Skip to main content
Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Does Fish Oil Have an Anti-Obesity Effect in Overweight/Obese Adults? A Meta-Analysis of Randomized Controlled Trials

  • Shichun Du ,

    dushichun211@163.com

    Affiliation Department of Endocrinology, Shanghai Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

  • Jie Jin,

    Affiliation Department of Endocrinology, Shanghai Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

  • Wenjun Fang,

    Affiliation Department of Endocrinology, Shanghai Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

  • Qing Su

    Affiliation Department of Endocrinology, Shanghai Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Abstract

Context

Accumulating evidence has suggested favorable effects of fish oil on weight loss in animal experiments; however, findings remain inconsistent in humans.

Objects

The meta-analysis was performed to investigate the influence of fish oil on some parameters of body composition in overweight/obese adults.

Design

Human randomized, placebo-controlled trials were identified by a systematic search of Embase, PubMed, the Cochrane Library, web of science and reference lists of related reviews and articles. The random-effects model was used to estimate the calculated results.

Results

In total, 21 studies with 30 study arms were included in this analysis. Calculated results of the meta-analysis demonstrated that fish oil had no effect on reducing body weight (overall SMD = -0.07, 95% CI -0.21 to 0.07, P = 0.31) and BMI (overall SMD = -0.09, 95% CI -0.22 to 0.03, P = 0.14) whether alone or combined with life modification intervention in overweight/obese subjects. However, waist circumference was significantly reduced (SMD = -0.23, 95% CI -0.40 to -0.06, P = 0.008) in those with fish oil supplementation combined with life modification intervention. Waist hip ratio (WHR) was significantly reduced (overall SMD = -0.52 95% CI -0.76 to -0.27, P < 0.0005) in fish oil supplemented individuals with or without combination life modification intervention.

Conclusion

Current evidence cannot support an exact anti-obesity role of n-3 polyunsaturated fatty acids (PUFAs) in overweight/obese subjects. However, these subjects may benefit from reducing abdominal fat with fish oil supplementation especially when combined with life modification intervention. Further large-scale and long-term clinical trials are needed to gain definite conclusions.

Introduction

The prevalence of overweight/obese humans worldwide brings an enormous risk of metabolic and cardiovascular diseases as well as large healthcare costs. Fish oil is associated with a body weight/fat reduction effect in high fat diet-fed obese animal models [14]. The potential anti-obesity mechanisms involved in fish oil have been proposed in these studies, including increased adipocyte apoptosis [2], increased plasma adiponectin levels [3, 5], and altered fat oxidation and energy expenditure [4, 6]. However, it remains unknown whether fish oil consumption can combat obesity in humans though there is emerging evidence that it can improve lipid profile [79] and cardiovascular function [10] in many human trials. The results of previous randomized controlled trials on possible weight reduction effects of fish oil in overweight/obese human are controversial, partly because of the limited number of included subjects or varied intervention methods. Therefore, this meta-analysis aimed to systematically examine the possible anti-obesity effects of fish oil with/without combination of life modification intervention in overweight/obese adults.

Method and Search Strategy

This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance [11]. We searched electronic databases in Embase, PubMed, web of knowledge, and the Cochrane Library for relevant records using the terms “fish-oil”, “fish oil”, “ducosahexaenoic acid”, “DHA”, “eicosapentaenoic acid”, “EPA”, and “n-3 polyunsaturated fatty acids”. These terms were paired with the vocabulary “body composition”, “obese”, “overweight”, “weight loss”, “weight reduction”, or “obesity”. The search was limited to human randomized and placebo-controlled studies. Meanwhile, we manually searched reference lists of relevant review or original articles.

Study selection criteria

Studies were included for analysis if they qualified the following criteria: 1) they were reported as a prospective, randomized (parallel or crossover), blind (double or single) and controlled trials, regardless of sample size; 2) they analyzed human subjects (≥18 y of age and body mass index (BMI) ≥25) who were assigned to either fish oil /marine diet or a control group for ≥4 weeks; 3) reported at least one of the following body composition parameters including body weight, BMI, waist circumference, and waist/hip ratio (WHR).

Data extraction and quality assessment

The literature search and data extraction were performed independently by two authors (S.D. and J.J.) according to standardized inclusion criteria with standardized individual results. Discrepancies were resolved by discussion with a third author (W.F.).The extracted data included the following parts: study design characteristics (crossover or parallel, double or single blind), participants characteristics (number, sex, age, and general health status), intervention strategies (dose of n-3 PUFA, ratio of EPA to DHA, treatment options in control groups, and combination with life modification intervention), study duration, reported changes in the body composition measurement (changes of body weight, BMI, waist circumstance, and WHR). For trials with more than one intervention group (with different doses of fish oil or with different intervention), multiple comparisons were considered. An assessment of study quality was performed independently by S.D. and J.J. according to the quality scores proposed by Jadad et al [12]. Some authors were contacted by email for original data if they were not available in the literatures.

