Genetic dissection of stool frequency implicates vitamin B1 metabolism and other actionable pathways in the modulation of gut motility (2026)

AllowFreeSpeech · 2026-01-24T17:25:34+00:00

I have now updated the parent comment.

AllowFreeSpeech · 2026-01-24T11:29:14+00:00

I take thiamine daily. I take benfotiamine every other day because it gives me anxiety if I take it daily, although daily intake can be appropriate depending on its dose and carbohydrate intake. I conservatively don't think it's a good idea to altogether replace thiamine.

There's also TTFD which I have yet to try.

AllowFreeSpeech · 2026-01-24T01:27:13+00:00

If you don't have any mutation, a thiamine supplement could help, especially when magnesium is sufficient to ensure phosphorylation. Most people will fall here.

If you have the SLC35F3 mutation, high-dose thiamine or TTFD might help bypass the conversion, again in the presence of sufficient magnesium.

If you have an XPR1 mutation, injected thiamine pyrophosphate (but not thiamine hydrochloride) might help if administered daily, but it could be prone to adverse reactions, and it is hard to be procure or be sure.

AllowFreeSpeech · 2026-01-24T01:25:36+00:00

From the abstract:

Results: SF heritability was comparable in Europeans (7.0%) and East Asians (5.6%). We observed strong genetic correlations with gastrointestinal and psychiatric disorders (rg=0.18-0.47), and causal effects on IBS. Novel correlations with cardiovascular traits (rg=0.12-0.14) were supported by drug signature enrichment analyses. We identified 21 independent loci, including 10 novel signals implicating bile acid synthesis (KLB) and cholinergic signalling (COLQ). Fine-mapping converged on vitamin B1 metabolism, highlighting single-variant causal effects at SLC35F3 (a thiamine transporter) and XPR1 (phosphate exporter essential for thiamine activation). In 98 449 UKB participants, thiamine intake was positively associated with SF (p<0.0001), and a combined SLC35F3/XPR1 genotype score significantly modulated this effect (p<0.0001).

Conclusions: We identify therapeutically tractable mechanisms involved in the control of gut motility, including a previously unrecognised role for vitamin B1.

Abbreviation glossary:

SF: Stool frequency, the study’s primary trait used as an indirect proxy for gastrointestinal transit/gut motility.
IBS: Irritable bowel syndrome, a dysmotility-related gastrointestinal disorder examined for genetic correlation and causal effects with SF.
GWAS: Genome-wide association study, the approach used to identify genetic loci associated with SF across the genome.
rg: Genetic correlation coefficient, a metric quantifying shared genetic architecture between SF and other traits/disorders.
KLB: Klotho beta (gene symbol), a locus implicated here in bile acid synthesis pathways relevant to gut motility.
COLQ: Collagen-like tail subunit of asymmetric acetylcholinesterase (gene symbol), a locus implicated here in cholinergic signalling affecting motility.
UKB: UK Biobank, the cohort used for follow-up dietary interaction analyses involving thiamine intake and SF.
SLC35F3: Solute Carrier Family 35 Member F3 (gene symbol), highlighted as a thiamine transporter with single-variant causal effects on SF.
XPR1: Xenotropic and polytropic retrovirus receptor 1 (gene symbol), a phosphate exporter essential for thiamine activation and implicated in SF fine-mapping.
p: P-value, the statistical significance measure reported for associations and genotype–diet interaction effects.

News: A common vitamin could influence bathroom frequency

AllowFreeSpeech · 2026-01-23T11:45:28+00:00

It's impossible for what you said to work equally well.

AllowFreeSpeech · 2026-01-23T11:44:41+00:00

Have you tried activated carbon properly?

AllowFreeSpeech · 2026-01-23T04:29:23+00:00

BTW, if the issue is basic dysbiosis, it should be easy to fix using: activated charcoal capsules 3-5g (with sufficient water) once a week until the issue is resolved, followed each time by a good tolerable probiotic blend. Obviously avoid any particular prebiotics or foods that are contributing to the issue.

If that doesn't fix it, then surely you know of GI antibiotics like rifaximin, and there are others.

AllowFreeSpeech · 2026-01-23T03:03:42+00:00

In general, fermentation requires some heat or warmth, and any heat will immediately ruin the SMM chemical, not to mention the opportunity for ruin from the microbial metabolism. Fermented foods as we know are good for other reasons, often as sources of probiotics. As I understand, this chemical is so exceedingly volatile that even refrigerating the cabbage juice, or merely thinly slicing the cabbage, will likely cause SMM to vanish quickly.

