Safety concerns over the use of intestinal permeation enhancers: A mini-review
http://www.tandfonline.com/doi/abs/10.1080/21688370.2016.1176822?journalCode=ktib20 any input on this?
Great question. I will do my best to address this, but I am just an enthusiastic researcher, I hope one of our more knowledgeable members will add to the discussion if I've missed anything.
In short: I don't think we have anything to worry about with Phosphatidylcholine (PC). In fact, it may actually be beneficial to the gut lining.
For the longer answer:
The intestinal permeation enhancers (PEs) referenced in this review are: fatty acid salts, bile salts, a carnitine, and a chelating agent. PC is a phospholipid, so while it does have beneficial effects on permeation enhancement, it is not one of the compounds in question in this review.
There are two primary reasons PC as a PE should not likely be a concern for us.
1. PC is, among other things, a zwitterionic surfactant. As a zwitterionic surfactant, PC shares some similarities to some of the compounds' primary MOA referenced in this review, but 2 are completely different and of those that share similarities, the secondary and tertiary effects are different. PC may reduce interfacial tension by fluidizing the membrane, but without any cytotoxity (damage to cells). In fact, this review points out that PE surfactants, (such as PC), have a "history of use in man in drug products and in the food processing industry, and that extensive safety testing was carried out on many of these..." PC doesn't share any of the other negative effects noted in some of these other PEs.
2. The epithelial membrane perturbation from fluidization to which they allude is observed to be rapidly reversible. "This indicates that the intestinal epithelia is highly robust and would suggest that any damage caused by PEs should be equally capable of being rapidly repaired, and this has been confirmed in a range of in vitro, ex vivo and in vivo preclinical intestinal models, as well as in a human study.." It's really no different than the constant damage/repair our gut linings go through on a daily basis being bombarded with various foods, alcohols, etc.
The alleged concern is over how sustainable the "damage-repair" cycle is over
chronic use of PEs. The keyword here is "chronic". Presumably, in the context of these compounds' potential for eventual damage, chronic would seem to be many months/years of use of prescription drugs with PEs. So not only does PC appear to be much safer than some/all of these other PEs in and of itself, but most users here are only using PhytoFuse products for 4-8 week cycles anyway, negating the potential for "chronic" damage.
Additional concerns from the review:
3. One additional concern of note is that altering the state of junction openings of the intestinal lining may allow "translocation of potentially dangerous bystanders" such as endotoxin. In the following study, PC was found to actually help stop this.
"Both the transepithelial permeability of endotoxin and the transepithelial stimulation of leukocytes were nearly completely abolished after the apical supplementation of PC"
Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation - Mitzscherling - 2008 - Alcoholism: Clinical and Experimental Research - Wiley Online Library
Additionally, this study showed that adding PC to an NSAID helped to protect from damage to intestinal epithelial cells:
In vitro evidence that phosphatidylcholine protects against indomethacin/bile acid-induced injury to cells. - PubMed - NCBI
4. Finally, they suggest that, even though all studies to date have demonstrated short-term safety with PEs, we may want to be careful in prescribing them to those with intestinal disorders/diseases such as IBS. While this suggestion may have some merit with other PEs, it's important to note that phosphatidylcholine and other phospholipids serve as major components of the intestinal mucus layer, and PC in particular has been shown to be helpful for those with IBS.
PC "produced significant benefit in the treatment of Ulcerative Colitis":
First multicenter study of modified release phosphatidylcholine "LT-02" in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine... - PubMed - NCBI
PC "exerted significant effects to aid in therapy of IBS (ulcerative colitis) by exerting both potent anti-inflammatory effects and improving membrane health and immune response, increasing hydrophobicity to potentially decrease diarrhea, and aiding the neurological signaling potential of the gut":
Lipid based therapy for ulcerative colitis-modulation of intestinal mucus membrane phospholipids as a tool to influence inflammation. - PubMed - NCBI
