating dairy products. The carnitine in ALCAR and L-carnitine supports the same functions. The most important role of carnitine 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. Unlike L-carnitine, which does not contain an acetyl group, ALCAR can support acetylcholine synthesis, because the acetyl group in ALCAR can be delivered to coenzyme A to yield acetyl-CoA, which in turn can be used for the synthesis of the neurotransmitter acetylcholine. Acetyl-CoA can also be used for cell energy production as it is the primary substrate for the Krebs cycle in mitochondria, essential for the production of ATP. Accordingly, ALCAR has been shown to enhance cholinergic neurotransmission and support brain energy metabolism in several studies; it has also shown significant neuroprotective effects [2–5].

NEUROHACKER’S ACETYL-L-CARNITINE SOURCING

ALCAR supplies carnitine, which 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). It is also a source of acetyl groups that can be used to make acetylCoA.
While ALCAR and L-carnitine support the same mitochondrial functions, the ALCAR form tends to be preferentially used in research for brain and nervous system support.
ALCAR sourcing is focused on ensuring it’s NON-GMO and vegan.

ACETYL-L-CARNITINE DOSING PRINCIPLES AND RATIONALE

Brain and cognitive function

  • Supports learning and memory [6,7]
  • Supports attention [6]
  • Supports cognitive function [6–10]
  • Supports mental energy and may help counter mental fatigue [11,12]
  • Source of acetyl groups for acetylcholine synthesis [3,13,14]
  • Supports cholinergic neurotransmission [3,4,13,14]
  • Supports brain energy metabolism [4,15–22]
  • Supports dopamine release [23,24]
  • Supports noradrenaline levels [15]
  • Supports serotonin levels [15]
  • Supports synaptic plasticity [25,26]
  • Supports neuronal membrane lipid/phospholipid metabolism [4,16,27]
  • Supports hip
  • pocampal neurogenesis [28]
  • Supports neuroprotective functions [4,7,21,22,29–35]
  • Supports neural cytokine signaling [7,31,32] 

Mood

  • Supports positive affect [36–43]

Physical strength and fatigue

  • Supports energy and may help counter fatigue [11,44]
  • Supports muscle fuel metabolism [45]

Mitochondrial function

  • Supports mitochondrial function and structure [10,32,33,46]
  • Supports mitochondrial biogenesis [47]

Healthy aging and longevity

  • Supports cerebral metabolism during aging [19]
  • Supports mitochondrial function during aging [10,33,48]
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Betaine

BETAINE COMMON NAME

Betaine | Trimethylglycine | TMG | Glycine Betaine

TOP BENEFITS OF BETAINE

Supports NAD metabolism *
Supports liver health *
Supports cardiovascular health *
Supports aspects of sports performance *
Supports neurotransmitter and melatonin synthesis *

WHAT IS BETAINE?

Betaine was originally found in sugar beets (Beta vulgaris), which is the source of its name. Betaines are a group of structurally similar compounds. But because the first betaine discovered was trimethylglycine (the type of betaine found in sugar beets), betaine is commonly used as a synonym for trimethylglycine (TMG), though TMG is more specifically called glycine betaine (there can be non-glycine containing betaines but they are not typically used as dietary supplements). Betaine is an amino acid derivative (i.e., it falls into the protein category). It is found in some foods—in addition to beet roots, other good sources include quinoa, spinach, lamb and wheat brain. Betaine can also be made in the body from choline. This is thought to be a main metabolic fate of dietary choline. However, according to the National Institute of Health most adults don’t get the recommended amount of choline in their diet, so relying on choline (which is also needed to produce phosphatidylcholine for cell membranes and the neurotransmitter acetylcholine) to make betaine can be akin to the saying “Robbing Peter to pay Paul.” Betaine is an important cofactor in methylation, a process that occurs in cells where methyl groups (-CH3) are donated for other processes in the body. These processes include (1) synthesizing neurotransmitters such as dopamine and serotonin, (2) making melatonin and CoQ10, (3) methylation of DNA for epigenetics, (4) remethylation of homocysteine[1] (which has a key role in cardiovascular health[2]), and (5) influencing S-Adenosyl Methionine (SAMe) and folate levels (since they are actively involved in methylation). Betaine is thought to be the source of up to 60% of the methyl groups required for the methylation of homocysteine[3]. Strategies that boost NAD can decrease betaine[4,5] (NAD metabolites are methylated for elimination). Because of this, experts recommend supplementing betaine when strategies are used to boost NAD. Betaine has been largely used to support heart and liver function, but more recently has been receiving attention as a possible ergogenic (i.e., sports performance) and nootropic. Some biohackers use betaine to support sleep.

