D-Serine and D-Amino Acids in Schizophrenia: What the Research Really Says

Schizophrenia is a chronic mental health disorder that affects how a person thinks, feels, and behaves. It impacts about 1 in 100 people worldwide and often includes symptoms such as hallucinations, delusions, and social withdrawal. While antipsychotic medications remain the standard treatment, they do not work for everyone. Many patients continue to struggle with symptoms, which has led researchers to investigate new treatment options. One area of growing interest involves D-serine, the best-studied member of the D-amino acid family once thought to be unimportant in humans. Today, scientists are also studying compounds like D-alanine and sodium benzoate (a D-amino acid oxidase inhibitor) to see whether they can improve schizophrenia symptoms when added to traditional medications. Medical disclaimer. For informational purposes only. It is not medical advice and does not suggest that you take any supplement. Joe Cannon, MS has been investigating dietary supplement research for over 30 years.

Do D-Amino Acids Help Schizophrenia?

D-amino acids are “right-handed” amino acids that interact with NMDA receptors in the brain. Research suggests they may play a role in schizophrenia, which is linked to underactive NMDA receptors.

Key findings from human studies:

D-serine: Some trials show improvements in positive, negative, and cognitive symptoms when added to antipsychotics [Tsai 1998].
D-alanine: A 6-week trial found benefits for positive and cognitive symptoms [Tsai 2006].
Sodium benzoate (DAO inhibitor): A 6-week trial improved overall symptoms and cognition [Lane 2013], but another study in early psychosis found no effect [Scott 2020].
D-aspartate and D-cysteine: Limited or no human clinical data so far.

Bottom line:
D-amino acids such as D-serine and D-alanine, and DAO inhibitors like sodium benzoate, may help some people with schizophrenia when used alongside standard antipsychotics. Results are mixed, doses are not standardized, and safety at high levels remains a concern. More large clinical trials are needed before supplements can be recommended.

What Is D-Serine and Other D-Amino Acids?

Amino acids are the building blocks of proteins. Almost all the amino acids in our body exist in the L-form, also called “left-handed.” For decades, scientists believed that only L-amino acids mattered in humans.

But researchers later discovered that D-amino acids (the “right-handed” form) also exist in small amounts in the brain and body. This was surprising. It meant our biology was more complex than we thought.

The most studied D-amino acids in schizophrenia are:

D-serine
D-aspartate
D-alanine
D-cysteine (a newer discovery)

Why D-Serine and D-Amino Acids Matter in Schizophrenia

One leading theory of schizophrenia is called the glutamate hypothesis. It proposes that people with schizophrenia may have reduced activity at a brain receptor known as the NMDA receptor. This receptor is essential for memory, learning, and mood regulation.

D-amino acids such as D-serine and D-alanine act as co-agonists, or helpers, at NMDA receptors. When levels of these amino acids are too low, NMDA receptors may not function correctly. This dysfunction has been linked to symptoms of schizophrenia and psychosis in clinical studies.

Because of this connection, researchers are investigating whether boosting D-amino acids can improve symptoms or cognition in people living with schizophrenia.

Human Clinical Trials of D-Serine and D-Amino Acids in Schizophrenia

Here’s what research in people has found so far:

D-Serine Clinical Trials in Schizophrenia

In a 6-week double-blind trial of 31 patients, D-serine (30 mg per kilogram of body weight) taken with antipsychotic medications improved schizophrenia symptoms, including hallucinations, social withdrawal, and cognition, compared to placebo.

Follow-up studies have confirmed some benefits, although results are inconsistent. For example, patients taking clozapine often do not respond. At high doses, D-serine may stress the kidneys, but most human studies report short-term safety.
Bottom line: D-serine shows promise but needs larger, long-term trials.

D-Alanine Clinical Evidence

In one 6-week human trial, D-alanine (100 mg/kg daily) improved positive, negative, and cognitive schizophrenia symptoms as an add-on to antipsychotics.
Bottom line: Results are promising, but more human trials are needed to confirm safety and effectiveness.

What We Know About D-Aspartate and Schizophrenia

Postmortem studies show lower D-aspartate levels in the prefrontal cortex of people with schizophrenia. One study of high-risk individuals also found metabolic changes linked to early psychosis.
Bottom line: Evidence is mostly from lab studies, not supplementation trials in people.

D-Cysteine and Psychosis: Early Research Only

D-cysteine is a newer discovery. So far, no human clinical trials in schizophrenia exist. Early lab studies suggest it may influence brain development.
Bottom line: Too early to draw conclusions.

Sodium Benzoate (DAO Inhibitor) and Schizophrenia

Another approach is to reduce the breakdown of D-amino acids. The enzyme, DAO, breaks down D-serine and D-alanine.

A 6-week clinical trial of 52 patients found that sodium benzoate, a DAO inhibitor, improved total schizophrenia symptoms and cognition.
However, a 12-week trial in 100 people with early psychosis found no benefit.
Meta-analyses suggest DAO inhibitors may improve positive symptoms and cognition, but not negative symptoms.

Bottom line: DAO inhibitors like sodium benzoate show mixed results, with some benefit for positive symptoms and thinking skills.

Are D-Serine or D-Amino Acid Supplements Safe?

Right now, there are no FDA-approved D-amino acid supplements for schizophrenia or psychosis. The human clinical trials completed so far are small and show mixed results. Some people may experience improvements in symptoms, while others may see no benefit.

Key safety points to know:

High doses of D-serine may stress the kidneys, although short-term studies report general safety.
Most clinical research uses medical-grade preparations, not the dietary supplements sold online or in stores.
Drug interactions are possible, especially with prescription antipsychotic medications.

👉 Important: If you or a loved one lives with schizophrenia or psychosis, do not start D-amino acid supplements on your own. Always consult a psychiatrist or qualified healthcare provider first.

FAQ

Do D-serine supplements help schizophrenia?
Some small human trials show D-serine may improve positive, negative, and cognitive symptoms when added to antipsychotics. Results are inconsistent, and safety at high doses remains a concern.

Is sodium benzoate effective for schizophrenia?
A 6-week trial found sodium benzoate improved total symptoms and cognition. However, a larger 12-week study in early psychosis found no effect.

Are there FDA-approved D-amino acid supplements for schizophrenia?
No. As of now, there are no FDA-approved D-amino acid supplements for schizophrenia or psychosis.

Bottom Line on D-Serine, D-Amino Acids, and Schizophrenia

D-amino acids are an emerging area of schizophrenia research.
Human clinical trials suggest that D-serine, D-alanine, and sodium benzoate (a DAO inhibitor) may improve certain symptoms when used with standard antipsychotic treatment.
Results are inconsistent, and more large, high-quality studies are needed.
D-aspartate and D-cysteine are still experimental, with little or no human trial data.
At this time, there are no FDA-approved D-amino acid supplements for schizophrenia or psychosis.

👉 Bottom line: D-amino acid research is promising but not conclusive. If you live with schizophrenia, the safest and most effective option remains evidence-based medical care from a psychiatrist.