**Background:** The niacin skin flush test (NSFT) is a simple, non-invasive method that assesses fatty acid content in cell membranes by measuring skin redness after topical application of methyl nicotinate. The test is grounded in David Horrobin's theory that schizophrenia represents a prostaglandin deficiency disease linked to essential fatty acid imbalances in modern diets. The authors aim to update the evidence on NSFT utility in psychotic disorders (schizophrenia, bipolar disorder, schizoaffective disorder) and present the SKINREMS device as a novel measurement method.
**Methods:** The authors conducted a narrative review of literature from PubMed, Google Scholar, and Web of Science databases covering 1977–2022. Inclusion criteria were English-language human studies. Search terms combined niacin skin flush test with psychiatric diagnoses (schizophrenia, bipolar, schizoaffective, psychosis, depression) and related mechanisms (prostaglandin, phospholipase A2, polyunsaturated fatty acids, omega-3, omega-6). Ultimately, 86 articles were included.
**Key Results:** The NSFT mechanism involves niacin binding to the hydroxycarboxylic acid receptor 2 (HM74A) on epidermal cells, increasing cytosolic calcium, activating phospholipase A2 (PLA2), releasing arachidonic acid (AA) from membrane phospholipids, and converting AA to prostaglandin D2 and E2 via cyclooxygenase-2 (COX-2), causing vasodilation. Blunted or delayed flushing in schizophrenia is well-documented across multiple studies despite methodological differences. However, Berger et al. paradoxically found increased sensitivity in ultra-high risk (UHR) patients, inversely correlated with omega-3 and omega-6 levels but positively with PLA2 activity, suggesting a "pro-inflammatory state" preceding psychosis onset. Tavares et al. showed significantly higher PLA2 activity in schizophrenia patients. Nilsson et al. demonstrated that niacin non-responders had lower IQ scores and impaired psychomotor function. Regarding diagnostic accuracy, the authors report from their prior work: sensitivity 71% and specificity 66% for schizophrenia vs. controls; 55% and 54% for bipolar disorder vs. controls; and 91% and 72% for schizophrenia vs. bipolar disorder. Factors affecting NSFT results include: gender (women show stronger reactions, decreasing with age), alcohol dependence (impaired flushing), and genetic polymorphisms—Covault et al. found a C to T polymorphism in FACL4 associated with stronger flushing, with T allele excess in major depression (49% vs. 38%, p=0.003) and non-significant excess in schizophrenia (44%, p=0.29). Nadalin et al. showed G alleles of PLA2G4A and PTGS2 polymorphisms associated with more intense reactions. Factors not affecting results include age (inconsistent findings), smoking, cannabis use (mixed evidence), antipsychotic medication, illness duration, number of hospitalizations, family history of schizophrenia, and PANSS scores. The SKINREMS device uses a camera inside an illuminated tube to capture 90 images over 15 minutes (one every 30 seconds) across three methyl nicotinate concentrations (0.1 M, 0.01 M, 0.001 M). The authors expect this standardized method to improve sensitivity and specificity. Regarding dietary interventions, the review notes that the Western diet has an omega-6 to omega-3 ratio of 15–20:1 versus the recommended 1:1 to 4:1. Robinson et al. reported omega-3 supplementation relieves depression and anxiety after recent psychosis. Hsu et al. found omega-3 reduces conversion to psychosis in UHR adolescents and improves symptoms and functioning. Jones et al. suggested schizophrenia patients may have impaired conversion of short-chain to long-chain PUFAs.
**Clinical Implications:** The NSFT could serve multiple clinical roles: (1) creating a pathophysiology-based classification of psychosis; (2) identifying patients with membrane lipid metabolism disorders who may respond to PUFA supplementation; (3) enabling early intervention and staging, as proposed in McGorry et al.'s clinical staging model where NSFT is suggested as a risk estimation tool in early stages; (4) guiding individualized dietary interventions. The WFSBP and CANMAT guidelines already emphasize omega-3's preventive role in high-risk youth with fatty acid deficiency. The authors note that omega-3 supplementation has biological effects similar to antipsychotics without metabolic side effects and may be effective before first symptom onset. However, standardized NSFT methodology is urgently needed, and further research should combine NSFT with EEG, near-infrared techniques, and biological markers.