D-Alanine for Schizophrenia
Erin Hawkes, MSc
D-alanine acts as a “helper” molecule to open N-methyl-D-aspartate (NMDA) receptors in the brain: when it is present, the main neurotransmitter, glutamate, can open the receptor. D-alanine is not the only candidate; another natural “helper” is glycine, and other supplements work the same way. NMDA activity is decreased in people with schizophrenia and it has therefore been suggested that D-alanine may be therapeutic by enhancing the activity of NMDA receptors. Particularly, NMDA function is related to memory and learning, which are affected in schizophrenia.
While there is little research on the therapeutic value of D-alanine, what has been done is solid – including a double-blind, placebo-controlled trial (the most trusted model).
D-alanine is a nonessential amino acid, meaning it can be manufactured by the human body. However, good sources include meat, dairy, eggs, beans, yeast, bran, and grains. It is also available as a powder.
Likely Effectiveness: Possibly helpful as a supplement, used by some athletes.
Effective Dosage: 2 grams (1/2 tsp powder) daily.
Research: A few good studies (e.g., double-blind, placebo-controlled trial). Despite this research, it has not yet been approved by the FDA to treat illnesses such as schizophrenia.
Risks: In one reputable study, transient insomnia and nausea were experienced by one participant (out of 32 participants). Extreme levels of alanine can cause higher blood pressure, high cholesterol levels, increased body weight, and an increased risk of type-II diabetes.
1) Tsai GE, Yang P, Chang YC, and Chong MY. D-Alanine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 2006;59: 230-234.
This study was a 6-week, double-blind (administrator and patients both do not know who receives drug versus placebo) trial of D-alanine in 32 patients with schizophrenia. Those receiving D-alanine experienced fewer positive (e.g., hallucinations, delusions), negative (e.g., poverty of speech, “flat” emotions), and cognitive symptoms as measured by standard tests. There was a 11% to 17% improvement in the D-alanine group as compared to those receiving the placebo. The authors conclude that D-alanine, with its selective and potent “helper” role, may be a valuable adjunct therapeutic for the treatment of schizophrenia.
2) Hatano T, Ohnuma T, Sakai Y,et al.. Plasma alanine levels increase in patients with schizophrenia as their clinical symptoms improve—Results from the Juntendo University Schizophrenia Projects (JUSP). Psychiatry Res. 2010;177: 27-31.
This clinical report examined the changing levels of D-alanine in blood samples of 81 people with schizophrenia (and 50 controls) and how this correlated with their changing severity of symptoms. Specifically, lower levels of D-alanine corresponded to more severe symptoms at the beginning of the experiment. Between admission to the hospital and discharge, patients’ levels had increased significantly, both compared to controls and their pre-treatment levels. The researchers conclude that D-alanine levels may be a therapeutic marker for schizophrenia and its improvement.
3) Lee NY, Roh, MS, Kim, et al.. The prevalence of metabolic syndrome and its association with alanine aminotransferase in clozapine-treated Korean patients with schizophrenia. Int Clin Psychopharmacol.2013;28: 71-79.
Lee and colleagues’ Taiwanese study of 113 patients with schizophrenia examined blood levels of an enzyme, alanine aminotransferase (ALT), that changes alanine’s chemical structure. Among people taking clozapine, ALT levels predicted the development of a metabolic syndrome (MetS) that can include altered metabolism, weight gain, and diabetes. ALT levels in participants taking clozapine were over twice those of the general population. Levels of ALT in the blood predict later MetS; it is therefore proposed to be a reliable (an easy blood work) measure of susceptibility to MetS in patients taking clozapine.