A blog by Ronny Allan

Neuroendocrine Tumours (NETs) – Vitamin D (Cholecalciferol / Ergocalciferol)

Neuroendocrine Tumours (NETs) – Vitamin D (Cholecalciferol / Ergocalciferol)

Vitamin D is a fat-soluble vitamin (along with A, E and K).  Fat-soluble vitamins are absorbed with the other fats from the food you eat.  Fat-soluble vitamins can stay in your body for a while. When they’re stored in your body’s fat, they can be stored for up to 6 months until your body needs them.  Vitamin D doesn’t occur naturally in most foods. Instead, your body produces vitamin D when sunlight directly hits your skin (not through a window).  

Vitamin D deficiency is demonstrably more common in people with neuroendocrine tumours (NETs) — but that does not automatically mean your deficiency is caused by NET. Vitamin D deficiency is widespread in the general population, particularly in northern latitudes, older adults, and people with limited sun exposure. However, NET patients accumulate multiple, well‑recognised risk factors, and 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, malabsorption, pancreatic insufficiency, and somatostatin analogue therapy (SSA) are repeatedly identified as contributors. Although NET‑specific prevalence studies are limited, broader GI cancer data show Vitamin D deficiency in 40–60% of patients, and the mechanisms in NETs are biologically identical.

 

How NET biology and treatment can lead to Vitamin D deficiency

1. Primary tumour location

Pancreatic and duodenal NETs (sporadic and MEN1)

Pancreatic and duodenal NETs share the same mechanism for Vitamin D deficiency: fat malabsorption.

This may occur due to:

  • Pancreatic exocrine insufficiency (PEI)
  • Reduced bile flow
  • Somatostatin analogue therapy (SSA)
  • Whipple or distal pancreatectomy
  • Rapid intestinal transit

Because Vitamin D is fat‑soluble, anything that impairs fat digestion or absorption can reduce Vitamin D levels.

This mechanism applies equally to:

  • Sporadic pancreatic NETs
  • Sporadic duodenal NETs
  • MEN1 pancreatic NETs
  • MEN1 duodenal NETs

Surgery is surgery — the physiological consequences are the same whether the tumour is sporadic or hereditary.

 

Small intestine NETs (midgut NETs)

Small intestine NETs also carry a significant risk, but through different mechanisms.

Why:

  • Ileal resection or right hemicolectomy reduces bile acid recycling.
  • Bile acids are essential for absorbing fat‑soluble vitamins, including Vitamin D.
  • Carcinoid syndrome diarrhoea accelerates transit, reducing absorption time.
  • Bile acid malabsorption is common and often under‑diagnosed.

The mechanism here is fat malabsorption, which is central to Vitamin D physiology.

 

Gastric NETs (Type I autoimmune gastritis)

Gastric NETs have a smaller but still relevant role.

Why:

  • Autoimmune atrophic gastritis reduces stomach acid.
  • Low acid can impair the release of Vitamin D from food.
  • Autoimmune clustering (thyroid, parietal cell antibodies) is associated with lower Vitamin D levels in population studies.

This is a minor mechanism compared to pancreatic or small intestine NETs.

 

Pulmonary NETs

Pulmonary NETs do not directly affect Vitamin D physiology because they do not involve the digestive tract. However, many people with lung NETs receive somatostatin analogue (SSA) therapy, and SSAs can influence Vitamin D levels through their effects on the gut and biliary system. SSAs reduce gallbladder motility and increase the risk of gallstones, and some patients eventually require gallbladder removal. After cholecystectomy, a subset of people experience reduced fat absorption or bile acid–related diarrhoea, which can lower Vitamin D and other fat‑soluble vitamins.  These effects are treatment‑related, not tumour‑related.

Endocrine syndromes and Vitamin D

– MEN1 – Parathyroid tumours (a separate hormonal mechanism)

People with MEN1 frequently develop primary hyperparathyroidism, which raises calcium levels and suppresses Vitamin D activation. This leads to low or low‑normal Vitamin D for hormonal reasons, not malabsorption.

This mechanism is independent of the pancreatic/duodenal NET mechanism described above.

Supplementation can help bone health but must be monitored carefully to avoid worsening hypercalcaemia.

 

– Cushing’s syndrome (NET‑related and pituitary causes)

Cushing’s syndrome can occur when a tumour produces excess ACTH (ectopic ACTH syndrome) or when a pituitary tumour produces excess ACTH (Cushing’s disease). Chronic cortisol excess:

  • Suppresses Vitamin D activation
  • Reduces calcium absorption
  • Accelerates bone loss

This is a hormonal mechanism, not a malabsorption mechanism.

