Lysophosphatidic Acid
Also known as: LPA, lysophosphatidate, Lysophosphatidic acid
Overview
Lysophosphatidic acid (LPA) is a naturally occurring lysophospholipid derivative found in cell membranes and bodily fluids. It is enzymatically produced from lysophosphatidylcholine (LPC) by autotaxin (ATX). LPA acts as a bioactive lipid mediator, influencing a wide range of cellular processes including cell proliferation, survival, migration, and inflammation. While LPA is a crucial signaling molecule involved in various physiological and pathological processes such as inflammation, atherosclerosis, and neuronal activation, its direct use as a dietary supplement is less common compared to related compounds like phosphatidic acid (PA). Research on LPA is an emerging area, primarily focusing on its pathological roles and potential as a therapeutic target, with limited direct clinical evidence supporting its supplementation for health benefits. The current body of evidence is largely based on preclinical and mechanistic studies, with a scarcity of high-quality randomized controlled trials (RCTs) on its supplementation effects in humans.
Benefits
Currently, there is no strong evidence from randomized controlled trials (RCTs) to support that LPA supplementation alone improves muscle strength or mass beyond the effects of resistance training. Studies on related compounds, such as phosphatidic acid (PA), have shown no significant difference versus placebo in muscle strength or lean mass gains after 8 weeks of resistance training, although some trends suggested possible benefits. LPA is implicated in lipid metabolism, with elevated LPA species correlating with dyslipidemia and atherosclerosis in familial hypercholesterolemia models, suggesting a role in cardiovascular risk rather than a benefit. LPA also induces neuronal activation and modulates immune responses, including IL-6 production, potentially contributing to visceral hypersensitivity and inflammation, indicating a pro-inflammatory role in some contexts. No direct supplementation benefits have been established for specific populations, and no clinically significant improvements have been demonstrated in human supplementation trials to date. The pathological effects of LPA are observed in chronic disease models, but its beneficial effects as a supplement remain unproven.
How it works
Lysophosphatidic acid (LPA) primarily signals through a family of specific G protein-coupled receptors (LPA1-6) located on cell surfaces. Activation of these receptors triggers various intracellular signaling pathways that regulate fundamental cellular processes, including cell proliferation, survival, migration, and inflammation. LPA interacts with multiple body systems, influencing the function of vascular endothelium, immune cells, and neurons, and playing a role in lipid metabolism pathways. Its production is largely mediated by the enzyme autotaxin (ATX), which converts lysophosphatidylcholine (LPC) into LPA extracellularly. Data on the oral absorption and bioavailability of LPA as a supplement are limited, as endogenous LPA is primarily produced locally through enzymatic cleavage.
Side effects
The safety profile of direct LPA supplementation is not well characterized due to limited clinical research. In studies involving related compounds like phosphatidic acid (PA), no significant adverse effects have been reported, and PA has generally shown good tolerability. However, common, uncommon, or rare side effects specifically for LPA supplementation are largely unknown. Potential drug interactions, particularly with lipid-lowering or anti-inflammatory medications, are theoretical but have not been well studied or confirmed. There are no established contraindications for LPA supplementation, and its safety in special populations (e.g., pregnant women, children, individuals with pre-existing conditions) remains unknown. It is important to note that LPA is associated with increased cholesterol and atherosclerosis in animal models, suggesting it may contribute to dyslipidemia rather than alleviate it. Furthermore, LPA can induce inflammatory responses and cytokine production, indicating a pro-inflammatory role in certain biological contexts.
Dosage
The minimum effective dose for Lysophosphatidic Acid (LPA) supplementation has not been established. Studies on related compounds, such as phosphatidic acid (PA), have utilized dosages ranging from 250-375 mg per day. However, these dosages are not directly transferable to LPA, and the optimal or maximum safe dose for LPA remains unknown. There are no established timing considerations for LPA supplementation. While oral supplementation has been studied with phosphatidic acid, LPA itself is less commonly supplemented directly. Information regarding absorption factors or required cofactors for LPA is also not available. Due to the lack of established dosing guidelines and limited safety data, caution is advised regarding LPA supplementation.
FAQs
Does LPA supplementation increase muscle mass?
No conclusive evidence supports that LPA supplementation increases muscle mass. Studies on related compounds like phosphatidic acid showed no significant advantage over placebo in muscle mass gains during resistance training.
Is LPA safe?
Limited data exist on the safety of direct LPA supplementation. While related compounds show good tolerability, the safety profile of LPA itself is not well studied, and potential side effects are largely unknown.
Can LPA reduce cholesterol?
LPA is associated with increased cholesterol and atherosclerosis in animal models. Therefore, it is unlikely to reduce cholesterol and may contribute to dyslipidemia rather than alleviate it.
Is LPA anti-inflammatory?
LPA can induce inflammatory responses and cytokine production, indicating a pro-inflammatory role in some contexts rather than an anti-inflammatory one.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4974867/ – This randomized controlled trial investigated the effects of phosphatidic acid (PA) supplementation (250-375 mg/day) combined with resistance training over 8 weeks. The study found that PA supplementation did not significantly improve muscle strength or lean mass compared to placebo, although some trends suggested a possible benefit. The research had good methodology but a moderate sample size and focused on PA, not directly LPA.
- https://spj.science.org/doi/10.34133/research.0629 – This preclinical study, complemented by human plasma correlation data, explored the role of elevated LPA species. It found a correlation between elevated LPA and increased LDL and total cholesterol in human familial hypercholesterolemia patients. Furthermore, the study demonstrated that LPA 16:0 promoted atherosclerosis in mouse models, providing strong mechanistic insights into LPA's role in cardiovascular risk.
- https://academic.oup.com/ibdjournal/article/31/Supplement_1/S54/7978519 – This in vitro cell study investigated the effects of LPA on DRG neurons and enteric glial cells. The findings indicated that LPA induced neuronal activation and increased IL-6 production, suggesting a pro-inflammatory role and potential contribution to visceral hypersensitivity. This research provides mechanistic insights but lacks clinical data on human supplementation.
