Despite learning early on in my journey that nutrition was going to be a challenge, I sensed the initial focus of my treatment was on getting rid of as much tumour bulk as possible and then controlling (stabilising) the disease through monitoring and surveillance. Clearly I'm happy about that! However, it eventually became clear that the impact of this constant treatment/controlling, meant that some of the less obvious signs of nutrient deficiency were potentially being missed.
This is one of the key reasons I believe there is a gap in specialist follow on support for Neuroendocrine Cancer patients - at least in the UK. As I said in blog post 'I may be stable but I still need support', Neuroendocrine Cancer patients need specialist dietary and nutritional advice covering a much wider spectrum than most cancer patients. This is not just about what foods to avoid or eat in moderation, this is also about:
a. receipt of post surgical/treatment advice,
b. early knowledge and countermeasures for the side effects of ongoing and long-term treatment,
c. the intelligent use of supplements where they are applicable,
d. how to combat, treat or offset malabsorption and nutrient deficiencies caused by the complexities of their cancer and any treatment given.
e. how to deconflict these side effects with those of the various syndromes which can sometimes accompany Neuroendocrine Cancer.
Even those patients with very healthy diets can still succumb to these issues. Looking at the vast number of forum posts on this subject, perhaps this is also a problem outside of UK?
In early 2011, shortly after my first major surgery and commencement of my monthly somatostatin analogue - Lanreotide (Somatuline), I started to notice a number of issues developing. I carefully searched for clues and I could see that some of my issues pointed to side effects from treatment (both from surgery and somatostatin analogues) and potentially some vitamin and mineral deficiencies. I had already been taking an 'over 50' multivitamin tablet for some time before I was diagnosed and assumed I was already covered. Having analysed the issues I was experiencing at the time, I was specifically targeting B12 and my initial test score was just in range (i.e borderline). Surprisingly my multivitamin B12 content was 400% RDA - yet my blood test was borderline.
I later attended a fantastic patient day where I was introduced to the UK's solitary Neuroendocrine Cancer specialist dietician. This subject was a revelation for me and I was alerted to the possibility that other vitamins and minerals could be at risk due to a combination of surgery and/or treatment, in particular the fat soluble vitamins A, D, E, K. Following a hastily arranged series of blood tests, I found my Vitamin D was insufficient and this has now been resolved through additional supplementation and more effort to absorb it through conventional means (i.e. the sun!).
I'm now on top of this issue through learning, understanding and basically becoming my own advocate. Please note this is a massive subject and the amount of information on the internet can be overwhelming. Additionally, it is not an exact science and not everything will apply to every person. Personally I would stick to sites where the advice is given by a nutritionist/dietician who is also experienced with Neuroendocrine Cancer.
I'm thankful to Tara Whyland who is an Oncology Dietician specialising in Neuroendocrine Cancer at the Royal Free Hospital. Her research, advice and raising of these issues at patient meetings has been invaluable. As the only specialist in the UK (that I know of), she gets a lot of queries! If you're on twitter, you can follow Tara here:
Even though I've had to limit this post to vitamin and mineral issues, it's still much larger than what I normally produce. Consequently, I'm planning further blogs on associated and overlapping subjects.
In the meantime, I'm very grateful to Tara for the input below:
NET Patients are at Risk of Deficiencies
Over the past few years I have become more aware of vitamin and mineral deficiencies in NET patients, and the impact these can have on health and quality of life. When the focus of NET treatment is on eradicating and controlling the disease, the impact on nutrition, apart from obvious weight loss, means less obvious signs of micronutrient deficiency can be missed. Below is a list of nutrients which are those most at risk of becoming low enough to cause problems. It is important that the treatment of these deficiencies is discussed with your NET team so they can prescribe suitable doses.
Magnesium blood tests are an unreliable measurement and there is no way of accurately measuring body stores.
Magnesium is a vital mineral required for the function structure of the human body. Prevalence of low blood magnesium levels varies from 7% to 11% in hospital patients and clinical magnesium deficiency is frequently observed in conditions causing steatorrhoea or severe chronic diarrhoea, and the degree of magnesium depletion correlates with the severity of diarrhoea and stool fat content. Signs of deficiency include low energy, fatigue, weakness, PMS, menstrual cramps, hormonal imbalance, insomnia, bone mineral density loss, muscle tension, spasms, cramps, cardiac arrhythmia, headaches, anxiousness, nervousness and irritability. If you think you could be deficient you must ensure you consume enough magnesium (375mg per day).
