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Meta Analysis

Effects of Omega-3 Fatty Acids on Chinese Patients with Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis

Mei, Zhu; Song, Haixu; Tian, Xiaoxiang; Liu, Dan

Editor(s): Fu, Xiaoxia; Xu, Tianyu

Author Information
doi: 10.1097/CD9.0000000000000029




  • In this meta-analysis, we summarized the effects of fish oil (eicosapentaenoic acid and docosahexaenoic acid) on cardiovascular health in the Chinese population. Consuming fish oil could reduce the levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and proinflammatory factor tumor necrosis factor α (TNF-α) in the Chinese individuals.
  • Subgroup analysis indicated that consuming median and high dose of fish oil (≥1000 mg) could decrease TNF-α level among Chinese population.


  • Considering the benefits of fish oil in cardiovascular health, it was particularly important to supplement the fish oil products in the Chinese population.
  • The effect of fish oil on the level of TNF-α depended on dosage, it was necessary to use a suitable dose of fish oil among the Chinese population.


Cardiovascular disease (CVD) is the leading cause of death worldwide.[1] Measures to protect cardiovascular health and reduce mortality due to CVD have become the focus of global attention. In addition to drug treatment and surgical intervention, dietary intervention is an effective approach for preventing CVD.[2] Fish oils (FO) containing omega-3 long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA; C22: 6n3) and eicosapentaenoic acid (EPA; C20: 5n3) are associated with a reduced risk of CVD. The cardiovascular protective effects of these 2 substances have been extensively investigated.[3] Several epidemiological studies, including those on the Greenland Inuit population and Okinawa islanders,[4,5] reported that the abundance of FO in the diet is inversely associated with mortality by CVD. Early randomized controlled trials (RCTs) and animal studies have also demonstrated that FO has numerous cardiovascular protective effects, including lowering triglycerides,[6] regulating blood pressure (BP),[7] improving endothelial function,[8] improving blood glucose homeostasis, and anti-inflammatory effects.[9] However, recent evidence from RCTs for FO indicate conflicting results in lowering the risk of adverse cardiovascular events in both primary and secondary prevention populations.[10–12] These controversial findings suggest that the beneficial effects of FO are compromised by CVD risk factors.

CVD is also the leading cause of death in China.[13] The most important risk factors for CVD include obesity, hypertension, dyslipidemia, and insulin resistance. Approximately 50% of patients with hypertension are overweight or obese in China, across all age-groups, and in both men and women. Abdominal fat accumulation in patients with high BP leads to an increased risk of cardiometabolic disorders, which are a cluster of metabolic abnormalities predictive of cardiovascular mortality. Some potential advantages of lifestyle management of hypertension and obesity indicate that dietary intervention can serve as an adjunct or alternative to drug treatments. The current results of the cardiovascular protective effects of FO in the Chinese population are inconsistent.[14,15] This is due to several factors, such as sample size, population deviation, and FO dosage. The current study aimed to perform a meta-analysis to evaluate the effect of consumption of EPA and DHA on the reduction in cardiovascular risk factors for the primary prevention of CVD in the Chinese population.


Two professionally trained researchers (Zhu Mei, Haixu Song) searched the keywords “fish oil” “docosahexaenoic acid” “eicosapntemacnoic acid” “cardiovascular disease” “Chinese” and “China” in several databases, including PubMed, Cochrane Medline, CNKI, and, etc. Only human research was included in this study.

Inclusion criteria

The full text of all abstracts returned were screened. Then, articles were selected that met the following conditions to obtain the full text: (1) prospective crossover or parallel RCT study lasting for more than 4 weeks; (2) participants supplemented with oral FO capsules containing EPA and DHA or fish rich in EPA or DHA added to the diet; (3) research subjects were Chinese, over 18 years of age; and (4) provided continuous variable data with variables that could be used for calculation of baseline and follow-up endpoints.

