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Lipids and cardiovascular/metabolic health

Association of serum n-3 polyunsaturated fatty acids with C-reactive protein in men

Abstract

Background/Objectives:

N-3 polyunsaturated fatty acids (PUFAs) have been associated with reduced inflammation. We tested the hypothesis that high serum concentrations of the n-3 PUFAs are associated with lower serum C-reactive protein (CRP) concentrations in healthy middle-aged Finnish men. We also examined whether exposure to mercury, an environmental contaminant in fish, which is also a major source of long-chain n-3 PUFA, was associated with CRP.

Subjects/Methods:

Data from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analyzed cross-sectionally to determine the associations between serum n-3 PUFAs, hair mercury and serum CRP in 1395 healthy men, aged 42–60 years. Linear regression analyses were performed to analyze the associations.

Results:

In the multivariate models, the mean serum CRP in quartiles of serum total n-3 PUFA concentration was 1.23, 1.27, 1.18 and 1.08 mg/l, P for trend=0.01. Statistically significant inverse associations were also observed with the total serum long-chain n-3 PUFA concentration and with the individual long-chain n-3 PUFAs docosapentaenoic acid and docosahexaenoic acid, but not with eicosapentaenoic acid or with the intermediate-chain n-3 PUFA alpha-linolenic acid. Hair methylmercury content was not associated with serum CRP levels and it did not modify the associations between serum n-3 PUFAs and CRP either.

Conclusions:

Serum n-3 PUFAs and especially the long-chain n-3 PUFA concentration, a marker of fish or fish oil consumption, were inversely associated with serum CRP in men. Exposure to mercury was not associated with serum CRP.

Introduction

Chronic inflammation has an important role in the initiation and progression of cardiovascular diseases (CVD; Ross 1999; Albert et al., 2002; Basu et al., 2006).

Consumption of long-chain n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may decrease the risk of CVD (Mozaffarian and Rimm, 2006; Wang et al., 2006), and PUFAs have also been suggested to reduce inflammation (Simopoulos, 2002). In observational studies, fish consumption, or dietary or circulating long-chain n-3 PUFAs have been associated with lower C-reactive protein (CRP), a marker for inflammation, in most (Lopez-Garcia et al., 2004; Farzaneh-Far et al., 2009; He et al., 2009; Kalogeropoulos et al., 2010), but not all studies (Pischon et al., 2003). However, randomized controlled trials with fish oil supplementation in healthy people have found no effects on CRP (Madsen et al., 2003; Geelen et al., 2004; Skulas-Ray et al., 2011).

The relationship of the intermediate-chain length n-3 PUFA, alpha-linolenic acid (ALA) with CVD is less well known than that of EPA+DHA (Harris, 2005; Anderson and Ma, 2009). In few observational studies, higher ALA intake has been associated with reduced inflammation (Ferrucci et al., 2006; Poudel-Tandukar et al., 2009), but no effects of ALA supplements on CRP have been found in randomized controlled trials of healthy people (Geleijnse et al., 2010).

Currently, more data on the association between n-3 PUFAs and CRP are available for people with a disease than for healthy people. Therefore, the aim of this study was to test the hypothesis that high serum concentrations of the n-3 PUFAs are associated with lower serum CRP concentration in healthy middle-aged Finnish men. Fish is also a major source of methylmercury, which has previously been associated with increased risk of CVD and with attenuation of the beneficial impact of the long-chain n-3 PUFAs on the risk in this study population (Virtanen et al., 2005). High mercury exposure was also associated with increased lipid peroxidation (Salonen et al., 1995), but there is little data available on the association between mercury exposure and inflammation. Thus, we also wanted to evaluate the impact of mercury exposure on CRP.