NEUROHACKER’S BETAINE SOURCING

Betaine sourcing is focused on ensuring it is Non-GMO, gluten-free and vegan.

BETAINE DOSING PRINCIPLES AND RATIONALE

Betaine plays a central role in methylation and is involved in the synthesis of important neurotransmitters (dopamine and serotonin) and the neurohormone melatonin. It is also something that can be decreased when higher doses of niacin equivalent compounds are supplemented. For these reasons, it can play a role in a variety of different types of formulations. The dose of betaine used in a formulation will vary depending upon the purpose it is being used for. In general, Neurohacker Collective believes it’s prudent to supplement betaine (or a choline source) when niacin equivalents are used in amounts significantly greater than the daily value (DV) to ensure against unintended depletion. When used to ensure against depletion a general rule of thumb is that approximately 1mg of betaine can be used for each mg of niacin equivalent supplemented. When used for supporting homocysteine metabolism, heart or liver health, as a nootropic or ergogenic (i.e., not simply to ensure against depletion), or for supporting sleep, higher doses may be used. Doses above 1500 mg a day may increase cholesterol levels, so, even in these other applications, Neurohacker Collective believes in using a more moderate dose of betaine, combined with other supportive nutrients.

BETAINE KEY MECHANISMS

Homocysteine metabolism

Methylates homocysteine to produce the amino acid L-methionine[1]
Regulates the blood levels of homocysteine (a risk factor for cardiovascular disease)[6–8]

NAD metabolome

Supports the demand for methyl groups caused by the metabolism of niacin equivalents (e.g., niacin, niacinamide, nicotinamide riboside, NMN)[9]
Supports the production of hepatic S-adenosylmethionine[10–12]
Balances the reduction in hepatic levels of S-adenosylmethionine (SAMe) caused by the metabolism of niacin equivalents[9]

Mitochondrial function

Supports mitochondrial size/density/number[13]
Supports mitochondrial respiratory capacity[14,15]
Supports fatty acid oxidation[13,16]
Supports electron transport chain and oxidative phosphorylation performance[15,17,18]
Supports mitochondrial dynamics—upregulates mitochondrial fusion[19]
Supports mitochondrial membrane potential[15,17]
Supports mitochondrial antioxidant defenses[17]
Supports mitochondrial function[17,20]

Brain function

Supports memory[21–25]
Down-regulates the expression of GABA transaminase [21]
Supports betaine-GABA transporters [24,25]
Supports neuronal mitochondrial performance [14]
Supports brain phospholipid metabolism [16]
Supports brain antioxidant defenses [23,25–27]

Liver function

Supports hepatic fatty acid metabolism [10–13,18,28]
Supports liver protective functions [17,20]
Supports liver antioxidant defenses [20]

Ergogenic

Supports resistance training performance [29–33]
Supports anabolic signaling [34]

Gastrointestinal function

Supports intestinal digestive enzymes[35]
Supports gut microbiota[35–39]

Cell function

Osmolyte—regulates cell hydration[40]

Synergies

Choline — Supplementation with choline sources can increase betaine levels[41,42]
S-Adenosyl Methionine (SAMe)— Supplementation with betaine can increase SAMe levels[43]
Folic acid in regulating homocysteine levels[7]
Melatonin —appears to have synergies when combined for gut health[44,45]