Data extraction and quality assessment

Data extraction and quality evaluation were performed by 2 researchers (Zhu Mei, Haixu Song), and article information that met the inclusion criteria, including the details of the first author, publication year, type of experimental design, daily intake of EPA and DHA per person, follow-up time, and participant status were obtained. For the included studies, the mean values and standard deviations (SD) of BP, blood glucose, lipid metabolism indexes, and inflammation indexes of the experimental and the control groups were extracted at baseline and at the study endpoint. From each study, mean and SD data were obtained for all outcomes of interest, including the lipid profile (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, C-reactive protein (CRP), and tumor necrosis factor α (TNF-α) levels.

Statistical analysis

Review Manager version 5.4 was used to evaluate the mean difference (MD) of the data, and the heterogeneity of the variables was evaluated by I2. A random effects model was used when I2 ≥ 30%, and a fixed-effects model was used when I2 < 30%.


Basic characteristics of participants

More than 350 records were identified. A total of 218 records were retrieved, 116 records were evaluated as qualified, and 20 eligible trials were finally included [Figure 1]. Most of the data in the articles demonstrated low risk of bias, while some data was high-risk, and there were several pieces of data for which risk of bias was not clearly identified in the articles [Figure 2]. Table 1 presents the characteristics of the included articles.[14–33] These studies were published as early as 2006, but the most were published in 2015 and 2018. All studies were RCTs with a prospective crossover or parallel design. The durations of the studies were 8 to 23 weeks, with most including men and women aged ≥39 years. The health statuses of the participants varied, and the average daily intake of EPA and DHA was 831 and 643 mg/day, respectively. Most of the studies were identified as double-blind, except a few that did not specify.

Figure 1:
Study flow diagram. RCT: Randomized controlled trial.
Figure 2:
Summary of risk of bias: review authors’ judgments about each risk of bias item for each included study. Green label: Low risk; Red label: High risk; Yellow label: Unclear risk.
Table 1 - Design and characteristics of studies included in the meta-analysis
Study (first author and year) Design Blinding EPA (mg/day) DHA (mg/day) Duration (weeks) Participant status Age BMI Sex n
Ding 2020[16] CO NR 360 240 12 N 57.2 N F 60
Li 2014[17] P NR 880 234 12 NR 45 N M, F 111
Li 2018[18] P DB 728 516 12 SH 43 N M, F 165
Mao 2019[19] P NR 1418 1418 12 SH 40 N M, F 123
Peng 2015[20] P DB 167 165 8 HTG 52 N M, F 109
Qin 2015[14] P DB 728 516 12 NAFLD 45 N M, F 70
Shen 2017[15] P DB 624 404 12 N ≥50 N M, F 97
Song 2018[21] P DB 434 289 12 N >40 N NR 201
Tao 2015[22] CO DB 900 900 12 DM 64 N F 50
Wang 2008[23] P DB 540 360 14 HTN 42 O M, F 43
Wang 2017[24] P DB 1488 992 24 DM ≥60 N M, F 148
Wong 2009[25] P DB 1680 1000 12 DM 45 N M, F 97
Yang 2019[26] P DB 1200 8 00 12 HTN <45 or ≥45 N M, F 70
Yang 2020[27] P DB 1200 800 23 CVD 55.61 N M, F 77
Zeng 2017[28] P DB 728 516 12 N 39 N M, F 422
Zhang 2010[29] P DB 1110 1720 8 N 52 N M 92
Zhang 2012[30] P DB 483 993 8 DM 55 N F 126
Zhao 2009[31] P DB 720 480 12 CHF ≥60 N NR 76
Zhao 2016[32] P DB 728 516 12 SH 40 N M, F 198
Zheng 2018[33] P DB 1200 800 12 DM 45 N M, F 98
This article does not specify the specific dosage of EPA and DHA.BMI: Body mass index; CHF: Chronic heart failure; CO: Cross-over; CVD: Cardiovascular disease; DB: Double-blind; DHA: Docosahexaenoic acid; DM: Diabetes mellitus; EPA: Eicosapntemacnioc acid; F: Females; HTG: Hypertriglyceridemia; HTN: Hypertension; M: Males; N: Normal; NAFLD: Non-alcoholic fatty liver disease; NR: Not reported; O: Overweight; P: Parallel; SH: Suboptimal health.