Subjects and methods

Study population

The subjects were participants in the Kuopio Ischaemic Heart Disease Risk Factor Study (Salonen, 1988). The study was designed to investigate risk factors for CVD, atherosclerosis and related outcomes in a population-based, randomly selected sample of men from eastern Finland. The baseline examinations were performed between March 1984 and December 1989. The study sample consisted of 3235 men who were 42, 48, 54 or 60 years old at the baseline examination. Of these, 2682 (82.9%) men participated. The Kuopio Ischaemic Heart Disease Risk Factor Study protocol was approved by the Research Ethics Committee of the University of Kuopio. All subjects gave their written informed consent for participation.

Men with missing data on serum CRP (n=61) or serum n-3 PUFAs (n=148) were excluded from the analyses. To investigate the association with serum CRP in a healthy population, we excluded participants with a disease with inflammatory component.

This also reduces the possible bias that is introduced if participants had changed their diet after diagnosis, for example, increased fish consumption. In total, we excluded 1078 subjects with a history of ischemic heart disease or stroke, cardiac insufficiency, claudication, diabetes, colitis, rheumatoid arthritis, gall bladder disease, cancer, or liver or pancreas disease. These exclusions left 1395 men. Data of hair methylmercury was available for 1385 of the 1395 men.

Measurements

The subjects gave hair and venous blood samples between 0800 and 1000 h at the baseline examinations. They were instructed to abstain from ingesting alcohol for 3 days, and from smoking and eating for 12 h before giving the sample. Detailed descriptions of the determination of serum lipids and lipoproteins (Salonen et al., 1992), assessments of medical history and medications (Salonen et al., 1992), family history of diseases (Salonen et al., 1992), smoking (Salonen et al., 1992), alcohol consumption (Salonen et al., 1992), physical activity (Lakka et al., 1994) and blood pressure (Salonen et al., 1992) have been published previously. Dietary intake of foods and nutrients was assessed at the time of blood sampling using a 4-day food recording (Voutilainen et al., 2001). Mercury in hair was determined between May 1992 and August 1993 by flow injection analysis, cold vapor atomic absorption spectrometry and amalgamation as described previously (Salonen et al., 1995).

Serum fatty acids

Serum esterified and non-esterified fatty acids were determined in one gas chromatographic run without preseparation as described previously (Laaksonen et al., 2002). Fatty acids were chromatographed in an NB-351 capillary column (HNU-Nordion, Helsinki, Finland) by a Hewlett-Packard 5890 series II gas chromatograph (Hewlett-Packard Company, Avondale, PA, USA) with a flame ionization detector. The coefficient of variation for repeated measurements of major esterified fatty acids was 5%. Because the relative degree of saturation of fatty acids varies among esterified fatty acid types (i.e., cholesterol esters, phospholipids and triglycerides), the esterified fatty acid concentrations were adjusted for serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride concentrations. The coefficient of variation for major non-esterified fatty acids was 15%. No adjustment was conducted for non-esterified fatty acids. For serum total long-chain n-3 PUFAs, we used the sum of EPA (20:5n-3), docosapentaenoic acid (DPA, 22:5n-3) and DHA (22:6n-3).

Serum CRP

Serum CRP was measured with an immunometric assay (Immulite High Sensitivity CRP Assay, DPC, Los Angeles, CA, USA). This CRP assay has been standardized against the WHO International Reference Standard for CRP immunoassay 85/506. At the level of 3.2 mg/l, the within-run coefficient of variation was 2.8% and the total coefficient of variation was 3.1%.

Statistical analysis

The relationships between baseline characteristics and serum total n-3 PUFA were explored by means and linear (for continuous variables) or logistic regression (for dichotomous variables). The associations between serum fatty acids and CRP were analyzed with linear regression models, using log-transformed values. The means and the 95% confidence intervals in quartiles of serum fatty acids were calculated of log-transformed serum concentrations and the values were then exponentiated. Correlations were estimated by the Spearman's correlation coefficients. The models were adjusted for possible confounders, selected on the basis of previously published associations with CRP or associations with exposures or outcomes in the present analysis. The basic model (Model 1) included age and examination year. The multivariate-adjusted Model 2 included the Model 1 and smoking, body mass index and income. Further adjustments for aspirin use, multivitamin use, drug for high cholesterol, hair methylmercury, years of education, leisure-time physical activity, treated hypertension or intake of alcohol, energy, fruits and vegetables, milk and milk products, meat and meat products or whole grains did not appreciably change the associations. The cohort mean was used to replace the missing values (<1.7%) of covariates. Tests of linear trend were conducted by assigning the median values for each category of exposure variable and treating those as a single continuous variable. All P-values were two-tailed (α=0.05). Data were analyzed with SPSS 14.0 for Windows (SPSS Inc., Chicago, IL, USA).

