Zollinger-Ellison Syndrome: Nutritional Therapy

As a result of Zollinger-Ellison syndrome, there is inadequate neutralization of stomach contents entering the small intestine, leading to impaired digestion and absorption (uptake) of nutrients and vital substances. As a result, affected individuals often suffer from vital substance deficiency symptoms. Osmotic products of incomplete food breakdown enter the intestines and cause diarrhea (diarrhea). Constant watery diarrhea causes high losses of water-soluble vitamins – vitamin C, B vitamins – and important electrolytes, such as calcium, magnesium, potassium and sodium. Symptoms and complications

Increased acidity causes inactivation of fat-splitting enzymes and precipitation of bile acids, resulting in steatorrhea (fatty stools). Increased fat diarrhea interferes with the absorption of fats as well as fat-soluble vitamins, which are lost in increased amounts with steatorrhea.
Increased acid secretion impairs the gastric mucosa to produce the intrinsic factor necessary for vitamin B12 absorption. Vitamin B12 can only be poorly absorbed.
60% of patients struggle with heartburn and resulting dysphagia. Affected people tend under these circumstances to a reduced food intake, which in turn is associated with an insufficient intake of nutrients and vital substances.

Nutritional recommendations

For therapy, the tumor must be specifically removed – if there is no metastasis, to normalize gastrin production. If operability is not present, the use of proton pump blockers can effectively suppress acid secretion and thus symptoms. Importance of secondary plant compounds
For the prevention of gastrin-producing tumors, bioactive substances in particular, such as carotenoids, saponins, polyphenols, and sulfides, should be supplied in sufficient quantities. These are able to inhibit the growth of cancer cells in gastric and colorectal cancers

Carotenoids – found, for example, in apricots, broccoli, peas, and kale – can block the phase 1 enzymes responsible for cancer development.
Saponins – found primarily in beans, green beans, chickpeas, as well as soybeans – bind primary bile acids, helping to reduce the formation of secondary bile acids. In high concentrations, secondary bile acids may act as tumor promoters [3.1].
Flavonoids belonging to the polyphenols – found primarily in citrus fruits, red grapes, cherries, berries, as well as plums – have structural similarities to nucleotides and can therefore mask DNA-binding sites for active carcinogens (cancer-causing substances). They also have the ability to prevent the growth of DNA-damaged cells. Furthermore, flavonoids have a positive effect on the vital substance status. They increase the effect of vitamin C and coenzyme Q10 by a factor of ten, have a stabilizing influence on the plasma level of vitamin C and delay the consumption of vitamin E [3.1]. Phenolic acids – especially found in various cabbages, coffee, radishes and whole wheat grains – have a strong antioxidant effect and can therefore inactivate numerous cancer-promoting substances from the environment, such as nitrosamines and mycotoxins.
Sulfides – abundant in garlic, onions, chives, asparagus and shallots – exhibit similar anti-cancer effects as carotenoids, saponins and polyphenols. They also have an additional immunomodulatory effect, activating natural killer cells as well as cell-killing T lymphocytes to halt carcinogenesis

In addition, phytochemicals possess a protective effect against esophageal, gastric, liver, lung, bladder, breast, cervical, prostate, as well as skin cancer. In addition to anticarcinogenic (anti-cancer) effects, carotenoids, saponins, polyphenols and sulfides also exhibit antioxidant, antimicrobial, antiviral, cholesterol-lowering and anti-inflammatory effects. Polyphenols – flavonoids and phenolic acids – are particularly useful in preventing myocardial infarction (heart attack).

Zollinger-Ellison syndrome and enteral protein loss syndrome

Inflammatory symptoms or functional impairment of the small intestinal wall lead to increased intestinal protein loss because the leakage of plasma proteins through the intestinal mucosa into the interior of the intestine exceeds the rate of protein formation.The decrease in circulating plasma proteins is usually accompanied by a severe protein deficiency. In addition, increased intestinal protein loss leads to a decrease in oncotic pressure and thus, depending on the extent of the decreased concentration of plasma proteins – hypoproteinemia – to the formation of edema. Importance of MCT fats1 in the dietary management of steatorrhea and enteral protein loss syndrome.

