The effects of conjugated linoleic acid supplementation on blood pressure and endothelial function in adults: A systematic review and dose-response meta-analysis (original) (raw)
Abstract
Background
Findings of studies investigating the effect of conjugated linoleic acid (CLA) supplementation on blood pressure (BP) and endothelial function are controversial.
Method
This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on BP and endothelial function. Two authors independently searched electronic databases using PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs.
Conclusion
This systematic review and meta-analysis showed CLA association with reduction of ICAM.
The PROSPERO registration number: CRD42022331108.
Introduction
Hypertension (HTN) is a major risk factor for cardiovascular diseases (CVDs), representing a growing challenge in terms of prevention and treatment (Du et al., 2019; Joffres et al., 2013). According to the World Health Organization statistics, HTN is accounted for 7.5 million deaths per year (roughly 12.8% of all deaths) (Kearney et al., 2005). It has also been predicted that 1.56 billion people of the world will develop HTN by the year 2025 (Singh et al., 2017). Accordingly, the pro-inflammatory state in CVD pathogenesis is also associated with endothelial dysfunction (Esposito et al., 2004). Therefore, scalable and cost-effective prevention measures together with therapeutic options are needed to control blood pressure and endothelial function.
The therapeutic interventions for HTN mainly focus on lifestyle modifications and blood pressure-lowering medications, but some patients fail to respond or have side effects (Cameron et al., 2016; Tykarski et al., 2015). Currently, several nutraceuticals are used in the treatment of HTN (Cicero et al., 2019). One of the interesting therapeutic approaches as an aid to control blood pressure and endothelial function is CLA supplementation (Zhao et al., 2009b). CLA is a mixture of linoleic acid isomers with conjugated double bonds that cannot be produced in human body. Yet, ruminal fermentation in ruminants can form CLA in a relatively small amount. Therefore, the major dietary sources of CLA are dairy products and meat of ruminants. The predominant isomer of CLA in food is c9t11-CLA (∼90% of dietary CLA), followed by negligible amounts of t10c12-CLA (∼10% of dietary CLA) (Rubin et al., 2012). Currently, food manufacturers are interested to produce CLA by employing alkali isomerization of linoleic acid-rich vegetable oils, such as soybean and safflower oil (Attar-Bashi et al., 2007). Among various beneficial effects of CLA, anti-atherogenic and anti-hypertensive properties are of great importance (Koba et al., 2002; Zhao et al., 2009b).
A possible explanation for blood pressure-lowering property of CLA is elevation of adiponectin and endothelial nitric oxide synthase activity (Basak and Duttaroy, 2020). There has been a considerable variation between human and animal studies examining the effect of CLA on blood pressure control. Although several rat models (DeClercq et al., 2012b; Inoue et al., 2004; Nagao et al., 2003) confirmed anti-hypertensive property of CLA, results from human trials are inconsistent. There is a human study which reflects decreased levels of SBP and DBP, following the CLA supplementation (Rezvani et al., 2018), while other studies show no effects (Carvalho et al., 2012). Some studies suggest that CLA can exacerbate endothelial function (Taylor et al., 2006; Watras et al., 2007), whereas other studies confirm that CLA has no impaired effects on endothelial function (Pfeuffer et al., 2011). However, the findings of a systematic review and meta-analysis study of eight RCTs does not support the overall favorable effect of CLA supplementation on blood pressure regulation (Yang et al., 2015b). Given the inconsistent findings of previous studies and the lack of any comprehensive review, the current meta-analysis of RCTs was conducted to evaluate the effectiveness of CLA supplementation on SBP, DBP, ICAM, and VCAM.
Section snippets
Materials and methods
The present study followed the Preferred Reporting Items for Systematic Reviews and Meta- Analysis (PRISMA) statement (Moher et al., 2009).
Study selection
Flow diagram of literature search and study selection process is presented in Fig. 1. Our initial search yielded 310 relevant records, of which 123 were excluded for duplication, leaving 187 publications for further review. After title and abstract evaluation, 156 studies were excluded and 31 trials remained eligible for full text review. Thirteen records were removed because they provided insufficient data (9) or were without appropriate control group (4). Finally, 18 RCTs with 20 effect sizes
Discussion
Animal, and in vitro studies suggest that CLA can promote health in many ways. For example, it has anti-inflammatory, anti-diabetic, anti-cancer, anti-atherosclerotic properties, and can elicit immune regulation. However, human clinical studies on CLA have provided ambiguous results. By pooling 18 RCTs, this meta-analysis revealed that CLA consumption did not change blood pressure values (SBP and DBP), and marker of endothelial dysfunction (VCAM). Yet, it could decrease ICAM, as another marker
Funding
This work was supported by Shiraz University of Medical Sciences [grant number: 26328].
CRediT authorship contribution statement
Omid Asbaghi: Writing – original draft, Visualization, Supervision. Ghazaleh Shimi: Writing – original draft. Kaveh Naseri: Writing – original draft. Saeede Saadati: Writing – review & editing. Mahnaz Rezaei Kelishadi: Writing – review & editing. Saeid Doaei: Writing – review & editing. Neda Haghighat: Writing – review & editing.
Declaration of competing interest
The authors declared that there is no conflict of interest.
Acknowledgements
Not applicable.
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Various cell or extracellular factors activate phospholipase, particularly phospholipase A2, to release AA from phospholipids [22]. Conversely, LC is a polyunsaturated fatty acid commonly found in plant oils, seeds, and nuts; it is also a membrane phospholipid component that acts as a structural component to maintain skin barrier function and can cause damage to hemoglobin and red blood cells through oxidative reactions [23]. In fecal samples, we found that the LC level increased in a time- and dose-dependent manner, whereas both fecal and serum samples showed initial decline followed by an increase in the AA level, which indicates the temporal sequence of LC and AA involvement in the cascade reaction of RE.
2023, Food Chemistry: X
The effects of CLA on weight loss and other health parameters have shown variability across studies, and not all individuals may respond in the same way. For example, high doses of CLA supplements may lead to side effects such as digestive issues, hepatic steatosis and induction of colon carcinogenesis in humans, and potential liver problems (Asbaghi, Shimi, Shiraseb, Karbasi, Nadery, Ashtary-Larky, et al., 2022; Jaudszus, Moeckel, Hamelmann, & Jahreis, 2010; Putera et al., 2023). Therefore, long-term safety of CLA has not been extensively studied.
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