Results

Baseline characteristics

The baseline characteristics of the subjects are presented in Table 1. The mean age of the cohort was 52.1 years (s.d. 5.5 years). The mean serum concentrations as a percentage of all serum fatty acids were 1.65% (s.d. 0.92%) for EPA, 0.56% (s.d. 0.10%) for DPA, 2.46% (s.d. 0.72%) for DHA and 0.75% (s.d. 0.23%) for ALA. The correlations with fish consumption were 0.43 for EPA, 0.20 for DPA and 0.44 for DHA (P for all <0.001). At baseline, men with higher serum total n-3 PUFA, compared with men with lower concentrations, were more likely to have higher education and income, higher intake of fish, fruits and vegetables and alcohol, and higher hair methylmercury concentration (Table 1). They also had lower intakes of energy, milk and milk products, whole grains and total fats, and were also less likely to be current smokers.

Table 1 Baseline characteristics according to serum total n-3 polyunsaturated fatty acids

Serum n-3 PUFAs and CRP

The mean CRP concentration was 1.95 mg/l (s.d. 3.25 mg/l). After adjustment for age, examination year, smoking, body mass index and income (Model 2 in Table 2), we found a statistically significant inverse association between serum total n-3 PUFA, total long-chain n-3 PUFA (EPA+DPA+DHA), DPA, and DHA and CRP. Of the individual fatty acids, DPA was most strongly associated with CRP (Table 2). Serum ALA was associated with lower CRP after adjustment for age and examination year (Model 1), but further adjustments for smoking, body mass index and income attenuated the association. Serum EPA was not statistically significantly associated with CRP (Table 2).

Table 2 Concentration of serum CRP in serum n-3 polyunsaturated fatty acid quartiles

Because subjects with acute inflammatory conditions frequently have serum CRP concentrations 10 mg/l (Pepys and Hirschfield, 2003), we also repeated the analyses after excluding 29 participants with the serum CRP 10 mg/l. However, the results were not appreciably different (data not shown).

Hair methylmercury and CRP

The mean hair methylmercury concentration was 1.87 μg/g (s.d. 1.91 μg/g). We did not find an association between hair methylmercury and CRP. The age, examination year, smoking, body mass index and income-adjusted (Model 2 in Table 2) CRP concentrations in the hair methylmercury quartiles were 1.08, 1.15, 1.10 and 1.02 mg/l, P for trend=0.37. Hair methylmercury concentration did not modify the associations between serum n-3 PUFAs and CRP either (P for interactions >0.10).

Discussion

In this cross-sectional study among healthy middle-aged men from eastern Finland, serum total n-3 PUFA, total long-chain n-3 PUFA (EPA+DPA+DHA), DPA and DHA were inversely associated with serum CRP concentration. In contrast, serum ALA and EPA were not associated with serum CRP.

Our results are similar to most population-based studies, where consumption of non-fried fish or long-chain n-3 PUFA (He et al., 2009), or individual and total n-3 PUFA intake (Lopez-Garcia et al., 2004) has been associated with lower CRP, although not all studies have found an association (Pischon et al., 2003). In addition, higher levels of circulating long-chain n-3 PUFAs have been associated with lower CRP levels (Farzaneh-Far et al., 2009; Kalogeropoulos et al., 2010). However, randomized controlled trials with fish oil supplementation in healthy people have found no effects on CRP (Madsen et al., 2003; Geelen et al., 2004; Skulas-Ray et al., 2011). This suggests that fish consumption or higher serum long-chain n-3 PUFA concentrations may be a marker of other lifestyle factors associated with lower CRP in observational studies. The role of residual confounding cannot be wholly excluded either.

