Association between 19 dietary fatty acids intake and rheumatoid arthritis: Results of a nationwide survey

  • Ruijie Xie
    Department of Microsurgery, University of South China Affiliated Nanhua Hospital. Hengyang, China
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  • Ya Zhang
    Corresponding author at: Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, No.336 Dongfeng South Road, Zhuhui District, Hengyang City, Hunan Province, PR China 421002.
    Department of Gland Surgery, University of South China Affiliated Nanhua Hospital, Hengyang, China
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Published:December 26, 2022DOI:


      • We investigated for the first time the relationship between the intake of 19 different dietary fatty acids and rheumatoid arthritis in a relatively large sample size of the population.
      • Among the 19 dietary fatty acids, only 4 subclasses (hexadecanoic acid, octadecanoic acid, hexadecenoic acid, and docosahexaenoic acid) were significantly associated with Hs-CRP or RA risk.
      • We found the inverted U-shaped relationship between MUFAs and RA risk, which may provide insights for future interventional studies to find potential treatment or prevention strategies for RA.



      The relationship between dietary fatty acid intakes and rheumatoid arthritis (RA) is unclear and the available studies have focused on only a few fatty acids. This study investigated the association between the intake of 19 dietary fatty acids and RA in U.S. adults.


      This cross-sectional study using nationally representative data from the 2010-2020 National Health and Nutrition Examination Survey (NHANES). Multivariate linear regression model, multivariate logic regression models, smoothing curve fitting, and two-segment linear regression model were used to explore the relationships between 19 dietary fatty acids intakes with high-sensitivity C-reactive protein (Hs-CRP) and RA risk.


      A total of 16,530 participants were included (1053 participants with RA). Intake of hexadecanoic acid and octadecanoic acid were significantly associated with higher Hs-CRP levels, intake of hexadecenoic acid was significantly associated with higher RA risk, and intake of docosahexaenoic acid was significantly associated with lower RA risk. In addition, there was an inverted U-shaped relationship between total monounsaturated fatty acids (MUFAs) intake and RA risk, with the inflection point reached at 15.77% .


      Among the 19 dietary fatty acids, only 4 subclasses were significantly associated with Hs-CRP or RA risk. The inverted U-shaped relationship between MUFAs and RA risk may provide insights to find potential prevention strategies for RA.



