A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia
Open accessAbstract
Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.
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Vitamins and 3-omega fatty acids, when given separately, can be deleterious in a subgroup of patients.
“Interestingly, Bentsen et al. (2013) found that vitamins and 3-omega fatty acids, when given separately, can be deleterious in a subgroup of patients.”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Bentsen et al., 2013
Vitamins C and E or 3-omega fatty acids are detrimental for a subgroup of patients.
“As vitamins C and E or 3-omega fatty acids are detrimental for a subgroup of patients (Bentsen et al., 2013), it would be also advisable using biomarkers to identify patients that would most benefit from an antioxidant treatment.”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Bentsen et al., 2013
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- Authors
- Bentsen, H., Osnes, K., Refsum, H., Solberg, D. K., & Bøhmer, T.
- Affiliations
- Oslo University Hospital (NO)
- Diakonhjemmet Hospital (NO)
- Corresponding author
- Bentsen, H
- Venue
- Translational Psychiatry
- Published
- 2013-12-17
- Volume
- 3
- Issue
- 12
- Pages
- e335-e335
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3906471
- OpenAlex
- W1992302122
- Cited by
- 97
- References
- 65
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 7 · 2022: 2 · 2021: 8 · 2020: 13 · 2019: 10 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 10 · 2014: 2
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Stanley Medical Research Institute (01T-106)
- Universitetet i Oslo
- Diakonhjemmet
- H. Lundbeck A/S
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- schizophrenia, omega-3 fatty acids, eicosapentaenoic acid, vitamin E, vitamin C, polyunsaturated fatty acids, persecutory delusions, psychotic symptoms
- MeSH terms
- Adolescent, Adult, Ascorbic Acid, Double-Blind Method, Drug Therapy, Combination, Fatty Acids, Unsaturated, Humans, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Vitamin E, Vitamins, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Treatment Outcome, Young Adult
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