MCTs are cleaved more rapidly in the small intestine than LCT fats2 under the influence of the pancreatic enzyme lipase.
Due to their better water solubility, the small intestine can absorb MCT fats more easily
The presence of bile salts is not required for the absorption of MCTs
MCT fats can still be exploited both in the absence and deficiency of lipase and bile salts inside the intestine, respectively
The small intestine has a greater absorption capacity for MCT than for LCT.
Binding of MCT fats to the transport lipoproteins chylomicrons is not necessary, because medium-chain fatty acids are removed via portal blood and not via intestinal lymph
Due to the removal with the portal blood, the lymphatic pressure does not increase during the absorption of MCT and there is less lymph leakage into the intestine, reducing intestinal protein loss – increase in plasma proteins.
During the resorption of long-chain fatty acids, on the other hand, the lymphatic pressure increases and thus the passage of lymph into the intestine – lymphatic congestion leads to a high loss of plasma proteins
MCT are oxidized faster in the tissue than LCT
Medium-chain triglycerides reduce water loss with stool by low stimulation of gallbladder contraction, resulting in low bile salt concentration inside the intestine – reduction of chologenic diarrhea
MCT fats improve the overall nutritional status

Substitution of MCTs for LCTs subsequently leads to a reduction in fecal fat excretion – alleviation of steatorrhea – and enteric protein loss syndrome. MCT fatty acids are available in the form of MCT margarine – not suitable for frying – and MCT cooking oils – usable as cooking fat. The transition to medium-chain triglycerides (dietary fats) should be gradual, otherwise pain in the abdomen, vomiting and headaches may occur – increasing the daily amount of MCT from day to day by about 10 grams until the final daily amount of 100-150 grams is reached. MCT fats are heat labile and should not be heated for too long and never above 70°C. In addition, care should be taken to cover the requirements of fat-soluble vitamins A, D, E and K and essential fatty acids such as omega-3 and omega-6 compounds. When MCTs are administered, fat-soluble vitamins are adequately absorbed.

