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Randomised double blind crossover Publication date verified at source

Short chain fatty acids delivered to the colon protected the gut barrier and spared no glycogen at all

AI narration, generated on first listen
Journal
The Journal of Physiology, article JP291470
Authors
Karl JP
Institution
U.S. Army Research Institute of Environmental Medicine
Published
11 August 2026
Source
PMID 42581384 · DOI 10.1113/JP291470
Design
Randomised, double blind crossover with a seven day controlled feeding and exercise lead in, a two week washout, and a laboratory test day combining steady state cycling and a 5 km time trial.
Sample
Twelve active men aged 18 to 30, oxygen uptake 40.0 plus or minus 7.1 mL per kilogram per minute.

Twelve active men completed two seven day blocks of prescribed exercise on a provided diet, supplemented either with acetylated and butyrylated high amylose maize starch or with low amylose maize starch as the control, separated by a two week washout.

On day eight they cycled for 90 minutes at around 60 percent, then ran a 5 km treadmill time trial, with indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers.

The starch raised both faecal and circulating short chain fatty acids relative to the control, and several markers of intestinal barrier damage and permeability were lower. Respiratory exchange ratio during steady state was higher by 0.02 (95% CI 0.01 to 0.03, p<0.001).

Muscle glycogen depletion differed by 14 umol per kilogram per gram dry weight (95% CI -116 to 143, p=0.613). The 5 km time trial differed by 5 seconds (95% CI -44 to 54, p=0.816).

The numbers

Muscle glycogen depletion difference14 umol/kg/g dry wt, 95% CI -116 to 143, p=0.613
5 km time trial difference5 s, 95% CI -44 to 54, p=0.816
Respiratory exchange ratio during steady state+0.02, 95% CI 0.01 to 0.03, p<0.001
Faecal and serum short chain fatty acidsincreased with the modified starch

Why this might happen

Proposed by the authors This is the explanation the authors offer in their discussion. This study did not test it.

The premise the authors set out to test is that short chain fatty acids are the fuel colon cells run on, and that raising their availability should both protect the intestinal barrier and spare muscle glycogen.

Their Key Points confirm the delivery worked. The strategy increased colonic and systemic short chain fatty acid concentrations before and during exercise, and preserved intestinal barrier function.

For the half of the hypothesis that failed they offer no positive account. They report that increasing availability did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen.

Their own conclusion is that the effects were not sufficient to spare glycogen or increase performance, leaving the practical relevance unclear and underscoring the challenge of translating promising preclinical findings to humans.

Drawn from Key Points statement, full text paywalled.

What this does not show

  • It does not show that anyone felt better. Barrier markers moved. No gastrointestinal symptom outcome and no race day outcome was measured, and the authors themselves describe the practical relevance as unclear.
  • It does not show what dietary fibre would do. This is a seven day course of an engineered starch designed to deliver short chain fatty acids past the small intestine. It is not a test of eating more fibre.
  • It does not test the setting where barrier damage matters. Ninety minutes of temperate laboratory cycling plus a 5 km run. Gut barrier damage becomes a practical problem in long, hot, high carbohydrate racing, which this protocol does not resemble.
  • It does not apply to women or to trained athletes. Twelve active men aged 18 to 30, with an oxygen uptake of 40.0 plus or minus 7.1 mL per kilogram per minute.

Where this leaves us

The gut barrier half of the short chain fatty acid story survived a human test, and the glycogen sparing half, which came from animal work, did not. That contradicts the preclinical expectation rather than refining it.

Twelve young active men, seven days of an engineered starch, one temperate laboratory session.

The same delivery tested in hot conditions over a race length effort with gastrointestinal symptoms as the outcome would show whether the barrier finding is worth anything to an athlete.

Caveats worth holding

  • Twelve participants, all male.
  • The abstract states that barrier markers were lower without naming which ones or by how much, and the full text is paywalled, so the size of the barrier effect is unconfirmed here.
  • Volume, issue and page numbers are not yet assigned.
  • A seven day supplementation period says nothing about longer exposure.

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