Plasmalogens turn up in psychiatric research more often than most readers expect, and for a reason that has nothing to do with supplements: they are a large fraction of neuronal membrane phospholipid, and membrane composition changes how receptors sit and signal. Several independent groups have now measured plasmalogens in the blood of people with schizophrenia or bipolar disorder and found them reduced. One study measured them in patients who had never taken an antipsychotic, which rules out the most obvious confounder. None of this is a treatment finding, and one well-designed study points the other way. Nothing here is medical advice, and nobody should change a psychiatric medication on the strength of a lipid measurement.
Key Takeaways
- In 20 drug-naive patients experiencing a first psychotic episode, plus 20 recently unmedicated patients in relapse, multiple plasma phosphatidylcholine and phosphatidylethanolamine plasmalogens were significantly lower than in 17 matched controls[1]. Because the first group had never been medicated, the reduction cannot be an antipsychotic side effect.
- A lipidomics study of 23 patients and 27 age-matched controls found plasma choline and ethanolamine plasmalogens reduced by 23% to 45%, with DHA down about 30% in both plasma and platelets[2].
- The largest of these studies quantified 812 lipids in the erythrocyte membranes of 80 patients and 40 controls. Phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogens, were significantly decreased, membrane fluidity fell, and oxidised lipids accumulated[3].
- In bipolar disorder, 34 patients had lower plasma ethanolamine plasmalogen than 38 matched controls, p equal to 0.0033, with the effect concentrated in bipolar I[4].
- The counterweight: in youth at familial risk for bipolar I disorder, DHA deficits were present but erythrocyte plasmalogen and every other measure of peroxisomal function were normal[5]. Reduced plasmalogens do not appear to be an inherited trait that precedes the illness.
- No trial has tested a plasmalogen supplement in schizophrenia or bipolar disorder. Every study here is cross-sectional or case-control.
The Medication Confounder, and Why One Study Settles It
The obvious objection to any blood-lipid finding in schizophrenia is that antipsychotics change metabolism, so patients and controls differ for reasons that have nothing to do with the illness. A 2012 study was built to address that. It compared three groups: 20 drug-naive patients experiencing their first psychotic episode, 20 patients in psychotic relapse after stopping prescribed medication, and 17 matched healthy controls. Multiple plasma phosphatidylcholine and phosphatidylethanolamine plasmalogens were significantly lower in both patient groups. The authors concluded that reduced plasmalogen levels look like a trait present at the onset of psychotic illness and after repeated relapses, and that the reduction is attributable to the illness rather than to its treatment[1].
That does not make it causal. A first psychotic episode brings sharp changes in diet, sleep, smoking and stress, any of which can move a lipid panel. What the design rules out is one specific alternative explanation, which is worth something but is not the same as establishing a mechanism.
How Large Is The Reduction
A 2015 lipidomics study of 23 patients with schizophrenia and 27 age-matched controls put numbers on it. Plasma levels of both choline and ethanolamine plasmalogens were reduced by 23% to 45%. Docosahexaenoic acid was down roughly 30% in both plasma and platelets. The platelet result is the one worth noticing, because it did not simply mirror plasma: ethanolamine plasmalogens were decreased there, while choline plasmalogen was increased[2]. A single directional claim about plasmalogens in schizophrenia does not survive contact with that detail.
The largest study in this group, published in 2022, quantified 812 lipids in erythrocyte membranes from 80 patients and 40 healthy controls. Phosphatidylcholines and phosphatidylethanolamines, with the plasmalogen species specifically named, were significantly decreased. Total membrane polyunsaturated fatty acids were reduced, which the authors measured as a decrease in membrane fluidity, and both membrane oxidised lipids and peripheral lipid peroxides were increased[3]. The vinyl ether bond that makes plasmalogens preferentially consumed by oxidants is described in our article on the antioxidant mechanism, and it offers a coherent reading of that combination: more oxidative pressure, less of the lipid that absorbs it.
Bipolar Disorder, and a Difference Between Types
A 2020 Japanese study compared 34 patients with bipolar disorder against 38 controls matched for age, sex and ethnicity. Plasma ethanolamine plasmalogen was significantly lower in patients, p equal to 0.0033. Broken down by subtype, the reduction held for bipolar I against controls, p equal to 0.0047, and plasma phosphatidylethanolamine was lower in bipolar I than in both controls, p equal to 0.016, and bipolar II, p equal to 0.010[4]. A 2025 review of plasma and serum lipidomic fingerprints across bipolar disorder and schizophrenia reported decreased plasmalogens as one of the recurring patterns in the literature[6].