Cardiovascular risk factors and consumption of EPA and DHA

A total of 7 articles reported BP data, comprising 1054 patients, with 528 in the FO group and 526 in the control group. The SBP result had a large degree of heterogeneity (P < 0.001, I2 = 91%), which had a decreasing trend in the FO group compared with the control group (MD = −1.88, 95% CI: −4.97 to 1.20, P = 0.23) [Supplementary Figure 1,]. Meta-analysis indicated that DBP had a moderate degree of heterogeneity in the study group (P = 0.07, I2 = 48%), and thus, a random-effects model was used. DBP of the FO group demonstrated a decreasing trend compared with the control group (MD = −0.86, 95% CI: −1.79 to 0.06, P = 0.07) [Supplementary Figure 2,].

Nine articles reported fasting blood glucose (FBG) data. Meta-analysis indicated a moderate degree of heterogeneity in the study groups (P = 0.05, I2 = 48%) comprising 1369 patients; thus, a random-effects model was used. The results showed that the reduction in FBG levels in the FO group demonstrated a decreasing trend compared with the control group (MD = −0.05, 95% CI: −0.16 to 0.06; P = 0.40) [Supplementary Figure 3,].

In serum lipid analysis, a total of 17 studies reported LDL-C data, comprising 2164 patients, with 1089 in the FO group and 1075 in the control group; for HDL-C data, 2234 patients were included, with 1134 in the FO group and 1100 in the control group. Meta-analysis showed a large heterogeneity among the study groups (P < 0.001, I2 = 98%) in LDL-C data, wherein the reduction in LDL-C in the FO group was significantly greater than that observed in the control group (MD = −0.12, 95% CI: −0.23 to −0.01, P = 0.04) [Figure 3A]. In contrast, a large heterogeneity was observed among the HDL-C study groups (P < 0.001, I2 = 67%), wherein the increase in HDL-C in the FO group was significantly greater than that in the control group (MD = 0.03, 95% CI = 0.01 to 0.05, P < 0.001) [Figure 4A].

Figure 3:
Meta-analysis of LDL-C in Chinese patients consuming fish oil. (A) Forest plot for LDL-C. (B) Funnel plot for LDL-C. The size of the square represents the weight that the corresponding study exerts on the meta-analysis. CI: Confidence interval; IV: Inverse variance methods; LDL-C: Low-density lipoprotein cholesterol; MD: Mean difference; SD: Standard deviations; SE: Standard error.
Figure 4:
Meta-analysis of HDL-C in Chinese patients consuming fish oil. (A) Forest plot for HDL-C. (B) Funnel plot for HDL-C. The size of the square represents the weight that the corresponding study exerts on the meta-analysis. CI: Confidence interval; IV: Inverse variance methods; HDL-C: High-density lipoprotein cholesterol; MD: Mean difference; SD: Standard deviations; SE: Standard error.

Five studies reported TNF-α data, comprising 542 patients, with 294 in the FO group and 248 in the control group. These studies exhibited large heterogeneity among the study groups (P < 0.01, I2 = 96%). Compared with the control group, people who took FO demonstrated a decreasing trend (MD = −1.03, 95% CI: −1.87 to −0.19, P = 0.02) [Figure 5A].

Figure 5:
Meta-analysis for TNF-α in Chinese patients consuming fish oil. (A) Forest plot for TNF-α. (B) Funnel plot for TNF-α. The size of the square represents the weight exerted by the corresponding study on the meta-analysis. CI: Confidence interval; IV: Inverse variance methods; MD: Mean difference; SD: Standard deviations; SE: Standard error; TNF-α: Tumor necrosis factor α.

