This post is about a clinical trial of clinoptilolite zeolite clay to prevent aspects of leaky gut in endurance athletes.  Leaky gut, loss of intestinal barrier function, is a problem with endurance athletes who experience transient intestinal ischemia.  A related study demonstrated that curcumic, the active compound in turmeric root extracts, protects against gastrointestinal ishchemia reperfusion injury in a rat model that involves increased expression of Zonula occludens-1, ZO-1. 
The Ribeiro review and exercise induced leaky gut
Topics covered in the Ribeiro review  are pertinent to much more than those times when our skeletal energy expenditure decrease splanchnic blood flow that is triggered at around 70–80% of the maximum oxygen consumption (VO2max). The decrease in splanchnic circulation is enough to induce hypoxia.  Splanchnic hypo perfusion induced hypoxia and subsequent ischemia can damage the specialized anti microbial protein-secreting cells Paneth cells. Paneth cells secrete anti-microbial peptides called defensins.  Mucus-producing goblet cells and the tight junction proteins claudin and occludin prevent infiltration of pathogenic organisms.  Proinflammatory cytokines released in response to bacterial components may increase intestinal barrier function and cause “leaky gut.” How the increase in sympathetic system stimuli associated with endurance running causes these symptoms is largely unknown. 
Endurance exercise induced leaky gut symptoms
- lower-abdominal bloating
- urge to defecate
- abdominal pain
- abnormal defecation/diarrhea
- bloody stools
How we think it happens
The exercise induced increase in permeability appears to be mediated by tumor necrosis-alpha (TNF-α). These are the cytokines listed in the Ribiero review  some of which were assayed for in feces of participants in the Lambrecht clinical trial. 
- interleukin-6 (IL-6)
- TNF-α, a cytokine that binds to membrane bound receptors to alter gene transcription
- interferon-gamma (IFN-γ)
- gut microbiota changes
The Lambrecht clinical trial 
The participants were mostly bicyclist with some triathletes as well. Subjects were both males and females between 25 and 50 years of age. Smokers, those who had changed their exercise routine or had taken dietary supplements in the past four weeks were excluded. These subjects had VO2max from 45 mL/kg . min-1 to 65 mL/kg . min-1., U.S. cyclist Lance Armstrong (84 mL/kg . min-1) made the list of world CO2max record holders. According to Fitness City all of these men and women are were in excellent physical condition.
The subjects randomized to zeolite-clinoptilolite (n = 28) received boxes with capsules containing (per capsule):
- Zeolite 307.50 mg
- Dolomite 75.17 mg (Magnesium 15.79 mg; Calcium 34.9 mg), dolomite is a mixture of calcium and magnesium hydroxides.
- Maca 27.33 mg,
- Cellulose 90 mg (PANACEO SPORT®,
- Panaceo International Active Mineral Production GmbH, Villach, Austria).
The placebo consisted of identical appearing capsules with 500 mg Cellulose per capsule. All subjects were instructed to take 6 capsules per day, 3 capsules in the morning with breakfast and the other 3 capsules with the last meal of the day throughout 12 weeks. To ensure good compliance, subjects were called and e-mailed biweekly to remind and motivate them to adhere to the suggested instructions.
A cartoon of what Ribeiro think happens and what Lamprecht  saw
The mostly hard core bicyclists in this study seem to be subjecting themselves to continuous G.I. stress. What is not clear is why some parameters like C reactive protein (CP) and TNF-α increasing with time. 
Note that ZO-1 concentrations in the feces of these athletes started out above the reference range. Clinoptilolite consumption brought the ZO-1 in the feces to within the reference range for some of the subjects.
Melatonin, the elephant in the room?
Availability of fresh produce and lesser dietary factors may be contributing to the time effects.
Curcumin and ZO-1
In this study ischemia reperfusion injury in rats was not caused by intermittent intense exercise followed by rest, but transient surgical ligation..  Rats were pretreated with 200mg/kg curcumin via gastric lavage.  Ileal tissue was excised and H&E stained to asses tissue damage. ZO-1 was visualized with anti ZO-1 antibodies. 
Our story continues with TNF-αand diamine oxidase (DAO).Tian and coauthors were not clear as to why they were looking at DAO. Wikipedia authors view DAO as a copper cofactor enzyme responsible for oxidation of polyamines. Curcumin decreased DAO activity to half of the untreated I/R values. It was not clear if curcumin was chelating the Cu from DAO or by some other mechanism.
A Western blot showing curcumin increased expression of ZO-1 is not shown in this post.
My personal perspective
Having run several ultra marathons from 50 km to 50 miles(in my 30s) , I found the Ribeiro interesting, but contrary to what I experience. Ultra marathon runners generally eat almost non stop hydrox cookies and other high carbohydrate, often salty, foods. To not eat at all can result in G.I. issues as can eating high protein foods. Ultra marathons are not run at anything close to VO2max, I might add. I thought it confusing the way the small and large intestines were not differentiated. Food transit via the small intestine is generally faster in spite the greater length. The bacteria load is in the colon.
I liked the Lamprecht clinical trial  in that they demonstrated that a clay did something measurable. I liked their use of well disciplined participants. I found their very strong time effect for a number of markers listed in the Ribeiro review troublesome. For many individuals, bowel movements have a strong diurnal component, not just one brought on by physical activity. I’m resisting the urge to add PubMed references on melatonin and G.I. barrier function to this post.
I added the Tian study  to this post because they demonstrated a protective of curcumin on ZO-1 expression that is reminiscent of the Lamprecht trial showing less ZO-1 in the feces in the athletes that used the clinotilolite/zeolite clay.  Would humic or fulvic acids had the same effect? Fulvic and/or humic acids seem to be commonly added to zeolite clay supplements.
It might be better to take humic/fulvic acid separately from clays if one binds to the other. Some how in examining ZO-1 I have forgotten about the intestinal mucus layers. Do clinoptilolite bind to mucus? The intestinal mucus layer does relate back to autism and other neurological disorders. 
- Ribeiro FM, Petriz B, Marques G, Kamilla LH, Franco OL. Is There an Exercise-Intensity Threshold Capable of Avoiding the Leaky Gut? Front Nutr. 2021 Mar 8;8:627289. PMC free article
- Lamprecht M, Bogner S, Steinbauer K, Schuetz B, Greilberger JF, Leber B, Wagner B, Zinser E, Petek T, Wallner-Liebmann S, Oberwinkler T, Bachl N, Schippinger G. Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects. J Int Soc Sports Nutr. 2015 Oct 20;12:40. PMC free article
- Tian S, Guo R, Wei S, Kong Y, Wei X, Wang W, Shi X, Jiang H.( 2016) Curcumin protects against the intestinal ischemia-reperfusion injury: involvement of the tight junction protein ZO-1 and TNF-α related mechanism. Korean J Physiol Pharmacol. 2016 Mar;20(2):147-52. PMC free article
- Herath M, Hosie S, Bornstein JC, Franks AE, Hill-Yardin EL.(202) The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders. Front Cell Infect Microbiol. 2020 May 28;10:248. PMC free article