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Pancreatic Neuroendocrine Tumor : A Rare Cancer

Feb 13, 2021

Highlights

A nutritional intervention including the supplementation of Vitamin D, capsaicin, berberine, resveratrol and EGCG, and intake of foods such as alfalfa, turnip, allspice, mulberry and kiwi may have potential benefits in pancreatic neuroendocrine tumor (PNET) by alleviating symptoms, improving quality of life or treatment outcomes. However, the intake of foods such as anise, corn, currant, margarine and cherry, and supplements such as cinchona, eleuthero, feverfew, poppy and clove may not help these patients. Drinking alcohol and eating obesity-causing foods such as processed meat, red meat, sugary beverages, and margarines may increase the risk of this cancer. Additionally, pancreatic neuroendocrine tumor patients should avoid amine rich foods and spicy foods if experiencing carcinoid syndromes. Hence, following a personalized nutrition plan customized for the specific cancer type and treatment becomes crucial to gain benefits and stay safe.

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What are Pancreatic Neuroendocrine Tumors (Pancreatic NET or PNET)?

Neuroendocrine cells are nerve-like cells, as they receive signals from the nervous system, and in response, release hormones just like endocrine cells. Neuroendocrine tumors/NETs are rare cancers that develop in the neuroendocrine cells. One of the most common neuroendocrine tumors is Pancreatic Neuroendocrine Tumor (PNET).

Pancreatic Neuroendocrine Tumors (PNET) are a rare type of pancreatic cancer, which occurs in the hormone-producing cells of the pancreas. It accounts for about 7% of all cancers that develop in the pancreas. The neuroendocrine cells in the pancreas are present in small clusters called islets of Langerhans which can make hormones and release them into the blood. Hence, pancreatic neuroendocrine tumors also known as Islet Cell Tumors.

The incidence of pancreatic neuroendocrine tumors is low with only 0.8 per 100000 people per year. According to the American Cancer Society, in 2021, around 4200 people may be newly diagnosed with pancreatic neuroendocrine tumors in the United States. Pancreatic NETs are commonly diagnosed in older people aged above 60. PNET is slightly more common in men than women.

Symptoms, treatment and diet for pancreatic neuroendocrine tumor (PNET)

What are the Risk Factors of Pancreatic Neuroendocrine Tumors?

Some of the common risk factors of pancreatic neuroendocrine tumors include:

  • Drinking alcohol
  • Smoking
  • Inherited genetic conditions such as :
    • Neurofibromatosis type 1 caused by mutations of a gene called NF1 
    • Multiple endocrine neoplasia type I (MEN1) caused by mutations of a gene called MEN1 
    • Von Hippel-Lindau (VHL) syndrome caused by mutations of a gene called VHL 
  • Diabetes
  • Long-term inflammation of the pancreas

What are the Symptoms of Pancreatic Neuroendocrine Tumor/PNET?

There are two types of pancreatic neuroendocrine tumors.

  • Non-functional pancreatic neuroendocrine tumors 
  • Functional pancreatic neuroendocrine tumors

Non-functional pancreatic neuroendocrine tumors may not cause any symptoms in the initial stages and may grow quite large before they are diagnosed. In this case, the signs and symptoms may be shown only when the tumor grows. However, functional tumors produce hormones such as gastrin, insulin, and glucagon, that cause signs and symptoms.

Some of the symptoms of pancreatic neuroendocrine tumors include:

  • Jaundice – Yellowing of your skin or eyes
  • Abdominal or back pain
  • Stomach ulcers
  • Lump in the belly
  • Indigestion
  • Diabetes
  • Heartburn
  • Weakness or Fatigue
  • Constipation
  • Low blood sugar
  • Weight loss
  • Diarrhea

What are the Treatment Options for Pancreatic Neuroendocrine Tumors?

Treatment for pancreatic neuroendocrine tumor may be decided based on different factors such as cancer type, the extent of spread and stage of the cancer, medical history and general health of the patient.

There are different types of treatment options available for patients with pancreatic neuroendocrine tumors. Following are some of the treatment options for pancreatic NETs:

  • Surgery
  • Chemotherapy
  • Hormone therapy
  • Targeted therapy
  • Supportive care
  • Chemoembolization (minimally invasive procedure to restrict a tumor’s blood supply)

What is the Role of Diet/Foods in Pancreatic Neuroendocrine Tumors?

While managing pancreatic neuroendocrine tumors, the therapeutic approach should also be supported by a well-balanced diet which includes the right foods and supplements to alleviate issues associated with the symptoms, improve the quality of life and treatment outcomes.

One should also be careful while selecting the foods and supplements, as some foods may trigger or worsen the symptoms and may also have a negative impact on treatment outcomes and quality of life.

1. Vitamin D supplementation may be beneficial for Patients with Pancreatic NETs

Different studies have shown that a majority of patients with pancreatic neuroendocrine tumors have Vitamin D deficiency. 

In a recent study done on 138 patients with gastro- entero-pancreatic neuroendocrine tumors by the researchers from the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Italy, they found that 94 patients were vitamin D deficient. They also found that supplementing Vitamin D played an important role in the correction of 25-OH vit D values, and influenced the clinical outcomes in the pancreatic neuroendocrine tumor patients. (Sara Massironi et al, Neuroendocrinology., 2017)

Another study done by the researchers from Coventry, United Kingdom also found that advising patients to increase Vitamin D intake using over-the-counter preparations significantly improved the status of Vitamin D deficiency in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). They also did mention that Vitamin D deficiency was known to be linked to a reduced overall survival in patients with GEP-NET. (Helen L Robbins et al, Nutr Cancer., 2018)

Hence, a nutritional intervention involving Vitamin D supplementation may be beneficial in improving treatment outcomes in patients with Pancreatic Neuroendocrine Tumors.