Statistical analysis

Analysis endpoints were calculated based upon the changes from baseline to post-treatment. Pooled effects were reported as standardized mean differences (SMDs) and 95% confidence intervals (CIs). The Cochrane's test was used to assess inter-study heterogeneity. Heterogeneity was identified as significant among the trials if the P value was <0.10, or I2 > 50% [13]. A random-effects model was used to estimate the pooled effects, which provided more generalized results. Furthermore, the predefined subgroup analyses were performed to explore the possible influence of study characteristics on study outcomes. Sensitivity analyses were also performed by omitting the studies with short follow-up duration. Egger regression asymmetry tests [14] and funnel plots were used to assess potential publication bias. P values were 2-tailed with statistical significance set at 0.05. Statistical analyses were performed with Stata software (version 12.0; Stata Corp).

Results

Search results

In total, 456 articles were initially identified through the database search. Of these, 4 records were duplicated and 412 records were excluded because the objectives of these studies were irrelevant to the current meta-analysis, or because lacking randomization and control. Of the 40 potentially relevant records identified, 21 [9, 1534] met the inclusion criteria for this meta-analysis. 19 were excluded because 3 were not randomized controlled trials [8, 35, 36], 1 compared fish diet with fish oil supplements [37], 1 compared the mixture of linoleic acid and n-3 PUFAs with placebo [38], 1 did not provide n-3 PUFAs dosage [39], 2 had a treatment duration of only 3 weeks [40, 41], 3 included infants or children [4244], 7 did not provide related body compositions data [35, 4550], and 1 did not report the number of both groups [51] (Fig 1).

thumbnail
Fig 1. PRISMA 2009 flow diagram illustrates the study selection procedure.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097. For more information, visit www.prisma-statement.org.

https://doi.org/10.1371/journal.pone.0142652.g001

Study characteristics

Data extracted from 1652 individuals who participated in the 21 studies were analyzed in this meta-analysis (Table 1). The studies investigated by Hill et al [18], Mori et al [26], and Munro et al [27] included two randomized comparisons in participants who underwent both fish oil alone and combined with a weight loss program. The studies investigated by Thorsdottir et al [30], Sjoberg et al [29], and Crochemore et al [21] included two randomized comparisons in participants who were treated with two different doses of n-3 PUFAs. Finally, 30 sets of data comparing fish oil treatment with controls were enrolled. All of the included comparisons were randomized controlled trials with 23 in a double-blind and 7 in a single-blind design. All of the studies included subjects of 18 years or older who were overweight or obese. Fish oil capsules were supplied orally in all of the studies except one, which fed marine food to the treatment group [30]. For the convenience of data pooling, the "high dose fish oil" group was selected as the "treatment" group while the "low dose fish oil" was selected as the control group for analysis in the study of Moore et al [9]. Overall, the median n3-PUFAs dose was 1.92 g/day (range: 0.54–11.3 g/day), and the ratio of EPA to DHA varied from 0.23 to 1.55. One study used highly purified EPA only [20]. Median treatment duration with n-3 PUFAs was 12 weeks (range: 4–24 weeks). For those with life modification intervention, subjects were given dietary caloric restriction in eleven studies, both caloric restriction and physical exercise in one study [16] or physical exercise only in one study [18].

thumbnail
Table 1. Overview and characteristics of included studies.

https://doi.org/10.1371/journal.pone.0142652.t001

Effects of fish oil on body weight changes

In total, 21 comparisons with 1329 subjects investigated the effect of fish oil on body weight changes. No significant heterogeneity (I2 = 25.2%, P = 0.14) was found. The calculated results indicated that fish oil was not associated with a body weight reduction (SMD = -0.07, 95% CI -0.21 to 0.07, P = 0.31; Fig 2A) compared with controls.

thumbnail
Fig 2. Forest plots from meta-analyses for the effects of fish oil on changes in body weight (A), BMI (B), waist circumference (C), and WHR (D).

https://doi.org/10.1371/journal.pone.0142652.g002

Comparisons were divided into two independent analyses to assess whether fish oil in combination with life modification altered the analysis results. Of the studies, 10 comparisons [9, 18, 19, 22, 2628, 31, 32] with 607 subjects investigated the effects of fish oil on changes in body weight alone. No significant heterogeneity (I2 = 24.8%, P = 0.22) was found. The calculated results indicated that fish oil was not associated with reduced body weight (SMD = -0.004, 95% CI -0.20 to 0.19, P = 0.97). Further subgroup analyses according to predefined study characteristics (including mean age, male proportion, total dose and ratio of EPA to DHA, follow-up duration, study design, and quality score) were also not statistically significant, which indicated that the relationship of fish oil supplementation with body weight changes seemed to not be influenced by these factors (Table 2).

thumbnail
Table 2. Subgroup estimation of the effects of fish oil on body weight changes.

