Macroamylasemia

What Is Macroamylasemia?

[dropcap]M[/dropcap]acroamylasemia is an acquired enzyme disorder that causes elevated levels of the enzyme amylase (hyperamylasaemia) in the bloodstream. It is characterized by altered amylase molecules that have become abnormally bound with plasma proteins in the bloodstream, commonly IgG (immunoglobulin G) and/or IgA (immunoglobulin A).

The resulting molecule is too large to be properly filtered by the kidneys and excreted in the urine as would be normal unbound amylase, causing sustained elevation of amylase levels in the plasma.

With normal kidney function, a hyperamylasemia without an increase in urine amylase suggests the diagnosis of macroamylasemia, and is confirmed by identifying the macromolecular components.¹

Amylase is a an enzyme produced by the pancreas and the parotid glands to digest starch in the diet. Comparatively small amounts are also produced by other organs.

Q: How do the pancreas and parotid glands deliver their amylase for digestion of starch?

A: The parotid glands deliver their amylase into the mouth. The action of amylase in the mouth starts the breakdown of starch as it is chewed and moistened with saliva.

After the starchy food is liquified in the stomach, the mass empties into the duodenum. Here pancreatic amylase is delivered through the common bile duct into the duodenum where it turns starch into maltose sugar. The next step to final digestion of starch is carried out by enzymes in the small intestinal lining that split maltose into its component sugar which is glucose.

Glucose is a simple sugar that can be absorbed into the bloodstream for use in the body. Humans cannot live without adequate glucose.

Distinquishing macroamylasemia from hyperamylasemia due to pancreatic disease is necessary to prevent needless treatment and investigation for pancreatitis.²

What Is Macroamylasemia In Celiac Disease and/or Gluten Sensitivity?

• Relationship between macroamylasemia and celiac disease. Macroamylasemia is a classic sign of celiac disease. The better understanding of this biochemical anomaly allows differentiation from other situations associated to hyperamylasemia, in order to avoid additional invasive explorations and unnecessary treatments.¹
• Relationship between macroamylasemia and risk. Untreated persons with celiac disease having elevated IgA and IgG antibodies are at high risk to develop macroamylasemia.
• Relationship between macroamylasemia and macrolipasemia. Macroamylasemia may present simultaneously with elevated lipase.³
• Relationship between macroamylasemia and Down syndrome. Macroamylasemia also occurs in Down syndrome with celiac disease.⁴

How Prevalent Is Macroamylasemia In Celiac Disease and/or Gluten Sensitivity?

Macroamylasemia occurs in approximately 0.4% of general population and 16.9% in celiac disease patients.⁵

A study evaluating the prevalence of macroamylasemia or elevated total amylase in patients with macroamylasemia that led to the diagnosis of celiac disease found that three healthy controls (3.4%), 21 newly diagnosed celiac (16.8%), and seven patients on gluten free diet (7%) had significantly elevated macroamylase activity in their sera.⁶

What Are The Symptoms Of Macroamylasemia?

• Macroamylasaemia should be considered in any patient with high plasma amylase, no clinical signs and negative additional investigations for pancreatic or parotid diseases.
• With a normal renal function, a hyperamylasemia without an increase in urine amylase suggests the diagnosis, and is confirmed by identifying the macromolecular components.¹
• Blood analysis shows macroamylase and a 24-hour urine collection analysis shows low urine amylase and amylase clearance/creatinine clearance ratio.

How Does Macroamylasemia Develop In Celiac Disease and/or Gluten Sensitivity ?

• Macroamylasemia results from elevated IgG and/or IgA antibody levels binding to amylase enzyme in blood.⁷

Does Macroamylasemia Respond To Gluten-Free Diet?

Yes in some patients. Serum macroamylase remained elevated in some patients on strict gluten free diet.⁶

Macroamylase response varies on gluten free diet.⁷

6 Steps To Improve Macroamylasemia In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both macroamylasemia and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.⁸
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.⁹
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.⁹
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.⁹.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.⁹
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.⁹
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.⁹[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Certain medications may rarely promote macroamylasemia. Ask your doctor or pharmacist about this possible adverse effect if you are taking medications. Do not stop prescribed medications without supervision.

