Intrinsic Factor and low Vitamin B-12 levels Cognitive Impact

What is Intrinsic Factor?

Intrinsic factor (IF), also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the ileum of the small intestine.[5] In humans, the gastric intrinsic factor protein is encoded by the GIFgene.[6]:989


With CFS/ME, Lyme and other conditions being low in Vitamin B12, suggests that an issue with GIF could have developed. This may be due to an epigenetic event. The incidence of defects in the GIF Gene is very low.

However, wikipedia is incomplete, because it is not only parietal cells.

These findings demonstrate a potential for cellular expression of human intrinsic factor in nonparietal cells. Because such expression occurs normally at the margins of anatomical gastric regions, it suggests that local factors may influence expression of intrinsic factor.

Human gastric intrinsic factor expression is not restricted to parietal cells. [1996]

These data in humans with and without gastritis are consistent with the hypothesis that local factors influence ectopic gastric IF expression, arising from either the anatomical location, the focal inflammation, or both.

Production of ectopic gastric intrinsic factor in gastric mucosa of humans with chronic gastritis [2011]

The earliest recorded history of autoimmune gastritis can be traced to 1849 in London, when Thomas Addison described “a very remarkable form of anemia” later called pernicious (fatal) anemia (PA). This was followed by the recognition of a gastric mucosal defect suspected to have a nutritional basis, the discovery of the megaloblast that characterized the anemia, the insufficiency of a dietary extrinsic factor characterized as vitamin B12 (cobalamin), and a gastric-secreted intrinsic factor. Treatment with vitamin B12 proved curative. The link between PA and gastritis and atrophy was first confirmed histologically after immediate fixation of the stomach postmortem and later, in the 1940s, by peroral tube biopsy. The causes of gastritis remained enigmatic until the era of autoimmunity, when autoantibodies were detected first to gastric intrinsic factor and then to gastric parietal cells. Hints of a dichotomy in pathogenesis of gastritis were crystallized by the description in 1973 of Type A (Autoimmune) and Type B (later, Bacterial) gastritis.

Autoimmune gastritis: historical antecedents, outstanding discoveries, and unresolved problems. [2005]

Proton pump inhibitors also reduce the absorption of vitamin B(12) probably by inhibiting intragastric proteolysis 

Effect of proton pump inhibitors on vitamins and iron [2009]

 The results suggest that IF insufficiency may occur during cimetidine treatment in patients 

Effect of cimetidine on intrinsic factor secretion stimulated by different doses of pentagastrin in patients with impaired renal function. [1983]

Issues reported in the literature with low B12, includes:

  • “The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. Neurological involvement includes mainly combined spinal sclerosis, peripheral neuropathy and dementia. ” [2015]
  • “These symptoms seem to fall into several clinically separate categories: slow cerebration; confusion; memory changes; delirium, with or without hallucinations and/or delusions; depression; acute psychotic states; and (more rarely) reversible manic and schizophreniform states. ” [1988]

Bottom Line

From the literature, it is well established that one bacteria influences GIF, Helicobacter pylori. In terms of drugs that reduces GIF, we see these drugs impact a lot of bacteria families (linked to from drug below):

It appears that GIF production is influenced by the local environment/factors. An important factor for this is the microbiome – bacteria involved.


First choice is always to stop drugs that reduces GIF. Second choice, is to eliminate any known bacteria that reduces GIF, explicitly, testing for
Helicobacter pylori (you may lack symptoms and still have it). Third choice is supplementing with Vitamin B12.

Fourth choice (which may also impact the 2nd choice), probiotics that produces or processes B12.