Skip to main content
Download PDF
Download ePub

Association of omega-3, omega-6 fatty acids intakes and omega-6: omega-3 ratio with the prevalence of suicidal ideation: mediating role of C-reactive protein

Lipids in Health and Disease volume 24, Article number: 178 (2025) Cite this article

Abstract

Background

Although dietary omega fatty acids have been recognized for positive effects on mental health, the specific association between omega fatty acids intake and suicidal ideation remains ambiguous. This study aims to explore the potential association between the prevalence of suicidal ideation and dietary omega fatty acids intake in American adults.

Methods

The data of 27,944 American adults collected from National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. To assess the association between dietary omega fatty acids intake and suicidal ideation as measured by Item 9 of PHQ-9, logistic regression, restricted cubic spline regression, and stratified analyses, mediation analyses were employed.

Results

Logistic regression analyses indicate that the intakes of omega-3 and omega-6 fatty acids were inversely associated with the prevalence of suicidal ideation, and dietary omega-6/omega-3 ratio was positively associated with the prevalence of suicidal ideation. Subgroup analyses further revealed a stronger association between suicidal ideation and omega fatty acids intake in individuals with a history of stroke. Furthermore, a saturation effect and non-linear association were identified between omega-3 and omega-6 fatty acids intake and the prevalence of suicidal ideation, characterized by an L-shaped curve with an inflection point at 1.36 g/d, 13.69 g/d, respectively. Notably, C-reactive protein (CRP) partially mediated the association between omega-6, omega-3 fatty acids intake and suicidal ideation by a proportion of 3.8% and 4.0%.

Conclusion

The findings of this study suggest that higher omega-3 and omega-6 fatty acids intake and lower omega-6/omega-3 ratio is associated with a declined prevalence of suicidal ideation.

Clinical trial number

Not applicable.

Introduction

Globally, suicide represents a major public health issue accounting for over 700,000 deaths annually [1]. In response, World Health Organization (WHO) has enacted a strategic initiative with the objective of declining suicide mortality by 33% across each member state from 2013 to 2030 [2]. According to ideation-to-action models of suicide, suicidal ideation can serve as a pivotal precursor to both suicide attempts and completed suicides [3]. Empirical studies have demonstrated that the probability of committing suicide in the first year following the onset of suicidal ideation is approximately 1.40% in psychiatric patients [4]. Consequently, the identification of modifiable risk factors associated with suicidal ideation is crucial for the effective prevention of suicide. Although existing literature has identified various risk factors, such as personality traits, mood disorders, and sociodemographic characteristics [5, 6], many of which are frequently unmodifiable.

Epidemiologic studies have shown that depression is related to genetic and environmental factors, especially dietary factors [7,8,9]. Moreover, specific dietary interventions may be employed as routine treatments, potentially exerting beneficial effects on psychiatric conditions [10, 11]. Studies have shown that the consumption of nutrients including polyunsaturated fatty acids (PUFAs), folic acid, vitamin B12, zinc, and vitamin D may mitigate the prevalence of psychiatric disorders such as depression [12,13,14].

PUFAs are essential lipids that must be acquired from dietary sources [15]. Within this category, omega-6 and omega-3 fatty acids constitute the two primary families of PUFAs, each playing vital roles in neurodevelopment and function, cardiovascular health, immune system enhancement, inflammation modulation, cancer prevention, and mental health maintenance, in other physiological processes [16, 17]. Some studies with limited sample sizes suggest that omega-3 fatty acids intake may reduce the prevalence of suicidal ideation in individuals with depression [18,19,20]. Nevertheless, the association between dietary intake of omega-3 and omega-6 fatty acids and the prevalence of suicidal ideation in the general population has not been inadequately explored. Furthermore, there is a lack of research that clearly delineates the specific intake levels of omega-3 and omega-6 fatty acids and their association with the prevalence of suicidal ideation.

There is research evidence that suicidal ideation is significantly associated with chronic systemic inflammation [21]. Chronic inflammation can mediate a permanent reorganization of inflammatory neurotransmitter pathways, resulting in the transition from acute to chronic pain and promoting depression, anxiety, and suicidal ideation [22,23,24]. Furthermore, there is a strong relationship between diet and chronic systemic inflammation; dietary omega-3 fatty acids have been shown to effectively reduce inflammation by decreasing levels of inflammatory biomarkers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and CRP [25, 26].

Consequently, this study aims to explore the association between dietary omega-3 and omega-6 fatty acids, along with their ratio, and the prevalence of suicidal ideation, utilizing data from NHANES. Additionally, the secondary goal was to analyze whether dietary omega fatty acids intake mediated the intended association through the CRP. The results may provide valuable insights for the clinical management and prevention of suicidal ideation.

