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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