Dear Editor
Fish are rich in marine omega-3 fatty acids (FA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since marine omega-3 FAs have anti-inflammatory and immunomodulatory properties1, their potential use as a dietary adjunct in the treatment of psoriasis has been explored2,3. Fish oil supplements have shown potentially protective effects on progression of psoriasis in small-scale (n=9~145) clinical studies2–4. However, fish oil’s benefit for psoriasis has been difficult to confirm because of the lack of baseline measures of dietary and nutritional status5. To our knowledge, no prospective data are available on the association between dietary intake of omega-3 FAs and risk of psoriasis and psoriatic arthritis6. Therefore, we examined the association between consumption of polyunsaturated FAs and risk of incident psoriasis in the Nurses’ Health Study II (NHSII).
Since 1989, NHS II participants have biennially completed a self-administered questionnaire regarding their personal medical history and lifestyle factors. Food frequency questionnaires (FFQ) for dietary intake in the previous year were also asked every four years since 1991. Participants were asked how often they had consumed a given unit or one portion size of each food item in the FFQ on average during the previous year, with nine frequency responses ranging from ‘almost never’ to ‘6 or more per day.’ Nutrient intakes of participants were calculated by multiplying the consumption frequency of each food item with nutrient database prepared for specified amount of the food item. The nutrient database was based on the Harvard University Food Composition Database derived from the US Department of Agriculture (USDA) sources7 and supplemented with information from manufacturers. Dietary supplement intake was considered in calculation of each nutrient as well. Nutrient intake was adjusted with total energy intake by the residual method8. Previous studies have demonstrated reasonable levels of reproducibility and validity of the FFQ for ranking individuals by consumption of nutrients and foods9,10. The fatty acid intake measured by the FFQ has also been validated in Nurses’ Health Study showing moderate-to-strong correlations between dietary intakes and plasma biomarkers11. Personal history of clinician-diagnosed psoriasis and the time-period of diagnosis were assessed in the 2005 questionnaire (before 1991, 1991–1994, 1995–1998, 1999–2002, or 2003–2005). Participants with self-reported psoriasis were mailed to complete the Psoriasis Screening Tool questionnaire (PST) and Psoriatic Arthritis Screening and Evaluation questionnaire (PASE). The validity of PST has been evaluated with 99% sensitivity and 94% specificity for psoriasis screening12. The PASE also distinguished psoriatic arthritis from non-psoriatic arthritis patients with high sensitivity (70%–82%) and specificity (73%–80%)13,14. The age-standardized baseline characteristics of participants in 1991 were examined according to quintiles of marine omega-3 FA consumption. The intakes of EPA, DHA, marine omega-3 FAs (sum of EPA and DHA), linoleic acid, arachidonic acid, omega-6 FAs (sum of linoleic acid and arachidonic acid) and omega-6/omega-3 FA ratio were categorized into quintiles. Cox proportional hazards models were used to estimate the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between consumption of polyunsaturated FAs and risk of psoriasis and psoriatic arthritis, adjusting for smoking status, personal history of cardiovascular disease, type 2 diabetes, hypertension, and hypercholesterolemia, body mass index (BMI), physical activity, alcohol intake, and total energy intake. All statistical analyses were conducted using SAS (version 9.4; SAS Institute Inc., Cary, NC) with two-sided p values at the significance level of 0.05.
Participants who consumed more marine omega-3 FAs were older, more physically active, consumed more alcohol, and had higher prevalence of hypertension and hypercholesterolemia at baseline (Table 1). After 1,137,635 person-years of follow-up, 602 cases of incident psoriasis were identified. Among them, 152 had concurrent psoriatic arthritis. The consumption of marine omega-3 FAs (EPA and DHA) either in total or individually was not associated with risk of psoriasis and psoriatic arthritis (Table 2). Consumption of individual fish items (canned tuna, dark meat fish, and other fish), which are a major source of marine omega-3 FAs, also showed no association with risk of psoriasis and psoriatic arthritis (data not shown). Interestingly, higher consumption of omega-6 FA and linoleic acid was not associated with psoriasis but associated with a lower risk of psoriatic arthritis (multivariate HR 0.55, 95% CI: 0.33–0.90 for top vs. bottom quintiles of omega-6 FA, and multivariate HR 0.45, 95% CI: 0.27–0.73 for linoleic acid) (Table 2).
Table 1.