Methods

Research subjects and design

NHANES, administered by National Center for Health Statistics (NCHS) [27], is an extensive study to assess the association between nutrition, disease prevention, and health promotion. This survey is conducted biennially by taking physical examinations, interviews, with a variety of sections encompassing demographic, dietary, laboratory data, and examinations. Further details about the NHANES database can be accessed at http://www.cdc.gov/nhanes.

In this study, the data from ten cycles of the NHANES dataset during the period from 1999 to 2018 were analyzed through a retrospective analysis. Subjects aged 18 years old or older (n = 59204) were included in this study. And according to the exclusion criteria, subjects lacking the data of suicidal ideation (n = 27880), those without the data of dietary omega fatty acids intake (n = 1016), pregnant females (n = 599), those without the data of body mass index (BMI) and other covariable (n = 1765) were excluded. Consequently, the final samples were comprised of 27,944 subjects, as illustrated in Fig. 1.

Fig. 1
figure 1

Flowchart of the sample selection from the 1999–2018 NHANES

Full size image

Assessment of dietary Omega fatty acids intake

Data on the unsaturated fatty acid and total energy intake of the subjects in this study were obtained from the dietary module in the NHANES. Dietary omega fatty acids and total energy intake were assessed on two distinct occasions: The first assessment was conducted in person, while the second was conducted by call. Owing to substantial data deficiencies encountered during the second round of interviews, the analysis in this study exclusively utilized the dietary information collected during the initial session [28].

This study also aims to comprehensively identify the various components of omega-3 and omega-6 fatty acids. The dietary omega-3 fatty acids examined included eicosapentaenoic acid (EPA, 20:5), alpha-linolenic acid (ALA, 18:3), docosahexaenoic acid (DHA, 22:6), and docosapentaenoic acid (DPA, 22:5), as well as additional forms such as stearidonic acid (SDA, 18:4). The dietary omega-6 fatty acids analyzed comprised arachidonic acid (AA, 20:4) and linoleic acid (LA, 18:2) [29].

Assessments on suicidal ideation

Suicidal ideation was assessed by analyzing responses to Item 9 of Patient Health Questionnaire-9 (PHQ-9), a questionnaire which inquires: “How often have you engaged in self-harm or considered that it would be preferable to die over the past two weeks?” Subjects scored from 1 to 3 were classified as experiencing suicidal ideation, whereas those scored zero were classified as not experiencing suicidal ideation [30].

Covariable

Based on previous studies [30] and variables provided by NHANES, covariable of interest including self-reported health information, physical examination results, and sociodemographic variables were identified as potential confounding factors. Trained interviewers collected self-reported health information and sociodemographic variables, including smoking status, past medical history, and alcohol abuse during Mobile Examination Center (MEC) and household interviews. Sociodemographic variables included education level, age, marital status, gender, family poverty income ratio (PIR), and race. Physical examination results, including blood pressure and BMI, were collected by trained health technicians at MEC. Additionally, blood samples were collected at MEC for the assessment of albumin, CRP, creatinine, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). The definitions for diabetes mellitus, hypertension, and hyperlipidemia were consistent with those previously reported [31]. The incidence of cancers, stroke, and coronary heart disease (CHD) was determined through self-reported diagnoses. Alcohol abuse was characterized by the intake at least 12 alcoholic beverages within one year. Smoking was defined by the consumption of a minimum of 100 cigarettes over an individual’s lifetime. According to the 2018 Physical Activity Guidelines from the United States, moderate to vigorous aerobic physical activity (MVPA) has been classified into categorical variables: low (< 150 min per week) and high (≥ 150 min per week) [32].

Boruta algorithm

The outcomes of feature screening utilizing Boruta’s algorithm are presented in Fig. 2. Following 500 iterations, it was identified that the fifteen variables most closely linked with suicidal ideation included gender, age, race, alcohol abuse, BMI, smoking status, CHD, hyperlipidemia, education level, PIR, albumin, marital status, creatinine, dietary omega-3 and omega-6 fatty acids intake and cancers. Despite the omission of certain key characteristics, such as physical activities and stroke due to their low z-values relative to the most strongly associated characteristics, these factors were still incorporated into subsequent analyses based on clinical experience and prior research.

