New BMJ Study Creates Doubts About Omega-3 Fish Oil
by Jeffrey Dach MD

A new BMJ study by Dr. Chen (2024) on Omega-3 Fish Oil and cardiovascular disease merely creates confusion among the population. The problem is this new BMJ study is “junk science”, a prospective cohort study with bizarre endpoints that merely confuse the issue. This 2024 BMJ study by Chen should be unceremoniously placed into the garbage can.

Here is the Correct Information:

For the correct information see this recent study by Dr. ShiChun Shen, (2022), a meta-analysis of 14 Randomized Clinical Trials shows Omega 3 fish oils are very beneficial in preventing cardiovascular death. This meta-analysis includes 14 Randomized Clinical Trials with 135,291 subjects, finding that Omega-3 Fish Oils reduces risk of heart attack and cardiovascular death. (1-4)

Conclusion: Fourteen Randomized Controlled Trials showing cardiovascular benefit of Omega-3 Fish-Oils trumps one negative prospective observational study.

Jeffrey Dach MD
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Davie, Fl 33314
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my blog: www.jeffreydachmd.com

Header Image: Courtesy of Wikimedia Commons English: Salmon oil capsule. Salmon oil capsules contain salmon oil, which is extracted from salmon and is primarily in capsules available, as it has a very strong odor. Salmon oil has a high content of triglycerides, which contain omega-3 fatty acid residues. Date 27 February 2016, 22:32:49 Source Own work
Author Marco Almbauer. This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

References:
1)    https://bmjmedicine.bmj.com/content/3/1/e000451.abstract

Chen, Ge, et al. “Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study.” BMJ Medicine 3.1 (2024).

For people with a healthy cardiovascular profile, regular use of fish oil supplements, a choice of primary prevention, was associated with an increased risk of atrial fibrillation. For participants with a diagnosis of atrial fibrillation, however, regular use of fish oil supplements, as secondary prevention, had a protective effect or no effect on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to death, and major adverse cardiovascular events to death. When we divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction), we found associations that could suggest a mildly harmful effect between regular use of fish oil supplements and transitions from a healthy cardiovascular state to stroke, whereas potential beneficial associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to myocardial infarction, atrial fibrillation to death, and heart failure to death.

Objective To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.

Design Prospective cohort study.

Setting UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years).

Participants 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study.

Main outcome measures Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage).

Results Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99).

Conclusions Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

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This study lends further support for use of Fish oil…..

2) https://hal.science/hal-03486871/document

Bellenger, Jérôme, et al. “N-3 polyunsaturated fatty acids: an innovative strategy against obesity and related metabolic disorders, intestinal alteration and gut microbiota dysbiosis.” (2019): 66-71.

Dietary n-3 PUFAs, affecting gut integrity, have been shown to reduce clinical colitis and colonic immunopathology by improving epithelial barrier function in animal models (37,38). EPA has been shown to up-regulate the expression of tight junctions and to increase the trans-epithelial electrical resistance (TER), thus reducing the permeability of the endothelial cells (39). EPA and DHA, by lowering permeability-induced inflammatory cytokines such as TNFa, IFNg and IL-4, can maintain gut barrier integrity (40, 41). In agreement, it has been shown that, following intravenous injections of E. coli LPS to animal models, dietary DHA supplementation significantly enhanced the expression of intestinal tight junctions as occludin and claudin-1 and decreased intestinal expression of TLR4 (42). Very few studies assessed the impact of n-3 fatty acids on metabolic endotoxemia. Nevertheless, Mani and co-workers (43) have shown in pigs that post-prandial endotoxemia was decreased by fish oil supplementation when it was increased by coconut oil (rich in saturated fatty acids). Recently,
enhanced levels of metabolic endotoxemia and systemic low-grade inflammation were observed in high n-6 PUFA-fed mice, whereas these parameters are drastically reduced in transgenic mice able to convert n-6-to-n-3 PUFAs in their tissues (44).