A total of 4 studies reported CRP data, comprising 489 patients, with 252 in the FO group and 237 in the control group. These studies exhibited large heterogeneity among the study groups (P = 0.05, I2 = 61%). Compared with the control group, people who took FO demonstrated a decreasing trend (MD = −0.12, 95% CI: −0.29 to 0.04, P = 0.15) [Supplementary Figure 4,].

Additionally, we combined the changes in TC and TG, after patients consumed FO. These measures also demonstrated a decreasing trend compared with the control group [Supplementary Figure 5, and 6,].

Subgroup analysis

According to total daily omega-3 intake of patients in different experimental groups, all experimental components were divided into 3 categories: an omega-3 ≥ 2000 mg/day group, a 1000 mg/day ≤ omega-3 < 2000 mg/day group, and omega-3 < 1000 mg/day group [34,35] which were considered high-dose, medium-dose, and low-dose groups, respectively. The analysis showed that a total of 16 studies reported the TC results in the study subjects, although the overall results were not statistically significant. The subgroup analysis identified 5 studies with omega-3 ≥ 2000 mg/day, 8 studies with 1000 mg/day ≤ omega-3 < 2000 mg/day, and 3 studies with omega-3 < 1000 mg/day. The meta-analysis indicated a significant heterogeneity among the subgroups (P = 0.002, I2 = 83.4%), and thus, a random-effects model was used. Analysis showed that the low-dose group (MD = −0.44, 95% CI: −0.55 to −0.34, P < 0.001) had the largest reduction in TC among the study subjects [Figure 6]. The results of the TNF-α subgroup analysis showed that only 1 study reported the high-dose group, while 3 studies reported the medium-dose group. There was another study in the low-dose group. The meta-analysis indicated significant heterogeneity among the subgroups (P < 0.001, I2 = 88.6%); therefore, a random-effects model was used. The results showed that the medium-dose group (MD = −1.34, 95% CI: −2.02 to −0.65, P < 0.001) and high-dose group (MD = −1.23, 95% CI: −2.48 to 0.02, P = 0.05) had a decrease in TNF-α levels among the study subjects when compared to control groups [Figure 7].

Figure 6:
Subgroup analysis for TC in Chinese patients consuming fish oil. The size of the square represents the weight that the corresponding study exerts on the meta-analysis. CI: Confidence interval; IV: Inverse variance methods; SE: Standard error; FO: Fish oil; TC: Total cholesterol.
Figure 7:
Subgroup analysis for TNF-α in Chinese patients consuming fish oil. The size of the square represents the weight that the corresponding study exerts on the meta-analysis. CI: Confidence interval; IV: Inverse variance methods; MD: Mean difference; SD: Standard deviations; SE: Standard error; TNF- α: Tumor necrosis factor α.

Publication bias and sensitivity analysis

Omitting 1 trial in each turn was used to verify the source of heterogeneity of the merged data. The analysis indicated that heterogeneity in DBP were mainly contributed by reports by Zeng et al[28] and Zhao et al.[32] The change in variables and the sample size were too large in these studies. Furthermore, the heterogeneity in HDL-C was mainly contributed by reports by Zhang et al[29] and Li et al.[18] The reason for the heterogeneity may be excessive sample size in the literature and the small changes in variables [Figures 3B, 4B, and 5B].


This systematic review and meta-analysis of 20 RCTs, comprising 2422 participants in China, showed significant effects of supplementation with EPA and DHA on BP, FBG, LDL-C, and HDL-C. The mean differences in the levels of lipids in the present study are consistent with those reported by previous studies.