Of the individual fatty acids, DPA had the strongest association with CRP in our study. There is little prior information about DPA and CRP or inflammation. Compared with EPA or DHA, concentration of DPA in serum is low, because DPA is converted into DHA or EPA (Kaur et al., 2011). The low concentration likely contributes to the magnitude of the regression coefficient with CRP (Table 2). Serum DPA also had a weaker correlation with fish intake compared with EPA and DHA, which suggests that it is not a very good marker for fish consumption. In our previous analysis, serum DPA was not associated with the risk of atrial fibrillation in this study population (Virtanen et al., 2009). The impact of DPA on inflammation and CVD risk requires further investigation.

ALA has been associated with lower risk of CVD, but the association has not been very strong and consistent (Wang et al., 2006). ALA intake has been associated with lower CRP in some (Lopez-Garcia et al., 2004; Poudel-Tandukar et al., 2009), but not all studies (Pischon et al., 2003). However, less is known about the association between circulating ALA concentrations and inflammation. In a community-based sample from Italy, an inverse association between plasma ALA and CRP was observed, but interestingly, no significant independent correlation between ALA and interleukin-6 was found (Ferrucci et al., 2006), taken into account that the production of CRP is mainly regulated by interleukin-6 (Gabay and Kushner, 1999). The few small randomized controlled trials that have been conducted do not support the protective association between ALA and inflammation (Geleijnse et al., 2010), which suggests that ALA does not have a major role in protection against inflammation.

The anti-inflammatory properties of long-chain n-3 PUFAs may be explained by their unsaturated double bonds. These bonds may inactivate reactive oxygen species and prevent their interaction with, for example, nuclear factor-κB (De Caterina and Libby, 1996; De Caterina et al., 1999). Indeed, fish oil has been associated with anti-inflammatory gene expression, for example, with decreased expression of nuclear factor-κB (Bouwens et al., 2009).

Although we have previously shown that exposure to mercury was associated with increased risk of CVD and overall mortality in this study population (Virtanen et al., 2005), the current results do not support that this is explained by its effects on chronic low level inflammation.

Strength of this cross-sectional study is the use of serum n-3 PUFA measurements instead of dietary intakes for estimating the impact of these fatty acids on CRP. Serum long-chain n-3 PUFA concentration is a good measurement for dietary intakes of fish or fish oil (Hunter, 1998), and the serum concentrations reflect dietary intakes during the previous weeks (Nikkari et al., 1995). In contrast, a large proportion of ALA is oxidized (Burdge, 2006), so serum levels would depend more on recent intake. Serum ALA also correlates only weakly with dietary ALA intake (Hunter, 1998). We also excluded people with diseases that might have caused a diet change and biased associations. Other strengths of the study are the extensive examination of potential confounders and risk factors, and its population-based recruitment. A few limitations need to be taken into account. The study population consisted of middle-aged Finnish men, so the results may not be generalizable to other populations. Furthermore, because of the cross-sectional study design, conclusions on causality cannot be drawn. We only had data on total serum fatty acid concentrations available, although different serum compartments (e.g., phospholipids or cholesterol esters) reflect different time periods of fatty acid intake, and may have different associations with CRP (Klein-Platat et al., 2005). Theoretically, because several associations were evaluated in this study, it is possible that some may have been found due to type I error. However, although a single association could be a chance finding, the totality of evidence that supports the association of PUFAs with CRP is unlikely produced by chance alone.

In conclusion, this study suggests that higher concentrations of serum long-chain n-3 PUFA are associated with lower serum CRP concentrations. As inflammation has been suggested to increase the risk of CVD, the beneficial impact on long-chain n-3 PUFAs on the risk of CVD may partly be explained by their impact on inflammation. Further studies are needed to investigate the effect of different n-3 PUFAs on inflammation.