      Rheumatoid arthritis ((RA)), National Health and Nutrition Examination Survey ((NHANES)), High-sensitivity C-reactive protein ((Hs-CRP)), Saturated fatty acids ((SFAs)), Monounsaturated fatty acids ((MUFAs)), Polyunsaturated fatty acids ((PUFAs)), Short-chain fatty acids ((SCFAs)), SFA 4:0 ((Butanoic)), SFA 6:0 ((Hexanoic)), SFA 8:0 ((Octanoic)), SFA 10:0 ((Decanoic)), SFA 12:0 ((Dodecanoic)), SFA 14:0 ((Tetradecanoic)), SFA 16:0 ((Hexadecanoic)), SFA 18:0 ((Octadecanoic)), MUFA 18:0 ((Hexadecenoic)), MUFA 18:1 ((Octadecenoic)), MUFA 20:1 ((Eicosenoic)), MUFA 22:1 ((Docosenoic)), PUFA 18:2 ((Octadecadienoic)), PUFA 18:3 ((Octadecatrienoic)), PUFA 18:4 ((Octadecatetraenoic)), PUFA 20:4 ((Eicosatetraenoic)), PUFA 20:5 ((Eicosapentaenoic)), PUFA 22:5 ((Docosapentaenoic)), PUFA 22:6 ((Docosahexaenoic)), Arthritis in older adults ((ARTIEL))
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        • England BR
        • Thiele GM
        • Anderson DR
        • Mikuls TR
        Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications.
        BMJ. 2018; 361: k1036
        • Aletaha D
        • Smolen JS
        Diagnosis and management of rheumatoid arthritis: a review.
        JAMA. 2018; 320: 1360-1372
        • Safiri S
        • Kolahi AA
        • Hoy D
        • Smith E
        • Bettampadi D
        • Mansournia MA
        • Almasi-Hashiani A
        • Ashrafi-Asgarabad A
        • Moradi-Lakeh M
        • Qorbani M
        • et al.
        Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017.
        Ann. Rheum. Dis. 2019; 78: 1463-1471
        • Philippou E
        • Nikiphorou E
        Are we really what we eat? Nutrition and its role in the onset of rheumatoid arthritis.
        Autoimmun. Rev. 2018; 17: 1074-1077
        • Fritsche KL
        The science of fatty acids and inflammation.
        Adv. Nutr. 2015; 6: 293s-301s
        • Siri-Tarino PW
        • Sun Q
        • Hu FB
        • Krauss RM
        Saturated fat, carbohydrate, and cardiovascular disease.
        Am. J. Clin. Nutr. 2010; 91: 502-509
        • Dierge E
        • Debock E
        • Guilbaud C
        • Corbet C
        • Mignolet E
        • Mignard L
        • Bastien E
        • Dessy C
        • Larondelle Y
        • Feron O
        Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects.
        Cell Metab. 2021; 33 (e1705): 1701-1715
        • Nagpal R
        • Neth BJ
        • Wang S
        • Craft S
        • Yadav H
        Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment.
        EBioMedicine. 2019; 47: 529-542
        • Calder PC
        n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases.
        Am. J. Clin. Nutr. 2006; 83: 1505s-1519s
        • Saini RK
        • Keum YS
        Omega-3 and omega-6 polyunsaturated fatty acids: dietary sources, metabolism, and significance - A review.
        Life Sci. 2018; 203: 255-267
        • Gioia C
        • Lucchino B
        • Tarsitano MG
        • Iannuccelli C
        • Di Franco M
        Dietary habits and nutrition in rheumatoid arthritis: can diet influence disease development and clinical manifestations?.
        Nutrients. 2020; 12
        • Olson MV
        • Liu YC
        • Dangi B
        • Paul Zimmer J
        • Salem Jr., N
        • Nauroth JM
        Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis.
        Inflamm. Res. 2013; 62: 1003-1013
        • Lee YH
        • Bae SC
        • Song GG
        Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis.
        Arch. Med. Res. 2012; 43: 356-362
        • Curtin LR
        • Mohadjer LK
        • Dohrmann SM
        • Montaquila JM
        • Kruszan-Moran D
        • Mirel LB
        • Carroll MD
        • Hirsch R
        • Schober S
        • Johnson CL
        The national health and nutrition examination survey: sample design, 1999-2006.
        Vital Health Stat. 2012; 2: 1-39
        • Rossato LT
        • de Branco FMS
        • Azeredo CM
        • Rinaldi AEM
        • de Oliveira EP
        Association between omega-3 fatty acids intake and muscle strength in older adults: A study from National Health and Nutrition Examination Survey (NHANES) 1999-2002.
        Clin. Nutr. 2020; 39: 3434-3441
        • Huang G
        • Ren G
        Interaction between ω-6 fatty acids intake and blood cadmium on the risk of low cognitive performance in older adults from National Health and Nutrition Examination Survey (NHANES) 2011-2014.
        BMC Geriatr. 2022; 22: 292
        • Willett W
        Nutritional Epidemiology.
        Oxford university press, 2012
        • Zong G
        • Li Y
        • Wanders AJ
        • Alssema M