Fig. 2
figure 2

(A)Feature selection process for suicidal ideation based on Boruta’s algorithm, including dietary omega-3 intake. (B) Feature selection process for suicidal ideation based on Boruta’s algorithm, including diet omega-6 intake

Full size image

Statistical analysis

Dietary omega-3, omega-6 or omega-6/3 ratio fatty acids intake was stratified into quartiles as follows: Q1: <0.90 g/d, Q2: 0.90–1.45 g/d, Q3: 1.45–2.27 g/d, Q4: >2.27 g/day for omega-3 intake. Q1: <8.61 g/d, Q2: 8.61–13.79 g/d, Q3: 13.79–20.95 g/d, Q4: >20.95 g/day for omega-6 intake. Q1: <7.53, Q2:7.53–9.10, Q3:9.10-11.41, and Q4:>11.41 for omega-6/3 ratio. The normality of continuous variables was assessed by presenting them as either the median with interquartile range or mean ± SD. The association between dietary omega intake and the prevalence of suicidal ideation was examined by ORs and 95% CI derived from multivariable logistic regression models. Boruta algorithm was utilized in this study for variable selection, resulting in the construction of three distinct models: Model 1, unadjusted; Model 2, adjusted for gender and age; and Model 3, comprehensively adjusted for a range of factors, including gender, age, race, alcohol abuse, BMI, total energy intake, smoking status, hypertension, physical activities, CHD, hyperlipidemia, stroke, PIR, education level, marital status, albumin, creatinine and cancers. Heterogeneity between dietary omega intake and the prevalence of suicidal ideation was assessed through interaction and subgroup analyses across various variables. Additionally, the non-linear association between suicidal ideation and dietary omega fatty acids intake was explored through restricted cubic spline (RCS) curves.

Finally, “mediation” package in R 4.2.2. was utilized to perform Mediation analysis assessing the mediating effects of CRP on the associations of dietary omega fatty acids intake with suicidal ideation, adjusted by Model3. The presence of a mediating effect was defined as satisfying all of the following conditions having a significant indirect effect, a significant total effect, and a positive proportion of the mediator effect. Related data were analyzed with Free Statistics software and R software.

Results

Subjects’ characteristics

Table 1 delineates the principal characteristics of the study cohort. Out of 27,944 subjects, 1037 (3.7%) reported experiencing suicidal ideation, at the mean age of 47.8 years old, with females representing 49.6%. Subjects reporting suicidal ideation were more likely to live alone. Moreover, subjects with suicidal ideation demonstrate a lower education level, albumin, and PIR. This group also exhibited a higher prevalence of comorbid conditions, including stroke, diabetes mellitus, CHD, hypertension, and hyperlipidemia, in addition to increased BMI, CRP and omega-6/3 ratio levels. Furthermore, dietary omega-3 and omega-6 fatty acids intake was significantly lower in subjects with suicidal ideation (Fig. 3) (all p < 0.05).

Table 1 Characteristics of the study population based on suicidal ideation
Full size table
Fig. 3
figure 3

Dietary omega intake levels in participants with or without suicidal ideation

Full size image

Association between suicidal ideation and dietary Omega fatty acids intake

Table 2 illustrates the findings from the logistic regression analysis for the association between dietary omega fatty acids intake and suicidal ideation. When dietary omega-3 and omega-6 fatty acids intake was stratified into quartiles, the fully adjusted model (Model 3) indicates that compared to subjects in the lowest Q1, the risk reduction in Q2, Q3 and Q4 were 25%, 32% and 40% for omega-3 fatty acids intake, and 25%, 25%, 30% for omega-6 fatty acids intake, respectively.

Table 2 Associations between dietary Omega fatty acids intake and the prevalence of suicidal ideation
Full size table

The omega-6/3 ratio was further categorized into quartiles. In the fully adjusted Model 3, individuals in the fourth quartile (Q4) exhibited a 25% increase in the prevalence of suicidal ideation compared to those in the first quartile (Q1), as shown in Table 2.

Non-linear association between dietary omega-3 and omega-6 fatty acids intake and suicidal ideation

After controlling for all variables, a non-linear association between dietary omega-3 and omega-6 fatty acids intake and suicidal ideation was identified, as depicted in Fig. 4A-B. Specifically, an L-shaped association was observed, with an inflection point at 1.36 g/d for omega-3 fatty acids intake, and 13.69 g/d for omega-6 fatty acids intake, respectively. Below this threshold, dietary omega-3 and omega-6 fatty acids intake demonstrates a significant effect value of 0.54, 0.94, respectively, whereas above this level, the effect value was not statistically significant (see Table 3). In addition, RCS analyses demonstrate a linear association between omega-6/3 ratio and suicidal ideation (as shown in Fig. 4C).