ANTIBIOTICS disrupt intestinal permeability which complicates celiac disease.

• Cipro antibiotic therapy has been reported in association with macroamylasemia.

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• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination that provides 100% once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Macroamylasemia In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Macroamylasemia in patients with celiac disease.” This study evaluating the prevalence of macroamylasemia or elevated total amylase  in patients with macroamylasemia that led to the diagnosis of Celiac Disease found that three healthy controls (3.4%), 21 newly diagnosed celiac (16.8%), and seven patients on Gluten Free Diet (7%) had significantly elevated macroamylase activity in their sera.⁶

CASE REPORT SUMMARIES

“Macroamylasemia as the first manifestation of celiac disease.” This case report describes diagnosis of celiac disease in a 52-year-old woman who was referred to an outpatient clinic with a 6-month history of weakness, weight loss of 6 kg, maculopapular rash on her legs and persistent hyperamylasemia for 3 months (amylase >1,400 U [normal 35–120 U] and very low 24-hour urine amylase and amylase clearance/creatinine clearance ratio (1.9% [normal 3.0 ± 1.1%]), consistent with macroamylasemia.

Her medical history was remarkable only for several years of chronic normocytic normochromic anemia (Hb 9.9 g%) and osteoporosis. She was not receiving any medications. Other than a sallow pallor and the maculopapular rash on both legs, the physical examination was completely negative. Laboratory results: thrombocytosis (510,000 platelets/ml), albumin 3.1 g, AST 60 U (normal 15–30), rheumatoid factor 81 (normal 0–15), anti-mitochondrial antibody (AMA) 1:80. The rest of the laboratory results were normal. An abdominal computerized tomogram with contrast yielded no pathological findings. Biopsy from the skin lesions on her legs revealed leukocytoclastic vasculitis.

The patient had macroamylasemia and anemia, which can present as an autoimmune disease, such as celiac disease. Her serology for celiac disease was strongly positive, and she underwent esophagogastroduodenoscopy which revealed scalloping of folds in the second part of the duodenum. A histological evaluation confirmed the diagnosis of celiac disease. The patient was started on a gluten-free diet which led to a significant clinical improvement two months later: she felt generally stronger, had gained weight, the rash had disappeared, the serum amylase values were normal, hemoglobin had increased to 11.7 g%, and there was a return of serum albumin to normal values.

“This case demonstrates an association between celiac disease and other medical conditions that present as macroamylasemia. Celiac disease was the cause and first manifestation of her persistent hyperamylasemia. We recommend ruling out celiac disease in cases of unexplained hyperamylasemia.”¹⁰

“Multiple immune disorders in unrecognized celiac disease: a case report.” This case report describes the course of a 34 year old female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy, thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.

After six months of controlled gluten free diet, the patient’s body weight increased 12 kg; laboratory investigations demonstrated normalization of serum amylase, serum lipase and immunoglobulin levels; antigliadin, anti-2-glicoprotein-1 and anti-thyreoglobulin antibodies were no longer detectable, but antiendomysial antibodies were still present. Endoscopy showed a normal appearance of duodenal mucosa, and duodenal biopsy revealed a partial recovery of duodenal morphology. Due to the persistence of proteinuria (2.3 g/day), microscopic hematuria and hyaline and granular casts, a kidney biopsy showed that it was IgA nephropathy. After 18 months of gluten-free diet, antiendomysial antibodies disappeared; creatinine clearance increased, but proteinuria further worsened (2.9 g/day, Table 1), and albumin levels were still low. After 24 months of gluten-free diet, a new duodenal biopsy showed complete recovery of villous architecture. Renal function further improved and proteinuria markedly decreased (Table 1). Amylase, lipase, and immunoglobulin levels were within the normal range. Anti-2-glicoprotein-1, anti-thyreoglobulin, antigliadin, antiendomysial and anti-TTG antibodies were undetectable. A coagulation study was normal.