EPA and DHA supplements may be included with other dietary regimens to control BP. Changes in endothelial function caused by omega-3 are also a key factor in reducing systemic vascular resistance.[36] Additionally, free fatty acids may increase the reactivity of vascular α1 adrenal receptors or the activity of the sympathetic nervous system.[37] They also induce the proliferation and migration of vascular smooth muscle cells via a protein kinase C-dependent mechanism.[38] Omega-3 also induces changes in membrane transport, increases the density of calcium ion channels in vascular smooth muscle cells, alters the dynamics of membrane channels, increases the levels of angiotensin II, and worsens the oxidative stress response.[39]

Insulin resistance is also a risk factor for CVD.[1] Increased insulin signaling pathway and glucose transporter type 4 (GLUT4) content in insulin-targeted tissues (such as muscle and adipose tissue) could be the mechanism linking consumption of FO to blood sugar control.[40] Due to the close relationship between blood cholesterol and CVD, studies have emphasized that blood cholesterol content, especially high LDL-C/ HDL-C ratio, is an important risk factor.[41] Serum LDL-C levels are positively correlated with occurrence of CVD.[42] HDL-C can be used as an effective biomarker for reverse cholesterol transport, thereby reducing the risk of CVD.[43]

CRP is an acute-phase reactive protein that plays a key role in the inflammation/infection process. It is primarily synthesized and secreted by hepatocytes and smooth muscle and is involved in many aspects of atherosclerosis[44] and thrombus[45] formation. There is sufficient evidence to support that the concentration of CRP in the serum of patients is related to major diseases, such as CVD.[46] Although there was no statistical difference in the results, due to publication bias and other reasons, the current analysis still shows that FO was of great significance to the Chinese population in reducing inflammation and preventing other diseases [Supplementary Figure 6,].

Subgroup analysis showed that patients consuming a lower concentration of omega-3 (<1000 mg/day) demonstrated a greater reduction in serum TC levels when compared to moderate and high concentrations. The same daily low-dose intake of omega-3 (<1000 mg/day) also showed a greater decrease in serum TC levels when compared to the United States and other European countries (MD −0.44 vs. MD −0.236),[20] which may be related to Chinese traditional eating customs. The results of the subgroup analysis for the varying intake of omega-3 showed that all doses of omega-3 changed TNF-α secretion. TNF-α is a member of the tumor necrosis factor family. It is produced by activated monocytes, macrophages, and various other cells. It is an important clinical indicator of inflammation.[47] Several studies showed that inhibiting TNF-α can effectively control atherosclerosis, similar to sclerosis[21,22] and heart failure.[23] The results of the subgroup analysis suggest that, to effectively control inflammation, it is necessary to find a suitable omega-3 dose for the Chinese population.

EPA and DHA, rich in FO, are essential fatty acids for the human body. Chinese people typically consume less omega-3 than the Western people,[48] and even the daily intake of those in the coastal areas is significantly less than the recommended intake of 0.25 to 2 g/day.[49] This meta-analysis found that including FO to the diet of the Chinese population can significantly reduce BP and blood glucose levels and improve blood lipid levels. Therefore, it is particularly important to supplement the Chinese population with FO products.

However, despite the results of this study being statistically significant, the changes in BP, lipid metabolism, and inflammation were small. There is a certain bias due to the ethnic specificity, the different health status, and the short period of time investigated by the included trails. Data from the long-term clinical trials on FO is needed in the Chinese population to further test the clinical effects of omega-3.


This meta-analysis summarizes the effects of FO in different types of patients in the Chinese population and the effects of different dosages of FO on CVD-related risk factors. The results show that consuming FO can improve lipid metabolism and reduce levels of proinflammatory markers in the Chinese individuals.

Author contributions

Zhu Mei performed the data analyses and wrote the manuscript; Haixu Song and Xiaoxiang Tian contributed significantly to analysis and manuscript preparation; Dan Liu helped perform the analysis with constructive discussions, and contributed to the conceptualization of the study.


This work was supported by the funding from the National Natural Science Foundation of China (82070308, 82070300, 82070875 and 32071116).

Conflict of interest



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Chinese population; Fish oil; Lipid metabolism; Meta-analysis; Omega-3; Proinflammatory markers

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