Fig. 4
figure 4

Restricted cubic spline fitting for the association between suicidal ideation and (A)dietary omega-3 intake, (B) dietary omega-6 intake, (C) dietary omega-6/3 ratio

Full size image
Table 3 Threshold effect analysis of dietary Omega fatty acids intake and suicidal ideation using the two-piecewise linear regression model
Full size table

Subgroup analyses

A stratified multivariate logistic regression analysis was conducted to explore the association between dietary omega fatty acids intake and suicidal ideation among various subgroups (Fig. 5). The interaction test revealed no statistically significant differences in the association between suicidal ideation and dietary omega fatty acids intake with respect to gender, age, diabetes mellitus, BMI, hypertension, CHD, hyperlipidemia, and cancers. Additionally, the association between dietary omega-3 and omega-6 fatty acids intake and suicidal ideation was more pronounced in subjects with a history of stroke.

Fig. 5
figure 5

Association between suicidal ideation and (A)dietary omega-3 intake, (B) dietary omega-6 intake, (C) dietary omega-6/3 ratio in various subgroups

Full size image

Mediation analysis

The mediation model and its associated pathways are depicted in Fig. 6. The analysis revealed a significant indirect effect of dietary omega-3 and omega-6 fatty acids intake on suicidal ideation, mediated by CRP. These findings indicate that CRP partially mediates the association between dietary omega-3 and omega-6 fatty acids intake and suicidal ideation, explaining approximately 4.0% and 3.8% of the total effect, respectively.

Fig. 6
figure 6

Mediated analysis model path diagram. Notes: dietary omega-3, omega-6 intake was defined as the independent variable; suicidal ideation as the dependent variable; and CRP as the mediating variable

Full size image

Discussion

In this cross-sectional study comprising 27,944 subjects, it was observed that the intake of omega-3 and omega-6 fatty acids was inversely associated with the prevalence of suicidal ideation, whereas dietary omega-6/3 ratio exhibited a positive association with this risk. The association between dietary omega-3 and omega-6 consumption and the prevalence of suicidal ideation was characterized by an L-shaped curve, with identified thresholds at 1.36 g/d and 13.69 g/d, respectively. This association was particularly pronounced among individuals with a history of stroke. Additionally, mediation analysis reveals that CRP partially mediated the association between dietary omega-3 and omega-6 fatty acids intake and suicidal ideation.

To the best of our knowledge, this study represents the first exploration into the association between dietary intake of omega fatty acids and the prevalence of suicidal ideation in the general population. Omega-3 fatty acids are regarded as essential nutrients and are predominantly acquired from external sources, such as seafood, due to the limited efficiency of endogenous synthesis from precursors [33]. The significant antioxidant and anti-inflammatory properties of omega-3 fatty acids have been shown to confer beneficial effects in various chronic inflammatory conditions, including diabetes mellitus, CVD, hypertension, cancers, and even rheumatoid arthritis [34]. In particular, several studies have identified an association between omega-3 deficiency and conditions such as catatonia and benign depression, with omega-3 supplementation reportedly alleviating symptoms of depression, irritability, and anxiety [35,36,37]. In the elderly population, omega-3 supplementation has been demonstrated to be an effective and low-cost preventive strategy against depression [38]. The research of Chika Horikawa et al. [39] further supports the protective effect of omega-3 fatty acids on depression, as evidenced through an established cohort study. Additionally, a recent meta-analysis [40] explored the dose-response association between omega-3 fatty acids and depression, revealing a reverse J-shaped effect.

Omega-6 fatty acids have traditionally been associated with pro-inflammatory effects, and diets high in omega-6 have been thought to counteract the anti-inflammatory benefits of omega-3 fatty acids [41]. However, recent evidence suggests that increased omega-6 fatty acids intake, such as LA, does not necessarily elevate inflammatory markers and may even contribute to reduced inflammation [41, 42]. Given that inflammation is implicated in the pathogenesis of depression [43], these findings are particularly relevant. Thesing et al. found an inverse association between omega-6 fatty acids intake and the prevalence of depression [44]. Similarly, Shi et al. found that infertile female consuming moderate amounts of omega-6 fatty acids exhibited a reduced prevalence of depressive symptoms [45]. These studies align with the findings of this study, which, for the first time, suggest that a moderate intake of omega-6 fatty acids (less than 13.69 g/d) may be advantageous in mitigating the prevalence of suicidal ideation.