https://doi.org/10.1371/journal.pone.0142652.t002

Of the studies, 11 comparisons [16, 18, 23, 24, 26, 27, 30, 33, 52] with 722 subjects investigated the effects of fish oil on body weight changes combined with diet restriction and/or exercise. No significant heterogeneity (I2 = 24.7%, P = 0.21) was found among them. The calculated results indicated that fish oil had no additional weight loss effects (SMD = -0.13, 95% CI 0.32 to 0.06, P = 0.17). Subgroup analyses according to treatment duration demonstrated that studies with treatment less than 12 weeks favored significant weight loss effects of fish oil (P = 0.004). Sensitivity analysis excluded study with only 6 weeks of treatment [25], but they still suggested an insignificant relationship with fish oil and change in body weight (P = 0.22). Other predefined study characteristics were also not statistically significant (Table 2). Only one study included in this meta-analysis examined the combined effects of fish oil and regular exercise on body composition [18]. Sensitivity analysis excluding this trial did not seem to change the results (P = 0.28).

Effects of fish oil on BMI changes

Of the studies, 27 comparisons with 1514 subjects investigated the effects of fish oil on BMI changes. No significant heterogeneity (I2 = 25.9%, P = 0.11) was found. The calculated results indicated that fish oil was not associated with a significant reduction in BMI (SMD = -0.09, 95% CI -0.22 to 0.03, P = 0.14; Fig 2B).

Among the studies, 16 comparisons [9, 15, 1721, 2628, 3133] with 792 subjects investigated the effects of fish oil on changes in body weight alone. No significant heterogeneity (I2 = 0.0%, P = 0.66) was found. The calculated results indicated that fish oil had no effect in reducing BMI (SMD = -0.03, 95% CI -0.17 to 0.11, P = 0.64).

Of the studies, 11 comparisons [16, 18, 2327, 29, 30, 52] with 722 subjects investigated the effect of fish oil on changes in BMI in combination with weight loss programs. The calculated results indicated that fish oil had no additional effect in reducing BMI (SMD = -0.17, 95% CI -0.42 to 0.07, P = 0.17) when combined with weight loss programs. In view of considerable heterogeneity (I2 = 53.8%, P = 0.02), subgroup analyses were performed to explore the potential difference between study characteristics and the effect of fish oil on changes in BMI. The results of subgroup analyses suggested that those with distinctive anti-obesity effects were studies with duration less than 12 week (P = 0.001), which could largely explain the considerable heterogeneity. After excluding the study with only 6 weeks of treatment [25], sensitivity analyses decreased heterogeneity (I2 = 46.3%, P = 0.06); however, the non-significant anti-obesity results remained (P = 0.32). Other factors including mean age, sex proportion, and total fish oil dose seemed irrelevant with the possible effects of fish oil on change in BMI combined with a weight loss program (Table 3). Furthermore, excluding the study that investigated the additional anti-obesity effect of fish oil combined with physical exercise [18] did not seem to change the results (P = 0.28).

thumbnail
Table 3. Subgroup estimation of the effects of fish oil on BMI changes.

https://doi.org/10.1371/journal.pone.0142652.t003

Effects of fish oil on waist circumference changes

In total, 19 comparisons with 1273 subjects investigated the effects of fish oil on changes in waist circumference. No significant heterogeneity (I2 = 33.3%, P = 0.08) among the patients was observed. The calculated results indicated that fish oil could significantly reduce waist circumference (SMD = -0.16, 95% CI -0.31 to -0.02, P = 0.03; Fig 2C).

Of the comparisons, 11 [9, 1921, 2628, 31, 32] with 649 subjects investigated the effects of fish oil on change in waist circumference alone. No significant heterogeneity (I2 = 43.2%, P = 0.06) was observed. The calculated results indicated that fish oil did not have a significant effect to reduce waist circumference alone (SMD = -0.14 95% CI -0.36 to 0.09, P = 0.22).

However, 8 comparisons [16, 24, 26, 27, 52] with 624 subjects investigated the effects of fish oil on change in body waist circumference combined with a weight loss program. The results determined that fish oil had a significant additional effect in reducing waist circumference (SMD = -0.23 95% CI -0.40 to -0.06, P = 0.008; I2 = 6.8%, P = 0.38) in combination with a weight loss program.

Effects of fish oil on changes in waist hip ratio

Of the comparisons, 11 with 619 subjects investigated the effects of fish oil on changes in WHR. The calculated results suggested that fish oil could significantly reduce WHR (SMD = -0.52, 95% CI -0.76 to -0.27, P <0.0005; Fig 2D).

In total, 5 comparisons [15, 19, 2628, 52] with 216 subjects investigated the effects of fish oil on change in WHR alone. The calculated results indicated that fish oil had a significant effect in reducing WHR alone (SMD = -0.39 95% CI -0.72 to -0.07, P = 0.02) without significant heterogeneity (I2 = 37.3%, P = 0.17).