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This is an animal study in 24 pigs first fed saturated fat to induce leaky gut, endotoxemia, and increased LPS in blood stream. The pigs were then fed omega 3 oils (marine fish oil) n-3 polyunsaturated fatty acids (PUFA) which reduced the endotoxemia by 50 percent. If cardiovascular disease is a result of endotoxemia, as I believe it is, then Marins fish oil (Omega3 oils) are beneficial, as long as the product is fresh and not rancid. And as long as the product is not contaminated with mercury heavy metals which go directly to the heart muscle and cause arrhythmia and CHF.
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Further support for Omega 3 oils for prevention of cardiovascular disease…

3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577458/
Mani V, Hollis JH, & Gabler NK (2013) Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutrition & Metabolism (Lond) 10(1):6.

Intestinal derived endotoxin and the subsequent endotoxemia can be considered major predisposing factors for diseases such as atherosclerosis, sepsis, obesity and diabetes.

We hypothesized that oils rich in saturated fatty acids (SFA) would augment, while oils rich in n-3 polyunsaturated fatty acids (PUFA) would attenuate intestinal endotoxin transport and circulating concentrations.

Postprandial endotoxemia was measured in twenty four pigs following a porridge meal made with either water (Control), fish oil (FO), vegetable oil (VO) or coconut oil (CO). Blood was collected at 0, 1, 2, 3 and 5 hours postprandial and measured for endotoxin. Furthermore, ex vivo ileum endotoxin transport was assessed using modified Ussing chambers and intestines were treated with either no oil or 12.5% (v/v) VO, FO, cod liver oil (CLO), CO or olive oil (OO). Ex vivo mucosal to serosal endotoxin transport permeability (Papp) was then measured by the addition of fluorescent labeled-lipopolysaccharide.

Postprandial serum endotoxin concentrations were increased after a meal rich in saturated fatty acids and decreased with higher n-3 PUFA intake. Compared to the no oil control, fish oil and CLO which are rich in n-3 fatty acids reduced ex vivo endotoxin Papp by 50% (P < 0.05). Contrarily, saturated fatty acids increased the Papp by 60% (P = 0.008). Olive and vegetable oils did not alter intestinal endotoxin Papp.
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This meta-analysis included 14 Randomized Clinical Trials including 1,35,291 subjects, finding Omega-3 Fish Oils reduced risk of heart attacks….

4) https://www.frontiersin.org/articles/10.3389/fnut.2022.809311/full

Shen, ShiChun, et al. “Omega-3 fatty acid supplementation and coronary heart disease risks: a meta-analysis of randomized controlled clinical trials.” Frontiers in nutrition 9 (2022): 809311.

Results: This meta-analysis included 14 clinical RCTs, including 135,291 subjects. Omega-3 FA supplementation reduced the risk of MACE (RR; 0.95; CI: 0.91–0.99; p for heterogeneity 0.27; I2 = 20%; p = 0.03), cardiovascular death (RR; 0.94; CI: 0.89–0.99; p for heterogeneity 0.21; I2 = 25%; p = 0.02), and MI (RR; 0.86; CI: 0.79–0.93; p for heterogeneity 0.28; I2 = 19%; p < 0.01), but had no significant effect on all-cause death, stroke, and revascularization.

In the subgroup analysis, omega-3 FA supplementation decreased the incidence of MACE [Major Adverse Cardiac Event] and cardiovascular death in acute patients with MI, the risk of MI and stroke in patients with CHD, and the risk of MI in patients with high-risk CHD. 0.8–1.2 g omega-3 FA supplementation reduced the risk of MACE, cardiovascular death, and MI.

Conclusions: Omega-3 FA supplementation had a positive effect in reducing the incidence of MACE, cardiovascular death, MI. Regardless of the stage of CHD, omega-3 FA supplementation can prevent the occurrence of MI. The 0.8–1.2 g omega-3 FA supplementation alleviated CHD risk more effectively than lower or higher doses.

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Published on May 28th, 2024 by Jeffrey Dach MD