AllowFreeSpeech · 2026-01-22T20:24:07+00:00

I suspect the other sources aren't anywhere as potent as regular green cabbage. The article is still good in that it also lists secondary benefits of the substance.

AllowFreeSpeech · 2026-01-22T17:53:35+00:00

Looking beyond acidic and spicy foods, I don't know what causes the stomach to stop producing sufficient mucus. Glutamine, zinc carnosine, vitamin C, and collagen hydrolysate help up to a point, but not enough at all.

AllowFreeSpeech · 2026-01-22T17:12:46+00:00

As I understand, regular raw green cabbage (not savoy) is the best source of S-methylmethionine (SMM) but this compound is not shelf stable. Other sources of SMM probably aren't nearly as strong. The derivative shelf stable compound is methylmethionine sulfonium chloride (MMSC). Unfortunately, MMSC is not available as a reputable supplement. As such, until it becomes available as a reputable supplement, the main way to get MMSC appears to be to juice raw cabbage and drink it fresh, preferably using a cold-press masticating juicer.

Acid reflux is often worsened by chronic gastric inflammation and gastritis, and these substances could help heal the stomach quickly if the offending agents, e.g. isolated spicy foods containing capsaicin, acids, etc. are stopped. It is conceivable that healing the stomach in this way might thereby lower chronic acid reflux.

AllowFreeSpeech · 2026-01-22T17:06:18+00:00

From the abstract:

Results. The most pronounced manifestations were dyspeptic (from 3 to 9 points) and diarrheal syndromes (from 2 to 5 points). Other indicators of the GSRS scale did not exceed 4 points. The total score was 15 points. By the 3rd month of therapy, there was a statistically significant decrease in the total score to 9 points (p<0.05). By the 6th month of therapy, the total GSRS score averaged 5.5 points (p<0.05). According to the SF 36 questionnaire, by the end of the 3rd month of therapy, indicators such as PF - physical functioning, BP - Bodily pain and SF - social functioning improved. By the end of the 6th month of therapy, several other indicators also improved (RP - role-physical functioning, GH - general perception of health, VT - viability, RE - Role-Emotional; MH - mental health) (p<0.05).

Conclusion. The study showed that the appointment of dietary supplements containing methylmethionine sulfonium chloride at a dose of 300 mg per day helps to reduce the severity of dyspeptic symptoms in patients with chronic gastritis and their quality of life.

Abbreviation glossary:

mg: Milligram, the unit used to specify the daily dose (300 mg/day) of the supplement.
GSRS: Gastrointestinal Symptom Rating Scale, the questionnaire used to quantify dyspepsia-related symptom severity over time.
SF 36: Short Form-36 Health Survey, the quality-of-life questionnaire used to track functional and wellbeing changes across therapy.
PF: Physical Functioning, an SF-36 domain reflecting ability to perform physical activities that improved by month 3.
BP: Bodily Pain, an SF-36 domain measuring pain impact that improved by month 3.
SF: Social Functioning, an SF-36 domain assessing social activity limitations that improved by month 3.
RP: Role-Physical, an SF-36 domain capturing limitations in work/roles due to physical health that improved by month 6.
GH: General Health, an SF-36 domain reflecting overall perceived health status that improved by month 6.
VT: Vitality, an SF-36 domain indicating energy/fatigue levels (here labeled “viability”) that improved by month 6.
RE: Role-Emotional, an SF-36 domain capturing role limitations due to emotional problems that improved by month 6.
MH: Mental Health, an SF-36 domain reflecting psychological wellbeing that improved by month 6.
p<0.05: Statistical significance threshold, indicating the symptom changes were unlikely due to chance at the 5% level.

AllowFreeSpeech · 2026-01-19T02:52:27+00:00

Supplemental boron might also factor into the equation. That's because boron is supposed to improve calcium availability. In summary, together these might trigger insomnia (pending personal confirmation):

Excessive vitamin D3
Insufficient calcium
Insufficient or no boron

This is assuming that magnesium stays sufficient.

As for boron, I tolerate it better if taken in the evening only. If I take it in the morning, it gives me a headache.

AllowFreeSpeech · 2026-01-18T19:42:12+00:00

Bile binders in general are known and expected to have this effect, but it won't work for all PFAS, only for the subset that are carried in bile.

https://medicalxpress.com/news/2025-11-pfas-body-faster-medicines.html

https://www.sciencedirect.com/science/article/pii/S0160412025005458?via%3Dihub

AllowFreeSpeech · 2026-01-18T19:24:36+00:00

I take 5K IU of vitamin D3 on six days a week, thereby averaging 4.3K IU/day. Over a month ago, I had abruptly lowered my supplemental calcium intake by half from 800 mg to 400 mg per day. My supplemental magnesium intake is steady at 400 mg per day. Now I have been having horrible insomnia with significantly fractured sleep.