These findings indicate a positive association between omega-6/3 ratio and the prevalence of suicidal ideation, aligning with several studies suggesting that a lower omega-6/3 intake ratio may enhance health outcomes and mitigate the prevalence of various chronic diseases [46, 47]. Although the mechanisms between omega-6/3 ratio and the increased the prevalence of suicidal ideation are not fully understood, several possibilities have been proposed. Primarily, a high omega-6/3 ratio promotes the production of arachidonic acid (AA) derived from omega-6 eicosanoids, and AA has been shown to increase the production of proinflammatory factors, which may increase the incidence of suicidal ideation [48]. Another possible mechanism is that a high omega-6/3 ratio is related to catecholaminergic or serotonergic neurotransmission [49], which may also contribute to an increased risk of suicidal ideation. Serotonin primarily influences mood, while catecholamines are involved in motivational aspects; deficiencies in catecholamines can lead to symptoms such as apathy, asthenia, abulia, and anhedonia [36].

The findings of this study provide further clarification on the L-shaped association between dietary omega fatty acids intake and the prevalence of suicidal ideation in American adults, indicating that the consumption of increased omega fatty acids may function as a non-pharmacological preventive measure. Additionally, combined with our findings, it appears that the potential therapeutic value of exceeding the threshold of omega-3, and omega-6 fatty acids intake may be limited. For individuals at risk, it is advisable to meet the recommended daily omega-3 or omega-6 fatty acids intake of 1.36 g/d and 13.69 g/d, respectively. Considering individual differences and dietary patterns, it is necessary to conduct additional research to explore the optimal level of omega fatty acids intake.

The results of this study suggest that CRP may partially mediate the association between dietary omega fatty acids intake and suicidal ideation, highlighting the importance of monitoring inflammation levels in individuals with lower omega consumption. Omega-3 and omega-6 fatty acids is known for its potent anti-inflammatory properties, and its higher intake has been associated with declined levels of inflammatory markers [42]. Consequently, increasing dietary omega fatty acids intake may attenuate the inflammatory response by reducing CRP levels, thereby potentially reducing the prevalence of suicidal ideation. Hence, it is plausible to hypothesize that in patients experiencing suicidal ideation, the concurrent use of anti-inflammatory medications and omega fatty acids derived from natural food sources could synergistically enhance the therapeutic outcomes.

The inverse association between omega fatty acids intake and suicidal ideation may be attributed to several mechanisms potentially influencing the pathology of suicidal ideation. Omega fatty acids, especially DHA and EPA, significantly influence the fluidity and signaling functions of cell membranes [50, 51]. The presence of these fatty acids improves the structure and function of neuronal membranes, thereby affecting neurotransmitter release and neural signaling. Omega fatty acids deficiency has been documented to be linked with impairments in dopamine, serotonin, and norepinephrine neurotransmission, which are associated with emotional disorders, including suicidal ideation [52]. Moreover, a substantial body of research indicates that individuals with psychiatric disorders tend to exhibit elevated levels of oxidative stress and inflammation, coupled with a comparatively low intake of dietary antioxidants [53, 54]. A cross-sectional study involving 364 patients undergoing secondary prevention for CVD demonstrates an inverse association between increased dietary intake of omega-3 and omega-6 fatty acids and the levels of IL-1β, CRP, IL-12, and IL-10 [55]. Omega-3 and omega-6 fatty acids, acting as signaling molecules, can activate peroxisome proliferator-activated receptors, which in turn regulate various processes including inflammatory responses, oxidative stress, lipogenesis, and glucose and lipid metabolism [56]. This comprehensive effect may potentially contribute to a declined risk of suicidal ideation.

Study strengths and limitations

This study exhibits several notable strengths. Firstly, a nationally representative and substantial sample of American adults was employed. Secondly, the study concurrently examined the association between omega-3 and omega-6 fatty acids intake, as well as omega-6/3 ratio, with the prevalence of suicidal ideation, while also exploring the dose–response association. However, the study has its limitations: (1) The cross-sectional design limits the ability to establish causality, as it captures associations at a single point in time. This limitation renders the causal relationship between dietary omega fatty acid intake and suicidal ideation indeterminate. (2) The assessment on suicidal ideation predominantly relied on questionnaires, which may introduce measurement errors. (3) It is crucial to recognize that variables such as treatment modalities for individuals experiencing suicidal ideation, as well as the presence of food allergies or gastrointestinal disorders, may significantly influence the findings of this study. Future studies should systematically integrate these factors and their potential confounding effects to enhance the understanding of the association between suicidal ideation and dietary omega fatty acids intake.

Conclusion

This study demonstrates an inverse association between the intake of omega-3 and omega-6 fatty acids and the prevalence of suicidal ideation, while a positive association was observed with omega-6/3 ratio and the prevalence of suicidal ideation. These findings imply that adequate omega fatty acid intake, particularly omega-3, may contribute to the prevention of suicidal ideation. However, further research is necessary to validate these results and to explore the underlying mechanisms linking dietary omega fatty acid consumption with suicidal ideation.

