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Amino Acid Treatments for Depression

The relationship between neurotransmitters and mood is complicated to say the least. We know that serotonin and norepinephrine have something to do with depression, but exactly what is hard to say. One thing we know is that people who are depressed are likely to have low levels of these chemicals in there blood. However, if you artificially drop the level of serotonin in someone's blood who is not depressed, it will usually have no effect on their mood at all. This seems to indicate that either low serotonin is a side-effect of depression (rather than a cause) or that it can cause depression only in certain people. There is some reason to believe that a genetic polymorphism could be involved in what makes serotonin effect some people's mood more than others. It is also (obviously) going to involve lots of other factors, especially attachment relationships.

It is from this very blurry picture that we seek to understand whether is it a good idea to take 5-HTP or tyrosine if you are depressed. These amino acids are the main building blocks for serotonin and norepinephrine respectively.

From the current research, it is not clear that increasing the levels of these chemicals in your blood has any positive effects beyond placebo. (It should be remembered that placebo is a highly effective treatment for depression.) The current research is not of high enough quality to make a determination and better research is needed. For example, I have been unable to find a study that gives prophylactic 5-HTP to people with genetically-determined low transcription of serotonin. This seems like the most likely effective use for the amino acid.

All of that said, there is some reason to believe that if you have a certain genetic polymorphism, it would be dangerous to have a low level of 5-HTP in your diet and effect your mood. The evidence is less clear than many other treatments, but it could be helpful for some people.


Amino Acid Treatments for Depression

Meyers, S. Use of Neurotransmitter Precursors for Treatment of Depression. Altern Med Rev 2000;5(1):64-71.

Reviewed available evidence on precursors to serotonin (typtophan and 5-HTP) and norepinephrine (L-phenylalanine and tyrosine) to treat depression. Found the evidence to be conflicting and insufficient to make a conclusion about their efficacy.

Kelly Shaw, Jane Turner, Christopher Del Mar. Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Australian and New Zealand Journal of Psychiatry. Volume 36 Issue 4, Pages 488 - 491.

While there is some evidence of superiority to placebo, this review found that the quality of research investigating 5-HTP and tryptophan is too poor to discern if they have any antidepressant properties.

Tyrosine and L-Phenylalanine Supplements. Nutr Health. 1984;3(3):163-73.

Reviews the theory behind advocating for neurotransmitter precurosrs in the treatment of depression and its relationship to the neurotransmitter theories of depression. Mentions that the supposed effectiveness of SSRI's is largely responsible for the neurotransmitter theory of depression.

Thomson, J. The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo.Psychol Med. 1982 Nov;12(4):741-51.

One hundred and fifteen patients from 5 general practices participated in a 12-week, double-blind study comparing L-tryptophan, amitriptyline, L-tryptophan-amitriptyline combination and placebo in the treatment of depression. Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo.

The Relationship Between Amino Acids and Depression

Neumeister, A. et al. Association Between Serotonin Transporter Gene Promoter Polymorphism (5HTTLPR) and Behavioral Responses to Tryptophan Depletion in Healthy Women With and Without Family History of Depression. Arch Gen Psychiatry. 2002;59:613-620.

Serotonin transporter gene promoter polymorphism (5HTTLPR)–dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. This study looked at the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles. The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermediate between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects.

Åberg-Wistedt, A. Serotonergic'vulnerability' in affective disorder: a study of the tryptophan depletion test and relationships between peripheral and central serotonin indexes in citalopram-responders. Acta Psychiatrica Scandinavica. Volume 97 Issue 5, Pages 374 - 380.

A double-blind study of the tryptophan depletion (TD) challenge was performed on a sample consisting of 20 patients with a major depressive disorder in clinical remission after citalopram treatment. TD was induced by the intake of 43 g of an amino acid mixture containing the five large neutral amino acids. The control group received the same mixture, to which 2.3 g tryptophan had been added. Five of the 12 challenged patients showed a worsening of depressive symptoms during the day of the test. In contrast, there was no mood alteration in the eight control patients. Baseline Cortisol levels were significantly higher in responders to TD compared to those in non-responders and controls. Thus low mood appeared to be associated with low serotonin precursor availability as well as with high Cortisol levels.



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