Age-adjusted baseline characteristics of the study population according to quintiles of marine omega-3 fatty acid consumption in 1991 in the NHSII (Nurses’ Health Study II)
| Marine omega-3 fatty acids | |||||
|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | |
| Age, years, mean (SD)* | 35.7 (4.7) | 35.9 (4.7) | 36.1 (4.6) | 36.4 (4.6) | 37.0 (4.5) |
| White race, % | 97.4 | 97.2 | 96.7 | 95.5 | 92.9 |
| Body mass index, kg/m2, mean (SD) | 24.4 (5.3) | 24.6 (5.3) | 24.6 (5.2) | 24.6 (5.2) | 24.4 (5.1) |
| Physical activity, metabolic equivalent hrs/wk, mean (SD) | 17.4 (23.7) | 18.5 (24.3) | 20.0 (25.5) | 21.9 (27.2) | 25.7 (31.2) |
| Current smoker, % | 11.4 | 11.6 | 11.7 | 11.0 | 11.5 |
| Alcohol intake, g/d, mean (SD) | 2.4 (5.7) | 2.7 (5.8) | 3.00 (5.7) | 3.7 (6.5) | 3.9 (6.5) |
| Total energy intake, kcal, mean (SD) | 1783.2 (555.4) | 1807.6 (540.4) | 1784.1 (541.5) | 1840.5 (544.5) | 1733.9 (534.9) |
| Hypertension, % | 5.9 | 5.7 | 6.0 | 6.4 | 6.9 |
| Hypercholesterolemia, % | 13.5 | 13.8 | 14.6 | 14.5 | 15.8 |
Abbreviations: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid. SD, standard deviation
All variables other than age are standardized to the age distribution of the study population.
Table 2.
Hazard ratios (HRs) of psoriasis and psoriatic arthritis according to quintiles of marine omega-3 fatty acid and fish consumption in the NHSII (Nurses’ Health Study II)
| Quintiles of marine omega-3 fatty acid consumption | P for trend | ||||||
|---|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | |||
| Risk of psoriasis | |||||||
| Omega-3 fatty acids | |||||||
| EPA | |||||||
| Median (g/d) | 0.01 | 0.02 | 0.04 | 0.08 | 0.13 | ||
| No. of cases/No. of person-years | 127/238580 | 119/240142 | 109/199957 | 129/232302 | 118/226654 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.94 (0.73, 1.21) | 0.97 (0.75, 1.25) | 1.01 (0.79, 1.29) | 0.94 (0.73, 1.21) | 0.76 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.91 (0.71, 1.17) | 0.93 (0.72, 1.20) | 0.98 (0.76, 1.25) | 0.94 (0.73, 1.22) | 0.87 | |
| DHA | |||||||
| Median (g/d) | 0.04 | 0.08 | 0.12 | 0.17 | 0.27 | ||
| No. of cases/No. of person-years | 114/228761 | 127/220512 | 122/236116 | 119/220479 | 120/231767 | ||
| Age-adjusted HR (95% CI) | 1.00 | 1.13 (0.88, 1.46) | 1.03 (0.79, 1.32) | 1.05 (0.81, 1.35) | 1.00 (0.78, 1.30) | 0.73 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 1.11 (0.86, 1.42) | 1.00 (0.77, 1.29) | 1.02 (0.78, 1.32) | 0.99 (0.76, 1.29) | 0.69 | |
| Total marine omega-3 fatty acidsb | |||||||
| Median (g/d) | 0.06 | 0.10 | 0.15 | 0.25 | 0.40 | ||
| No. of cases/No. of person-years | 114/228752 | 136/225161 | 115/230902 | 113/225144 | 124/227676 | ||
| Age-adjusted HR (95% CI) | 1.00 | 1.20 (0.94, 1.54) | 0.99 (0.76, 1.28) | 0.98 (0.76, 1.27) | 1.05 (0.81, 1.36) | 0.75 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 1.17 (0.91, 1.50) | 0.96 (0.74, 1.25) | 0.95 (0.73, 1.24) | 1.04 (0.80, 1.35) | 0.76 | |
| Omega-6 fatty acids | |||||||
| Linoleic acid | |||||||
| Median (g/d) | 7.00 | 8.27 | 9.21 | 10.30 | 12.20 | ||
| No. of cases/No. of person-years | 119/229525 | 119/227235 | 124/226664 | 116/227231 | 124/226980 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.99 (0.77, 1.28) | 1.04 (0.81, 1.34) | 0.96 (0.75, 1.24) | 1.03 (0.80, 1.32) | 0.90 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.95 (0.74, 1.23) | 0.96 (0.75, 1.24) | 0.88 (0.68, 1.14) | 0.92 (0.71, 1.18) | 0.42 | |
| Arachidonic acid | |||||||
| Median (g/d) | 0.09 | 0.12 | 0.14 | 0.17 | 0.22 | ||
| No. of cases/No. of person-years | 102/220578 | 107/223149 | 127/238007 | 130/226890 | 136/229012 | ||
| Age-adjusted HR (95% CI) | 1.00 | 1.03 (0.79, 1.36) | 1.17 (0.90, 1.52) | 1.24 (0.95, 1.60) | 1.28 (0.99, 1.65) | 0.03 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.99 (0.75, 1.30) | 1.09 (0.84, 1.41) | 1.12 (0.86, 1.45) | 1.11 (0.85, 1.44) | 0.32 | |
| Total Omega-6 fatty acidsc | |||||||
