Medical Policy: 10.01.15 

Original Effective Date: May 2010 

Reviewed: April 2021 

Revised: April 2021 



This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.


Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.


This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.



The U.S. Food and Drug Administration (FDA) defines a medical food in the Orphan Drug Amendment as a food which is formulated to be consumed or administered under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.


In 1994, the American Academy of Pediatrics Committee on Nutrition issued its recommendations on reimbursement for medical foods for inborn errors of metabolism. Inborn errors of metabolism are a group of rare disorders resulting in the excessive accumulation of an amino acid or other product along the metabolic pathway for lack of a natural enzyme required to digest certain foods. Manifestations of these disorders generally include central nervous system dysfunction, developmental delay, seizures and liver dysfunction.


The clinical manifestations in many of these disorders can be prevented if diagnosis is achieved early and necessary treatment with dietary protein or amino acid restriction is instituted immediately. These disorders are named for the accumulating amino acid and include, but are not limited to, phenylketonuria (PKU), maple syrup urine disease, citrullinemia, cystinosis, homocystinuria, methylmalonic acidemia, propionic acidemia, isovaleric acidemia type I, tyrosinemia types I and II, and urea cycle disorders.


Treatment might include restriction of specific amino acids, restriction of total nitrogen intake, or supplementation of certain substances. For some of the inborn errors of metabolism, special formulas and medical foods have been developed which eliminate the amino acid that cannot be metabolized from the protein context of the food. As adults, they must avoid certain foods as well. Geno typical women with classic PKU desiring pregnancy need to alter their diet by using a special maternal dietary supplement low in phenylalanine. The use of this supplement reduces the risk of severe retardation in the infant of a mother with PKU.


Inborn errors of metabolism (IEM) are inherited genetic disorders that interfere with specific metabolic pathways. These interferences may result in either a deficiency or excess of a particular product. There are three major categories of IEMs: protein disorders, fatty acid oxidation disorders, and carbohydrate disorders. Special food products are required to treat inborn errors of metabolism in order to avoid long-term complications which can result in mental retardation, seizures, coma or death. Inborne errors of metabolism are considered present at birth and permanent.


Examples of an inherited metabolic disorder (inborn errors of metabolism) include, but are not limited to:

  • Phenylketonuria (PKU)
  • Maple syrup urine disease (MSUD)
  • Homocystinuria
  • Urea cycle disorders
  • Organic acidemias (e.g., Isovaleric Acidemia, propionic academia, methylmalonic academia)
  • Histidinemia
  • Tyrosinemia
  • von Gierk's disease
  • Pyruvate dehydrogenase deficiency 


Individuals with inborn errors of metabolism require "exempt" specialized metabolic infant formulas. The FDA has requirements for the minimum and maximum amount of nutrients in infant formulas; if these requirements are not met, the infant formula may be "exempt" from these nutrient requirements. "An exempt infant formula is any infant formula which is represented and labeled for use by an infant who has an inborn error of metabolism (IEM), or low birth weight, or who otherwise has an unusual medical or dietary problem." Exempt amino acid-based metabolic formulas require a prescription. Examples include:

  • BCAD 1 or 2
  • Complesx MSD
  • Glutarex 1 and 2
  • Glytactin BetterMilk
  • Glytactin RTD 15
  • Hom 1 and 2
  • HCUAnamix
  • Ketonex 1 or 2
  • Lofenalac
  • Lophlex
  • Maxamaid
  • Milupa PKU
  • OA 1 or 2
  • Periflex/Periflex Junior
  • PFD 2 or Toddler
  • Phenex 1 and 2
  • Phenyl-Free 1 or 2
  • Phenyl-Free HP
  • PhenylAde
  • Provimin
  • TYR Anamix
  • Tyromex
  • XMET Maxamum
  • X Phe Analog
  • X Phe Maxamaid 


Food allergies are not considered an inborn error of metabolism.


Medical Foods can be classified into the following categories:

  1. Nutritionally complete formulas; or
  2. Nutritionally incomplete formulas, including individual "modular" type products that may be mixed with other products before use (e.g., protein, carbohydrate, or fat modulars); or
  3. Formulas for metabolic (genetic) disorders in patients over 12 months of age; or
  4. Oral rehydration products.