References

  1. Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM (2002). Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 105, 2595–2599.

    CAS  Article  Google Scholar 

  2. Anderson BM, Ma DWL (2009). Are all n-3 polyunsaturated fatty acids created equal? Lipids Health Dis 8, 33.

    Article  Google Scholar 

  3. Basu A, Devaraj S, Jialal I (2006). Dietary factors that promote or retard inflammation. Arterioscler Thromb Vasc Biol 26, 995–1001.

    CAS  Article  Google Scholar 

  4. Bouwens M, van de Rest O, Dellschaft N, Grootte Bromhaar M, de Groot LC, Geleijnse JM et al. (2009). Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr 90, 415–424.

    CAS  Article  Google Scholar 

  5. Burdge GC (2006). Metabolism of α-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids 75, 161–168.

    CAS  Article  Google Scholar 

  6. De Caterina R, Libby P (1996). Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids 31, S57–S63.

    CAS  Article  Google Scholar 

  7. De Caterina R, Spiecker M, Solaini G, Basta G, Bosetti F, Libby P, Liao J (1999). The inhibition of endothelial activation by unsaturated fatty acids. Lipids 34, S191–S194.

    CAS  Article  Google Scholar 

  8. Farzaneh-Far R, Harris WS, Garg S, Na B, Whooley MA (2009). Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study. Atherosclerosis 205, 538–543.

    CAS  Article  Google Scholar 

  9. Ferrucci L, Cherubini A, Bandinelli S, Bartali B, Corsi A, Lauretani F et al. (2006). Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocr Metab 91, 439–446.

    CAS  Article  Google Scholar 

  10. Gabay C, Kushner I (1999). Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340, 448–454.

    CAS  Article  Google Scholar 

  11. Geelen A, Brouwer IA, Schouten EG, Kluft C, Katan MB, Zock PL (2004). Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects. Eur J Clin Nutr 58, 1440–1442.

    CAS  Article  Google Scholar 

  12. Geleijnse JM, de Goede J, Brouwer IA (2010). Alpha-linolenic acid: is it essential to cardiovascular health? Curr Atheroscler Rep 12, 359–367.

    CAS  Article  Google Scholar 

  13. Harris WS (2005). Alpha-linolenic acid: a gift from the land? Circulation 111, 2872–2874.

    Article  Google Scholar 

  14. He K, Liu K, Daviglus ML, Jenny NS, Mayer-Davis E, Jiang R et al. (2009). Associations of dietary long-chain n-3 polyunsaturated fatty acids and fish with biomarkers of inflammation and endothelial activation (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol 103, 1238–1243.

    CAS  Article  Google Scholar 

  15. Hunter D (1998). Biochemical indicators of dietary intake. In: Willett W (ed). Nutritional Epidemiology. Oxford University Press: New York, NY. pp 174.

    Google Scholar 

  16. Kalogeropoulos N, Panagiotakos DB, Pitsavos C, Chrysohoou C, Rousinou G, Toutouza M et al. (2010). Unsaturated fatty acids are inversely associated and n-6/n-3 ratios are positively related to inflammation and coagulation markers in plasma of apparently healthy adults. Clin Chim Acta 411, 584–591.

    CAS  Article  Google Scholar 

  17. Kaur G, Cameron-Smith D, Garg M, Sinclair AJ (2011). Docosapentaenoic acid (22:5n-3): A review of its biological effects. Prog Lipid Res 50, 28–34.

    CAS  Article  Google Scholar 

  18. Klein-Platat C, Drai J, Oujaa M, Schlienger JL, Simon C (2005). Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents. Am J Clin Nutr 82, 1178–1184.

    CAS  Article  Google Scholar 

  19. Laaksonen DE, Lakka TA, Lakka HM, Nyyssönen K, Rissanen T, Niskanen LK et al. (2002). Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men. Diabetic Med 19, 456–464.

