Watch the gap! You know I love a good diagnostic test probably (way!) more than the next person but I am slow to come around when there’s suddenly a ‘new-kid-on-the-block’ that every functional testing company wants to offer you. This is how I felt about serum zonulin testing as marker of intestinal permeability too. In spite of Fasano’s important work, identifying this molecule and its role in the reversible opening of tight junctions in the small intestine – I didn’t embrace the test. Why not? Didn’t I love Fasano’s ability to add this piece to the jigsaw that had been missing til now? Well I did. Does that make it an accurate and reliable marker of intestinal permeability in every client with any kind of digestive issue…? Well heck no! That’s not how science works friends and I suspect we may have really jumped the gun a little on this one.
The number of health conditions suddenly being associated with raised serum zonulin has got bigger and bigger: obesity, CVD, PCOS, depression…oh yes this molecule was truly turning out to be the key to the kingdom and therefore a fantastic test for my patients. Or not.
You see the test needs validating & we need more time to understand this marker. Fasano et al had demonstrated only that there were raised levels in coeliac patients and that these levels came down with adherence to a gluten free diet. They also found raised levels in 50% of T1DM patients in one study. Other researchers have, as I said, found correlations with a vast array of other pathology but there are some LARGE gaps in the evidence we have right now. Like, what about healthy populations? What about other groups with established dysfunctional IP? And could elevated serum zonulin be a marker of something other than IP? Well this is where the evidence has started to paint a very different and less consistent picture.
Am I just being a fuddy-duddy and clinging to the old? We have of course another test for abnormal intestinal permeability that has been around for yonks, has a huge body of evidence to support its validity and because it’s regarded as the gold standard of IP testing, has been extensively used in studies – so we have had the time to learn more about its confounders, its limitations and strengths and therefore how to better interpret its results. But I thought I better put my bias to the test and spend all my spare(!) time over the last month reading everything I could on zonulin, IP and accurate assessment. And here’s where I have come to:
There are at least 7 Zonulin Myths we need to bust. Here are the first 2 to get you started:
- Zonulin is a validated test for intestinal permeability in all patients with all conditions causing leaky gut & in fact superior to other IP tests – N…O…that is not the consensus of the current research, regardless of what companies who offer this test might be telling you!
- Any patient who has altered IP will have elevated serum zonulin – well no, firstly this comes down to genes (heck wouldn’t you know it!) and while about 80% of Aussies do have the capacity to produce zonulin that leaves 20% who physically can’t. Are these guys still able to have elevated IP – absolutely..but a serum zonulin test would fail to reflect this = the risk of a ‘false negative’ result
And that’s just the beginning!!! I’ve finally come out from under my ridiculous pile of papers on the topic and I’ve come up for air just long enough to record the latest Update in Under 30 , Mind the Gap with Zonulin testing! If you want to understand what serum zonulin really does tell you about your clients’ health and what it doesn’t and what test we should be using for detecting IP issues then jump on and have a listen 🙂
Following the important discovery of the role of intestinal zonulin in the pathophysiology of coeliac disease our fascination with measuring zonulin in non-coeliac patients suspected of ‘leaky gut’, has moved faster than the facts. It’s time to critically reassess what value, if any, there is in testing serum zonulin – which patients and when? And what is the true gold standard for detecting increased intestinal permeability in our patients?