Diabetic-Safe Digestive Enzymes For Gastroparesis

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What is Gastroparesis?

Gastroparesis is a common condition that causes symptoms of delayed gastric (stomach) emptying of food in the absence of an actual physical blockage or narrowing. The most common causes of gastroparesis are idiopathic (unknown), diabetes, and postsurgical disease. Some forms of gastroparesis are thought to be due to autoimmune diseases, cancer-associated syndromes, and neurologic conditions.

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In one study, the proportion of cases was due to diabetes is 29%, unknown in 36%, and postsurgical in 13% while another study attributed 64% cases to idiopathic causes and 31% to diabetes. [1,2] In one study, delayed gastric emptying was found in 27-65% of patients with long-standing type 1 diabetes and in 30% of patients with type 2 diabetes.

The onset of gastroparesis coincides with the vascular complications of diabetes such heart attacks, strokes, and gangrene [3]. In one study, 62% of patients with type 1 diabetes and gastroparesis also had neuropathy. 


What are the symptoms of gastroparesis?

The symptoms associated with gastroparesis are nausea (most common at 90%) and vomiting in 68-84% of people. Sixty percent describe an early sense of fullness and pain is another common symptom [1] Pain is described as epigastric, constant, induced by meals, and at night; the last two are the most common. Bloating is reported in 80% of people and is more common in females. Obesity is another common finding in people with gastroparesis which is odd considering that caloric intake was measured as 60% less than recommended levels [5].

In patients with diabetic gastroparesis, the delayed gastric emptying promotes unpredictable food delivery to the small intestine and that increases the risk of hypoglycemic (low sugar) and hyperglycemic (high sugar) episodes. In one study, patients with type 1 or type 2 diabetes that also required insulin, those with delayed gastric emptying were at much higher risk of early post-meal hypoglycemic episodes [6].

Diabetic Gastroparesis

Both neurologic and muscular problems are found with diabetic gastroparesis. Contractions of the stomach muscle are reduced, and the size of the lower stomach is increased. There are associated spasms of the pylorus (opening to the small intestine).In some patients, the upper part of the stomach does not sense the added fullness which causes the person to be able to accommodate more food [7,8]. Overall, the problem is related to poor glycemic control that leads to nerve damage that causes GI dysfunction.

Genetic factors affecting the mitochondria in the cells can predispose patients with type 2 diabetes to gastroparesis [9].  Acute hyperglycemia can activate multiple processes that slow the gut [10-13]. Furthermore, some studies have shown that hyperglycemia reduces sensations of hunger in both healthy individuals and patients with type 1 diabetes. Hyperglycemia also increases the senses of postprandial (after meals) fullness in patients with diabetes who require insulin [13-15]. Conversely, insulin-induced hypoglycemia accelerates both solid and liquid stomach emptying in patients with type 1 diabetes [16]. Autoimmune factors that after calcium influx into the stomach muscles may play a role in gastroparesis in people with type I diabetes [17]

Treatment Options for Gastroparesis

Gastroparesis therapies include dietary changes, medications to stimulate stomach emptying or reduce vomiting, endoscopy (tube to view the stomach), surgery, and psychological interventions. It has not been determined whether multiple therapies are superior to placebo. Most studies looked at the treatment of the symptoms.  Medication for gastroparesis can be administered in pills, capsules, liquids, rectal suppositories, transdermal, or IV especially for those with vomiting.

Treatment depends on the severity of the condition.

  • Grade 1 (mild) have periodic, well-controlled symptoms with normal nutritional status
  • Grade 2 (moderate) have moderate symptoms that can be controlled with stimulating or anti-nausea drugs
  • Grade 3 (severe) have not responded to medical therapy and cannot maintain nutrition and need intravenous fluids and supplemental nutrition.

Reasons for hospitalization associated with gastroparesis include poor glucose control, medication noncompliance or intolerance, and adrenal insufficiency [18].

Dietary and Nonmedicinal Measures

Eating frequent, small meals along with a predominantly liquid diet, avoiding hard to digest solids and fatty meals can minimize stomach problems. In patients with type 1 diabetes, ingesting small particles speeds up gastric emptying and reduces changes in glucose levels [19]. 

Dietary fiber contributes to bloating and bezoars (masses of food and other solid substances that do not pass out of the stomach) and should be minimized in patients with gastroparesis.  Drugs that inhibit motility, such as calcium channel blockers, anti-cholinergics, opiates and exenatide, should be stopped.

Prokinetic (Pro-movement) Medications

Novel prokinetics include ghrelin agonists, 5-HT4 agonists and cholinesterase inhibitors show promise for this condition. New research is assessing if tricyclic antidepressants and antiemetic therapies (for example NK1 antagonists) will be effective in reducing the symptoms of gastroparesis.

Prokinetic drugs are used primarily in those with moderate or severe gastroparesis.  A 1999 meta-analysis demonstrated that erythromycin is the most potent stimulator of gastric emptying, and erythromycin combined with domperidone are superior to metoclopramide for symptom control [20]. Tolerance to its effects may develop, except for its role in reducing nausea and vomiting. Adverse effects do limit the use of metoclopramide in one-third of patients. Fatigue, agitation, sleep disruption and abnormal muscle movements are frequently reported, but are more common in younger patients <30 years old.