    CAS  Article  Google Scholar 

  20. Lakka TA, Venäläinen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT (1994). Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction in men. N Engl J Med 330, 1549–1554.

    CAS  Article  Google Scholar 

  21. Lopez-Garcia E, Schulze MB, Manson JE, Meigs JB, Albert CM, Rifai N et al. (2004). Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr 134, 1806–1811.

    CAS  Article  Google Scholar 

  22. Madsen T, Christensen JH, Blom M, Schmidt EB (2003). The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose–response study. Brit J Nutr 89, 517–522.

    CAS  Article  Google Scholar 

  23. Mozaffarian D, Rimm EB (2006). Fish intake, contaminants, and human health, evaluating the risks and the benefits. JAMA 296, 1885–1899.

    CAS  Article  Google Scholar 

  24. Nikkari T, Luukkainen P, Pietinen P, Puska P (1995). Fatty acid composition of serum lipid fractions in relation to gender and quality of dietary fat. Ann Med 27, 491–498.

    CAS  Article  Google Scholar 

  25. Pepys M, Hirschfield G (2003). C-reactive protein: a critical update. J Clin Invest 111, 1805–1812.

    CAS  Article  Google Scholar 

  26. Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willet WC, Rimm EB (2003). Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108, 155–160.

    CAS  Article  Google Scholar 

  27. Poudel-Tandukar K, Nanri A, Matsushita Y, Sasaki S, Ohta M, Sato M et al. (2009). Dietary intakes of α-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men. Nutr Res 29, 363–370.

    CAS  Article  Google Scholar 

  28. Ross R (1999). Atherosclerosis-an inflammatory disease. N Engl J Med 340, 115–126.

    CAS  Article  Google Scholar 

  29. Salonen JT (1988). Is there a continuing need for longitudinal epidemiologic research? The Kuopio Ischaemic Heart Disease Risk Factor Study. Ann Clin Res 20, 46–50.

    CAS  PubMed  Google Scholar 

  30. Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Seppanen R, Salonen R (1992). High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation 86, 803–811.

    CAS  Article  Google Scholar 

  31. Salonen JT, Seppanen K, Nyyssonen K, Korpela H, Kauhanen J, Kantola M et al. (1995). Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation 91, 645–655.

    CAS  Article  Google Scholar 

  32. Simopoulos AP (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21, 495–505.

    CAS  Article  Google Scholar 

  33. Skulas-Ray AC, Kris-Etherton PM, Harris WS, Vanden Heuvel JP, Wagner PR, West SG (2011). Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr 93, 243–252.

    CAS  Article  Google Scholar 

  34. Virtanen JK, Mursu J, Voutilainen S, Tuomainen T-P (2009). Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men. Circulation 120, 2315–2321.

    CAS  Article  Google Scholar 

  35. Virtanen JK, Voutilainen S, Rissanen TH, Mursu J, Tuomainen TP, Korhonen MJ et al. (2005). Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland. Arterioscler Thromb Vasc Biol 25, 228–233.

    CAS  Article  Google Scholar 

  36. Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT (2001). Low dietary folate intake is associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Circulation 103, 2674–2680.

    CAS  Article  Google Scholar 

  37. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B et al. (2006). n3 Fatty acids from fish or fish-oil supplements, but not α-linolenic acid, benefit cardiovascular disease outcomes in primary-and secondary-prevention studies: a systematic review. Am J Clin Nutr 84, 5–17.

    CAS  Article  Google Scholar 

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Reinders, I., Virtanen, J., Brouwer, I. et al. Association of serum n-3 polyunsaturated fatty acids with C-reactive protein in men. Eur J Clin Nutr 66, 736–741 (2012). https://doi.org/10.1038/ejcn.2011.195

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Keywords

  • cardiovascular diseases
  • C-reactive protein
  • inflammation
  • polyunsaturated fatty acids
  • prospective study
  • mercury

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