Gut motility is perhaps the single most important factor controlling endotoxin absorption from the gut into the bloodstream. Constipation increases gut transit time, allowing Gram-negative bacteria to proliferate and release large quantities of lipopolysaccharide (LPS) . Endotoxin then triggers systemic inflammation, serotonin release (90% of serotonin is in the gut), and a host of chronic diseases. Ray Peat has long recommended raw carrot salad (with coconut oil and vinegar) as a gentle, fiber-based way to bind endotoxin and improve motility. I have written extensively about antibiotics (such as penicillin or doxycycline) for more severe cases. Now, a large genetic study published in Gut has identified that vitamin B1 (thiamine) metabolism is a key determinant of gut motility and IBS risk. While the article focuses on the genetic associations, the real mechanism — which the authors do not discuss — is the bioenergetic role of B1 in supporting oxidative metabolism and raising CO₂ levels.
As the study below demonstrates, researchers analyzed data from more than 268,000 people across six biobanks (European and East Asian) and identified 21 genetic locations associated with stool frequency (SF) — a proxy for gut motility. The top variant affects SLC35F3, a gene that transports vitamin B1 (thiamine) into cells. Another variant affects XPR1, a phosphate exporter that is essential for converting thiamine into its biologically active form, thiamine pyrophosphate (TPP) . Observational dietary data confirmed that higher thiamine intake was associated with higher stool frequency (i.e., less constipation), and the effect depended on which gene variants a person carried.
The study concludes that vitamin B1 metabolism plays a “surprising role” in gut motility and opens possibilities for dietary or drug interventions targeting thiamine pathways. But the mechanism is not surprising at all to anyone familiar with bioenergetics. Vitamin B1 (thiamine) is the essential cofactor for three critical enzymes:
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Pyruvate dehydrogenase (PDH) — the rate-limiting enzyme for carbohydrate oxidation. PDH converts pyruvate to acetyl-CoA, allowing glucose to enter the TCA cycle and be oxidized to CO₂. Without sufficient B1, pyruvate is instead converted to lactate (the Warburg effect), producing far less ATP and creating a reductive, inflammatory state.
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Alpha-ketoglutarate dehydrogenase (KGDH) — another key enzyme in the TCA cycle, also dependent on B1.
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Carbonic anhydrase — B1 is a known carbonic anhydrase inhibitor. By inhibiting carbonic anhydrase, B1 raises CO₂ levels in the body. Ray has written extensively about CO₂ as a metabolic signaling molecule with anti-inflammatory, vasodilatory, antioxidant, anti-serotonin, and anti-estrogen effects. Mainstream medicine still ridicules CO₂ as a mere “waste product” — yet elevated CO₂ relaxes smooth muscle, improves blood flow, and reduces inflammation, all of which would directly improve gut motility.
Thus, the benefits of B1 for gut motility are likely mediated by two synergistic bioenergetic mechanisms: (1) improved oxidative metabolism (via PDH and KGDH), which increases ATP production and powers the smooth muscle contractions of peristalsis; and (2) elevated CO₂ (via carbonic anhydrase inhibition), which relaxes the gut, reduces inflammation, and counteracts serotonin’s constipating effects.
The human-equivalent dose is not explicitly stated in the article, as this was a genetic study, not an intervention trial. However, based on the literature and my previous writings, therapeutic doses of thiamine for gut motility are typically in the range of 300–1,500 mg per day of thiamine HCl or allithiamine (a fat-soluble form) . For those with genetic variants in SLC35F3 or XPR1, higher doses may be required to overcome reduced transport or activation efficiency.
This study is a perfect example of how mainstream genetics is finally catching up to what bioenergetic researchers have known for decades: vitamins are not just for preventing deficiency diseases. They are powerful metabolic therapies that can treat a wide range of conditions, including common digestive disorders like constipation and IBS. The researchers mention “repurposing” existing drugs, but the simplest repurposing is already available over the counter: vitamin B1 supplements.
https://gut.bmj.com/content/early/2026/01/05/gutjnl-2025-337059
“…By analyzing bowel movement frequency in more than 268,000 people , researchers uncover how thiamine-processing genes shape gut motility , link constipation and diarrhea to shared biology, and point to new therapeutic possibilities for IBS and related disorders.
“…The top variant affects SLC35F3 , a gene that transports vitamin B1 into cells , influencing expression in the brain and digestive tract and potentially integrating central and enteric nervous system control of motility.
“…The second variant affects XPR1 , a phosphate exporter… Phosphate export by XPR1 is essential for converting thiamine into its biologically active form, thiamine pyrophosphate (TPP) .
“…Analysis of 98,449 participants confirmed that higher thiamine intake was associated with higher stool frequency in observational dietary data, with the effect depending on which gene variants a person carried. This suggests these genes regulate how the body uses vitamin B1 to control gut motility rather than acting through a single organ or pathway.
“…The study uncovered a surprising role for vitamin B1 metabolism in gut motility. This discovery opens possibilities for dietary or drug interventions targeting thiamine pathways.
“…Many existing medications, particularly cardiovascular drugs, could be repurposed to treat IBS and other gut motility disorders , but further experimental and clinical investigation is required.