Among the studies, 6 comparisons [26, 27, 30, 52] with 403 subjects investigated the effects of fish oil on changes in WHR combined with a weight loss program. The results also indicated that fish oil had a significant effect in reducing WHR when combined with a weight loss program (SMD = -0.63 95% CI -1.00 to -0.25, P = 0.001). However, there was significant heterogeneity (I2 = 63.7%, P = 0.02) among these studies. Subgroup analyses were not available for these outcomes because of the limited number of the studies included.

Publication bias

No significant publication biases were observed through funnel plots (Fig 3A and 3B) and Egger’s regression asymmetry tests for the effects of fish oil on changes in body weight (Egger’s test P = 0.79) or BMI (Egger’s test P = 0.18).

thumbnail
Fig 3. Funnel plots from meta-analyses for the effects of fish oil on changes in body weight (A) and BMI (B).

https://doi.org/10.1371/journal.pone.0142652.g003

Discussion

In the current meta-analysis, we investigated the association between changes in body composition and fish oil supplementation in 21 randomized, placebo controlled trials involving overweight or obese adults. Interestingly, in contrast to the results found in obese animal models, we did not detect a remarkable anti-obesity benefit of fish oil in overweight/obese subjects. However, fish oil might assist with improving waist hip ratio (WHR). We performed subgroup analyses to investigate the potential influences of study characteristics on pooled BMI and body weight outcomes. The results favoring significant weight reduction effects in the fish oil group combined with a weight loss program were those with treatment duration of less than 12 weeks. Furthermore, sensitivity analysis excluded the study that was only 6 weeks in duration, which demonstrated more stable negative results of fish oil supplementation compared with placebo. Gender differences have been considered as a potential factor to influence the effect of fish oil on reducing weight [27, 30, 40, 53]; however, in the subgroup analysis, we did not detect a significant difference with fish oil and weight reduction in different male proportions.

Munro et al [52] explained that perhaps n-3 PUFAs were more effective in preventing weight gain rather than assisting in weight loss. In humans, several studies have reported a significantly higher concentration of n-3 PUFAs in normal weight individuals compared with obese individuals [54, 55]. In addition, Couet C et al [56] observed that body fat mass was decreased and basal fat oxidation was significantly increased in 6 healthy volunteers with fish oil supplementation. However, Jakobsen et al [57] investigated 1998 lean adults and did not observe that the proportion of plasma n-3 PUFA was associated with a subsequent 1-year change in body weight. Large scale (both lean and obese subjects) and long term trials were needed to draw definite results.

Our results were supported by some previous observational studies. Garaulet et al [58, 59] investigated the n-3 PUFAs content of perivisceral and omental adipose tissue samples in 84 obese patients. Their study determined that n-3 PUFAs (in particular the DHA) were inversely related to abdominal obesity and adipocyte size. Matsumura et al [60] evaluated visceral fat by abdominal computed tomography in 91 subjects who had been fed with EPA 1800 mg/day and 74 control during a 6-month period. Their study observed that visceral fat area of male subjects in the EPA group trended to decrease (P = 0.06) during the 6 months of treatment. A number of pre-clinical and clinical studies [6163] demonstrated an ameliorative effect of supplemental fish oil in reducing hepatic lipid content in non-alcoholic fatty liver disease (NAFLD). There were 2 review articles [64, 65] suggesting n3-PUFAs as potential treatments for liver inflammation associated with fat accumulation.

Because of the current limited information, we could not completely explain why fish oil decreased abdominal fat. However, increased n-3 PUFAs induced lipogenic gene down-regulation in adipose tissues. Second, it might have been related to changes in lipid synthesis and/or storage as a result of the profound reduction in postprandial lipemia associated with n-3 PUFAs [66]. Deck et al [67] reported that modest doses of fish oil supplementation caused a significant reduction in triglyceride levels by a mean of 2.21mmol/L and increased the high-density lipoprotein cholesterol by a mean of 0.13mmol/L. This was the first comprehensive meta-analysis to examine the effects of fish oil on changes of body composition in overweight and obese adults. We included only randomized controlled trials, which had a low probability of bias and other confounding factors of the original studies. Multiple electronic databases had been searched to minimize database bias. Selected trails had been carefully checked to minimize multiple publication bias. Individual search and extraction were conducted to minimize the bias in the provision of data and inclusion criteria.

Previous systematic reviews [68, 69] concluded that n-3 PUFAs might have potential benefits improving body composition in humans. However, their enrollment ranges (including lean and overweight/obese adults) were larger, and their study duration (3–12 weeks) less than ours. Furthermore, they did not use the meta-analysis method, which allow for greater statistical power than individual trials.