Zinc levels are best measured using a combination of blood serum and urinary excretion levels.
Zinc affects the human body through a large number of channels affecting not only cell division, protein synthesis and growth, but also gene expression and a variety of reproductive and immunologic functions. Zinc deficiency is common in undernourished patients. The absence of sufficient levels of zinc in the human body is associated with a large number of adverse health outcomes, including lower immunity, alopecia, tiredness and impaired wound healing. If you are at risk of deficiency make sure you consume enough zinc (10mg per day). If you are clinically deficient your diet must be supplemented.
Iron deficiency (hypoferremia) and clinical iron deficiency anaemia is easily measured with a simple blood test.
Iron is essential for the formation of haemoglobin in red blood cells which binds oxygen and transports it around the body. Iron is also an essential component in many enzyme reactions and has an important role in the immune system. In addition, it is required for normal energy metabolism and for the metabolism of drugs and foreign substances that need to be removed from the body. Lower iron levels are common in NET patients and there may be several causes of this. Poor iron intake, dietary iron absorption-regulating factors (e.g., vitamin C and copper) or iron distribution factors (e.g. vitamin A), are believed to be causes. Patients may also lose iron due to blood loss from the bowel in intestinal or rectal NETs or after surgery. It may also be possible that diarrhoea in NETs causes malabsorption of iron in the intestine too. Symptoms include tiredness, paleness, thinning hair, impaired immunity and feeling breathless. If you are at risk of having lower than normal iron levels you must consume enough iron (14mg per day). If you are clinically deficient your diet must be supplemented.
Diagnosis of copper deficiency is based on low serum levels of copper and ceruloplasmin, although these tests are not always reliable.
Copper is an essential trace mineral that is required for human health. This micronutrient is necessary for the proper growth, development, and maintenance of bone, connective tissue, brain, heart, and many other body organs. Copper is involved in the formation of red blood cells, the absorption and utilization of iron and the synthesis and release of life-sustaining proteins and enzymes. These enzymes in turn produce cellular energy and regulate nerve transmission, blood clotting, and oxygen transport. Copper stimulates the immune system to fight infections, to repair injured tissues, and to promote healing. Copper also has an antioxidant effect against oxidative stress. Gastrointestinal surgery can lead to malabsorption of copper and other micronutrients. Long term malabsorption of food from the gastrointestinal tract can also lead to copper deficiency which puts many more NET patients at risk. Symptoms of deficiency include neutropenia, impaired bone calcification, myelopathy, neuropathy, and hypochromic anemia not responsive to iron supplements. If you are at risk of lower than normal levels of copper you must consume enough (1mg per day). If you are clinically deficient your diet must be supplemented.
Selenium levels are measured using plasma selenium blood tests.
Selenium is an essential micronutrient in humans and functions in many biochemical pathways. Proposed antioxidant pathways of selenium, include the repair and prevention of oxidative damage, alteration of metabolism of carcinogenic agents, regulation of immune response and repair of DNA damage. It works alongside vitamin E and selenium levels are often low during cancer and in patients on long-term intravenous nutrition. Symptoms of deficiency include muscle pain and tenderness. Everyone is required to have 55 µg a day and if you are clinically deficient your diet will need to be supplemented.
Water Soluble Vitamins
Thiamine is not usually tested as diagnosis is based on symptoms and a trial of thiamine supplementation. If a doctor is unsure, they will measure erythrocyte transketolase activity and run a 24-hour urinary thiamine excretion.
Vitamin B1, or thiamine is an essential B vitamin which is required for the breakdown of sugars and amino acids. Absorption of thiamine is greatest in the jejunum and ileum, but it is it is inhibited by alcohol consumption and by folic acid deficiency. The most common cause of deficiency is alcoholism, although states causing malabsorption such as gastrointestinal surgery are also a factor. It may also be possible that diarrhoea causing malabsorption of nutrients from the intestines could put a patient at NET patient at risk of deficiency. Symptoms initially include fatigue, irritability, poor memory, sleep disturbances, anorexia, and abdominal discomfort. When more severe it involves hospitalisation due the effects on the nervous system and heart.