Data availability

The datasets generated and analysis during the current study are available in the NHANES, http://www.cdc.gov/nchs/NHANEs/.

References

  1. Mudiyanselage SPK, Tsai YT, Tsai YJ, Yang YH, Lu ZT, Ko NY. Global overview of suicidal behavior and risk factors among the general population during the COVID-19 pandemic: a scoping review. BMC Psychol. 2024;12:727.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Singh OP. Comprehensive mental health action plan 2013–2030: we must rise to the challenge. Indian J Psychiatry. 2021;63:415–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Klonsky ED, Saffer BY, Bryan CJ. Ideation-to-action theories of suicide: a conceptual and empirical update. Curr Opin Psychol. 2018;22:38–43.

    Article  PubMed  Google Scholar 

  4. Hubers AAM, Moaddine S, Peersmann SHM, Stijnen T, van Duijn E, van der Mast RC, Dekkers OM, Giltay EJ. Suicidal ideation and subsequent completed suicide in both psychiatric and non-psychiatric populations: a meta-analysis. Epidemiol Psychiatr Sci. 2018;27:186–98.

    Article  CAS  PubMed  Google Scholar 

  5. Lee JI, Lee MB, Liao SC, Chang CM, Sung SC, Chiang HC, Tai CW. Prevalence of suicidal ideation and associated risk factors in the general population. J Formos Med Assoc. 2010;109:138–47.

    Article  PubMed  Google Scholar 

  6. Nock MK, Borges G, Bromet EJ, Alonso J, Angermeyer M, Beautrais A, Bruffaerts R, Chiu WT, de Girolamo G, Gluzman S, et al. Cross-national prevalence and risk factors for suicidal ideation, plans and attempts. Br J Psychiatry. 2008;192:98–105.

    Article  PubMed  PubMed Central  Google Scholar 

  7. D’Souza S, Thompson JM, Slykerman R, Marlow G, Wall C, Murphy R, Ferguson LR, Mitchell EA, Waldie KE. Environmental and genetic determinants of childhood depression: the roles of DAT1 and the antenatal environment. J Affect Disord. 2016;197:151–8.

    Article  PubMed  Google Scholar 

  8. Wang Q, Shelton RC, Dwivedi Y. Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis. J Affect Disord. 2018;225:422–8.

    Article  CAS  PubMed  Google Scholar 

  9. Xia Y, Wang N, Yu B, Zhang Q, Liu L, Meng G, Wu H, Du H, Shi H, Guo X, et al. Dietary patterns are associated with depressive symptoms among Chinese adults: a case-control study with propensity score matching. Eur J Nutr. 2017;56:2577–87.

    Article  CAS  PubMed  Google Scholar 

  10. Lassale C, Batty GD, Baghdadli A, Jacka F, Sanchez-Villegas A, Kivimaki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2019;24:965–86.

    Article  PubMed  Google Scholar 

  11. Romero-Blanco C, Hernandez-Martinez A, Parra-Fernandez ML, Onieva-Zafra MD, Prado-Laguna MDC, Rodriguez-Almagro J. Food addiction and lifestyle habits among university students. Nutrients. 2021;13.

  12. Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, et al. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. 2019;18:308–24.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gianfredi V, Koster A, Odone A, Amerio A, Signorelli C, Schaper NC, Bosma H, Kohler S, Dagnelie PC, Stehouwer CDA et al. Associations of dietary patterns with incident depression: the Maastricht study. Nutrients. 2021;13.

  14. Zhang R, Sun J, Li Y, Zhang D. Associations of n-3, n-6 fatty acids intakes and n-6:n-3 ratio with the risk of depressive symptoms: NHANES 2009–2016. Nutrients. 2020;12.

  15. Kapoor B, Kapoor D, Gautam S, Singh R, Bhardwaj S. Dietary polyunsaturated fatty acids (PUFAs): uses and potential health benefits. Curr Nutr Rep. 2021;10:232–42.

    Article  PubMed  Google Scholar 

  16. Djuricic I, Calder PC. Beneficial outcomes of Omega-6 and Omega-3 polyunsaturated fatty acids on human health: an update for 2021. Nutrients. 2021;13.

  17. D’Angelo S, Motti ML, Meccariello R. omega-3 and omega-6 polyunsaturated fatty acids, obesity and Cancer. Nutrients. 2020;12.

  18. Hallahan B, Hibbeln JR, Davis JM, Garland MR. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial. Br J Psychiatry. 2007;190:118–22.