However, the results of this meta-analysis should be interpreted with caution because of several limitations. First, potential sources of heterogeneity included participant variations as well as intervention intensity and duration. The included trials had many differences including subject health status, concurrent therapy, fish oil supplement doses and compositions, follow-up durations, and treatment methods. These differences might have substantially contributed to the research heterogeneity. However, we expounded the influence of these factors through subgroup analyses. Second, treatment durations of the included study were relatively short (4 to 24 weeks), which made subgroup analysis according to study duration not compelling. Notably, plasma DHA levels increased significantly from 12 to 24 weeks [50]; however, in our meta-analysis, short- and long-term studies were assigned equal importance. We have limited information from RCTs on the relationship of body weight and fish oil in the longer term. Only 3 studies [9, 16, 24] included in this meta-analysis had treatment duration of 24 weeks. Tapsell et al [70] investigated the anti-obesity effects of fish diet for 12 month. However, the participants were in a “free living” state with self-reported food intake, and the dropout rate was as high as 47%. Some authors [27] suggested that it might be easier to manage dietary compliance when working with laboratory animals compared with humans. This might be an important reason underlying why the anti-obesity effects of fish oil supplementation were not as obvious in humans as animals.

In conclusion, from the results of our meta-analysis, we cannot obtain effective proof that fish oil intakes may decrease body weight in overweight/obese adults. However, it may help reduce the waist hip ratio especially when combined with life modification interventions. Because of the limited follow-up duration, the results should be treated with caution. Further large-scale research over a long time is needed to determine definitive conclusions.

Acknowledgments

The study was supported by the research grant of Shanghai municipal commission of health and family planning, No.20144Y0140.

We thank Dr. Trevor A Mori and Dr. Bianca K Itariu for generously sharing the unpublished data from their studies.

Author Contributions

Conceived and designed the experiments: SD. Performed the experiments: SD JJ. Analyzed the data: SD JJ WF. Contributed reagents/materials/analysis tools: SD QS. Wrote the paper: SD QS.