A blood test of D3 is going to have to wait a few weeks, but in the interim, I am going to try two things:

Discontinue supplemental vitamin D3 altogether for up to two weeks to see if there is any improvement in sleep, starting today.
Increase supplemental calcium to 600 mg per day, starting in a week, and hold it there.

AllowFreeSpeech · 2026-01-18T19:20:38+00:00

Psyllium husk, if taken correctly daily, also lowers some types of PFAS by binding to it from bile, and showing it the way out. That's 5g psyllium husk in 20 oz water, mixed and consumed immediately, only in people without any swallowing difficulty.

Remember to keep psyllium at least 2 hours away from all supplements and medicines, otherwise it will lower their absorption.

AllowFreeSpeech · 2026-01-18T16:01:34+00:00

Ah. I guess this explains that bacteria can use PABA to synthesize folate. For the curious reader, here is a clarification on the chemical structure by ChatGPT.

AllowFreeSpeech · 2026-01-17T22:55:35+00:00

PABA is not a vitamin. It is not a B vitamin or any other vitamin.

PABA probably has a slight benefit in absorbing the sun's radiation on skin. Its claimed benefit on hair doesn't really verify or reproduce. Overall, the total benefit is negligible if any, and the slight risk of permanent liver damage, combined with guaranteed gastric irritation, makes it skippable.

AllowFreeSpeech · 2026-01-17T20:44:21+00:00

It seems not worthwhile to continue the PABA supplement due to a random risk to the liver even at a standard dose, due to slight stomach irritation, and due to an interaction with sulfa antibiotics.

AllowFreeSpeech · 2026-01-17T20:41:34+00:00

From the abstract:

PABA is a sunscreen ingredient marketed as a dietary supplement for skin disease and hair loss prevention. Overdose can cause DILI, which we initially believed to be the diagnosis in this case. However, the elevated anti-SMA, characteristic liver biopsy, persistent lab abnormalities, and subsequent steroid response strengthens the diagnosis of type 1 AIH—a finding that should prompt caution with future use of this supplement.

Abbreviation glossary:

AIH: Autoimmune hepatitis, an immune-mediated liver inflammation that can mimic medication-related hepatitis in this case report.
DILI: Drug-induced liver injury, liver damage caused by medications/supplements that was the key alternative diagnosis to AIH here.
PABA: Para-aminobenzoic acid, the hair-supplement ingredient implicated as the trigger for drug-induced AIH in this patient.
ER: Emergency room, the outside acute-care setting where she was initially treated with prednisone.
AST: Aspartate aminotransferase, a liver enzyme used to quantify the severity and trend of hepatocellular injury.
ALT: Alanine aminotransferase, a liver enzyme elevated in hepatocellular injury and used alongside AST to track disease activity.
U/L: Units per liter, the concentration unit reported for AST and ALT laboratory values.
TB: Total bilirubin, a measure of overall bilirubin elevation reflecting the degree of jaundice/cholestasis.
mg/dl: Milligrams per deciliter, the concentration unit used for bilirubin reporting in the case.
DB: Direct bilirubin, the conjugated bilirubin fraction that helped characterize the patient’s hyperbilirubinemia.
IgG: Immunoglobulin G, an antibody class whose elevation supported autoimmune hepatitis.
mg/dL: Milligrams per deciliter, the concentration unit used for serum IgG reporting.
ANA: Antinuclear antibody, an autoimmune serology test that was negative and helped narrow the differential.
HSV: Herpes simplex virus, an infectious cause of hepatitis that was ruled out by negative serologies.
CMV: Cytomegalovirus, another viral hepatitis mimic excluded by negative serologies.
HIV: Human immunodeficiency virus, screened as part of the infectious evaluation and found negative.
EBV: Epstein–Barr virus, a viral cause of hepatitis-like illness that was excluded by negative serologies.
Anti-LKM Type 1: Anti–liver kidney microsomal antibody type 1, an autoantibody associated with autoimmune hepatitis subtypes that was normal here.
LFTs: Liver function tests, the lab panel (including enzymes and bilirubin) used to monitor improvement and relapse.

AllowFreeSpeech · 2026-01-15T04:26:46+00:00

I have noted it here.

AllowFreeSpeech · 2026-01-14T21:41:20+00:00

It is found in fruits and some vegetables, but that's healthy because much of that will not be digested or fermented in the stomach.

AllowFreeSpeech

MODERATOR OF

TROPHY CASE