Glycomacropeptide (GMP)

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • Acetyl galactosamine, branched-chain amino acids (BCAAs), carbohydrate, casein glycomacropeptide (cGMP), casein glycopeptide (CGP), casein macropeptide (CMP), casein-derived peptide (CDP), caseinglycopeptide, caseinmacropeptide, caseinoglycomacropeptide, cheese, cholecystokinin (CCK), galactosamine, galactose, glucosamine, isoleucine, kappa-casein, milk, phosphorus, sialic acid (N-acetylneuraminic acid), sweet whey, valine, whey.

Background

  • Purified glycomacropeptide (GMP) has been used in dietary supplements and in functional foods and beverages, which are products that claim to provide some health benefit beyond basic nutrition. GMP is produced in cheese making when an enzyme called chymosin (also known as rennin) is added to milk. Chymosin breaks down the milk protein kappa-casein into para-kappa-casein and glycomacropeptide (GMP). Para-kappa-casein is a component of the cheese curd, while the GMP peptide is part of the whey. GMP is also formed in the stomach as a product of digestion by the enzyme pepsin.

  • GMP differs from other whey proteins, because it contains low levels of certain amino acids, namely phenylalanine, tryptophan, and tyrosine. Because GMP is the only known naturally occurring protein that does not contain phenylalanine, it may be beneficial to incorporate it into the diet of phenylketonuria (PKU) patients, who cannot metabolize phenylalanine. Research is ongoing in this area.

  • GMP also has relatively high amounts of branched-chain amino acids (BCAAs). BCAAs are believed to stimulate the production of cholecystokinin (CCK), a peptide released after eating that may act as a satiety-providing appetite suppressant. The effects of GMP supplementation on satiety have not been consistent in clinical trials. Other clinical studies have tested the effects of GMP in infant formulas and weight loss.

  • Well-designed clinical trials are needed before firm conclusions can be made regarding the use of GMP for any health condition.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Nutrition

GMP is present in infant formulas that contain whey. Results from clinical trials testing the benefits of supplementing infant formula with GMP are conflicting. Additional research is needed before firm conclusions can be made.

Obesity/weight loss

Whey protein, which contains GMP, has been found to be more filling than other types of protein. The effects of supplementary GMP on weight loss have been inconsistent in clinical trials. Additional research is needed.

Phenylketonuria (PKU)

Individuals with PKU cannot metabolize the amino acid phenylalanine and must strictly follow a diet in which most dietary protein is provided by a phenylalanine-free amino acid (AA) formula. In clinical trials, purified GMP was found to be a safe and acceptable alternative to synthetic amino acids as the primary protein source in the nutritional management of PKU. Additional research is needed to confirm these results.

Supplementation in preterm and very low birthweight infants

Hyperthreoninemia (high threonine levels) has been documented in infants fed a whey protein-predominant formula. This condition is associated with a risk of neurotoxicity during early development. Research has shown that an experimental formula based on acid whey without GMP lacked these toxic effects.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Antibacterial, anti-inflammatory, antiplatelet, antithrombotic (blood thinning), antitoxin, antiviral, appetite suppressant, athletic performance enhancement, burns, colitis, dental cavities, diarrhea, dietary source of protein, enhanced muscle mass / strength, fatigue, food additive, gastrointestinal conditions, general health maintenance (probiotic), heart disease risk, ileitis, immunomodulatory (immune effects), inflammatory bowel disease, kidney failure, liver disease, memory, post-surgical recovery, trauma (serious body-altering physical injury), well-being, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • For obesity or weight loss, one 50-gram dose of bovine cheese whey product (containing GMP) has been taken by mouth. Meal replacements containing 15 grams of protein from GMP-enriched whey protein isolate diluted with 200 milliliters of water have been taken by mouth twice daily for 12 months. A beverage containing whey protein isolate plus added GMP has been taken by mouth. Breakfasts containing whey (with GMP) with 10, 55, and 35% or 25, 55, and 20% of protein, carbohydrate, and fat, respectively, have been taken by mouth.

  • For phenylketonuria (PKU), GMP food products have been taken by mouth for four days.

Children (under 18 years old)

  • For infant nutrition, alpha-lactalbumin-enriched formulas, with GMP accounting for 10% or 15% of the protein, have been taken by mouth for approximately 4.5 months.

  • For phenylketonuria (PKU), GMP food products have been taken by mouth for four days.

  • For supplementation in preterm and very-low-birthweight infants, a formula based on sweet whey with GMP for seven days was detrimental (it caused hyperthreoninemia) compared to a formula based on acid whey (without GMP).

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid with known allergy or hypersensitivity to casein, whey, milk, or cheese. In clinical research where infant formula was supplemented with GMP, some infants developed a cow’s milk protein allergy.

Side Effects and Warnings

  • GMP is likely safe when used in normal amounts for weight loss for up to one year, and when used in typical amounts in infant formulas for up to 4.5 months.

  • Most clinical trials have reported a lack of adverse effects associated with GMP products, although individuals with allergies to milk products may theoretically have a reaction to the GMP protein. A formula containing sweet whey with GMP used for seven days in infants caused excessively high blood plasma levels of the amino acid threonine compared to a formula based on acid whey that lacked GMP.

  • GMP may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or those taking drugs, herbs, or supplements that may increase the risk of bleeding. Dosing adjustments may be necessary.

  • GMP may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • GMP may lower blood pressure. Caution is advised in patients with low blood pressure and in those taking drugs, herbs, or supplements that affect blood pressure.

  • Use cautiously in pregnant or breastfeeding women, due to a lack of sufficient safety data.