References

  1. 1. Janovska P, Flachs P, Kazdova L, Kopecky J. Anti-obesity effect of n-3 polyunsaturated fatty acids in mice fed high-fat diet is independent of cold-induced thermogenesis. Physiological research / Academia Scientiarum Bohemoslovaca. 2013;62(2):153–61. pmid:23234412.
  2. 2. Perez-Matute P, Perez-Echarri N, Martinez JA, Marti A, Moreno-Aliaga MJ. Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. The British journal of nutrition. 2007;97(2):389–98. pmid:17298710.
  3. 3. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia. 2006;49(2):394–7. pmid:16397791.
  4. 4. Perez-Echarri N, Perez-Matute P, Marcos-Gomez B, Martinez JA, Moreno-Aliaga MJ. Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats. The British journal of nutrition. 2009;101(7):1059–67. pmid:18755047.
  5. 5. Wakutsu M, Tsunoda N, Mochi Y, Numajiri M, Shiba S, Muraki E, et al. Improvement in the high-fat diet-induced dyslipidemia and adiponectin levels by fish oil feeding combined with food restriction in obese KKAy mice. Bioscience, biotechnology, and biochemistry. 2012;76(5):1011–4. pmid:22738976.
  6. 6. Haugaard SB, Madsbad S, Hoy CE, Vaag A. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity. Clinical endocrinology. 2006;64(2):169–78. pmid:16430716.
  7. 7. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness, and exercise tolerance: a systematic review. Atherosclerosis. 2006;184(2):237–46. pmid:16084516.
  8. 8. Belalcazar LM, Reboussin DM, Haffner SM, Reeves RS, Schwenke DC, Hoogeveen RC, et al. Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes care. 2010;33(1):197–9. pmid:19841042; PubMed Central PMCID: PMC2797972.
  9. 9. Moore CS, Bryant SP, Mishra GD, Krebs JD, Browning LM, Miller GJ, et al. Oily fish reduces plasma triacylglycerols: a primary prevention study in overweight men and women. Nutrition. 2006;22(10):1012–24. pmid:17027436.
  10. 10. Raatz SK, Rosenberger TA, Johnson LK, Wolters WW, Burr GS, Picklo MJ Sr. Dose-dependent consumption of farmed Atlantic salmon (Salmo salar) increases plasma phospholipid n-3 fatty acids differentially. Journal of the Academy of Nutrition and Dietetics. 2013;113(2):282–7. pmid:23351633; PubMed Central PMCID: PMC3572904.
  11. 11. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. Journal of clinical epidemiology. 2010;63(8):e1–37. pmid:20346624.
  12. 12. Jadad AR, McQuay HJ. Meta-analyses to evaluate analgesic interventions: a systematic qualitative review of their methodology. Journal of clinical epidemiology. 1996;49(2):235–43. pmid:8606325.
  13. 13. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557–60. pmid:12958120; PubMed Central PMCID: PMC192859.
  14. 14. Egger M, Smith GD, Phillips AN. Meta-analysis: principles and procedures. Bmj. 1997;315(7121):1533–7. pmid:9432252; PubMed Central PMCID: PMC2127925.
  15. 15. Cussons AJ, Watts GF, Mori TA, Stuckey BG. Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. The Journal of clinical endocrinology and metabolism. 2009;94(10):3842–8. pmid:19622617.
  16. 16. DeFina LF, Marcoux LG, Devers SM, Cleaver JP, Willis BL. Effects of omega-3 supplementation in combination with diet and exercise on weight loss and body composition. The American journal of clinical nutrition. 2011;93(2):455–62. pmid:21159785.
  17. 17. Gammelmark A, Madsen T, Varming K, Lundbye-Christensen S, Schmidt EB. Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects. Nutrition research. 2012;32(1):15–23. pmid:22260859.
  18. 18. Hill AM, Buckley JD, Murphy KJ, Howe PR. Combining fish-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. The American journal of clinical nutrition. 2007;85(5):1267–74. pmid:17490962.
  19. 19. Itariu BK, Zeyda M, Hochbrugger EE, Neuhofer A, Prager G, Schindler K, et al. Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. The American journal of clinical nutrition. 2012;96(5):1137–49. pmid:23034965.
  20. 20. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arteriosclerosis, thrombosis, and vascular biology. 2007;27(9):1918–25. pmid:17569885.
  21. 21. Crochemore IC, Souza AF, de Souza AC, Rosado EL. omega-3 polyunsaturated fatty acid supplementation does not influence body composition, insulin resistance, and lipemia in women with type 2 diabetes and obesity. Nutrition in clinical practice: official publication of the American Society for Parenteral and Enteral Nutrition. 2012;27(4):553–60. pmid:22661243.
  22. 22. Kabir M, Skurnik G, Naour N, Pechtner V, Meugnier E, Rome S, et al. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. The American journal of clinical nutrition. 2007;86(6):1670–9. pmid:18065585.
  23. 23. Kratz M, Swarbrick MM, Callahan HS, Matthys CC, Havel PJ, Weigle DS. Effect of dietary n-3 polyunsaturated fatty acids on plasma total and high-molecular-weight adiponectin concentrations in overweight to moderately obese men and women. The American journal of clinical nutrition. 2008;87(2):347–53. pmid:18258624; PubMed Central PMCID: PMC2265085.
  24. 24. Krebs JD, Browning LM, McLean NK, Rothwell JL, Mishra GD, Moore CS, et al. Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. International journal of obesity. 2006;30(10):1535–44. pmid:16552404.
  25. 25. Mendez-Sanchez N, Gonzalez V, Aguayo P, Sanchez JM, Tanimoto MA, Elizondo J, et al. Fish oil (n-3) polyunsaturated fatty acids beneficially affect biliary cholesterol nucleation time in obese women losing weight. The Journal of nutrition. 2001;131(9):2300–3. pmid:11533270.