| Median (g/d) | 6.74 | 8.26 | 9.44 | 10.80 | 13.13 | ||
| No. of cases/No. of person-years | 117/226227 | 111/227564 | 144/228122 | 105/228044 | 125/227678 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.94 (0.72, 1.21) | 1.21 (0.95, 1.55) | 0.88 (0.67, 1.14) | 1.04 (0.81, 1.34) | 0.91 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.90 (0.69, 1.17) | 1.15 (0.90, 1.46) | 0.81 (0.62, 1.06) | 0.95 (0.74, 1.23) | 0.54 | |
| Omega-6c:omega-3 FAa | |||||||
| Median | 26.65 | 47.14 | 71.79 | 108.04 | 220.20 | ||
| No. of cases/No. of person-years | 121/227673 | 127/227765 | 118/227975 | 120/227571 | 116/226650 | ||
| Age-adjusted HR (95% CI) | 1.00 | 1.07 (0.83, 1.37) | 0.99 (0.77, 1.28) | 1.02 (0.79, 1.32) | 1.00 (0.77, 1.29) | 0.77 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 1.03 (0.80, 1.33) | 0.95 (0.73, 1.23) | 0.99 (0.76, 1.28) | 0.98 (0.76, 1.28) | 0.75 | |
| Risk of psoriatic arthritis | |||||||
| Omega-3 fatty acids | |||||||
| EPA | |||||||
| Median (g/d) | 0.01 | 0.02 | 0.04 | 0.08 | 0.13 | ||
| No. of cases/No. of person-years | 32/238580 | 29/240142 | 25/199957 | 29/232302 | 37/226654 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.88 (0.53, 1.46) | 0.86 (0.51, 1.45) | 0.85 (0.52, 1.42) | 1.08 (0.67, 1.74) | 0.54 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.85 (0.51, 1.41) | 0.84 (0.49, 1.42) | 0.87 (0.52, 1.45) | 1.20 (0.74, 1.96) | 0.24 | |
| DHA | |||||||
| Median (g/d) | 0.04 | 0.08 | 0.12 | 0.17 | 0.27 | ||
| No. of cases/No. of person-years | 228761 | 220512 | 236116 | 220479 | 231767 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.88 (0.52, 1.48) | 0.84 (0.50, 1.41) | 1.12 (0.69, 1.83) | 1.01 (0.61, 1.65) | 0.64 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.87 (0.51, 1.47) | 0.84 (0.50, 1.42) | 1.17 (0.71, 1.91) | 1.06 (0.64, 1.76) | 0.47 | |
| Total marine omega-3 fatty acids | |||||||
| Median (g/d) | 0.06 | 0.10 | 0.15 | 0.25 | 0.40 | ||
| No. of cases/No. of person-years | 32/228752 | 29/225161 | 22/230902 | 31/225144 | 38/227676 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.91 (0.55, 1.51) | 0.66 (0.38, 1.13) | 0.92 (0.56, 1.52) | 1.07 (0.67, 1.71) | 0.45 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.90 (0.54, 1.49) | 0.65 (0.38, 1.13) | 0.95 (0.58, 1.57) | 1.16 (0.71, 1.88) | 0.24 | |
| Omega-6 fatty acids | |||||||
| Linoleic acid | |||||||
| Median (g/d) | 7.00 | 8.27 | 9.21 | 10.30 | 12.20 | ||
| No. of cases/No. of person-years | 43/229525 | 31/227235 | 25/226664 | 27/227231 | 26/226980 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.71 (0.45, 1.12) | 0.56 (0.34, 0.92) | 0.60 (0.37, 0.97) | 0.57 (0.35, 0.92) | 0.02 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.66 (0.41, 1.05) | 0.50 (0.30, 0.82) | 0.50 (0.31, 0.82) | 0.45 (0.27, 0.73) | 0.001 | |
| Arachidonic acid | |||||||
| Median (g/d) | 0.09 | 0.12 | 0.14 | 0.17 | 0.22 | ||
| No. of cases/No. of person-years | 32/220578 | 23/223149 | 23/238007 | 31/226890 | 43/229012 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.70 (0.41, 1.20) | 0.66 (0.39, 1.13) | 0.91 (0.55, 1.49) | 1.22 (0.77, 1.92) | 0.12 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.65 (0.38, 1.11) | 0.58 (0.34, 1.00) | 0.75 (0.46, 1.24) | 0.91 (0.57, 1.45) | 0.74 | |
| Omega-6 fatty acidsb | |||||||
| Median (g/d) | 6.74 | 8.26 | 9.44 | 10.80 | 13.13 | ||
| No. of cases/No. of person-years | 38/226227 | 34/227564 | 34/228122 | 19/228044 | 27/227678 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.88 (0.55, 1.39) | 0.87 (0.55, 1.38) | 0.47 (0.27, 0.82) | 0.66 (0.41, 1.09) | 0.03 | |
| Multivariable-adjustedc HR (95% CI) | 1.00 | 0.82 (0.51, 1.30) | 0.79 (0.49, 1.25) | 0.42 (0.24, 0.73) | 0.55 (0.33, 0.90) | 0.003 | |
| Omega-6c:omega-3 FAb | |||||||
| Median | 26.65 | 47.14 | 71.79 | 108.04 | 220.20 | ||
| No. of cases/No. of person-years | 43/227673 | 30/227765 | 24/227975 | 27/227571 | 28/226650 | ||