  • Use cautiously in combination with probiotics. Several studies have demonstrated that GMP may have prebiotic effects and may thus alter the number and kinds of bacteria present in the digestive tract.

  • Use cautiously in patients with autoimmune disorders or those using immunosuppressants.

  • Use cautiously in patients with a history of anorexia or other eating disorders, or those who are using weight loss agents, as GMP may enhance feelings of fullness and cause weight loss.

  • Use cautiously in patients with a history of constipation or those using laxatives, as GMP may inhibit these effects.

  • Use cautiously in patients with phenylketonuria (PKU), because commercially available GMP may contain phenylalanine.

  • Use nonpurified commercial GMP cautiously, because it may contain residual phenylalanine and may not provide the essential amino acids needed to use it as a replacement for synthetic amino acid dietary supplements.

  • Avoid administration of formula containing GMP to premature babies, due to the risk of hyperthreoninemia (excessively high blood levels of threonine).

  • Avoid with known allergy or hypersensitivity to casein, whey, milk, or cheese, due to the risk of allergic reaction.

  • Avoid ingesting large quantities of GMP on an empty stomach, due to the risk of cyclic-repetitive vomiting.

Pregnancy and Breastfeeding

  • Use cautiously in pregnant or breastfeeding women, due to a lack of sufficient available scientific evidence.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • GMP may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

  • GMP may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • GMP may lower blood pressure. Caution is advised in patients with low blood pressure and in those taking drugs that affect blood pressure.

  • GMP may also interact with antibiotics, anti-inflammatory agents, antiobesity agents, antiviral agents, cholesterol- and lipid-lowering drugs, dental and periodontal agents, drugs that weaken the immune system, gastrointestinal agents, laxatives, and neurologic agents.

Interactions with Herbs and Dietary Supplements

  • GMP may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

  • GMP may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

  • GMP may lower blood pressure. Caution is advised in patients with low blood pressure and in those taking herbs or supplements that affect blood pressure.

  • GMP may also interact with antibacterials, anti-inflammatory herbs, antiobesity herbs and supplements, antivirals, cholesterol- and lipid-lowering herbs and supplements, dental rinses, gastrointestinal herbs and supplements, immunosuppressants, laxatives, neurologic herbs and supplements, a phenylketonuria (PKU) diet, probiotics, and zinc.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Andersson Y, Hammarstrom ML, Lonnerdal B, et al. Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding. J Immunol 2009;183(7):4322-4328. View Abstract
  2. Bruck WM, Redgrave M, Tuohy KM, et al. Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants. J Pediatr Gastroenterol Nutr 2006;43(5):673-679. View Abstract
  3. Burton-Freeman BM. Glycomacropeptide (GMP) is not critical to whey-induced satiety, but may have a unique role in energy intake regulation through cholecystokinin (CCK). Physiol Behav 2008;93(1-2):379-387. View Abstract
  4. Gunther G, Boehm G, Georgi G, et al. Glycomacropeptide in premature babies’ nutrition is a main cause of hyperthreoninamia in premature babies fed on a formula diet. The Cochrane Library 2010;(1)
  5. Keogh JB, Woonton BW, Taylor CM, et al. Effect of glycomacropeptide fractions on cholecystokinin and food intake. Br J Nutr 2010;104(2):286-290. View Abstract
  6. Keogh JB, Clifton P. The effect of meal replacements high in glycomacropeptide on weight loss and markers of cardiovascular disease risk. Am J Clin Nutr 2008;87(6):1602-1605. View Abstract
  7. Laclair CE, Ney DM, MacLeod EL, et al. Purification and use of glycomacropeptide for nutritional management of phenylketonuria. J Food Sci 2009;74(4):E199-E206. View Abstract
  8. Lam SM, Moughan PJ, Awati A, et al. The influence of whey protein and glycomacropeptide on satiety in adult humans. Physiol Behav 2009;96(1):162-168. View Abstract
  9. MacLeod EL, Clayton MK, van Calcar SC, et al. Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria. Mol Genet Metab 2010;100(4):303-308. View Abstract
  10. Rigo J, Boehm G, Georgi G, et al. An infant formula free of glycomacropeptide prevents hyperthreoninemia in formula-fed preterm infants. J Pediatr Gastroenterol Nutr 2001;32(2):127-130. View Abstract
  11. Sandstrom O, Lonnerdal B, Graverholt G, et al. Effects of alpha-lactalbumin-enriched formula containing different concentrations of glycomacropeptide on infant nutrition. Am J Clin Nutr 2008;87(4):921-928. View Abstract
  12. van Calcar SC, MacLeod EL, Gleason ST, et al. Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. Am J Clin Nutr 2009;89(4):1068-1077. View Abstract
  13. Veldhorst MA, Nieuwenhuizen AG, Hochstenbach-Waelen A, et al. A breakfast with alpha-lactalbumin, gelatin, or gelatin + TRP lowers energy intake at lunch compared with a breakfast with casein, soy, whey, or whey-GMP. Clin Nutr 2009;28(2):147-155. View Abstract
  14. Veldhorst MA, Nieuwenhuizen AG, Hochstenbach-Waelen A, et al. Effects of complete whey-protein breakfasts versus whey without GMP-breakfasts on energy intake and satiety. Appetite 2009;52(2):388-395. View Abstract
  15. Veldhorst MAB, Nieuwenhuizen AG, Hochstenbach-Waelen A, et al. Effects of high or normal casein-, soy-, or whey with or without GMP- protein breakfasts on satiety, ‘satiety’ hormones, and plasma amino acid responses. Appetite 2007;49(1):336.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.