REFERENCES

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L-Tryptophan

L-Tryptophan Common Name

Tryptophan

Top Benefits of L-Tryptophan

  • Supports cell energy generation *
  • Supports healthy aging *
  • Supports healthy sleep*
  • Supports mood *
  • 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’s been known for decades that L-tryptophan has niacin equivalent activity in the body (i.e., we can make the NAD+ molecules from it). L-tryptophan is unique because it’s the only way to build NAD+ that doesn’t start from one of the older or newer vitamin B3’s. L-tryptophan does this by a de novo synthesis pathway, which creates a niacin molecule through a series of biological reactions (many other important molecules are also created in this process). In the morning, most L-tryptophan—as much as 95%—is used in this pathway. L-tryptophan has enhanced aspects of exercise performance when taken before working out, presumably because of this role in cellular energy production. At night, while most L-tryptophan is still funneled into the de novo pathway, relatively more gets directed to a different pathway, 5-hydroxytryptophan (5-HTP) → serotonin → melatonin. This alternate pathway is involved in regulating sleep-wake cycles and nighttime body clock functions. This alternate pathway might be why low-to-moderate doses of L-tryptophan supports skills that fall into the social cognitive domain: these include prosocial behaviors like cooperation, empathy, getting along with others, and altruism. Since this alternate pathway can be used to make the neurohormone melatonin, L-tryptophan has been used to support healthier sleep cycles. Giving extra L-tryptophan allows the body to use it where it is needed most 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 early in the day also helps support the 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 in the evening 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

One of our dosing principles is to determine whether there is a dosing range, in which many of the benefits occur and above which there appears to be diminishing returns (i.e., a threshold), and to provide a dose within this threshold range (see Neurohacker Dosing Principles). We consider L-tryptophan to be one of these threshold compounds, because many of the benefits appear to occur at a low dose, and in some functional areas a worse response may occur at higher doses. As an example, in a comparative study for sleep, the lowest dose used produced a healthier deep sleep response than the higher doses [1]. 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 sufficient to produce positive subjective responses during the day, with sleep that night, and with overall body clock function. 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 [6]
  • Substrate for serotonin synthesis [7,8]
  • Substrate for melatonin synthesis [9]
  • Supports sleep [1,10–17]

Social Cognition

  • Promotes social behaviors [18,19]
  • Supports prosocial interactions [19–24]
  • Promotes charitable behaviors [25]

Mood

  • Supports emotional processing and mental energy [26]
  • Supports a positive mental-emotional bias [12,27–29]
  • Supports a calm mood [12,27,30]
  • Supports healthy functional connectivity between the default mode network and emotion-related brain regions [31]

Exercise performance (ergogenic effect)

  • Supports power output [32,33]
  • Delays time to exertion [32,33]

Synergies

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

REFERENCES

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Taurine

Scientific Name:
2-aminoethanesulphonic acid

COMMON NAME

Taurine

BENEFITS

  • Supports brain health *
  • Supports healthy vision *
  • Supports heart health *  

DESCRIPTION

Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid. It is found in the diet and can be produced in the human body, with the combination determining body stores. Animal products, including shellfish, fish, poultry and red meat, are the best food source. Vegan diets contain almost no taurine [1]. Taurine is present in nearly all tissues, and is the most abundant free amino acid in muscle, heart, brain, and retina. Taurine has important roles in the human body in osmoregulation, as an antioxidant, and as a neuromodulator. Taurine is present in all ocular tissues—retina, lens, cornea, etc.—and is critical for retinal and photoreceptor cell function. Taurine also supports neuroprotective functions in the central nervous system [2,3]. Taurine may facilitate the bioavailability of lipid nutrients [4].

INGREDIENT SELECTION

Taurine is non-GMO and vegan. 

DOSING PRINCIPLES AND RATIONALE

Dietary intake of taurine in omnivores has been estimated to be in the range of 75-135 mg a day, while subsets with the highest intakes may average 200-500 mg. Vegan diets are virtually devoid of taurine [5,6] and vegans have lower blood levels of it [1]. Taurine has been used in clinical studies at doses ranging from a few hundred milligrams to a few grams. When used in combination with other ingredients, taurine has been used at lower doses. Neurohacker believes taurine follows a threshold response (see Neurohacker Dosing Principles) when given to healthy people, which means the majority of functional benefits occur within the range of average-to-high dietary intake. The amount of taurine included in a Neurohacker Collective product can vary depending on the product’s goal; however, we generally dose taurine closer to, but still above, the average dietary intake. The goal is to provide a supplemental dose of taurine that ensures adequate intake even for vegans and vegetarians.

