Good find. Don't know why I couldn't find any studies before. I did the search the day I bought (and tried) NALT along with L-theanine, so case in point, I guess.
There seems to be some conflicting data concerning NALT's usefulness. Several papers agree with the one dasheenster posted (
Hepatology. 1995 Apr;21(4):923-8), that NALT isn't good at raising plasma TYR levels, and has limited bioavailability and usefulness:
Aromatic amino acid metabolism of neonatal piglets receiving TPN: effect of tyrosine precursors.
Wykes LJ, House JD, Ball RO, Pencharz PB.
...The high urinary excretion of N-AcTyr (65%) confirms its low bioavailability...
PMID: 7977717 [PubMed - indexed for MEDLINE]
Utilization of tyrosine dipeptides and acetyltyrosine in normal and uremic humans.
Druml W, Lochs H, Roth E, Hübl W, Balcke P, Lenz K.
...In CON, whole body clearance (Ctot) of Ala-Tyr (3,169 +/- 198 ml/min) was higher than Gly-Tyr (1,781 +/- 184, P less than 0.001), and both exceeded NAc-Tyr (284 +/- 24, P less than 0.001). In HD, Ctot of Ala-Tyr was not different from CON, but Ctot of Gly-Tyr (858 +/- 73, P less than 0.001) and NAc-Tyr (129 +/- 30, P less than 0.02) was decreased...Plasma Tyr did not increase with NAc-Tyr in either group. Urinary loss of peptides was neglible, but 60% of NAc-Tyr infused was excreted by CON. ...These differential effects on peptide assimilation underscore the importance of peptide structure on metabolism. Both peptides, but not NAc-Tyr, may serve as a nutritional substrate in renal failure patients.
PMID: 1996632 [PubMed - indexed for MEDLINE]
While others conclude the opposite, suggesting that it is effective at raising plasma tyrosine levels, and is useful for the purpose of parenteral nutrition:
Amino acid solutions for premature neonates during the first week of life: the role of N-acetyl-L-cysteine and N-acetyl-L-tyrosine.
Van Goudoever JB, Sulkers EJ, Timmerman M, Huijmans JG, Langer K, Carnielli VP, Sauer PJ.
Tyrosine and cyst(e)ine are amino acids that are thought to be essential for preterm neonates. These amino acids have low stability (cyst(e)ine) or low solubility (tyrosine) and are therefore usually present only in small amounts in amino acid solutions. Acetylation improves the stability and solubility of amino acids, facilitating a higher concentration in the solution...On postnatal day 7, plasma amino acids were measured together with urinary excretion of amino acids and the total nitrogen excretion; 38% of the intake of N-acetyl-L-tyrosine and 53% of the intake of N-acetyl-L-cysteine were excreted in urine. Plasma levels of N-acetyl-L-tyrosine (331 +/- 74 mumol/L) and N-acetyl-L-cysteine (18 +/- 29 mumol/L) were higher than those of tyrosine (105 +/- 108 mumol/L) and cystine (11 +/- 9 mumol/L), respectively. Plasma tyrosine levels in the groups receiving small amounts of tyrosine remained just below the reference range. We show a linear correlation of plasma cystine with the intake of cysteine (r = .75, p = 0.01), but not with N-acetyl-L-cysteine...
PMID: 7815670 [PubMed - indexed for MEDLINE]
N-acetyl-L-tyrosine as a tyrosine source in adult parenteral nutrition.
Hoffer LJ, Sher K, Saboohi F, Bernier P, MacNamara EM, Rinzler D.
...RESULTS: Approximately 35% of administered NAT was excreted unchanged in the urine, with no important effect of infusion rate, N balance, or level of renal function on this value. Sufficient NAT was retained that the prescription of 1 g total amino acids/kg x day(-1) using this product exceeded the combined recommended dietary allowance for aromatic amino acids
PMID: 14621123 [PubMed - indexed for MEDLINE]
N-acetyl-L-tyrosine and N-acetyl-L-cysteine as tyrosine and cysteine precursors during intravenous infusion in humans.
Magnusson I, Ekman L, Wångdahl M, Wahren J.
Eleven healthy volunteers were given 5 g of either NAT or NAC as a 4-hour intravenous infusion. Plasma levels of NAT and NAC increased rapidly, accompanied by a 25% increase in tyrosine levels and a 35% decrease in total cysteine. Urinary excretion of NAT and NAC in 4 hours accounted for 56% and 11% of the infused amount, respectively. No net production of tyrosine or cysteine was found from the splanchnic area, but from the kidneys there was a small release of both tyrosine (10 +/- 3 mumol/min) and cysteine (64 +/- 3 mumol/min). We conclude that under these conditions the usefulness of NAT and NAC as precursors for the corresponding amino acids in humans is not apparent.
PMID: 2507878 [PubMed - indexed for MEDLINE]
Utilization of N-acetyl-L-tyrosine and glycyl-L-tyrosine during long-term parenteral nutrition in the growing rat. [free text]
Neuhäuser M, Wandira JA, Göttmann U, Bässler KH, Langer K.
