Expert Opinion: Omega-3 Fatty Acids and Bleeding—Cause for Concern?

doi:10.1016/j.amjcard.2006.11.021

The American Journal of Cardiology

Volume 99, Issue 6, Supplement 1, 19 March 2007, Pages S44-S46

https://doi.org/10.1016/j.amjcard.2006.11.021 Get rights and content

Omega-3 fatty acid ethyl esters have well-known triglyceride-lowering properties and were shown >30 years ago to inhibit platelet function. With the recent US Food and Drug Administration (FDA) approval of these agents for treating severe triglyceride elevations, concerns about excess bleeding naturally arise. However, an objective assessment of the evidence for clinically significant bleeding reveals that such concerns are unfounded. As such, the benefits of triglyceride lowering with omega-3 fatty acids more than outweigh any theoretical risks for increased bleeding.

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Cited by (178)

Fish oil supplementation during pregnancy and postpartum in mothers with overweight and obesity to improve body composition and metabolic health during infancy: A double-blind randomized controlled trial
2023, American Journal of Clinical Nutrition
Maternal obesity during pregnancy is associated with an increased risk of obesity and metabolic disease in the offspring. Supplementation with fish oil (FO), which is insulin sensitizing, during pregnancy in mothers with overweight or obesity may prevent the development of greater adiposity and metabolic dysfunction in their children.
To determine the effects of FO supplementation throughout the second half of pregnancy and lactation in mothers with overweight or obesity on infant body composition and metabolism.
A double-blind randomized controlled trial of 6 g FO (3.55 g/d of n-3 PUFAs) compared with olive oil (control) from mid-pregnancy until 3 mo postpartum. Eligible women had singleton pregnancies at 12–20 wk of gestation, and BMI ≥ 25 kg/m². The primary outcome was the infant body fat percentage (DXA scans) at 2 wk of age. Secondary outcomes included maternal metabolic markers during pregnancy, infant anthropometry at 2 wk and 3 mo of age, and metabolic markers at 3 mo.
A total of 129 mothers were randomized, and 98 infants had a DXA scan at 2 wk. Primary outcome: Imputed and nonimputed analyses showed no effects of FO supplementation on infant body fat percentage at age 2 wk. Secondary outcomes: There were no treatment effects on infant outcomes at 2 wk, but FO infants had a higher BMI z-score (P = 0.025) and ponderal index (P = 0.017) at age 3 mo. FO supplementation lowered maternal triglycerides by 17% at 30 wk of pregnancy (P = 0.0002) and infant triglycerides by 21% at 3 mo of age (P = 0.016) but did not affect maternal or infant insulin resistance. The rate of emergency cesarean section was lower with FO supplementation [aRR = 0.38 (95%CI 0.16, 0.90); P = 0.027].
FO supplementation of mothers with overweight or obesity during pregnancy did not impact infant body composition. There is a need to follow up the offspring to determine whether the observed metabolic effects persist.
Clinical trial registry number: This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001078347p). In addition, the Universal Trial Number, WHO, was obtained (U1111-1199-5860).
Impact of omega-3 fatty acids supplementation in children with sickle cell disease in Saudi Arabia
2022, Journal of King Saud University - Science
Citation Excerpt :
Moreover, there are concerns about infertility, and its safety during pregnancy and lactation with HU usage (Adeyemo et al., 2019). Most drugs show a negative interaction with omega-3 fatty acids (Di Minno et al., 2010) excepting large doses of anticoagulants (Harris, 2007), thereby making it a molecule of choice for interventional studies. They have also been shown to exhibit antioxidant potential, apart from their anti-sickling effects (Kotue et al., 2019).
Though hydroxyurea (HU) is one of the most widely used FDA approved drug in sickle cell disease (SCD), it is associated with certain side effects. Therefore, safer and effective alternatives need to be tried out. Earlier researchers have shown abnormalities in the blood cell fatty acid composition, in patients with SCD. Omega-3 fatty acids being a safer nutritional supplement, possessing anti-adhesion, anti-aggregatory, and anti-depressive properties could be tried out.
To explore the impact of omega-3 fatty acids eicosa-pentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) in reducing disease severity in children with SCD, in Saudi Arabia through a pilot interventional study.
Forty-three SCD patients, aged between 5 and 16 years, were supplemented omega-3 fatty acids for a period of six months. Their clinical complications and hematological markers were studied, pre and post supplementation.
Omega-3 supplementation resulted in overall favorable changes in the cell membrane and was found effective in reducing the number of vaso-occlusive crisis (VOC) as well as complications accompanying SCD.
Effects of omega-3 fatty acids supplementation on perioperative blood loss and complications after radical prostatectomy
2022, Clinical Nutrition ESPEN
Many dietary supplements, including omega-3 fatty acids (ω3), are suspected to affect blood coagulation and platelet function. Despite no clinical evidence, discontinuation is recommended before radical prostatectomy. However, long-chain ω3 (LCω3) appear beneficial against prostate cancer progression. Here, we aim to determine the effect of LCω3 supplements on perioperative bleeding, hemoglobin, platelets, and postoperative complications after radical prostatectomy.