KEY MECHANISMS

Brain function

  • Supports synaptic long-term potentiation [7]
  • Supports GABAergic neurotransmission [8–11]
  • Supports glycinergic neurotransmission [12]
  • Supports hippocampal neurotransmission [13]
  • Supports brain-derived neurotrophic factor (BDNF) [11] 
  • Supports neuroprotective functions [14]
  • Supports cerebral blood flow [14]
  • Supports neuronal mitochondrial function [14]
  • Supports short-term memory [11]

Mood

  • Supports positive mood responses and calm behaviors [12,15–19]

Vision

  • Supports resistance to visual fatigue [20]
  • Supports synaptic transmission in retinal ganglion cells [21]
  • Supports eyes against stress from blue light and ultraviolet light [22–24]
  • Supports retinal and optic nerve neuroprotective functions [25–34]
  • Supports retinal antioxidant defense functions [27,28,35]
  • Supports photoreceptor cell visual function [25]

Mitochondrial function and antioxidant defenses

  • Supports mitochondrial respiratory chain function [36,37]
  • Supports antioxidant defenses [38–41]
  • Supports tissue protection from oxidative damage [16,41–43]

Cardiovascular function

  • Supports vascular endothelial cell function [16,44]
  • Supports cardiac muscle cell function [42,43]
  • Supports the generation of new blood vessels (angiogenesis) [45]
  • Supports healthy blood flow [44]

Metabolism

  • Supports healthy insulin sensitivity and glucose metabolism [38,46,47]  

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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

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N-Acetyl-L-cysteine

Common Name

N-acetylcysteine | acetylcysteine | NAC

Top Benefits of N-acetylcysteine

  • Supports the production of glutathione*
  • Supports liver detoxification*
  • Supports healthy immune function*
  • Supports healthy gut microbiota*

What is N-acetylcysteine?

N-acetylcysteine (NAC), a sulfur-containing amino acid, is the acetylated form of L-cysteine. The acetylation increases bioavailability compared to cysteine. NAC increases body stores of L-cysteine, which, along with glutamine and glycine, is used to make an important detoxification and antioxidant molecule called “glutathione”[1]. This ability to support production of glutathione is NAC’s main mechanism of action[2]. L-cysteine availability limits the rate of glutathione production (it is thought to be rate-limiting)[3]. Supplying NAC allows the body to restore intracellular glutathione levels when demand has been increased or under circumstances when it is lower (such as older age or increased toxin exposure) in tissues throughout the body (including the brain, liver, and muscles). The combination of NAC and glycine appears to be additive[4,5], which makes sense since both are used in glutathione production. NAC promotes glutathione-related antioxidant defenses, which helps protect cells and mitochondria against free radicals, cell membrane damage, damage from metals and toxins, and other oxidative stress-related and aging issues. 

NEUROHACKER’S N-ACETYLCYSTEINE SOURCING

NAC is non-GMO, gluten-free and vegan.

N-ACETYLCYSTEINE DOSING PRINCIPLES AND RATIONALE

NAC is generally considered to be dose-dependent (see Neurohacker Dosing Principles) in the range it’s most commonly dosed (between 400-2400 mg a day). Minor side-effects of NAC also go up with higher doses. Since our use is solely to augment the supply of molecular precursors to make glutathione in combination with other ingredients, and not to use NAC alone, we opted to use a low dose, primarily to benefits of having a glutathione precursor while being at a dose that’s sufficiently low enough to minimize the risk of producing unwanted effects.

N-ACETYLCYSTEINE KEY MECHANISMS 

Antioxidant defenses

  • Supports glutathione levels in the plasma[6]
  • Supports glutathione levels in red blood cells[7]
  • Crosses the blood brain barrier and supports glutathione levels in the brain[6,8,9]

Mitochondrial function

  • Supports mitochondrial function[10]
  • Supports mitochondrial biogenesis[11]
  • Supports mitophagy (mitochondrial autophagy)[12]

Brain function

  • Supports neuroprotection (secondary to boosting glutathione and antioxidant defenses)[13–15]
  • Supports the auditory system from fatigue and noise-induced hearing loss[16–19]