...No differences in weight gain or N-balance could be detected as a result of administering either the solution with glycyl-L-tyrosine or with N-acetyl-L-tyrosine in place of the solution containing an adequate phenylalanine content. Daily urinary excretion rates for N-acetyl-L-tyrosine and glycyl-L-tyrosine were 11% and 0.5%, respectively, of the infused amount. Plasma amino acid pattern was affected differently by the four solutions. The results indicate that both N-acetyl-L-tyrosine and glycyl-L-tyrosine are efficiently utilized by the rat during total parenteral nutrition.
PMID: 3931451 [PubMed - indexed for MEDLINE]
N-acetyl-L-tyrosine as a tyrosine source during total parenteral nutrition in adult rats.
Im HA, Meyer PD, Stegink LD.
...Infusion of N-acetyl-U-14C-L-tyrosine as part of a total parenteral nutrition regimen in the rat at a level of 0.5 mmol/kg/day resulted in rapid labeling of tissue tyrosine pools, production of 14CO2, incorporation of 14C-labeled tyrosine into protein, and modest urinary losses (8.3%). Plasma tyrosine levels, however, remained at fasting values (73.8 +/- 5.40 microM). Infusion of N-acetyl-L-tyrosine at 2 mmol/kg/day increased plasma tyrosine above fasting levels (141 +/- 16.1 microM), resulted in a rapid labeling of tissue tyrosine pools, production of 14CO2, and incorporation of 14C-labeled tyrosine into protein. However, urinary losses were higher (16.8%). Rapid utilization of N-acetyl-L-tyrosine was noted at both infusion levels. Plasma- and tissue-free tyrosine pools were rapidly labeled, as was tissue protein. Radioactivity incorporated in tissue protein was shown to be tyrosine after acid hydrolysis.
PMID: 3925425 [PubMed - indexed for MEDLINE]
But it should be noted that most of this data doesn't necessarily have any bearing on what we're using it for. Plasma levels and physiological AA requirements are not the same as getting it to the brain, and utilized effectively to increase dopamine.
Z Ernahrungswiss. 1982 Mar;21(1):21-6 mentions that NALT is deacetylated primarily in the kidney, and also liver.
This is the only study I came across tonight mentioning NALT in the context of brain levels. The abstracted conclusion is somewhat imprecise, but seems to suggest that the phospho- and methyl- tyrosines were as effective as normal tyrosine at raising brain levels, and NALT was less so:
Brain tyrosine increases after treating with prodrugs: comparison with tyrosine.
Topall G, Laborit H.
After mice had been treated with L-tyrosine, O-phospho-L-tyrosine, L-tyrosine methyl ester or N-acetyl-L-tyrosine, tyrosine was assayed by HPLC coupled with fluorometric detection. O-Phospho-L-tyrosine behaved as a tyrosine prodrug after its hydrolysis by acid and alkaline phosphatases. After the intraperitoneal administration of O-phospho-L-tyrosine or the methyl ester, there was a substantial increase in bioavailability in terms of the effect of tyrosine. The two prodrugs were as powerful as tyrosine following oral administration. N-Acetyl-L-tyrosine was the least effective prodrug tested. The stability, solubility and bioavailability of O-phospho-L-tyrosine are consistent with proposing it for use as a tyrosine prodrug. In addition, it can be used parenterally. The use of a tyrosine aminotransferase inhibitor is necessary for limiting the hepatic breakdown of tyrosine and for increasing its bioavailability.
PMID: 2576051 [PubMed - indexed for MEDLINE]
(tyrosine aminotransferase inhibition for increasing bioavailability might be worth investigating further)
I think it's quite possible that NALT's increased ability to cross the BBB more than makes up for the lesser bioavailability. Indeed, in light of the fact that several members here (myself among them) report very strong effects from NALT in the 350-700mg range, I think it's quite probable. I'm pretty daring, and taking 2-3g of NALT seems somewhat reckless to me.
I've taken 2-3 g of tyrosine powder before, and the results set in from about 20-40 minutes +T0. It is similar to, though milder than, adderall. It allows one to focus more intently on a complex task, but makes simple...sometimes desirable tasks less appealing. It motivates you to do your hardest homework first in less time than ever, or take a hard test pretty well. But on a daily basis to study an intellectual passion, I can't recommend it.
This is in line with many of the tyrosine experiences I've read here. However, I would describe my experience with NALT to be just the oposite: highly complex tasks are very difficult to focus on, but motivation and appreciation for simpler, non-intellectual pleasures is increased.
Something I didn't consider until now is
the possibility that NALT produces effects distinct from L-tyrosine. For instance, ALCAR has many different effects in several systems than the non-acetylated L-carnitine. However, since NALT isn't an endogenous substance, I assumed that the only difference was in the pharmacokinetics of tyrosine delivery, and enhanced ability to cross the BBB.
Now I'm wondering if NALT possesses a characteristic or mechanism which might account for this subjective difference in experience. As most of the 49 papers in medline deal either with nutrition or chemistry, I'm unsure how to confirm this hypothesis. I'll start trying NALT and L-tyrosine more myself now that I'm considering this possibility (until now, I've considered NALT a quasi-recreational pseudo-nootropic that I've seldom been in the mood for). Hopefully others will chime in, and we can collect some more data about this.
Edited by chrono, 21 June 2010 - 07:22 PM.