    Article  PubMed  Google Scholar 

  19. Bellino S, Bozzatello P, Rocca G, Bogetto F. Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of the association with valproic acid. J Psychopharmacol. 2014;28:125–32.

    Article  CAS  PubMed  Google Scholar 

  20. Bozzatello P, Rocca P, Bellino S. Combination of Omega-3 fatty acids and valproic acid in treatment of borderline personality disorder: A Follow-Up study. Clin Drug Investig. 2018;38:367–72.

    Article  CAS  PubMed  Google Scholar 

  21. Xiao Y, Huang W. Association of dietary inflammatory index with depression and suicidal ideation in older adult: results from the National health and nutrition examination surveys 2005–2018. Front Psychiatry. 2022;13:944154.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hu YQ, Niu TT, Xu JM, Peng L, Sun QH, Huang Y, Zhou J, Ding YQ. Negative air ion exposure ameliorates depression-like behaviors induced by chronic mild stress in mice. Environ Sci Pollut Res Int. 2022;29:62626–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Benatti C, Blom JM, Rigillo G, Alboni S, Zizzi F, Torta R, Brunello N, Tascedda F. Disease-Induced neuroinflammation and depression. CNS Neurol Disord Drug Targets. 2016;15:414–33.

    Article  CAS  PubMed  Google Scholar 

  24. Turiaco F, Iannuzzo F, Bruno A, Drago A. Genetics of suicide ideation. A role for inflammation and neuroplasticity? Eur Arch Psychiatry Clin Neurosci. 2024;274:1527–41.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kavyani Z, Musazadeh V, Fathi S, Hossein Faghfouri A, Dehghan P, Sarmadi B. Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: an umbrella meta-analysis. Int Immunopharmacol. 2022;111:109104.

    Article  CAS  PubMed  Google Scholar 

  26. Singh JE. Dietary sources of Omega-3 fatty acids versus Omega-3 fatty acid supplementation effects on cognition and inflammation. Curr Nutr Rep. 2020;9:264–77.

    Article  PubMed  Google Scholar 

  27. Zipf G, Chiappa M, Porter KS, Ostchega Y, Lewis BG, Dostal J. National health and nutrition examination survey: plan and operations, 1999–2010. Vital Health Stat 1 2013:1–37.

  28. Wu Z, Ruan Z, Liang G, Wang X, Wu J, Wang B. Association between dietary magnesium intake and peripheral arterial disease: results from NHANES 1999–2004. PLoS ONE. 2023;18:e0289973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen J, Sun B, Zhang D. Association of dietary n3 and n6 fatty acids intake with hypertension: NHANES 2007–2014. Nutrients. 2019;11.

  30. Chen Y, Lin H, Xu J, Zhou X. Estimated glucose disposal rate is correlated with increased depression: a population-based study. BMC Psychiatry. 2024;24:786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhou X, Weng X, Xu J, Wang W. Correlation between remnant cholesterol and hyperuricemia in American adults. Lipids Health Dis. 2024;23:176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Piercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, George SM, Olson RD. The physical activity guidelines for Americans. JAMA. 2018;320:2020–8.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wei L, Wu Z, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids-an update. Cancer Lett. 2022;526:193–204.

    Article  CAS  PubMed  Google Scholar 

  34. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). 2008;233:674–88.

    Article  CAS  PubMed  Google Scholar 

  35. Bozzatello P, De Rosa ML, Rocca P, Bellino S. Effects of Omega 3 fatty acids on main dimensions of psychopathology. Int J Mol Sci. 2020;21.

  36. Pruneti C, Guidotti S. Need for multidimensional and multidisciplinary management of depressed preadolescents and adolescents: A review of randomized controlled trials on oral supplementations (Omega-3, fish oil, vitamin D(3)). Nutrients. 2023;15.

  37. DiNicolantonio JJ, O’Keefe JH. The importance of marine Omega-3s for brain development and the prevention and treatment of behavior, mood, and other brain disorders. Nutrients. 2020;12.

  38. Farioli Vecchioli S, Sacchetti S, Nicolis di Robilant V, Cutuli D. The role of physical exercise and Omega-3 fatty acids in depressive illness in the elderly. Curr Neuropharmacol. 2018;16:308–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Horikawa C, Otsuka R, Kato Y, Nishita Y, Tange C, Rogi T, Kawashima H, Shibata H, Ando F, Shimokata H. Longitudinal Association between n-3 Long-Chain Polyunsaturated Fatty Acid Intake and Depressive Symptoms: A Population-Based Cohort Study in Japan. Nutrients 2018;10.