 

2. Treatment‑related causes

Somatostatin analogues (SSA)

(Octreotide / Lanreotide)

SSAs are a universal risk factor for Vitamin D deficiency, regardless of tumour site.

Why:

  • Reduce pancreatic enzyme secretion
  • Reduce gallbladder emptying
  • Slow intestinal motility
  • All of which impair fat digestion and absorption

Because Vitamin D is fat‑soluble, SSA therapy is a well‑recognised contributor to deficiency.

 

Surgery

Several NET‑related surgeries increase Vitamin D deficiency risk:

  • Ileal resection → reduced bile acid recycling → impaired fat absorption
  • Right hemicolectomy → partial loss of terminal ileum → reduced bile acid pool
  • Whipple / pancreatic resection → pancreatic insufficiency + altered acid → impaired fat digestion
  • Gastrectomy → reduced acid → impaired release of Vitamin D from food

These mechanisms are all fat‑absorption‑related, which is central to Vitamin D physiology.

 

3. Secondary physiological effects

Chronic diarrhoea

Seen in:

  • Serotonin‑producing midgut NETs
  • Post‑surgical states
  • SSA therapy

Why:

  • Faster transit reduces contact time for fat‑soluble vitamin absorption
  • Vitamin D is particularly vulnerable
 

Bile acid malabsorption

Common after ileal resection.

Why:

  • Bile acids are essential for absorbing Vitamin D
  • Loss of bile acids → fat malabsorption → Vitamin D deficiency
  • Often under‑diagnosed unless specifically tested (e.g., SeHCAT)
 

Pancreatic exocrine insufficiency (PEI)

A major cause of Vitamin D deficiency in pancreatic NET patients.

Why:

  • Without lipase and other enzymes, fat digestion is impaired
  • Vitamin D cannot be absorbed effectively
  • Requires adequate PERT for correction
 

Reduced sun exposure

Common in NET patients due to:

  • Fatigue
  • Reduced outdoor activity
  • Long treatment cycles
  • Frequent hospital visits

This reduces natural Vitamin D synthesis.

 

Autoimmune clustering

Relevant mainly in Type I gastric NETs.

Why:

  • Autoimmune conditions are associated with lower Vitamin D levels
  • Mechanism is indirect but recognised
 

4. Practical implications for NET care

Although NET‑related mechanisms can increase the risk of deficiency, some people may also have general population risk factors such as diet, age, reduced sun exposure, or other medical conditions. However, we know that Vitamin D deficiency is common but often under‑recognised in  some NET patients.

Symptoms can be subtle:

  • Fatigue
  • Muscle weakness
  • Bone pain
  • Low mood
  • Increased falls
  • Worsening osteoporosis or osteopenia

5. Testing

The standard test is 25‑OH Vitamin D, which measures total Vitamin D from all sources (sunlight, food, supplements). This includes both:

  • 25‑OH Vitamin D3
  • 25‑OH Vitamin D2

Most patients only need the total value, not the breakdown.

Typical interpretation (varies by lab):

  • < 30 nmol/L → deficient
  • 30–50 nmol/L → insufficient
  • 50–125 nmol/L → adequate

Patients with malabsorption or on SSAs may need annual or semi‑annual monitoring.

 

6. Vitamin D2 vs Vitamin D3 — if I need supplements, which one should I take?

Vitamin D comes in two main forms:

  • Vitamin D2 (ergocalciferol) — plant‑derived
  • Vitamin D3 (cholecalciferol) — animal‑derived or synthesised in the skin from sunlight

Although both forms can raise Vitamin D levels, they are not equally effective, and this matters for NET patients who may already struggle with absorption.

Why Vitamin D3 is preferred

Most clinicians recommend Vitamin D3 for several reasons:

1. D3 is the form your body naturally makes

When sunlight hits the skin, the body produces cholecalciferol (D3) — not D2. This makes D3 more biologically familiar and easier to convert into the active hormone.

2. D3 raises blood levels more effectively

Multiple studies show that D3:

  • Raises 25‑OH Vitamin D levels higher
  • Maintains those levels for longer
  • Is more stable in the bloodstream

D2 is less potent and breaks down more quickly.