| Age-adjusted HR (95% CI) | 1.00 | 0.73 (0.46, 1.16) | 0.59 (0.36, 0.97) | 0.68 (0.42, 1.10) | 0.72 (0.44, 1.15) | 0.89 | |
| Multivariable-adjusteda HR (95% CI) | 1.00 | 0.67 (0.42, 1.06) | 0.52 (0.31, 0.86) | 0.59 (0.36, 0.96) | 0.63 (0.39, 1.03) | 0.66 | |
Abbreviation: CI, confidence interval; HR, hazard ratio; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; FA, fatty acid.
Multivariate-adjusted analyses were adjusted for age (continuous), smoking (never smoker, past smoker, current smoker (1–14 cig/d), current smoker (15–25 cig/d), current smoker (≥25 cig/d)), body mass index (<21 kg/m2, 21–22.9 kg/m2, 23–24.9 kg/m2, 25–26.9 kg/m2, 27.0–29.9 kg/m2, 30.0–32.9 kg/m2, 33–34.9 kg/m2, 35–39.9 kg/m2, ≥40 kg/m2), alcohol intake (0 g/d, 0.1–4.9 g/d, 5.0–9.9 g/d, ≥10 g/d), physical activity (quintile, MET/w), total calorie intake (continuous), race (white, others) and major comorbidities (diabetes, cardiovascular disease, hypertension, and hypercholesterolemia, (yes or no)).
Omega-3 fatty acids: EPA and DHA.
Omega-6 fatty acids: arachidonic fatty acid and linoleic cis fatty acid.
In this study, we found no inverse associations between consumption of marine omega-3 FAs or their major food sources (total fish as well as individual fish items) and the risk of incident psoriasis or psoriatic arthritis. Rather, we found a protective association of higher consumption of omega-6 FA and linoleic acid on the risk of psoriatic arthritis. Previous studies have investigated only the association of high dose omega-3 FAs, not omega-6 FAs, with psoriasis. For example in a recent clinical trial, obese patients with plaque-type psoriasis were given an energy-restricted diet enriched in omega-3 FAs (average 2.6 g/d) with minimized intake of omega-6 FAs, and subsequently had improved clinical outcomes15. However, the mean intake of omega-3 FAs was 0.19g/d in our cohort study, much lower than that in the clinical trial. When we stratified our results by obesity (<30 BMI or ≥30 BMI, only obese participants had a non-significant positive association between fish intake and psoriasis. Additionally, participants in the highest quintile of fish intake were at a lower risk of psoriatic arthritis compared to those in the lowest quintile of fish intake, although this was also not statistically significant.
In conclusion, we found no associations between consumption of marine omega-3 FAs and risk of incident psoriasis and psoriatic arthritis but inverse associations between consumption of omega-6 FA and linoleic acid and risk of psoriatic arthritis. Further studies are needed to elucidate this relationship.
What’s already known about this topic?
Marine omega-3 fatty acids (FAs) have anti-inflammatory and immunomodulatory properties
Fish oil supplements have shown potentially protective effects on progression of psoriasis in small-scale (n=9~145) clinical studies
No prospective data are available on the association between dietary intake of omega-3 FAs and risk of psoriasis and psoriatic arthritis
What does this study add?
We prospectively examined the association between consumption of polyunsaturated FAs and risk of incident psoriasis and psoriatic arthritis.
Acknowledgments
Funding/Support: This work was supported by the Department of Dermatology, Warren Alpert Medical School of Brown University, NIH grant UM1 CA176726, and National Psoriasis Foundation
We thank the participants and staff of the Nurses’ Health Study II, the Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School for their valuable contributions. We thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. The study sponsors had no role in the design of the study; the collection, analysis and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. The funding agency had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript.
Footnotes
Conflict of Interest Disclosures: None reported.
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