Immunity 

  • Supports general immune health[20–22]
  • Supports innate immunity[21–31]
  • Supports adaptive immunity[20,22,27,32]
  • Supports mucosal immunity[33,34]
  • Supports immune tolerance[35–39]
  • Supports cellular intrinsic immune defenses[40–48]   
  • Supports immune signaling[22,23,44,49–51]
  • Supports antioxidant defenses and oxidative stress[22,25,27,52] 
  • Supports leukocyte glutathione (GSH) levels[22,25,52]
  • Supports healthy natural killer cell function[21,22,30,31,53–55]
  • Supports healthy macrophage function[24,25,27,56]
  • Supports healthy neutrophil function[22,26,28,57,58]  
  • Supports healthy T cell function[50,59–62]    

Gastrointestinal function and gut microbiota

  • Supports gut microbiota[49,63–65]
  • Supports gut barrier function[34,63]
  • Supports gut antioxidant defenses and oxidative stress[63–65]
  • Supports gut immune signaling[34,66]

Synergies

  • L-Theanine in support of general immune health[67–73]
  • Sulforaphane in support of cellular antioxidant defenses[74–76]
  • Glycine in support of glutathione synthesis[5,77,78]

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L-Theanine

Scientific Name:
L-gamma-glutamylethylamide

L-THEANINE COMMON NAME

L-Theanine | L-γ-Glutamylethylamide | 5-N-Ethyl-Glutamine

TOP BENEFITS OF L-THEANINE

  • Supports cognitive function*
  • Supports relaxed mood*
  • Supports stress resilience*
  • Supports sleep*
  • Supports general immune health*

WHAT IS L-THEANINE?

L-theanine is a calming amino acid that naturally occurs in green tea. It is used as a nootropic because it supports focused attention, mental alertness, and a calm, relaxed sense of mental energy. L-theanine is often used with caffeine in nootropic stacks, because the combination supports task switching, accuracy, and focus. L-theanine promotes alpha brain waves (α-waves), which are thought of as a marker of relaxation[1]. This brain state also reduces the perception of stress. L-theanine has a few other lesser known functional actions. L-theanine can be broken down into glutamate, which is a building block for glutamatergic signaling (i.e., the glutamate-GABA pathway) and for glutathione, an antioxidant used for detoxification. And L-theanine, because of another metabolite, primes specialized immune cells—gamma delta T cells—that help the immune system respond more efficiently to new antigens and have enhanced immune memory.* The best dietary sources of L-theanine are green and black tea (made from Camellia sinensis): L-theanine comprises up to 50% of total amino acids in tea leaves.

NEUROHACKER’S L-THEANINE SOURCING

L-theanine is non-GMO, gluten-free, and vegan.

L-THEANINE DOSING PRINCIPLES AND RATIONALE

L-theanine has been studied clinically over a fairly wide range of doses, with the most common range being 100-400 mg. Evidence suggests a threshold response (see Neurohacker Dosing Principles) when L-theanine is given by itself (i.e., the best responses occur when it’s dosed within a range as opposed to more being better). That said, the dose of L-theanine used in a Neurohacker formulation can vary significantly depending upon what other ingredients it’s combined with and the intent of the formulation. Neurohacker looks for additive or synergistic ingredient combinations. In some cases, ingredients tend to be most complimentary when used at certain ratios. L-theanine falls into this category. As an example, when used as part of a nootropic formula combined with a source of caffeine, L-theanine might be dosed to provide about double the dose of caffeine and/or theobromine (i.e., ~2:1 ratio). But when used in combination with GABA before bedtime for supporting sleep, it might be dosed at as little as 20% of the GABA dose (i.e., 1:5 ratio). Following an oral dose, the amount of L-theanine in the brain increase within the first hour (i.e., it’s able to cross the blood-brain barrier,[2] so in general, L-Theanine has fairly quick onset and is often experienced within 30-45 minutes of taking it. 

L-THEANINE KEY MECHANISMS

Brain Function

  • Supports attention[3–5]
  • Supports memory[4–7]
  • Supports learning[8]
  • Supports executive function[4,9]
  • Supports faster reaction times[3]
  • Supports alpha (α) brain waves (α-waves are associated with relaxation, selective attention, and mental alertness)[1,3,10–13]
  • Supports hippocampal activity[14]
  • Supports dopamine signaling[15–21]
  • Supports serotonin signaling[21]
  • Supports GABA levels in the brain[21]
  • Binds to glutamate receptors (with low affinity)[22–24]
  • Supports hippocampal neurogenesis[6]
  • Supports brain-derived neurotrophic factor (BDNF)[6,24,25] 
  • Supports neuroprotective functions[7,8,26–28]