Patients who are at risk of deficiency must consume enough thiamine (1.1mg thiamine per day). Patients who are deficient must have their diet supplemented.
Niacin is not usually tested but may be useful to confirm diagnosis using urinary excretion of N 1 -methylnicotinamide (NMN).
Niacin also refers to both nicotinamide and nicotinic acid and is required as part of the way energy is produced by the body. When carcinoid tumours produce hormones such as serotonin, these patients suffer from carcinoid syndrome. These are symptoms such as flushing, diarrhoea, wheezing and damage to heart valves (carcinoid heart disease). When the tumours make large amounts of serotonin, the amino acid, tryptophan, gets used up. When tryptophan stores are low it cannot be converted into the vitamin niacin, which may then cause deficiency. In a NET study, 28 per cent of patients with gastroenteropancreatic /carcinoid tumours and carcinoid syndrome were niacin deficient. Patients without carcinoid syndrome did not have niacin deficiency. Niacin deficiency can also be caused by cirrhosis and diarrhea. Niacin deficiency leads to pellagra, the typical symptoms of which are diarrhea, dermatitis and dementia. All patients with carcinoid syndrome must take a nicotinamide containing supplement to treat and prevent this deficiency and it is a good idea to get enough niacin if you are at risk of deficiency for other reasons (approximately 40mg nicotinamide a day). Niacin or niacinamide may cause flushing!
Vitamin levels are not usually tested but measurement of serum pyridoxal phosphate is most commonly used.
Vitamin B6 comprises 3 forms: pyridoxine, pyridoxal and pyridoxamine, and has a central role in the metabolism of amino acids. It is involved in the breaking down of glycogen into glucose. In addition, vitamin B6 plays a key role in metabolism of neurotransmitters, such as dopamine and serotonin, and it ensures efficient functioning of the immune system and making of red blood cells. The symptoms of vitamin B6 deficiency are local inflammation of the skin and dysfunction of the nervous system. Some NET patients may be at risk of deficiency due to malabsorption in the intestines and undernutrition. If you are worried you may have lower levels make sure you consume enough (1.4mg per day). If you are deficient you diet must be supplemented.
Serum folate reflects folate status unless intake has recently increased or decreased.
Folic acid is the synthetic form of folate. It is used in supplements and for food fortification. Folate functions together with vitamin B12 to form healthy red blood cells. It is also required for normal cell division and the normal structure of the nervous system. It is possible to become deficient in folate due to malabsorption of nutrients in the intestine through diarrhoea and other malabsorption states such as surgery. If you are worried you may be at risk of deficiency ensure you get enough folate/folic acid (200 µg per day). If you are deficient your diet will need to be supplemented.
Vitamin B 12 must be measured alongside complete blood count and folate levels.
Cobalamin plays a role in DNA synthesis and regenerates methionine for protein synthesis. Low vitamin B12 levels have been observed in NET patients receiving somatostatin analogues and therefore monitoring of vitamin B12 levels is important during long-term therapy. Vitamin B12 deficiency has also been found to be common in type 1 gastric carcinoid NETs after Antrectomy and/or Gastrectomy. Patients with diseased or surgically removed ileums (end of the small bowel) and those who have bacterial overgrowth in the area are also at risk of Vitamin B12 deficiency. In addition, patients with insufficient pancreatic enzymes are also at risk of vitamin B12 deficiency as they play a key role in the steps before absorption occurs. If you are worried your levels may be low you must consume 2.5µg a day. If you are clinically deficient your diet must be supplemented, usually with regular injections.
Fat Soluble Vitamins
A, D, E and K
Somatostatin Analogues (Octreotide and Lanreotide) based injection treatments for a variety of NETs may cause deficiencies in some vitamins. This is because they may alter absorption of dietary fats which contain vitamins. Enzymes are usually released from the pancreas to break down nutrients such as fat, but pancreatic enzyme release can be reduced when somatostatin analogue medications are given. When fat is not broken down properly, stools become pale/yellow, loose, greasy, foul-smelling or frothy and floating –‘steatorrhoea’. Your precious vitamins therefore end up in your toilet instead. One study followed 54 patients, who mostly had carcinoid tumours and were on somatostatin analogues for at least 18 months. It found that only one fifth of patients had visible steatorrhoea, but 6% were deficient in vitamin A, 28% deficient in D, 58% in E and 63% in K1. This shows that even if you don’t have visible signs of steatorrhoea, you may still be deficient in one or more vitamin!
