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Nutrition Research Review: The association between dietary patterns and the novel inflammatory markers platelet-activating factor and lipoprotein-associated phospholipase A2: a systematic review.

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Inflammation as a cause of atherosclerosis

It is now understood that atherosclerosis, the main underlying cause of cardiovascular disease (CVD), is a disease of chronic inflammation. It is a chronic disease of the arteries that leads to fatty streaks and atheromas in the arterial wall and evidence has identified the role of inflammation in all stages of the disease.

This systematic review explores how dietary patterns influence two novel inflammatory markers; platelet-activating factor (PAF) and lipoprotein-associated phospholipase A₂ (Lp-PLA₂), that are involved in CVD.

What is PAF?

PAF is the most potent lipid inflammatory mediator, and it has many roles in atherosclerosis, for example, it is involved in the mediation of adhesion of monocytes to endothelium, the initiation of gene transcription within monocytes to produce inflammatory cytokines, stimulating the release of proinflammatory cytokine IL-6 from endothelial cells and monocytes and increasing endothelial permeability so as to allow LDL cholesterol and monocytes into the intima.

Patients with diabetes, heart failure, acute myocardial infarction, and CHD present with elevated levels of PAF.

What is Lp-PLA₂?

Lp-PLA₂ is also known as platelet-activating factor acetylhydrolase and has been identified as an enzyme with an anti-inflammatory role. However, Lp-PLA₂ exhibits non-specificity for its ligand, resulting in its hydrolysis products having been linked with disease. Lp-PLA₂ has been identified as an independent risk factor for a range of CVD issues.

What does this have to do with diet?

PAF

A traditional Mediterranean Diet includes foods which contain natural PAF inhibitors. They work by stopping PAF from binding to receptors, halting the intracellular signalling cascade and inflammatory processes. It is suggested that they may also work by ‘inhibiting metabolic enzymes used in the remodeling pathway for PAF synthesis’ (English et al., 2021, p. 3).

The authors summarise existing laboratory research identifying a range of foods that inhibit PAF. Many foods included in the traditional Mediterranean Diet appear to inhibit PAF, for example, fish, eggs, honey, wild plants, garden peas, dairy (particularly fermented dairy and products from goats and sheep), goat and sheep meat, flaxseeds, olive oil, wine, grapes, Cretan oregano, clove, cinnamon, onion, garlic, seed oils (including corn, safflower, sesame).

Foods associated with other cultural dietary patterns, such as soy sauce, tea, and curcumin, have also been found to inhibit PAF in the lab.

Lp-PLA₂:

English and colleagues identify that we know less about how diet influences Lp-PLA₂ levels but identify that there is some evidence suggesting that weight loss associated with a low energy diet can reduce Lp-PLA₂ levels, whereas increased energy intake is associated with higher levels.

Methodology overview:

PRISMA guidelines were followed, and four databases were searched using a comprehensive search strategy, with resulting titles and abstracts screened for inclusion in duplicate. Sixteen articles were included in the narrative review, 13 explored Lp-PLA₂, four explored PAF and one study explored both markers. The Quality Checklist Criteria was used to assess study quality.

The authors note that the novelty of these biomarkers, difficulties associated with their measurement and lack of an established reference range for levels in healthy adults is an explanation for the limited research found on dietary patterns and PAF and Lp-PLA₂.

Results:

A range of established healthful dietary patterns appear to favourably influence levels of PAF and Lp-PLA₂. These include the traditional Mediterranean Diet, vegetarian diet, and other heart-healthy dietary patterns (e.g., like those captured in country-specific dietary guidelines). By contrast, dietary patterns that include more highly processed foods, and those associated with a Western dietary pattern, negatively influenced these biomarkers.

Mediterranean dietary pattern

• Associated with favourable changes in PAF and Lp-PLA₂.
• Two of the included studies suggested that this dietary pattern may have even greater benefits relating to PAF in patients with Type 2 Diabetes Mellitus who are treated with medication and diet, compared with health controls.

Vegetarian dietary pattern

• Vegetarian diets both with, and without dairy and/or eggs, were associated with favourable changes in PAF and Lp-PLA₂.
• Vegetarian diets that emphasise low fat foods may not produce the same benefits, potentially due to the removal of fats which have anti-inflammatory properties (e.g., via sphingolipids, phospholipids, glycolipids).

Heart-healthy dietary patterns

• These dietary patterns are similar to those represented in country-specific dietary guidelines (e.g., Australia, UK, USA), aiming for higher intakes of vegetables and fruits, moderate dairy, plant-based oils, and unprocessed protein sources.
• The authors suggest that the benefit of this dietary pattern is potentially due to the increased consumption of polyphenols, known PAF inhibitors.

Western dietary pattern

• Unsurprisingly, this review found that a Western dietary pattern was associated with increased levels of inflammation.

Conclusion

While more research is needed, the available evidence suggests that several healthful dietary patterns may positively influence the novel inflammation biomarkers PAF and Lp-PLA₂.

– Anna Millichamp, APD, Senior Teaching Fellow, Bond University

Reference

• Carolyn J English, Hannah L Mayr, Anna E Lohning, Dianne P Reidlinger, The association between dietary patterns and the novel inflammatory markers platelet-activating factor and lipoprotein-associated phospholipase A₂: a systematic review, Nutrition Reviews, 2021; nuab051, https://doi.org/10.1093/nutrit/nuab051

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