Mood and Stress

  • Supports a calm/relaxed mood[4,8,9,13,14,29–32]
  • Supports a positive mental-emotional bias[4,9]
  • Supports psychological and physiological stress responses[33]
  • Supports healthy behavioral and cognitive responses to stress[26,34]
  • Reduces fight or flight nervous system activity (i.e., promotes relaxation response)[33]

Sleep

  • Supports sleep efficiency and quality[4,9,35,36]
  • Counters some of caffeine’s effects on deep sleep[37]

Immune function

  • Supports general immune health[38–40]
  • Supports post-exercise immunity[41–44]
  • Supports innate immunity[42,45,46]
  • Supports adaptive immunity[42,46,47]
  • Supports immune signaling[42,48]
  • Supports healthy gamma delta (γδ) T cell function[49,50]
  • Supports healthy dendritic cell function[45]
  • Supports healthy natural killer cell function[41,42,49,51]
  • Supports healthy neutrophil function[43,44,52]
  • Supports healthy mast cell function[46]
  • Supports healthy B cell function[51,53,54]

Gastrointestinal Function

  • Supports gut microbiota[55]
  • Supports amino acid absorption[56]

Healthy aging

  • Pro-longevity (Caenorhabditis elegans)[57]

Synergies

  • Caffeine in cognitive performance[58–61]
  • GABA for supporting sleep quality[62]
  • L-Cysteine in support of general immune health[38,41,43,44,51,53,63]
  • Green tea extracts in support of general immune health[39,40]

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DL-Phenylalanine

Scientific Name:
DL-Phenylalanine

COMMON NAME

DL-Phenylalanine | DLPA

TOP BENEFITS OF DL-PHENYLALANINE

  • Supports neurotransmitter synthesis *
  • Supports mood *
  • Supports nociceptive functions *

WHAT IS DL-PHENYLALANINE?

DL-phenylalanine (DLPA) is a mixture of two forms of the essential amino acid phenylalanine, the naturally occurring L-phenylalanine and the synthetic D-phenylalanine. These two forms are stereoisomers, meaning they have the same chemical formula and a similar structure that differs only in the orientations of their atoms—they are mirror images of each other. DLPA delivers both forms to our body, allowing it to take advantage of the specific benefits of each form. L-phenylalanine is a precursor, via L-tyrosine, for the synthesis of the neurotransmitters dopamine, noradrenaline and adrenaline. L-phenylalanine is also the precursor for the synthesis of phenylethylamine, a neurotransmitter and neuromodulator popularly known as the “love drug.” Via dopamine and phenylethylamine production, L-phenylalanine has an important role in the support of mood [1,2]. D-phenylalanine may influence molecules and enzymes involved in the neural encoding of information used to sense and avoid potentially tissue-damaging stimuli [3].

NEUROHACKER’S DL-PHENYLALANINE SOURCING

DL-phenylalanine sourcing is focused on ensuring it’s NON-GMO and vegan.

DL-PHENYLALANINE DOSING PRINCIPLES AND RATIONALE

DL-phenylalanine has been used in clinical trials at doses ranging from 50 mg/day to 400 mg three times a day. Mild sedation and fatigue have been reported for daily doses above 600 mg [4]. We chose a dose that is below the amount that has been linked to  sedation or fatigue and which would be expected to be complementary with other ingredients, such as N-acetyl-L-tyrosine (NALT) or velvet bean extract, that support the production of dopamine and related molecules.  

DL-PHENYLALANINE KEY MECHANISMS

Brain function

  • [L-phenylalanine]
  • Precursor (via L-tyrosine) for dopamine, noradrenaline and adrenaline synthesis [1]
  • Precursor for phenylethylamine synthesis [2]
  • Modulates acetylcholinesterase activity [5–7]
  • Modulates brain ATPase activity [5,7]
  • Modulates glutamatergic neurotransmission [8]

Nociceptive functions

  • Supports neural encoding of sensory information [9–13]
  • Influences Enkephalinase activity [D-phenylalanine] [3,14,15]

Mood

  • Supports positive affect [4,16–18]
  • Supports mood stability [4]

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