Food products are not considered medical food items, regardless of their intended use. Food products include food thickeners, baby food, gluten-free food products, high protein powders and mixes, low carbohydrate diet foods, grocery items, nutritional supplement puddings, weight-loss foods and formula, grocery items that are used in specialized diets or have been modified for a special nutritional need, regular grocery products that can be mixed in blenders and used with an enteral system regardless of whether these regular food products are taken orally or parenterally.


Foods that are considered low protein modified food products include, but are not limited to, cookies, bread, pasta, cheeses, soups and desserts that have been modified to reduce the protein content of the food are available without a prescription and are not necessary as other regular food can be used to provide a complete diet. These foods are for convenience.


Relizorb™ immobilized lipase cartridge was recently approved for in-line use to include digestive enzymes into the enteral feeding. It is designed to mimic the action of pancreatic lipase for use in adults receiving enteral tube feedings. Large studies with human subjects are not available.


Prior Approval:

Not applicable



For additional information regarding nutrition for inborn errors of metabolism, please refer to policy 01.02.01 Enteral Therapy and Oral Formula.


Medical foods are considered not a covered benefit for any diagnosis other than inborn errors of metabolism which are present at birth, and permanent in nature.


Modified grocery item foods, even if categorized as medical foods by the manufacturer, are considered not a covered benefit.


Medical Foods

  1. The product must be a medical food for oral feeding that falls into one of the following categories a) Nutritionally complete formulas for metabolic (genetic) disorders in patients;  b) individual "modular" type products that may be mixed with other products before use (e.g., protein, carbohydrate, or fat modulars); c) Oral rehydration products; and
  2. The product must be labeled and used for the dietary management of a specific medical disorder, disease, or condition for which there are distinctive nutritional requirements to avert the development of serious physical or mental disabilities or to promote normal development or function. The condition must be present at birth and considered a permanent condition and
  3. The product must be labeled for use under medical supervision.


Conditions associated with an inborn error of metabolism interfere with the metabolism of specific nutrients. Examples of an inherited metabolic disorder (inborn errors of metabolism) include, but are not limited to:

  • Phenylketonuria (PKU)
  • Maple syrup urine disease (MSUD)
  • Homocystinuria
  • Urea cycle disorders
  • Organic acidemias
  • Histidinemia
  • Tyrosinemia


There are currently no medical food requirements for mitochondrial disease that averts the development of serious physical or mental disabilities or promotes normal development or function. The use in this condition is considered not a covered benefit.


The purchase of food and formula that is modified for special diets is not considered a medical food available for coverage. This includes low protein/low phe groceries and over the counter formula. The coverage of over the counter foods are considered not a covered benefit.


Medical foods for conditions other than permanent inborne errors of metabolism, including but not limited to the following products and conditions, are considered not a covered benefit:

  • Metanx and Posiapn for Neuropathy
  • Vayarin for ADHD or Autism
  • Deplin for Depression and Schizophrenia
  • Vayacog and Axona for Alzheimer’s
  • Theramine for Chronic Pain
  • VSL #3 for Irritable Bowel Syndrome
  • Medical foods/Supplements for Mitochondral Disease
  • Management of Diabetes
  • Management of Pregnancy


Oral enteral nutrition is considered not a covered benefit when the criteria above have not been met.


Digestive enzymes added to enteral formula via a cartridge device attached to the tubing used for enteral feeding is considered investigational (e.g., Relizorb™ immobilized lipase cartridge). There is insufficient evidence based on the current literature to include lack of control groups, long term outcome, and accounting for nutritional variables within the studies are considered major drawbacks of available literature.


Food thickener and food additives are considered not a covered benefit.


Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • B4100 Food thickener, administered orally, per oz
  • B4104 Additive for enteral formula (e.g., fiber)
  • B4105 In-line cartridge containing digestive enzyme(s) for enteral feeding, each
  • S9433 Medical food nutritionally complete, administered orally, providing 100% of nutritional intake
  • S9434 Modified solid food supplements for inborn errors of metabolism
  • S9435 Medical foods for inborn errors of metabolism


Selected References:

  • Vanderhoof JA. Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with DHA and ARA. J Pediatr Gastroenterol Nutr. 2008 Nov;47 Suppl 2:S60-1.
  • Benhamou AH, Schappi Tempia MG, Belie DC, Eigenmann PA. An overview of cow's milk allergy in children. Swiss Med Wkly. 2009 May 30;139(21-22):300-7.
  • Potter BK, Chakraborty P, Kronick JB, Wilson K, et al. Achieving the "triple aim" for inborn errors of metabolism: a review of challenges to outcomes research and presentation of a new practice-based evidence framework. Genet Med. 2012 Dec 6. [Epub ahead of print]
  • Dellon E., Gonsalves N., et al. ACG Clinical Guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis. Am J Gastro. 2013; 108:679-692.
  • American Academy of Pediatrics Committee on Nutrition. Reimbursement for medical foods for inborn errors of metabolism Pediatrics. 1994;93(5):860.
  • National Institutes of Health, Consensus Development Panel. Phenylketonuria: Screening and Management Pediatrics. 2001;108:972–982.
  • National Institutes of Health. National Library of Medicine. Medical Encyclopedia. Inborn Errors of Metabolism Jun 2013.
  • U.S. Food and Drug Administration (FDA). Center for Food Safety and Applied Nutrition. Office of Nutritional Products, Labeling, and Dietary Supplements. Draft Guidance for Industry: Frequently Asked Questions about Medical Foods
  • National Institute for Health and Clinical Excellence (NICE). Quality Standard for Nutrition Support in Adults NICE quality standards [QS24]. November 2012.
  • FDA Guidance for Industry: Frequently Asked Questions About Medical Foods, Second edition. May 2016
  • Standards of Medical Care in Diabetes 2016, American Diabetes Association, Diabetes Care. 39 (Supplement 1): S1-S112, January 2016.
  • Camp, K., Lloyd-Puryear, M., Huntington, K. Nutritional treatment for inborn errors of metabolism: Indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example. Molecular Genetics and Metabolism, 107:3-9, 2012.
  • Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315(15):1624-1645.
  • Brennan, M., Yoon, S., Lininger, T. (2016). Medical foods hold promise in chronic pain patients.
  • National Institute of Health (NIH), Research reveals unintended consequences of inappropriate medical food use in managing patients with a type of metabolic disorder
  • Food and Drug Administration, Compliance Program Guidance Manual, 7321.002.
  • Freedman SD. Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation. Am J Manag Care. 2017;23(12 Suppl):S220-S228.
  • Freedman S, Orenstein D, Black P, et al. Increased fat absorption from enteral formula through an in-line digestive cartridge in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2017;65(1):97-101.
  • Medscape, LLC. FDA clears Relizorb for use with enteral tube feedings. Medscape, LLC. New York, NY. December 03, 2015. Accessed March 23, 2016.
  • Stevens J, et al. Absorption and safety with sustained use of RELiZORB evaluation (ASSURE) study in patients with cystic fibrosis receiving enteral feeding. J Pediatr Gastroenterol Nutr 2018 Oct;67(4):527-532.
  • Huntington K, Buist NRM. Medical food for treatment of inborn errors of metabolism and state legislative mandates. Top Clin Nutr. 2009;24(4):289–306.


Policy History:

  • April 2021 - Annual Review, Policy Revised
  • April 2020 - Annual Review, Policy Revised
  • April 2019 - Annual Review, Policy Revised
  • June 2018 - Interim Review, Policy Revised
  • April 2018 - Annual Review, Policy Revised
  • April 2017 - Annual Review, Policy Revised
  • April 2016 - Annual Review, Policy Revised
  • May 2015 - Annual Review, Policy Revised
  • June 2014 - Annual Review, Policy Renewed
  • June 2014 - Interim Review, Policy Revised
  • August 2013 - Annual Review, Policy Renewed
  • February 2013 - Interim Review, Policy Revised
  • September 2012 - Annual Review, Policy Renewed
  • September 2011 - Annual Review, Policy Renewed

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.


*CPT® is a registered trademark of the American Medical Association.