Although both celiac disease and the other manifestations of a deranged immunity might be explained on the basis of a common genetic predisposition to this kind of disorders, some findings suggest that celiac disease itself is responsible for the initiation of the immunological response. Indeed, persistent stimulation by some proinflammatory cytokines, such as interferon  and tumor necrosis factor , could induce further processing of autoantigens and their presentation to T lymphocytes by macrophage-type immunocompetent cells. As a matter of fact, the prevalence of immune diseases among patients with celiac disease seems proportional to the time of exposure to gluten[12], and many immune alterations disappear following the recognition of celiac disease and appropriate treatment, just as it occurred in this patient.¹¹

“Macroamylasaemia, IgA hypergammaglobulinaemia and autoimmunity in a patient with Down syndrome and celiac disease.” This case report of a 40 year old patient with Down Syndrome with multiple autoimmune abnormalities for 15 years describes macroamylasemia, IgA hypergammaglobulinemia and subsequent diagnosis of Celiac Disease. Follow-up on Gluten Free Diet showed a transitory decrease in seric immunoglobulin A and macroamylase with persistent autoantibodies and AST elevation¹²

“Macroamylasemia attributable to gluten-related amylase autoantibodies.” This case report describes diagnosis of celiac disease in an 11-year-old girl who was referred for chronic abdominal pain and growth retardation associated with persistent hyperamylasemia and suspected chronic pancreatitis.

Elevated serum amylase, normal serum lipase, and very low 24-hour urine amylase and amylase clearance/creatinine clearance ratio were confirmed, consistent with macroamylasemia. Serologic tests for celiac disease were positive, and the diagnosis was confirmed by small bowel biopsy showing subtotal villous atrophy. Thyroid function tests showed a pronounced hypothyroidism, associated with high titers of thyroid microsomal and thyroglobulin antibodies. A diagnosis of celiac disease, macroamylasemia, and hypothyroidism attributable to autoimmune thyroiditis was made. A gluten-free diet and oral replacement with L-thyroxine was started with clinical improvement. Serum amylase and amylase clearance/creatinine clearance ratio normalized, consistent with resolution of macroamylasemia. Auto-antibodies to alpha-amylase and to exocrine pancreas declined after institution of a gluten-free diet.¹³

Sources:

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2. Isham CA, Ridgeway NA, Hedrick R, Cate JC 4th. Screening for macroamylase in a community hospital. Clin Chem. 1984 May;30(5):741-2. [↩]
3. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G.Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol. 2003;9(6):1377-1380, Available at: http://www.wjgnet.com/1007-9327/9/1377.asp. Accessed Jan 3, 2005. [↩]
4. Bermejo JF; Carbone J; Rodriguez JJ, et al. Macroamylasaemia, IgA hypergammaglobulinaemia and autoimmunity in a patient with Down syndrome and coeliac disease. Scandanavian Journal of Gastroenterology. Apr 2003;38(4):445-7. [↩]
5. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G. Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol. 2003;9(6):1377-1380, Available at: . http://www.wjgnet.com/1007-9327/9/1377.asp.Accessed Jan 3, 2005. [↩]
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7. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G. Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol. 2003;9(6):1377-1380. [↩] [↩]
8. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
9. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
10. Depsames R, Fireman Z, Niv E, Kopelman Y. Macroamylasemia as the first manifestation of celiac disease. Case Rep Gastroenterol. 2008 Jun 6;2(2):196-8. doi: 10.1159/000132771. [↩]
11. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G. Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol 2003; 9(6): 1377-1380. [↩]
12. Bermejo JF; Carbone J; Rodriguez JJ, et al. Macroamylasaemia, IgA hypergammaglobulinaemia and autoimmunity in a patient with Down syndrome and coeliac disease. Scandanavian Journal of Gastroenterology. Apr 2003;38(4):445-7. [↩]
13. Barera G, Bazzigaluppi E, Viscardi M, Renzetti F, Bianchi C, Chiumello G, Bosi E. Macroamylasemia attributable to gluten-related amylase autoantibodies: a case report. Pediatrics. 2001 Jun;107(6):E93. [↩]