Neuroendocrine Tumours (NET) – Vitamin B12 (Cobalamin)

Vitamin B12 deficiency is demonstrably more common in people with neuroendocrine tumours (NETs) – what that means is there is a chance your deficiency as a NET patients may not be related to your NET. However, it’s a fairly common comorbidity reported in NET patients and it’s important to note the mechanisms differ by primary tumour location, tumour type, treatments, and secondary physiological effects. The strongest evidence comes from gastrointestinal NET cohorts, where bowel resection, diarrhoea, and somatostatin analogue therapy (SSA) are repeatedly identified as contributors.

A 2022 single‑centre review found B12 deficiency in 19% of NET patients, with a further 23% borderline, and highlighted that risk factors were often present even when B12 was not measured. See 1. Prevalence of vitamin B12 deficiency in neuroendocrine tumour-Single Centre Experience

How NET biology and treatment lead to B12 deficiency

1. Primary tumour location

Different NET sites affect B12 absorption through distinct mechanisms:

Ileal NETs (midgut NETs)
- The terminal ileum is the exclusive site of B12–intrinsic factor absorption.
- Ileal resection, common in midgut NET surgery, directly reduces B12 uptake.
- Chronic diarrhoea from serotonin‑producing tumours can accelerate transit and reduce absorption.
Gastric NETs
- Autoimmune atrophic gastritis (Type I gastric NETs) reduces intrinsic factor production.
- This mirrors the mechanism of pernicious anaemia.
- NICE notes that autoimmune gastritis is a recognised cause of B12 deficiency and a risk factor for gastric cancer surveillance .
Pancreatic NETs
- Exocrine insufficiency after Whipple surgery or pancreatic resection reduces digestion and release of B12 from food proteins.
- Post‑operative changes in gastric acid secretion also impair B12 liberation.
Pulmonary NETs
- Less direct impact on B12 physiology.
- Deficiency is still reported, often linked to SSA therapy or treatment‑related diarrhoea rather than tumour biology.

Treatment‑related causes

1. Somatostatin analogues (SSA)

SSAs reduce pancreatic secretions, slow gallbladder emptying, and alter gut motility.
They can impair absorption of multiple micronutrients, including B12.
In the 2022 NET cohort, 10 of the 12 B12‑deficient patients were on SSA therapy.

2. Surgery

Ileal resection → loss of B12 absorption site.
Right hemicolectomy → may remove part of the terminal ileum.
Whipple/pancreatic resection → reduced intrinsic factor, reduced gastric acid, and pancreatic insufficiency.
Gastrectomy or partial gastrectomy → reduced intrinsic factor and acid production.

3. Post‑operative diarrhoea and malabsorption

Common after small bowel or pancreatic surgery.
Accelerated transit reduces contact time for B12 absorption.

Secondary physiological effects

1. Chronic diarrhoea

Seen in functional midgut NETs (serotonin‑producing).
Leads to malabsorption of water‑soluble vitamins, including B12.

2. Bacterial overgrowth

Drugs such as somatostatin analogue therapy (SSA) can slow gut movement and reduce digestive juices. In people who have also had bowel surgery or already have slow bowel, this may allow extra bacteria to grow in the small intestine (called SIBO), which can further reduce absorption of vitamins like B12.
ENETS Research – Assessment of Small Intestinal Bacterial Overgrowth (SIBO) in NET Patients Abstract #1698 suggested Abdominal surgery, especially right hemicolectomy increases the likelihood of a positive glucose HBT. Glucose may still be sensitive in those with risk factors for distal SIBO. Additional lactulose use with H2 and CH4 measurement increases the sensitivity in diagnosing SIBO. Click here.
Bacteria consume B12, lowering host levels. Click here.

3. Autoimmune clustering

Particularly relevant in Type I gastric NETs, which arise from autoimmune gastritis.
Autoimmune gastritis reduces intrinsic factor and parietal cells, directly causing B12 deficiency. Again see Type I gastric NETs

Practical implications for NET care

B12 deficiency is common but under‑screened in NET patients.
Symptoms may be subtle (fatigue, neuropathy, cognitive changes).
Standard serum B12 can be falsely normal; holotranscobalamin (HoloTC) is more accurate and recommended in borderline cases (135–300 ng/L) .
Risk is highest in:
- Anyone with ileal resection
- Patients on long‑term SSA therapy
- Gastric NET patients with autoimmune gastritis
- Post‑Whipple or pancreatic resection patients
- Those with chronic diarrhoea and/or SIBO

A non‑obvious insight

The combination of SSA therapy + bowel resection + diarrhoea creates a multiplicative risk. Many NET patients accumulate these factors over time, which explains why deficiency often appears years after diagnosis rather than immediately.

Always speak to your specialist before taking vitamin and mineral supplements.

Can I take too much? Read more here.

Read more on Vitamins and Minerals at risk for NET patients. Click here or on the graphic below