Zollinger-Ellison syndrome – vital substance deficiency

Vital substance	Deficiency symptoms
Vitamin A	Fatigue, loss of appetite Decreased production of antibodies and weakened immune system. Decreased antioxidant protection Impaired dark adaptation, night blindness Diseases of the respiratory tract, respiratory infections due to changes in the mucous membrane. Disorders of spermatogenesis Anemia (anemia) Increased risk of Tumors of the lung, bladder, prostate, larynx, esophagus, stomach and intestine. Kidney stone formation Drying up to cornification of mucous membranes – in the mouth area, in the salivary gland excretory ducts. Enhancement of mucosal atrophy Favors tissue remodeling Attrition of cell and tissue mass of salivary glands and larynx, regression of organs. Dry, brittle nails and hair Dry, rough, itchy skin with rashes Reduced sense of smell, touch, hearing disorders. Deficiency symptoms in children Growth disorders of the long bones Disorders in the formation of dental tissue – dentin disorders. Malformations of the auditory, digestive and genitourinary tracts
Beta-carotene	Decreased antioxidant protection, increased risk for lipid peroxidation as well as oxidative DNA damage. Weakened immune system Drying up to cornification of mucous membranes – in the mouth area, in the salivary gland excretory ducts. Enhancement of mucosal atrophy Favors tissue remodeling Increased risk of skin, lung, prostate, cervical, breast, esophageal, stomach, and colon cancers Reduced skin and eye protection
Vitamin D	Loss of minerals from bones – spine, pelvis, extremities – results in Hypocalcemia Osteoporosis – decreased bone density. Deformities Muscle weakness, especially at the hips and pelvis Increased risk of later osteoporosis Formation of osteomalacia Symptoms of osteomalacia Bone pain – shoulder, spine, pelvis, legs. Spontaneous fractures, often in the pelvic ring. Funnel chest “Map heart shape” of the female pelvis. Loss of hearing, ringing in the ears Disturbed immune system with repeated infections. Increased risk of colon and breast cancer Deficiency symptoms in children Impairment of the development of bones and teeth. Reduced mineralization of bones with a tendency to spontaneous fractures and bone bending – formation of rickets. Symptoms of rickets Disturbances in the longitudinal growth of bones Deformed skeleton – skull, spine, legs. Atypical heart-shaped pelvis Delayed retention of deciduous teeth, jaw deformity, malocclusion
Vitamin E	Lack of protection against radical attack and lipid peroxidation. Decreases the immune response High susceptibility to infection Disease of muscle cells due to inflammation of muscle tissue – myopathies. Shrinkage as well as weakening of the muscles Disease of the peripheral nervous system, neurological disorders, disorders in neuromuscular information transmission – neuropathies. Reduced number and lifetime of red blood cells. Deficiency symptoms in children Anemia (anemia) Impairment of blood vessels leads to bleeding Disturbances in neuromuscular information transmission. Disease of the retina, visual disturbances – neonatal retinopathy. Chronic lung disease, respiratory distress – bronchopulmonary dysplasia. Cerebral hemorrhage
Vitamin K	Blood coagulation disorders leading to Hemorrhage into tissues and organs. Bleeding from body orifices Small amounts of blood in the stool can cause Decreased activity of osteoblasts leading to. Increased urinary calcium excretion. Severe bone deformities
B vitamins, such as vitamin B1, B2, B3, B5, B6.	Disorders in the central and peripheral nervous systems lead to Nerve disease in the extremities, pain or numbness of the extremities. Muscle pain, wasting or weakness, involuntary muscle twitching Hyperexcitability of the heart muscle, decrease in cardiac output – tachycardia. Memory loss General state of weakness Impaired collagen synthesis resulting in poor wound healing Insomnia, nervous disorders, sensory disturbances. Impaired response of white blood cells to inflammation. Anemia due to decreased production of red blood cells, white blood cells, and platelets Decreased production of antibodies Impairment of cellular and humoral immune defenses. States of confusion, headaches Gastrointestinal disorders, stomach pain, vomiting, nausea. Deficiency symptoms in children Disorders of protein biosynthesis and cell division. Disorders of the central nervous system Disturbance of nervous function and cardiac insufficiency – beriberi Skeletal muscle atrophy Increased risk of cardiac dysfunction and failure