The Study That Complicates The Picture
A 2016 study asked the question that matters for anyone tempted to read these findings as a cause. It examined medication-free youth at familial risk for bipolar I disorder, both asymptomatic and symptomatic, using a comprehensive peroxisomal blood panel: very-long-chain fatty acids, branched-chain fatty acids, bile acid intermediates, pipecolic acid, and erythrocyte plasmalogen and DHA. Significant erythrocyte DHA deficits showed up in the ultra-high-risk and first-episode groups. There were no significant group differences on any other measure of peroxisomal function, including plasmalogen, and DHA levels were not correlated with any peroxisomal measure[5].
That result is hard to reconcile with a simple story in which impaired peroxisomal plasmalogen synthesis drives psychiatric illness. It suggests the DHA deficit and the plasmalogen deficit are separable, and that the plasmalogen reduction seen in established illness arrives with the illness rather than preceding it. A 2016 red blood cell lipidomics study of 74 medicated, clinically stable outpatients against 40 healthy subjects points the same way from a different angle: the lipid abnormality most robustly associated with a schizophrenia diagnosis there was sphingomyelin content, not plasmalogen, and the patients split into two distinct lipid subgroups[7].
What This Means In Practice
It means the membrane-lipid hypothesis in psychiatry is a live research question with real measurements behind it, and an empty instruction set. No trial has given a plasmalogen supplement to anyone with schizophrenia or bipolar disorder, so there is no dose, no duration, no safety data in this population, and no outcome to report. Our evidence-tier page sets out what has actually been tested in humans, and the clinical trial summary covers the trials that do exist, none of which are psychiatric.
There is also a specific caution here that does not apply to most topics on this site. Psychiatric medication interacts with a great deal, discontinuation carries real risk, and relapse is dangerous. Anyone taking an antipsychotic or a mood stabiliser who is curious about a supplement should raise it with their prescriber rather than acting on a biomarker study. General tolerability information is in our side effect and safety page, and readers who have already decided to try a supplement for unrelated reasons can compare options in the reviewed product roundup.
Frequently Asked Questions
Are plasmalogen levels low in schizophrenia?
In the cohorts measured, yes. A 2012 study found multiple plasma phosphatidylcholine and phosphatidylethanolamine plasmalogens were significantly lower in both drug-naive first-episode patients and unmedicated relapsing patients than in matched controls. A 2015 study put the reduction at 23% to 45%, and a 2022 study of 812 lipids in 80 patients found plasmalogens decreased alongside reduced membrane fluidity.
Could antipsychotic medication explain the low plasmalogen levels?
The 2012 study was designed to test that. It included 20 patients who had never taken an antipsychotic, experiencing a first psychotic episode, and found the same reduction. That rules out medication as the explanation, though it does not rule out other changes that accompany a first episode, such as diet, sleep, smoking and stress.
Do people at genetic risk of bipolar disorder have low plasmalogens?
Apparently not. A 2016 study of medication-free youth at familial risk for bipolar I found significant erythrocyte DHA deficits but no significant differences in erythrocyte plasmalogen or in any other measure of peroxisomal function. That argues the plasmalogen reduction arrives with established illness rather than preceding it.
Is there a plasmalogen supplement trial in schizophrenia or bipolar disorder?
No. Every study in this area is cross-sectional or case-control and measured a marker without attempting to change it. There is no dose, duration, safety data or outcome to report in this population. Psychiatric medication decisions belong with a prescriber.
References
- Kaddurah-Daouk R, McEvoy J, Baillie R, et al. Impaired plasmalogens in patients with schizophrenia. Psychiatry research (2012). PMID 22513041
- Wood PL, Unfried G, Whitehead W, et al. Dysfunctional plasmalogen dynamics in the plasma and platelets of patients with schizophrenia. Schizophrenia research (2015). PMID 25497441
- Wang D, Sun X, Maziade M, et al. Impaired Membrane Lipid Homeostasis in Schizophrenia. Schizophrenia bulletin (2022). PMID 35751100
- Kurokawa T, Itoh H, Inoue T, et al. Altered ethanolamine plasmalogen and phosphatidylethanolamine levels in blood plasma of patients with bipolar disorder. Psychiatry and clinical neurosciences (2020). PMID 31841251
- McNamara RK, Jandacek R, Rider T, et al. Familial risk for bipolar disorder is not associated with impaired peroxisomal function: Dissociation from docosahexaenoic acid deficits. Psychiatry research (2016). PMID 27825781
- Separovic I, Rubic I, Beer Ljubic B, et al. Plasma and Serum LC-MS Lipidomic Fingerprints of Bipolar Disorder and Schizophrenia. International journal of molecular sciences (2025). PMID 40649910
- Tessier C, Sweers K, Frajerman A, et al. Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations. Translational psychiatry (2016). PMID 27701405
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