        • Zock PL
        • Willett WC
        • Hu FB
        • Sun Q
        Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies.
        BMJ. 2016; 355: i5796
        • Ahn SS
        • Kim HM
        • Park Y
        Assessment of disease activity in patients with rheumatoid arthritis using plasma tumour M2-pyruvate kinase test.
        Front. Immunol. 2022; 13901555
        • Chen L
        • Sun Q
        • Peng S
        • Tan T
        • Mei G
        • Chen H
        • Zhao Y
        • Yao P
        • Tang Y
        Associations of blood and urinary heavy metals with rheumatoid arthritis risk among adults in NHANES, 1999-2018.
        Chemosphere. 2022; 289133147
        • de Pablo P
        • Dietrich T
        • McAlindon TE
        Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population.
        J. Rheumatol. 2008; 35: 70-76
        • Peeters GM
        • Alshurafa M
        • Schaap L
        • de Vet HC
        Diagnostic accuracy of self-reported arthritis in the general adult population is acceptable.
        J. Clin. Epidemiol. 2015; 68: 452-459
        • Hu L
        • Hu G
        • Xu BP
        • Zhu L
        • Zhou W
        • Wang T
        • Bao H
        • Cheng X
        U-Shaped association of serum uric acid with all-cause and cause-specific mortality in US adults: a cohort study.
        J. Clin. Endocrinol. Metab. 2020; 105
        • Sun J
        • Zhang Z
        • Liu Z
        • Li J
        • Kang W
        The correlation of total percent fat with alterations in cholesterol and triglycerides in adults.
        Front. Nutr. 2022; 9881729
        • Xiao Q
        • Cai B
        • Yin A
        • Huo H
        • Lan K
        • Zhou G
        • Shen L
        • He B
        L-shaped association of serum 25-hydroxyvitamin D concentrations with cardiovascular and all-cause mortality in individuals with osteoarthritis: results from the NHANES database prospective cohort study.
        BMC Med. 2022; 20: 308
        • McInnes IB
        • Schett G
        Pathogenetic insights from the treatment of rheumatoid arthritis.
        Lancet. 2017; 389: 2328-2337
        • Das UN
        Current and emerging strategies for the treatment and management of systemic lupus erythematosus based on molecular signatures of acute and chronic inflammation.
        J. Inflamm. Res. 2010; 3: 143-170
        • Das UN
        Lipoxins as biomarkers of lupus and other inflammatory conditions.
        Lipids Health Dis. 2011; 10: 76
        • Das UN
        Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus?.
        Lipids Health Dis. 2011; 10: 19
        • Das UN
        Molecular pathobiology of scleritis and its therapeutic implications.
        Int. J. Ophthalmol. 2020; 13: 163-175
        • Charoenngam N
        • Holick MF
        Immunologic effects of Vitamin D on human health and disease.
        Nutrients. 2020; 12
        • Forsyth C
        • Kouvari M
        • D'Cunha NM
        • Georgousopoulou EN
        • Panagiotakos DB
        • Mellor DD
        • Kellett J
        • Naumovski N
        The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies.
        Rheumatol. Int. 2018; 38: 737-747
        • Schönenberger KA
        • Schüpfer AC
        • Gloy VL
        • Hasler P
        • Stanga Z
        • Kaegi-Braun N
        • Reber E
        Effect of anti-inflammatory diets on pain in rheumatoid arthritis: a systematic review and meta-analysis.
        Nutrients. 2021; 13
        • Johansson K
        • Askling J
        • Alfredsson L
        • Di Giuseppe D
        Mediterranean diet and risk of rheumatoid arthritis: a population-based case-control study.
        Arthritis Res. Ther. 2018; 20: 175
        • Abdulrazaq M
        • Innes JK
        • Calder PC
        Effect of ω-3 polyunsaturated fatty acids on arthritic pain: a systematic review.
        Nutrition. 2017; 39-40: 57-66
        • Yates CM
        • Calder PC
        • Ed Rainger G
        Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease.
        Pharmacol. Ther. 2014; 141: 272-282
        • Pedersen M
        • Stripp C
        • Klarlund M
        • Olsen SF
        • Tjønneland AM
        • Frisch M
        Diet and risk of rheumatoid arthritis in a prospective cohort.
        J. Rheumatol. 2005; 32: 1249-1252
        • Coras R
        • Pedersen B
        • Narasimhan R
        • Brandy A
        • Mateo L
        • Prior-Español A
        • Kavanaugh A
        • Armando AM
        • Jain M
        • Quehenberger O
        • et al.
        Imbalance between omega-6- and omega-3-derived bioactive lipids in arthritis in older adults.
        J. Gerontol. A. 2021; 76: 415-425
