Thiamine: Absorption, Transport, and What Happens Without It

Getting thiamine out of food

Raw fish, and food contaminated by certain bacteria, can contain thiaminases — enzymes that break down thiamine before the body ever gets to use it. This is thought to be part of why traditional diets built heavily around raw fish carry a real risk of thiamine deficiency. Ascorbic acid (vitamin C) is a documented inhibitor of thiaminase activity — reversible but strong — so its presence in the diet meaningfully blunts this degradation, though “inhibits” is the more accurate framing than “prevents” outright.

Absorption across the gut wall

Free thiamine is absorbed primarily in the jejunum, via a dual mechanism that depends on how much thiamine is actually present in the gut lumen:

• At high luminal concentrations, absorption is predominantly by simple passive diffusion.
• At low, physiological concentrations, absorption is an active, saturable, carrier-mediated process — but it’s sodium-independent, not sodium-dependent. At the brush border (apical) membrane, thiamine uptake occurs via a pH-sensitive thiamine/H⁺ antiport: an outwardly-directed proton gradient drives thiamine in, in an electroneutral exchange that doesn’t rely on the sodium gradient the way many other nutrient transporters do.

Once inside the enterocyte, thiamine is phosphorylated. Its onward transport out of the cell, across the basolateral membrane and into the bloodstream, is a separate and distinct process from brush-border entry — it isn’t the same H⁺-antiport mechanism, and its exact transporter has historically been less well characterised than the brush-border step, though older work in animal models found it to be ATP-dependent.

Chronic ethanol consumption impairs thiamine absorption at both steps — brush-border uptake and basolateral efflux — largely by reducing expression of the thiamine transporters themselves (THTR-1 and THTR-2) at the protein, mRNA, and transcriptional level. This is one of the central mechanisms behind thiamine deficiency in people who drink heavily, and it’s a whole-pathway effect rather than a block at just one membrane.

Thiamine in the blood

Circulating thiamine exists in three forms: free thiamine, thiamine bound to albumin, and thiamine monophosphate (TMP). Only free thiamine or TMP can cross cell membranes — the phosphorylated coenzyme forms cannot, which is part of how cells “trap” thiamine once they’ve taken it up and converted it.

Roughly 90% of the thiamine in blood is actually inside red blood cells rather than free in plasma. Transport into red blood cells is thought to occur by facilitated diffusion; transport into most other tissues is an active, energy-requiring process.

Storage and activation

The body holds a total of only around 30 mg of thiamine — a genuinely small reserve — distributed at relatively higher concentration in the liver, skeletal muscle, heart, kidney, and brain. Following absorption, most free thiamine is taken up by the liver and phosphorylated to its active coenzyme form, thiamine diphosphate (TDP). This conversion requires ATP and the enzyme thiamine pyrophosphokinase, found in the liver, brain, and other tissues.

TDP is the functional coenzyme form and is required for:

• Energy metabolism — the oxidative decarboxylation of pyruvate and α-ketoglutarate (i.e. as a cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase)
• Pentose and NADPH synthesis — as a cofactor for transketolase in the pentose phosphate pathway

The RDA for thiamine is in the order of 1 mg per day.

What happens without it

A decrease in the activity of thiamine-dependent enzymes limits the conversion of pyruvate to acetyl-CoA and the citric acid cycle’s ability to run, leading to a build-up of pyruvate and lactate. The resulting lactic acidosis is often accompanied by nausea, vomiting, and severe abdominal pain — a presentation described as gastrointestinal beriberi.

Wet (cardiac) beriberi presents with cardiovascular manifestations of deficiency: tachycardia, cardiac enlargement, severe peripheral oedema, dyspnoea, and — if untreated — congestive heart failure.

Cerebral beriberi can progress to Wernicke’s encephalopathy and, if that goes untreated, the irreversible neurological damage of Korsakoff’s psychosis — most classically seen in people with alcohol use disorder. Wernicke’s encephalopathy is thought to be significantly underdiagnosed, partly because its presentation overlaps with alcohol withdrawal/intoxication itself.

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References

1. National Institutes of Health, Office of Dietary Supplements. href=”https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/”>Thiamin — Health Professional Fact Sheet.
2. Linus Pauling Institute, Oregon State University. href=”https://lpi.oregonstate.edu/mic/vitamins/thiamin”>Thiamin.
3. Subramanya SB, Subramanian VS, Said HM. “Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process.” Am J Physiol Gastrointest Liver Physiol, 2010.
4. Dudeja PK, Tyagi S, Gill R, Said HM. “Evidence for a carrier-mediated mechanism for thiamine transport to human jejunal basolateral membrane vesicles.” Dig Dis Sci, 2003.
5. Rindi G, Laforenza U. “Thiamine Intestinal Transport and Related Issues: Recent Aspects.” Exp Biol Med, 2000.
6. Balaghi M, Wagner C. “Dietary factors potentially impacting thiaminase I-mediated thiamine deficiency.” Sci Rep, 2023.