Serum retinol blood tests are the means of measuring vitamin A in the body.
Vitamin A is a fat soluble vitamin absorbed through the small intestine either as retinol or carotene, and then converted to retinyl palmitate which is stored in the liver. Normally the liver contains a 2 year store of vitamin A. Vitamin A deficiency has a wide range of ocular manifestations including conjunctival and corneal xerosis, keratomalacia, retinopathy, visual loss, and nyctalopia, or night blindness, which is the earliest and most common symptom. If you are worried about having low levels make sure you consume enough (800 µg per day). If you are deficient your diet will need to be supplemented.
D 3 –cholecalciferol
Your 25(OH)D levels can be measured with a simple blood test.
Cholecalciferol is a nutrient and hormone. Recent evidence for the non-skeletal effects (those apart from bone mineralisation) of vitamin D, coupled with recognition that vitamin D deficiency is common, has revived interest in this vitamin. Low vitamin D levels are linked to higher rates of several other cancers. Vitamin D is produced by skin exposed to ultraviolet B radiation and obtained from dietary sources, including supplements. Persons commonly at risk for vitamin D deficiency include those with inadequate sun exposure, limited oral intake, or impaired intestinal absorption from the diet (as above). The most recent evidence actually points out that the sun is not to be relied on as a source of vitamin D and oral intake is important. If you are worried you may have low levels you must speak with your doctor to arrange supplementation with or without a test.
Vitamin E can be tested by looking at the α-tocopherol level or ratio of serum α-tocopherol to serum lipids.
Vitamin E is a powerful antioxidant that can be regenerated by vitamin C after oxidation in the human body. It prevents damage of polyunsaturated fatty acids in cellular membranes. Signs of deficiency include dry skin and neurological symptoms. If you think you may have low levels make sure you consume enough (12mg per day). If you are deficient your diet will have to be supplemented.
Vitamin K deficiency can be measured by looking at the prothrombin time.
Phylloquinone is required for blood clotting and deficiency results in bleeding. Since this deficiency is common in patients with fat malabsorption due to severe liver disease and somatostatin analogue treatment it is important that you consume enough (75 µg per day). If you are clinically deficient you will need to receive supplementation.
Of course these are only the nutrients which are at risk of deficiency, there are many other nutrients and botanical extracts which may help patients with NET’s. It is vital that nutrition is considered for every patient with a NET and we hope one day each NET unit will have NET Specialist Dietitian to make this possible.
Thanks for listening and very grateful to Tara for the input.
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<p>Firstly, there are thousands of sites stating facts without any scientific evidence so you probably need professional advice. There are a lot of factors involved, including age, condition, treatment, diet restrictions and current levels. </p>
<p>The issue of vitamins is of particular importance for Neuroendocrine Tumour patients due to malabsorption caused by treatment. They key areas of concern are the fat soluble vitamins (ADEK) and B12. Many patients also have low levels of pancreatic enzymes (digestive enzymes) and these also need supplementation to help with fat absorption. If you've had particular bits of your gastrointestinal tract taken out, then no matter now much food containing particular vitamins you eat (and there are certain foods to be avoided!), you will never make up the loss, so supplementation can be required. As a Neuroendocrine Tumour patient, I only listen to professional dieticians who have an understanding of Neuroendocrine Tumours (like the one who helped me with this blog). This fact is sometimes lost on professional dieticians who do not understand the nature of Neuroendocrine Tumours and think this is just about what to eat. It isn't! <br /><br />For example - I take 4 x level of B12 because of the surgery I've had. The terminal ileum is the most efficient place for B12 to be absorbed - I no longer have this part of my anatomy. In these scenarios, vitamin supplements have a greater chance of being absorbed than food.</p>
<p>I have noticed that most multivitamins provide many times the recommended daily serving. Is this a good thing or a bad thing?
<p>That's a very interesting and helpful article. Thanks for taking the time to share!</p>
<p>Would it be wiser to take vitamins and minerals as supplements or just from diet? A lot of experts doubt the benefits of vitamin supplements.</p>
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