        • Dawczynski C
        • Dittrich M
        • Neumann T
        • Goetze K
        • Welzel A
        • Oelzner P
        • Völker S
        • Schaible AM
        • Troisi F
        • Thomas L
        • et al.
        Docosahexaenoic acid in the treatment of rheumatoid arthritis: a double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil.
        Clin. Nutr. 2018; 37: 494-504
        • Pu B
        • Gu P
        • Zheng C
        • Ma L
        • Zheng X
        • Zeng Z
        Self-reported and genetically predicted effects of coffee intake on rheumatoid arthritis: Epidemiological studies and Mendelian randomization analysis.
        Front. Nutr. 2022; 9926190
        • de Pablo P
        • Romaguera D
        • Fisk HL
        • Calder PC
        • Quirke AM
        • Cartwright AJ
        • Panico S
        • Mattiello A
        • Gavrila D
        • Navarro C
        • et al.
        High erythrocyte levels of the n-6 polyunsaturated fatty acid linoleic acid are associated with lower risk of subsequent rheumatoid arthritis in a southern European nested case-control study.
        Ann. Rheum. Dis. 2018; 77: 981-987
        • Bathina S
        • Das UN
        PUFAs, BDNF and lipoxin A4 inhibit chemical-induced cytotoxicity of RIN5F cells in vitro and streptozotocin-induced type 2 diabetes mellitus in vivo.
        Lipids Health Dis. 2019; 18: 214
        • Das UN
        Bioactive lipids in age-related disorders.
        Adv. Exp. Med. Biol. 2020; 1260: 33-83
        • Das UN
        Arachidonic acid and lipoxin A4 as possible endogenous anti-diabetic molecules.
        Prostaglandins Leukot. Essent. Fatty Acids. 2013; 88: 201-210
        • Matsumoto Y
        • Sugioka Y
        • Tada M
        • Okano T
        • Mamoto K
        • Inui K
        • Habu D
        • Koike T
        Monounsaturated fatty acids might be key factors in the Mediterranean diet that suppress rheumatoid arthritis disease activity: the TOMORROW study.
        Clin. Nutr. 2018; 37: 675-680
        • Sun L
        • Zhu J
        • Mi S
        • Li Y
        • Wang T
        • Li Y
        Causal association of monounsaturated fatty acids with rheumatoid arthritis but not osteoarthritis: A two-sample Mendelian randomization study.
        Nutrition. 2021; 91-92111363
        • Rosser EC
        • Piper CJM
        • Matei DE
        • Blair PA
        • Rendeiro AF
        • Orford M
        • Alber DG
        • Krausgruber T
        • Catalan D
        • Klein N
        • et al.
        Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells.
        Cell Metab. 2020; 31 (837-851.e810)
        • Tajik N
        • Frech M
        • Schulz O
        • Schälter F
        • Lucas S
        • Azizov V
        • Dürholz K
        • Steffen F
        • Omata Y
        • Rings A
        • et al.
        Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis.
        Nat. Commun. 2020; 11: 1995
        • Martinsson K
        • Dürholz K
        • Schett G
        • Zaiss MM
        • Kastbom A
        Higher serum levels of short-chain fatty acids are associated with non-progression to arthritis in individuals at increased risk of RA.
        Ann. Rheum. Dis. 2022; 81: 445-447
        • Serhan CN
        • Clish CB
        • Brannon J
        • Colgan SP
        • Chiang N
        • Gronert K
        Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing.
        J. Exp. Med. 2000; 192: 1197-1204
        • Serhan CN
        • Gotlinger K
        • Hong S
        • Lu Y
        • Siegelman J
        • Baer T
        • Yang R
        • Colgan SP
        • Petasis NA
        Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes.
        J. Immunol. 2006; 176: 1848-1859
        • Neuhofer A
        • Zeyda M
        • Mascher D
        • Itariu BK
        • Murano I
        • Leitner L
        • Hochbrugger EE
        • Fraisl P
        • Cinti S
        • Serhan CN
        • et al.
        Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation.
        Diabetes. 2013; 62: 1945-1956
        • Watson JE
        • Kim JS
        • Das A
        Emerging class of omega-3 fatty acid endocannabinoids & their derivatives.
        Prostaglandins Other Lipid Mediat. 2019; 143106337
        • Zaiss MM
        • Wu HJ Joyce
        • Mauro D
        • Schett G
        • Ciccia F
        The gut-joint axis in rheumatoid arthritis.
        Nat. Rev. Rheumatol. 2021; 17: 224-237
        • Mustonen AM
        • Nieminen P
        Fatty acids and oxylipins in osteoarthritis and rheumatoid arthritis-a complex field with significant potential for future treatments.
        Curr. Rheumatol. Rep. 2021; 23: 41