2. Capsaicin may Help in Controlling Pancreatic NETs

Capsaicin is the hot pungent ingredient found in chili peppers. A laboratory study done by the researchers from the Charité-University Medicine Berlin in Germany and Poznań University of Life Sciences in Poland evaluated the effect of capsaicin on proliferation and apoptosis in pancreatic neuroendocrine cancer cells. Their study found that Capsaicin could reduce proliferation, and induce apoptosis or cell death of these neuroendocrine cells. (M Skrzypski et al, Cell Signal., 2014)

The experimental findings do suggest that intake of Capsaicin may be beneficial for patients with Pancreatic Neuroendocrine Tumors. These findings are yet to be validated in human trials.

However, sometimes patients with neuroendocrine tumor of the gastrointestinal tract or an NET with liver metastasis may have carcinoid syndrome, which is a collection of symptoms including diarrhoea, loss of appetite, flushing of the skin, faster heart rate and breathlessness. This happens due to the release of serotonin directly in the bloodstream, which otherwise used to be degraded by the liver. Capsaicin may not be the right choice for patients with these symptoms.

3. Berberine, Resveratrol, Capsaicin and EGCG may be Beneficial for Patients With Pancreatic NETs

Metformin, a commonly used anti-diabetic drug, is associated with a longer progression-free survival of patients with diabetes and pancreatic neuroendocrine tumors who received everolimus and/or somatostatin analogues as treatments. (Sara Pusceddu et al, Gastroenterology., 2018) Studies have shown that metformin does this by activating a kinase called AMP-activated protein kinase (AMPK), which can regulate cellular energy homeostasis.

In a review published by The Fourth Military Medical University in China, they had highlighted that similar to metformin, other bioactive compounds such as resveratrol (commonly found in grapes), berberine (commonly found in barberry), epigallocatechin gallate/EGCG (commonly found in green tea) and capsaicin (commonly found in chilli peppers), may also exhibit anti-cancer effects by activating AMPK. (Suning Chen et al, Mini Rev Med Chem., 2014)

Hence, intake of berberine, resveratrol, capsaicin and EGCG may be beneficial for patients with pancreatic neuroendocrine tumors.

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4. Obesity may Increase the Risk of Pancreatic NETs

In a study published in 2018 by few researchers from Portugal, data from 96 patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors were analyzed. The study found that visceral obesity was associated with an increased risk of Gastro-Entero-Pancreatic Neuroendocrine Tumors. (Ana P Santos et al, Cancers (Basel)., 2018)

Hence, obesity-causing foods such as processed meat, red meat, sugary beverages, fried foods and margarines should be avoided to reduce the risk of this cancer.

5. Foods that may Aggravate Carcinoid Symptoms in Neuroendocrine Tumors

Avoid Amine Rich Foods : Foods rich in amines including tyramine, dopamine and histamine may lead to carcinoid symptoms such as flushing and diarrhoea in neuroendocrine tumors. (Barbara Altieri et al, Rev Endocr Metab Disord., 2018; Anezka C Rubin de Celis Ferrari et al, Clinics (Sao Paulo)., 2018)

Following are examples of foods with very high amounts of amines

  • Alcoholic beverages
  • Aged cheeses
  • Smoked, salted, or pickled fish and meats
  • Yeast extracts
  • Fermented foods such as tofu, miso, sauerkraut, fish sauce, soy sauce

Following are examples of foods with moderately high amounts of amines:

  • Caffeinated drinks (sodas and coffee)
  • Chocolate
  • Avocados
  • Bananas
  • Raspberries
  • Nuts (Brazil nuts, peanuts, coconuts)

Avoid drinking alcohol : Different studies have shown that drinking alcohol may increase the risk of pancreatic neuroendocrine tumors. (Sven-Petter Haugvik et al, Neuroendocrinology., 2015; Qiwen Ben et al, Sci Rep., 2016)

Avoid spicy foods: Foods such as black pepper, chillies and cayenne pepper may trigger flushing or induce diarrhea in some neuroendocrine tumor patients.

Also, do note that, taking high fiber foods may be beneficial for cancer patients. Eating smaller, but more frequent meals should also help in reducing problems related to digestion. 

6. Other Foods Associated with Pancreatic Neuroendocrine Tumor (PNET)

When it comes to pancreatic neuroendocrine tumor care and prevention, taking foods such as alfalfa, turnip, allspice, mulberry and kiwi may be beneficial. However, intake of foods such as anise, corn, currant, margarine and cherry, and supplements such as cinchona, eleuthero, feverfew, poppy and clove may not help.

Conclusion

While managing pancreatic neuroendocrine cancers, nutritional interventions and lifestyle modifications should be an integral component. Taking the right diet may help in improving the symptoms, quality of life and nutritional status of the pancreatic neuroendocrine patients while undergoing treatment and may improve treatment outcomes. Different studies suggest that Vitamin D, Capsaicin, Berberine, Resveratrol and EGCG supplementation may have potential benefits in pancreatic neuroendocrine tumor (PNET). However, neuroendocrine tumor patients with carcinoid symptoms should avoid amine rich foods, drinking alcohol and eating spicy foods. Additionally, obesity-causing foods such as processed meat, red meat, sugary beverages, fried foods and margarines should be avoided to reduce the risk of this cancer.


Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.


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