  40. Grosso G, Micek A, Marventano S, Castellano S, Mistretta A, Pajak A, Galvano F. Dietary n-3 PUFA, fish consumption and depression: A systematic review and meta-analysis of observational studies. J Affect Disord. 2016;205:269–81.

    Article  CAS  PubMed  Google Scholar 

  41. Innes JK, Calder PC. Omega-6 fatty acids and inflammation. Prostaglandins Leukot Essent Fat Acids. 2018;132:41–8.

    Article  CAS  Google Scholar 

  42. Li Y, Tang H, Yang X, Ma L, Zhou H, Zhang G, Chen X, Ma L, Gao J, Ji W. Associations of omega-3, omega-6 polyunsaturated fatty acids intake and omega-6: omega-3 ratio with systemic immune and inflammatory biomarkers: NHANES 1999–2020. Front Nutr. 2024;11:1410154.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, Caraci F. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev. 2014;2014:313570.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Thesing CS, Bot M, Milaneschi Y, Giltay EJ, Penninx B. Omega-3 and omega-6 fatty acid levels in depressive and anxiety disorders. Psychoneuroendocrinology. 2018;87:53–62.

    Article  CAS  PubMed  Google Scholar 

  45. Hong Y, Jin X, Shi L. Association between polyunsaturated fatty acids and depression in women with infertility: a cross-sectional study based on the National health and nutrition examination survey. Front Psychiatry. 2024;15:1345815.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Simopoulos AP. An increase in the Omega-6/Omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016;8:128.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kew S, Banerjee T, Minihane AM, Finnegan YE, Williams CM, Calder PC. Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25–72 y. Am J Clin Nutr. 2003;77:1278–86.

    Article  CAS  PubMed  Google Scholar 

  48. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST. Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci U S A. 2003;100:1751–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003;48:195–203.

    Article  PubMed  Google Scholar 

  50. Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Sherratt SCR, Mason RP, Libby P, Steg PG, Bhatt DL. Do patients benefit from omega-3 fatty acids? Cardiovasc Res. 2024;119:2884–901.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Su KP. Biological mechanism of antidepressant effect of omega-3 fatty acids: how does fish oil act as a ‘mind-body interface’? Neurosignals. 2009;17:144–52.

    Article  CAS  PubMed  Google Scholar 

  53. Bhatt S, Nagappa AN, Patil CR. Role of oxidative stress in depression. Drug Discov Today. 2020;25:1270–6.

    Article  CAS  PubMed  Google Scholar 

  54. Huang Q, Liu H, Suzuki K, Ma S, Liu C. Linking what we eat to our mood: A review of diet, dietary antioxidants, and depression. Antioxid (Basel) 2019, 8.

  55. Bersch-Ferreira AC, Sampaio GR, Gehringer MO, Ross-Fernandes MB, Kovacs C, Alves R, Pereira JL, Magnoni CD, Weber B, Rogero MM. Association between polyunsaturated fatty acids and inflammatory markers in patients in secondary prevention of cardiovascular disease. Nutrition. 2017;37:30–6.

    Article  CAS  PubMed  Google Scholar 

  56. Echeverria F, Ortiz M, Valenzuela R, Videla LA. Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: relationship to tissue development and aging. Prostaglandins Leukot Essent Fat Acids. 2016;114:28–34.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the NHANES database for providing the data source for this study.

Funding

Not applicable.

Author information

Author notes

  1. Hao Lin and Zhibin Bai contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Pingyang Hospital of Wenzhou Medical University, Wenzhou City, China

    Hao Lin, Zhibin Bai & Qi Yang

  2. Digestive Endoscopy Center, Pingyang Hospital of Wenzhou Medical University, Wenzhou City, China

    Daoke Wu

  3. Department of Nursing, Pingyang Hospital of Wenzhou Medical University, Wenzhou City, China

    Shuangshuang Qu

Authors
  1. Hao Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Zhibin Bai
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Daoke Wu
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Qi Yang
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Shuangshuang Qu
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

SSQ designed the study; ZBB, DKW and QY collected biochemical data; HL drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shuangshuang Qu.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the National Centre for Health Statistics Research Ethics Review Board, and every participant signed informed consent. The written informed consent of all subjects was obtained following the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, H., Bai, Z., Wu, D. et al. Association of omega-3, omega-6 fatty acids intakes and omega-6: omega-3 ratio with the prevalence of suicidal ideation: mediating role of C-reactive protein. Lipids Health Dis 24, 178 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12944-025-02587-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12944-025-02587-6

Keywords

Lipids in Health and Disease

ISSN: 1476-511X