  26. 26. Mori TA, Bao DQ, Burke V, Puddey IB, Watts GF, Beilin LJ. Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. The American journal of clinical nutrition. 1999;70(5):817–25. pmid:10539741.
  27. 27. Munro IA, Garg ML. Dietary supplementation with long chain omega-3 polyunsaturated fatty acids and weight loss in obese adults. Obesity research & clinical practice. 2013;7(3):e173–81. pmid:23697585.
  28. 28. Rafraf M, Mohammadi E, Asghari-Jafarabadi M, Farzadi L. Omega-3 fatty acids improve glucose metabolism without effects on obesity values and serum visfatin levels in women with polycystic ovary syndrome. Journal of the American College of Nutrition. 2012;31(5):361–8. pmid:23529993.
  29. 29. Sjoberg NJ, Milte CM, Buckley JD, Howe PR, Coates AM, Saint DA. Dose-dependent increases in heart rate variability and arterial compliance in overweight and obese adults with DHA-rich fish oil supplementation. The British journal of nutrition. 2010;103(2):243–8. pmid:19664302.
  30. 30. Thorsdottir I, Tomasson H, Gunnarsdottir I, Gisladottir E, Kiely M, Parra MD, et al. Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content. International journal of obesity. 2007;31(10):1560–6. pmid:17502874.
  31. 31. Tierney AC, McMonagle J, Shaw DI, Gulseth HL, Helal O, Saris WH, et al. Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome—LIPGENE: a European randomized dietary intervention study. International journal of obesity. 2011;35(6):800–9. pmid:20938439.
  32. 32. Vargas ML, Almario RU, Buchan W, Kim K, Karakas SE. Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome. Metabolism: clinical and experimental. 2011;60(12):1711–8. pmid:21640360; PubMed Central PMCID: PMC3210884.
  33. 33. Wong AT, Chan DC, Barrett PH, Adams LA, Watts GF. Supplementation with n3 fatty acid ethyl esters increases large and small artery elasticity in obese adults on a weight loss diet. The Journal of nutrition. 2013;143(4):437–41. pmid:23365106.
  34. 34. Hartwich J, Malec MM, Partyka L, Perez-Martinez P, Marin C, Lopez-Miranda J, et al. The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation—insights from the LIPGENE study. Clinical nutrition. 2009;28(5):510–5. pmid:19481310.
  35. 35. Chan DC, Watts GF, Barrett PH, Beilin LJ, Redgrave TG, Mori TA. Regulatory effects of HMG CoA reductase inhibitor and fish oils on apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes. 2002;51(8):2377–86. pmid:12145148.
  36. 36. Warner JG Jr., Ullrich IH, Albrink MJ, Yeater RA. Combined effects of aerobic exercise and omega-3 fatty acids in hyperlipidemic persons. Medicine and science in sports and exercise. 1989;21(5):498–505. pmid:2691812.
  37. 37. Neale EP, Muhlhausler B, Probst YC, Batterham MJ, Fernandez F, Tapsell LC. Short-term effects of fish and fish oil consumption on total and high molecular weight adiponectin levels in overweight and obese adults. Metabolism: clinical and experimental. 2013;62(5):651–60. pmid:23190874.
  38. 38. Sneddon AA, Tsofliou F, Fyfe CL, Matheson I, Jackson DM, Horgan G, et al. Effect of a conjugated linoleic acid and omega-3 fatty acid mixture on body composition and adiponectin. Obesity. 2008;16(5):1019–24. pmid:18356842.
  39. 39. Kriketos AD, Robertson RM, Sharp TA, Drougas H, Reed GW, Storlien LH, et al. Role of weight loss and polyunsaturated fatty acids in improving metabolic fitness in moderately obese, moderately hypertensive subjects. Journal of hypertension. 2001;19(10):1745–54. pmid:11593093.
  40. 40. Kunesova M, Braunerova R, Hlavaty P, Tvrzicka E, Stankova B, Skrha J, et al. The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women. Physiological research / Academia Scientiarum Bohemoslovaca. 2006;55(1):63–72. pmid:15857162.
  41. 41. Hlavaty P, Kunesova M, Gojova M, Tvrzicka E, Vecka M, Roubal P, et al. Change in fatty acid composition of serum lipids in obese females after short-term weight-reducing regimen with the addition of n-3 long chain polyunsaturated fatty acids in comparison to controls. Physiological research / Academia Scientiarum Bohemoslovaca. 2008;57 Suppl 1:S57–65. pmid:18271691.
  42. 42. Vasickova L, Stavek P, Suchanek P. Possible effect of DHA intake on body weight reduction and lipid metabolism in obese children. Neuro endocrinology letters. 2011;32 Suppl 2:64–7. pmid:22101886.
  43. 43. Lopez-Alarcon M, Martinez-Coronado A, Velarde-Castro O, Rendon-Macias E, Fernandez J. Supplementation of n3 long-chain polyunsaturated fatty acid synergistically decreases insulin resistance with weight loss of obese prepubertal and pubertal children. Archives of medical research. 2011;42(6):502–8. pmid:22136960.
  44. 44. Dangardt F, Osika W, Chen Y, Nilsson U, Gan LM, Gronowitz E, et al. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis. 2010;212(2):580–5. pmid:20727522.
  45. 45. Bourque C, St-Onge MP, Papamandjaris AA, Cohn JS, Jones PJ. Consumption of an oil composed of medium chain triacyglycerols, phytosterols, and N-3 fatty acids improves cardiovascular risk profile in overweight women. Metabolism: clinical and experimental. 2003;52(6):771–7. pmid:12800105.
  46. 46. Bragt MC, Mensink RP. Comparison of the effects of n-3 long chain polyunsaturated fatty acids and fenofibrate on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects. Nutrition, metabolism, and cardiovascular diseases: NMCD. 2012;22(11):966–73. pmid:21429719.