This is a planned exploratory analysis of 130 patients diagnosed with prostate cancer grade group 2 or greater enrolled in a randomized controlled trial (NCT02333435) testing the effects of LCω3, on prostate cancer biological and pathological outcomes at radical prostatectomy as main outcomes. The LCω3 intervention (MAG-EPA 3 g daily) or equivalent placebo was given 4–10 weeks prior to radical prostatectomy. An intention-to-treat analysis approach was used with bi-variate statistical testing of bleeding and complications outcomes. We also estimated the difference between groups using linear regression and non-parametric quantile regression models. All models were adjusted for confounding variables selected on clinical relevance.
We found no clinically significant effect of LCω3 versus placebo on perioperative bleeding, laboratory tests or postoperative complications. In contrast, as expected, we found a significant increase in perioperative bleeding in open retropubic radical prostatectomy compared to robot-assisted radical prostatectomy (adjusted difference 115.8 mL, p = 0.04).
Our results suggest that ω3 supplements can be safely taken before radical prostatectomy without increasing surgical bleeding risk. These findings are relevant since ω3 may beneficially affect prostate cancer evolution.
Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events
2022, Journal of Pediatrics
Citation Excerpt :
This factor may be relevant because preterm infants are at risk for short bowel syndrome secondary to NEC and bleeding secondary to decreased coagulation factors, decreased vitamin K stores, and specific medications (ie, indomethacin and ibuprofen for PDA closure).19,20 Based on the data presented in this article, our previous work, and additional studies, we believe it is not necessary to temporarily discontinue FOLE before or after an elective surgery.11,13,14,17,21 Withholding FOLE, especially in preterm and growth-restricted infants who are not receiving enteral nutrition or who have malnutrition, may increase the risk for an essential fatty acid deficiency.
To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD).
In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73).
When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients.
Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE.
NCT00910104 and NCT00738101.
Transplant-associated thrombotic microangiopathy in pediatric patients: Pre-HSCT risk stratification and prophylaxis
2021, Blood Advances
Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen. From January 2012 through October 2019, 257 patients underwent 292 allogeneic HSCTs. Prospective risk stratification was introduced in December 2016. High-risk (HR) patients were treated with combination prophylaxis with eicosapentaenoic acid and N-acetylcysteine. The 1-year cumulative incidence of TA-TMA was 6.3% (95% confidence interval [CI], 3.2-9.4). Age ≥10 years, myeloablative conditioning with total body irradiation, HLA mismatch, diagnosis of severe aplastic anemia or malignancy, prior calcineurin inhibitor exposure, and recipient cytomegalovirus seropositivity were found to be pre-HSCT risk factors for development of TA-TMA. Before routine prophylaxis, TA-TMA rates were significantly different between the HR and standard-risk groups, at 28.2% (95% CI, 0-12.7) vs 3.2% (0.1-6.3), respectively (P < .001). After introduction of prophylaxis, the 1-year cumulative incidence of TA-TMA in the HR group decreased to 4.5% (95% CI, 0-13.1; P = .062, compared with the incidence before prophylaxis). Multicenter pediatric studies are needed to validate these risk criteria and to confirm the efficacy of the prophylactic regimen.
DO-HEALTH: Vitamin D3 - Omega-3 - Home exercise - Healthy aging and longevity trial - Design of a multinational clinical trial on healthy aging among European seniors
2021, Contemporary Clinical Trials
DO-HEALTH is a multi-center clinical trial among 2157 community-dwelling European men and women age 70 and older. The 2x2x2 randomized-control factorial design trial tested the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions: vitamin D 2000 IU/day, omega-3 fatty acids 1000 mg/day (EPA + DHA, ratio 1:2), and a 30-minute 3 times/week home exercise (strength versus flexibility). Each treatment tested has shown considerable prior promise from mechanistic studies, small clinical trials, or large cohort studies, in the prevention of common age-related chronic diseases, but definitive data are missing. DO-HEALTH will test these interventions in relation to 6 primary endpoints (systolic and diastolic blood pressure, non-vertebral fractures, Short Physical Performance Battery score, the Montreal Cognitive Assessment, and risk of infections), plus several secondary endpoints explored in ancillary studies (i.e. rate of any falls and injurious falls, joint pain, oral health, quality of life, and incident frailty). As the 3 interventions have distinct mechanisms of action for each of the 6 primary endpoints, a maximum benefit is expected for their additive benefit as a “multi-modal” intervention. The trial duration is 3 years with in-person contacts with all participants at 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples were collected in all participants to measure changes in 25-hydroxyvitamin D and poly-unsaturated fatty acid concentrations. Our objective was to test interventions that are expected to promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults.

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Omega-3 fatty acidExpert Opinion: Omega-3 Fatty Acids and Bleeding—Cause for Concern?

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Int J Cardiol

Lancet

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Am J Clin Nutr

Lancet

Am J Kidney Dis

J Pediatr

Safety considerations with omega-3 fatty acid therapy

Am J Cardiol

Omega-3 fatty acid
Expert Opinion: Omega-3 Fatty Acids and Bleeding—Cause for Concern?