Folic acid	Mucosal changes in the mouth, intestines, and urogenital tract lead to Indigestion – diarrhea Reduced absorption of nutrients and vital substances Weight loss Blood count disorders Anemia leads to rapid fatigue, shortness of breath, decreased ability to concentrate, general weakness Impaired formation of white blood cells leads to. Reduction of the immune response to infections. Decreased antibody formation Risk of bleeding due to decreased production of platelets Elevated homocysteine levels increase the risk for Atherosclerosis (arteriosclerosis, hardening of the arteries). Coronary heart disease (CHD) Neurological and psychiatric disorders, such as. Memory impairment Depression Aggressiveness Irritability Deficiency symptoms in children Disturbances in DNA synthesis – limited replication – and decreased cell proliferation increase the risk for Malformations, developmental disorders Growth retardation Maturation disorders of the central nervous system. Bone marrow alteration Deficiency of white blood cells as well as platelets. Anemia (anemia) Injuries to the mucosa of the small intestine Disorders of protein biosynthesis and cell division
Vitamin B12	Decreased vision and blind spots Functional folic acid deficiency Weakened antioxidant protective system Blood count – pernicious anemia Anemia (anemia) – decreases the ability to concentrate, leads to fatigue, decreased performance, poor memory, shortness of breath and a yellowish discolored skin. Reduction of red blood cells, larger than average and rich in hemoglobin. Impaired growth of white blood cells weakens the immune system Risk of bleeding due to reduced production of platelets. Gastrointestinal tract Tissue atrophy and inflammation of the mucous membranes. Rough, burning tongue Reduced absorption of nutrients and vital substances Loss of appetite, weight loss Neurological disorders Numbness and tingling of extremities, loss of sensation of touch, vibration and pain. Poor coordination of the muscles, muscle atrophy. Unsteady gait Spinal cord damage Psychiatric disorders Memory disorders, confusion, depression Aggressiveness, agitation, psychosis
Vitamin C	Antioxidant deficiency Weakness of blood vessels leads to Abnormal bleeding Mucosal bleeding Hemorrhage into the muscles associated with weakness in heavily used muscles Inflamed as well as bleeding gums (gingivitis). Joint stiffness and pain Poor wound healing Carnitine deficit leads to Symptoms of exhaustion, fatigue, indifference, irritability, depression. Increased need for sleep, decreased performance. Weakness of the immune system with increased risk of infection Decreased oxidation protection increases the risk of heart disease, apoplexy (stroke) Deficiency symptoms in children Weakened immune system Recurrent infections of the respiratory tract, urinary bladder, and the auditory tube, which is connected to the nasopharynx via the tympanic cavity of the middle ear Increased risk of vitamin C deficiency disease- Möller-Barlow disease in infancy with symptoms such as. Large bruises (hematomas). Pathological bone fractures associated with severe pain Wincing after every slightest touch – “jumping jack phenomenon”. Stagnation of growth
Calcium	Demineralization of the skeletal system increases the risk of Decreased bone density Osteoporosis, especially in women with estrogen deficiency. Bone softening as well as bone deformities – osteomalacia. Tendency to stress fractures of the skeletal system. Muscle cramps, tendency to spasm, increased muscle contraction. Cardiac arrhythmias Blood clotting disorders with increased bleeding tendency Increased excitability of the nervous system, depression. Increased risk of Hypertension (high blood pressure) Deficiency symptoms in children Impaired development of bones and teeth Decreased bone density in the newborn baby Decreased mineralization of bones with tendency to spontaneous fractures and bone bending – formation of rickets. Symptoms of rickets Disturbances in the longitudinal growth of bones Deformed skeleton – skull, spine, legs. Atypical heart-shaped pelvis Delayed retention of deciduous teeth, jaw deformity, malocclusion of teeth. Additional vitamin D deficiency leads to Hyperparathyroidism – enlarged parathyroid tissue – and increased production of parathyroid hormones – hyperparathyroidism. Hypercalcemic coma
Magnesium	Increased smooth muscle contraction waves in hollow organs. Increased state of tension and activity of the smooth muscle. Nausea, vomiting, stomach cramps, diarrhea as well as constipation Increased excitability of muscles and nerves leading to. Insomnia, difficulty concentrating Muscle and vascular spasms Numbness as well as tingling in the extremities. Heart palpitations and arrhythmias, feeling of anxiety. Increased risk of Decreased immune response Myocardial infarction (heart attack) Acute hearing loss Deficiency symptoms in children Growth retardation Hyperactivity Insomnia, difficulty concentrating Muscle tremors, cramps Heart palpitations and arrhythmias Decreased immune response
Sodium	Fatigability, possible unconsciousness, apathy, confusion, lack of drive, decreased performance – short-term memory. Nausea, vomiting, loss of appetite, lack of thirst. Hypertension (high blood pressure); tendency to collapse, hyperexcitability of the heart muscle, reduction in cardiac output – tachycardia. Muscle cramps Decreased urination
Potassium	Muscle weakness, muscle paralysis Fatigue, apathy Nausea and vomiting, loss of appetite, constipation, decreased bowel activity to intestinal obstruction. Decreased tendon reflexes Cardiac arrhythmias, cardiac enlargement, tachycardia, dyspnea
