L-Tyrosine or N-Acetyl-L-Tyrosine: What Is the Difference

N-acetyl-L-tyrosine (NALT) is often advertised as an “improved” form of L-tyrosine with higher bioavailability. It sounds convincing, since the acetylated molecule dissolves better in water. But does better solubility mean more tyrosine in the brain? The editorial team examined how these two forms actually differ and what research says about them.

Tyrosine and its role in the body

L-tyrosine is a conditionally nonessential amino acid. The body synthesizes it from phenylalanine with the help of the enzyme phenylalanine hydroxylase, and also obtains it from protein food: meat, fish, dairy products, soy, legumes. Therefore a person with an ordinary protein diet, as a rule, has no tyrosine deficiency.

The greatest interest in tyrosine is related to the fact that it is a precursor of catecholamines. The enzyme tyrosine hydroxylase converts it into L-DOPA, from which dopamine, noradrenaline and adrenaline are then formed. In addition, tyrosine is needed for the synthesis of thyroid hormones and of the pigment melanin.

Tyrosine hydroxylase is the “bottleneck” of this pathway, and at rest it is usually saturated with substrate. That is, additional tyrosine does not increase dopamine production under normal conditions. It is a different situation with intense stress, cold, sleep deprivation, when neurons actively expend catecholamines; then the availability of the precursor may matter.

It is precisely this “replenishing reserves under load” hypothesis that lies at the basis of tyrosine research. It explains why effects were observed mostly under stressful conditions and not in rested people.

How NALT differs chemically

NALT is L-tyrosine to whose amino group an acetyl group is attached. This modification makes the molecule significantly more soluble in water. Ordinary L-tyrosine dissolves poorly — and that is precisely why the acetylated form was developed for liquid solutions, in particular for parenteral (intravenous) nutrition.

For the body to use NALT, the acetyl group must be cleaved off by enzymes (acylases), primarily in the kidneys. Only after this is free L-tyrosine formed, identical to that which comes from food or from a classic supplement.

Because of the additional acetyl group, the mass of the NALT molecule is greater than that of tyrosine. By molecular mass, 1 g of NALT contains approximately 0.8 g of “tyrosine equivalent.” This must be taken into account when comparing doses on labels.

In other words, NALT is not a “stronger” version of tyrosine, but its prodrug with different physicochemical properties. The only question is how efficiently this prodrug is converted into the active form.

Absorption: solubility is not yet bioavailability

For the absorption of amino acids in the intestine there are special transporters, and L-tyrosine is successfully absorbed despite its poor solubility in water. Therefore the advantage of NALT in solubility changes little for the oral intake of tablets or capsules.

The best-known data on the fate of NALT in the body were obtained during intravenous administration. In the study by Magnusson and colleagues (1989) a significant part of the administered NALT was excreted in the urine unchanged, while the increase in plasma tyrosine concentration was modest. This cast doubt on the effectiveness of NALT as a source of tyrosine even in clinical nutrition.

There are few direct quality comparisons of oral NALT and L-tyrosine by the level of tyrosine in the blood or brain in healthy people. However, the known data do not support the thesis of the “higher bioavailability” of NALT; rather the opposite — part of the dose may be lost before conversion.

So the marketing claim about better absorption of NALT is based on a confusion between solubility and bioavailability. For a person taking the supplement orally, classic L-tyrosine has better pharmacological logic and significantly more research.

Evidence base and safety

Practically all studies of cognitive effects have been conducted with L-tyrosine specifically. The works of Banderet and Lieberman (1989) showed a reduction in the negative effect of cold and hypoxia on cognitive functions and mood. Deijen and colleagues (1999) described better results on cognitive tests in cadets during an intensive military course.

The review by Jongkees and colleagues (2015) concluded that tyrosine can support cognitive functions in short-term stressful and demanding situations but does not improve them under calm conditions. Data on physical performance are contradictory: in the study by Tumilty and colleagues (2011) tyrosine prolonged the time to exhaustion in the heat, but other works found no effect.

For NALT there are practically no analogous studies of cognitive or sports effects. Therefore everything that is said about its action is essentially an extrapolation from data on L-tyrosine — with a correction for poorer conversion.

• Hereditary tyrosinemia is a contraindication; in phenylketonuria tyrosine is part of the therapeutic diet, but its amount is determined only by a doctor.
• A possible interaction with MAO inhibitors — a risk of increased blood pressure.
• Caution with hyperthyroidism and when taking thyroid hormones, as well as levodopa.
• Possible side effects: nausea, headache, restlessness, insomnia when taken in the evening.

Editorial conclusions

L-tyrosine and NALT are one amino acid in two forms. NALT dissolves better in water, but this does not make it more bioavailable when taken orally; the available data indicate incomplete conversion and losses in the urine.

The entire evidence base regarding cognitive effects under stressful conditions concerns L-tyrosine specifically. These effects are moderate and appear mostly during loads, cold, sleep deprivation or multitasking.

Practical recommendations on choosing a form, doses from studies and situations in which tyrosine may be useful, we have gathered in the article “L-Tyrosine vs N-Acetyl-L-Tyrosine: What to Choose and for Whom.” We also recommend our articles on caffeine and on rhodiola as means for working under stress.

References

1. Magnusson I, Ekman L, Wångdahl M, Wahren J. N-acetyl-L-tyrosine and N-acetyl-L-cysteine as tyrosine and cysteine precursors during intravenous infusion in humans. Metabolism. 1989;38(10):957–961.
2. Banderet LE, Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull. 1989;22(4):759–762.
3. Deijen JB, Wientjes CJ, Vullinghs HF, et al. Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull. 1999;48(2):203–209.
4. Jongkees BJ, Hommel B, Kühn S, Colzato LS. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands — a review. J Psychiatr Res. 2015;70:50–57.
5. Tumilty L, Davison G, Beckmann M, Thatcher R. Oral tyrosine supplementation improves exercise capacity in the heat. Eur J Appl Physiol. 2011;111(12):2941–2950.
6. Fernstrom JD, Fernstrom MH. Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr. 2007;137(6 Suppl 1):1539S–1547S.