  47. 47. Chan DC, Nguyen MN, Watts GF, Ooi EM, Barrett PH. Effects of atorvastatin and n-3 fatty acid supplementation on VLDL apolipoprotein C-III kinetics in men with abdominal obesity. The American journal of clinical nutrition. 2010;91(4):900–6. pmid:20181806.
  48. 48. Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D, Maturi J, et al. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. The Journal of nutrition. 2011;141(2):207–13. pmid:21178084; PubMed Central PMCID: PMC3021440.
  49. 49. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200(1):135–40. pmid:18667204.
  50. 50. Berge K, Piscitelli F, Hoem N, Silvestri C, Meyer I, Banni S, et al. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men. Lipids in health and disease. 2013;12:78. pmid:23706001; PubMed Central PMCID: PMC3680309.
  51. 51. Harden CJ, Dible VA, Russell JM, Garaiova I, Plummer SF, Barker ME, et al. Long-chain polyunsaturated fatty acid supplementation had no effect on body weight but reduced energy intake in overweight and obese women. Nutrition research. 2014;34(1):17–24. pmid:24418242.
  52. 52. Munro IA, Garg ML. Prior supplementation with long chain omega-3 polyunsaturated fatty acids promotes weight loss in obese adults: a double-blinded randomised controlled trial. Food & function. 2013;4(4):650–8. pmid:23396496.
  53. 53. Lohner S, Fekete K, Marosvolgyi T, Decsi T. Gender differences in the long-chain polyunsaturated fatty acid status: systematic review of 51 publications. Annals of nutrition & metabolism. 2013;62(2):98–112. pmid:23327902.
  54. 54. Micallef M, Munro I, Phang M, Garg M. Plasma n-3 Polyunsaturated Fatty Acids are negatively associated with obesity. The British journal of nutrition. 2009;102(9):1370–4. pmid:19454127.
  55. 55. Karlsson M, Marild S, Brandberg J, Lonn L, Friberg P, Strandvik B. Serum phospholipid fatty acids, adipose tissue, and metabolic markers in obese adolescents. Obesity. 2006;14(11):1931–9. pmid:17135608.
  56. 56. Couet C, Delarue J, Ritz P, Antoine JM, Lamisse F. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity. 1997;21(8):637–43. pmid:15481762.
  57. 57. Jakobsen MU, Dethlefsen C, Due KM, Slimani N, Chajes V, May AM, et al. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change. Obesity facts. 2011;4(4):312–8. pmid:21921655.
  58. 58. Garaulet M, Perez-Llamas F, Perez-Ayala M, Martinez P, de Medina FS, Tebar FJ, et al. Site-specific differences in the fatty acid composition of abdominal adipose tissue in an obese population from a Mediterranean area: relation with dietary fatty acids, plasma lipid profile, serum insulin, and central obesity. The American journal of clinical nutrition. 2001;74(5):585–91. pmid:11684525.
  59. 59. Garaulet M, Hernandez-Morante JJ, Tebar FJ, Zamora S. Anthropometric indexes for visceral fat estimation in overweight/obese women attending to age and menopausal status. Journal of physiology and biochemistry. 2006;62(4):245–52. pmid:17615950.
  60. 60. Matsumura K. [Effects of eicosapentaenoic acid on visceral fat and heart rate variability: assessment by power spectral analysis]. Journal of cardiology. 2007;50(4):243–51. pmid:17987840.
  61. 61. Janczyk W, Socha P, Lebensztejn D, Wierzbicka A, Mazur A, Neuhoff-Murawska J, et al. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial. BMC pediatrics. 2013;13:85. pmid:23702094; PubMed Central PMCID: PMC3672084.
  62. 62. Sofi F, Giangrandi I, Cesari F, Corsani I, Abbate R, Gensini GF, et al. Effects of a 1-year dietary intervention with n-3 polyunsaturated fatty acid-enriched olive oil on non-alcoholic fatty liver disease patients: a preliminary study. International journal of food sciences and nutrition. 2010;61(8):792–802. pmid:20465434.
  63. 63. Hatzitolios A, Savopoulos C, Lazaraki G, Sidiropoulos I, Haritanti P, Lefkopoulos A, et al. Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian journal of gastroenterology: official journal of the Indian Society of Gastroenterology. 2004;23(4):131–4. pmid:15333967.
  64. 64. Bouzianas DG, Bouziana SD, Hatzitolios AI. Potential treatment of human nonalcoholic fatty liver disease with long-chain omega-3 polyunsaturated fatty acids. Nutrition reviews. 2013;71(11):753–71. pmid:24148001.
  65. 65. Shapiro H, Tehilla M, Attal-Singer J, Bruck R, Luzzatti R, Singer P. The therapeutic potential of long-chain omega-3 fatty acids in nonalcoholic fatty liver disease. Clinical nutrition. 2011;30(1):6–19. pmid:20619513.
  66. 66. Harris WS, Zucker ML, Dujovne CA. Omega-3 fatty acids in hypertriglyceridemic patients: triglycerides vs methyl esters. The American journal of clinical nutrition. 1988;48(4):992–7. pmid:3421209.
  67. 67. Deck C, Radack K. Effects of modest doses of omega-3 fatty acids on lipids and lipoproteins in hypertriglyceridemic subjects. A randomized controlled trial. Archives of internal medicine. 1989;149(8):1857–62. pmid:2669667.
  68. 68. Buckley JD, Howe PR. Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids. Obesity reviews: an official journal of the International Association for the Study of Obesity. 2009;10(6):648–59. pmid:19460115.
  69. 69. Buckley JD, Howe PR. Long-chain omega-3 polyunsaturated fatty acids may be beneficial for reducing obesity-a review. Nutrients. 2010;2(12):1212–30. pmid:22254005; PubMed Central PMCID: PMC3257626.
  70. 70. Tapsell LC, Batterham MJ, Charlton KE, Neale EP, Probst YC, O'Shea JE, et al. Foods, nutrients or whole diets: effects of targeting fish and LCn3PUFA consumption in a 12mo weight loss trial. BMC public health. 2013;13:1231. pmid:24369765; PubMed Central PMCID: PMC3890608.