Iron	Chronic fatigue syndrome (CFS) Loss of appetite Disorders of thermoregulation High susceptibility to infection of the upper respiratory tract Dry skin with itching Decreased concentration and retentiveness Increased lactic acid formation during physical exertion associated with muscle cramps. Increased absorption of environmental toxins Body temperature regulation may be disturbed Anemia Symptoms of deficiency in children Disturbance of physical, mental and motor development. Behavioral disorders Lack of concentration, learning disorders Disturbances in the child’s intelligence development Loss of appetite High susceptibility to infection of the upper respiratory tract Body temperature regulation may be disturbed
Selenium	Weight loss, intestinal sluggishness, indigestion. Depression, irritability, insomnia. Memory loss, difficulty concentrating, headaches Immunodeficiency Chronic fatigue syndrome (CFS) Thyroid dysfunction due to deficiency of selenium-dependent deiodases. Decreased activity of glutathione peroxidases leads to an increase in peroxides and thus to increased radical formation and increased formation of pro-inflammatory prostaglandins Joint pain due to pro-inflammatory processes. Increased susceptibility of the mitochondria Male infertility Increased risk of Liver damage Muscle pain and stiffness Keshan disease – viral infections, disease of the heart muscle – cardiomyopathy, heart failure, cardiac arrhythmias. Kashin-Beck disease – degenerative joint disease with disorders of bone and joint metabolism, which can lead to osteoarthritis and severe joint deformities. Deficiency symptoms in children Immunodeficiency Thyroid dysfunction Increased radical formation Increased susceptibility of the mitochondria Increased susceptibility to infections Increases the need for vitamin E
High quality protein	Disturbances in digestion and absorption of vital substances and resulting water and electrolyte losses. Muscle atrophy Tendency to accumulate water in the tissues – edema
Amino acids, such as leucine, isoleucine, valine, tyrosine, histidine, glutamine, carnitine.	Disturbances in the function of nerves and muscles Decreased performance Restricted energy production and resulting fatigue and muscle weakness. Impairment of hemoglobin formation Severe joint pain and stiffness in arthritis patients. High depletion of muscle mass and protein reserves. Insufficient protection against free radicals Weakening of the immune system, since amino acids are the main sources of energy for the immune system Disturbances in the digestive system Fluctuations in blood sugar levels Increased blood lipid and cholesterol levels Cardiac arrhythmias
Essential fatty acids – omega-3 and 6 compounds.	Weakened immune system, increased susceptibility to infections. Disturbed heart rhythm Disturbed vision Disturbed wound healing Disturbed blood clotting Hair loss Hypertension (high blood pressure) Hyperlipidemia (lipid metabolism disorder) Kidney damage and blood in the urine Reduced functionality of the red blood cells Skin changes – flaky, cracked, thickened skin. Fertility disorders in women and men Decreased liver function Increased symptoms of arthritis, allergies, atherosclerosis, thrombosis, eczema, premenstrual syndrome – fatigue, poor concentration, marked change in appetite, headache, joint or muscle pain Increased risk of cancer Deficiency symptoms in children Disorders in whole body growth Insufficient development of the brain Reduction in the ability to learn Neurological disorders – poor concentration and performance
Secondary plant compounds, such as carotenoids, saponins, sulfides, polyphenols.	Weakened immune defenses High LDL cholesterol level Insufficient protection against Pathogens – bacteria, viruses Inflammatory reactions Free radicals, such as highly reactive aggressive oxygen and nitrogen molecules, which can oxidatively damage DNA, proteins as well as lipids – oxidative stress Free radicals lead to Peroxidation of the unsaturated fatty acids contained in LDL cholesterol. Deposition of the oxidized LDL cholesterol on the inner walls of the blood vessels Narrowing of the vessels results in arteriosclerosis Increased risk of Atherosclerosis and heart disease Thrombosis (blood vessel occlusion) Cardiovascular diseases Heart and vascular diseases (cardiovascular diseases). Myocardial infarction (heart attack) – especially with low plasma levels of polyphenols. Hypertension (high blood pressure) – especially if the diet is low in sulfides. Esophageal, stomach, colon, skin, lung, liver, prostate, cervical, bladder and breast cancer

1 MCT = fats with medium-chain fatty acids; their digestion and absorption is faster and independent of bile acids, so they are preferred in diseases of the pancreas and intestine. 2 LCT = fats with long-chain fatty acids; they are absorbed directly into the body’s own fat depots without much conversion and are released from them only very slowly. They are also known under the term “hidden fats”.