Erythromycin causes stomach contractions and increases the motility of food [21]. Tolerance can develop and the adverse effects are abdominal pain, nausea, and vomiting.

Oral azithromycin has been shown to reduce vomiting and improve glucose control in patients with type 2 diabetes and gastroparesis [22]

Mitemcinal, a motilin receptor agonist, showed benefits in a clinical trial that included patients with diabetes and gastroparesis symptoms in individuals with a BMI <35 kg/m2 and a hemoglobin A1c level of <10% [23].

Studies show that ghrelin, one of the body’s own mediator of food intake, has potent effects to increase gastric emptying. In diabetic patients with severe gastroparesis, the intravenous ghrelin agonist TZP-101 (ulimorelin) was shown to reduce nausea, vomiting and other symptoms compared with placebo [24].

 Antiemetic Medications

Medications that act primarily as antiemetic (anti-nausea and vomiting) agents are often used for the treatment of gastroparesis, either alone or with prokinetics. Antiemetics in other drug classes are histamine H1 antagonists (promethazine), serotonin 5-HT3 antagonists (ondansetron) and cannabinoids (dronabinol)—are commonly given to patients with gastroparesis but there is little evidence to support their effectiveness.

The herbal extract STW5 (iberogast) has been shown to reduce symptoms in some patient with heartburn and has been used in patients with gastroparesis. Acupuncture may have a role in patients with diabetic gastroparesis. This therapy is reported to produce a 75% reduction in GCSI scores and possible faster gastric emptying in these individuals [25].

Novel Digestive Enzymes to Treat Gastroparesis

A recent study published by the American Academy of Gastroenterology, Zygluten showed promise as a potential treatment for gastroparesis. It is a combination of multiple digestive enzymes, herbs and Lactococci. Interestingly, during the preliminary research and development of Zygluten, it was observed that when it was added to food that was in a blender (for example pizza or bagels), Zygluten liquified the food. The enzyme combinations found in Zygluten (amylases, lipases, proteases, lactase) are derived from Aspergillus niger and are effective in pH range of 2 to 7.

The hypothesis was that by liquifying a food load in the stomach with the addition of Zygluten, gastric emptying would be accelerated and thus the symptoms of gastroparesis would improve. There are no other effective holistic therapies available for diabetic gastroparesis.

A total of 21 patients who were confirmed by endoscopy to have moderate to large amount of food in stomach despite 8—12 hours of fasting. None of the patients had GI ulcers or obstructions. Their symptoms included anorexia, bloating, nausea, vomiting, and post prandial (meal) fullness. None of the patients were on Prokinetic drugs or Erythromycin.All patients were given 1 capsule of Zygluten with each meal for two weeks and their symptoms were assessed

Out of 21 patients enrolled in the trial, 66.7% showed marked improvement in symptoms and 33.3% showed no improvement of symptoms. The good news is that there were no side effects compared to current drugs on the market [26].

Digestive Enzymes that May Provide Relief

  • Papaya enzyme
  • Betaine HCL
  • Complex of protease, amylase, lipase, and cellulase

Supplemental Nutrition

Some patients with gastroparesis who don’t respond to medical therapy do well with IV or food administer through a tube placed in the small intestine.  Reasons to do this are:

  • severe malnutrition (>10% weight loss over 6 months) that has not responded to dietary changes,
  • patients with mineral or electrolyte disturbances,
  • individuals who are frequently hospitalized for nutritional replenishment.

Psychological Measures

Patients with gastroparesis may experience significant psychological symptoms such as depression and anxiety that correlated with the severity of the disease [27].  


In a preliminary report from a large database of studies, nausea, vomiting, fullness, early satiety and weight loss were shown to improve under the care of motility specialists after 48 weeks; however, symptoms of bloating and pain were unchanged [28]. 



1. What are the common causes of gastroparesis, and how does diabetes contribute to its onset? Gastroparesis can result from various causes, with idiopathic factors, diabetes, and postsurgical conditions being prominent contributors. Studies indicate that around 29% of cases are attributed to diabetes, and its onset often aligns with vascular complications like heart attacks and strokes. Additionally, diabetic gastroparesis is associated with neuropathy, emphasizing the role of poor glycemic control in nerve damage affecting gastrointestinal function.

2. What are the symptoms of gastroparesis, and how does it affect individuals with diabetes in terms of glucose levels and hypoglycemic episodes? Gastroparesis manifests in symptoms such as nausea, vomiting, early satiety, and pain. In diabetic patients, delayed gastric emptying heightens the risk of unpredictable food delivery to the small intestine, increasing the chances of hypoglycemic and hyperglycemic episodes. Studies reveal a correlation between delayed gastric emptying and a higher risk of early post-meal hypoglycemia in individuals with type 1 or type 2 diabetes requiring insulin.

3. What treatment options are available for gastroparesis, and what role do novel digestive enzymes, such as Zygluten, play in managing symptoms, especially for diabetic patients? Treatment strategies for gastroparesis encompass dietary adjustments, medications, endoscopy, surgery, and psychological interventions. Severity determines the treatment approach, ranging from dietary changes to intravenous fluids and supplemental nutrition. In recent research, digestive enzymes like Zygluten have shown promise in accelerating gastric emptying, reducing symptoms in 66.7% of patients without side effects. This holistic approach provides a potential alternative for managing diabetic gastroparesis symptoms.



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