3. D3 is better stored in body tissues

Because Vitamin D is fat‑soluble, it is stored in fat and muscle. D3 binds more effectively to Vitamin D–binding proteins, making it more available to the body.

4. D3 is more reliable for people with malabsorption

This is particularly relevant for NET patients with:

  • Pancreatic exocrine insufficiency (PEI)
  • Ileal resection
  • Bile acid malabsorption
  • Chronic diarrhoea
  • SSA‑related fat malabsorption

D3 is simply more efficient at raising levels when absorption is compromised.

5. When would D2 used instead?

D2 is sometimes used in:

  • High‑dose prescription regimens
  • Vegan supplementation
  • Certain hospital protocols

But even in these cases, many clinicians might prefer D3 because of its superior performance.

 

7. Can I take too much Vitamin D — and does it matter?

Vitamin D is fat‑soluble, which means the body stores it rather than excreting excess amounts in urine. Because of this, it is possible to take too much — but genuine Vitamin D toxicity is rare and usually linked to very high‑dose supplements taken for long periods without monitoring.

Important: Vitamin D toxicity does not come from sunlight or food. It comes almost exclusively from supplements.

What happens if Vitamin D is too high?

Excess Vitamin D can raise calcium levels in the blood (hypercalcaemia), which may cause:

  • Thirst and dehydration
  • Nausea or vomiting
  • Constipation
  • Confusion
  • Kidney stones
  • Kidney damage (in severe cases)

These symptoms overlap with many other conditions, so blood tests are essential for diagnosis.

Who is more vulnerable?

Most NET patients are not at increased risk of Vitamin D toxicity. However, caution is sensible in:

  • People with kidney disease
  • Those already taking high‑dose Vitamin D
  • Anyone on calcium supplements
  • Patients receiving medications that affect calcium balance

NET‑specific treatments (e.g., SSAs) do not normally increase Vitamin D toxicity risk.

What levels are considered too high?

Laboratories vary, but toxicity is generally associated with:

  • 25‑OH Vitamin D > 250 nmol/L
  • Sustained high calcium levels

Most clinicians aim for a safe range of 50–125 nmol/L.

Practical advice

  • Always check your levels before starting supplements.
  • Avoid high‑dose “loading” regimens unless prescribed.
  • If you take pancreatic enzymes (PERT), remember that improved fat absorption may increase Vitamin D uptake — so levels can rise once PERT is optimised.
  • Regular monitoring is sensible for anyone with malabsorption, bowel surgery, or long‑term SSA therapy.

8. General population factors affecting Vitamin D

Not every Vitamin D deficiency in a NET patient is caused by the tumour or its treatments. Many people — with or without NETs — have low Vitamin D due to common lifestyle, environmental, or medical factors. These can overlap with NET‑related mechanisms and sometimes explain low levels even when the tumour is stable.

Reduced sunlight exposure

Limited outdoor time, high sunscreen use, or living in northern latitudes reduces Vitamin D production.

Ageing

Older adults produce less Vitamin D in the skin and often spend less time outdoors.

Dietary intake

Vitamin D is found in only a few foods (oily fish, fortified products, egg yolks). Many people do not consume enough to maintain adequate levels.

Higher body weight

Vitamin D is fat‑soluble and becomes sequestered in adipose tissue, lowering circulating levels.

Skin pigmentation

People with darker skin require more sunlight to produce the same amount of Vitamin D as those with lighter skin.

Medical conditions unrelated to NETs

Chronic kidney disease, liver disease, coeliac disease, inflammatory bowel disease, and certain medications (e.g., anticonvulsants, glucocorticoids) can reduce Vitamin D levels.

Seasonal variation

Levels naturally fall in late winter and early spring when sunlight exposure is lowest.

9. Personal note

Always speak to your specialist before taking vitamin and mineral supplements — you may not need them if your levels are normal.  Many NET patients assume Vitamin D deficiency is inevitable, but with proper monitoring and management (including PERT where appropriate), levels can remain stable.

A warning on taking vitamins and minerals generally.  I very often see patients discussing this on my public pages and in my private group.  I just wanted to say that you must always take advice from a professional, just because one patient takes a vitamin ‘x’ or mineral ‘y’, that does not mean you should take it too.  

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

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nutritional support
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Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.   

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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By Ronny Allan

Ronny Allan is a 3 x award-winning accredited patient leader advocating internationally for Neuroendocrine Cancer and all other cancer patients generally. Check out his Social Media accounts including Facebook, BlueSky, WhatsApp, Instagram and and X.

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