A Look at Lipid Replacement Therapy

There has been more interest of late in how to engineer ways to sneak useful proteins past the digestive system so that they can be added to the diet but still find their way into cells. Researchers here combine this with the idea that you can dilute the proportion of damaged lipids present in cell membranes by providing a patient with a supply of undamaged lipids, larger than the body would otherwise generate on its own. I am not familiar enough with this line of work to be able to comment on how useful it is in practice, or whether the balance of evidence suggests that the observed results in trials actually occur due to the replacement of damaged lipids, as the authors state below. It is nonetheless quite interesting in the context of the membrane pacemaker hypothesis:

Lipid Replacement Therapy, the use of functional oral supplements containing cell membrane phospholipids and antioxidants, has been used to replace damaged, usually oxidized, membrane glycerophospholipids that accumulate during aging and in various clinical conditions in order to restore cellular function.

This approach differs from other dietary and intravenous phospholipid interventions in the composition of phospholipids and their defense against oxidation during storage, ingestion, digestion and uptake as well as the use of protective molecules that noncovalently complex with phospholipid micelles and prevent their enzymatic and bile disruption.

Once the phospholipids have been taken in by transport processes, they are protected by several natural mechanisms involving lipid receptors, transport and carrier molecules and circulating cells and lipoproteins until their delivery to tissues and cells where they can again be transferred to intracellular membranes by specific and nonspecific transport systems. Once delivered to membrane sites, they naturally replace and stimulate removal of damaged membrane lipids.

Various chronic clinical conditions are characterized by membrane damage, mainly oxidative but also enzymatic, resulting in loss of cellular function. This is readily apparent in mitochondrial inner membranes where oxidative damage to phospholipids like cardiolipin and other molecules results in loss of trans-membrane potential, electron transport function and generation of high-energy molecules. Recent clinical trials have shown the benefits of Lipid Replacement Therapy in restoring mitochondrial function and reducing fatigue in aged subjects and patients with a variety of clinical diagnoses that are characterized by loss of mitochondrial function and include fatigue as a major symptom.

Link: http://dx.doi.org/10.1016/j.bbamem.2013.11.010


These guys talk a good game in their abstract, but it is not at all clear whether their proposals would not actually undermine, rather than support, the changes in membrane composition that might be expected to fortify membranes against aging per the Pacemaker Hypothesis. From their actual proposals and prior publication record, they certainly appear to me to be quack supplement hawkers (ie, willing to advocate for and sell their branded supplements on the basis of poor evidence). Additionally, they cite pubmed/12297801 as having used their multi-ingredient supplement, whereas from its full text the authors appear to have used straight lecithin polyunsaturated phosphatidylcholine (PPC).

Posted by: Michael at November 29th, 2013 2:40 PM

Hello Michael, as one of the two authors of this paper, I am pleased to see it caught your eye. The pacemaker hypothesis is an interesting proposal and certainly offers some direction in age related cell repair.

In terms of our interest in safe, natural agents for the improvement in cell membrane health and function, we explored in this invited review the role of a specific phospholipid composition in human and animal studies, some of which we included in the article.

We both acknowledge that additional studies are required, but we have clear evidence of membrane compositional changes and these include increased compositional qualities of inner membrane cardiolipin and related functional improvements.

Whilst as you propose lecithin may have compositional similarities our specific lipid concentrates are not found in 'lecithin supplements' without further quantification and extraction. The evidence to date supports the notion that this may be transported in an unoxidised format, but is undergoing additional studies at present and we will publish these in time.

However, your assertion that our prior publishing records suggest a 'hawking' effect is an unfair assertion, Prof Nicolson has published in excess of 600 peer reviewed papers and has won many research awards and accolades. In the same journal he completed a 40 year review of his seminal membrane paper, one of the most cited of all scientific papers in history.

Science. 1972 Feb 18;175(4023):720-31.
The fluid mosaic model of the structure of cell membranes.
Singer SJ, Nicolson GL.

Of note non pharma based research is always struggling with funds, for many reasons, not least the inability to patent the product in most cases, hence fund gathering will tend to have a commercial attachment until such time as independent funds can be more easily accessed.

We look forward to future reviews based on the paper rather than on personal rhetoric.

Posted by: Michael at June 3rd, 2014 6:45 PM
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