Formula Ingredients and Components

Formulas are made of 6 basic components - protein, fat, carbohydrate, vitamins, minerals, and other nutrients. such as probiotics and prebiotics. What makes one brand of formula different from the next is the specific combination of carbohydrates, fats, and proteins it uses, as well as any additional ingredients. These differences and their indicated use are explained below. The Medical Home Portal does not endorse a specific brand or preparation; however, commercially prepared formulas will be mentioned here to provide examples. International recommendations for formula composition can be found at [Koletzko: 2005].

Protein

Formulas are commonly differentiated by the type of proteins they contain. These include cow milk protein, soy protein, partially hydrolyzed, extensively hydrolyzed, and amino acid-based formulas. Common conceptions about the benefits of these different proteins are often not well grounded by evidence.
  • Cow milk protein. Cow milk proteins include whey and casein. While whey and casein are also in human milk, there are differences between the whey in human milk and the whey in cow milk. Protein content of cow milk based formulas tends to be higher than in human milk and can result in increased amino acid levels (of unclear clinical significance). [Committee: 2013]
    • Indications for use: Typically, first line replacement for breastmilk/donor milk
    • Contraindications: Cow milk protein allergy/intolerance and certain metabolic conditions including galactosemia
    • Examples of standard cow milk formulas: Enfamil Infant, Similac Advance, store brand Advantage
  • Soy protein. While many people think that soy formulas are an appropriate substitute for cow milk formulas, approximately 10-14% of infants with an allergy to cow milk protein will also have allergy to soy protein. [Committee: 2013] There have been theoretical concerns about high levels of dietary soy isoflavones adversely affecting human development, reproduction, or endocrine function but the current evidence does not demonstrate these negative outcomes. [Jatinder: 2008]
    • Indications for use: Galactosemia, hereditary lactase deficiency, IgE mediated allergy to cow milk, vegan, secondary lactose intolerance related to acute gastroenteritis. The routine use of isolated soy protein based formula has no proven value in the prevention or management of infantile colic, or prevention of atopic disease. [Jatinder: 2008]
    • Contraindications: Not designed or recommended for preterm infants who weigh <1800 g. [Committee: 2013] Avoid in infants with proctitis or enterocolitis.
    • Examples: Enfamil ProsoBee, Gerber Good Start Soy, Similac Soy Isomil
  • Partially hydrolyzed protein. Cow milk proteins (whey and/or casein) are broken into portions, making them somewhat easier to digest. Partially hydrolyzed infant formulas are not considered “hypoallergenic” by the FDA. [Carolyn: 2012]In many infants with cow milk protein allergy, partially hydrolyzed formula may be well tolerated and more palatable than extensively hydrolyzed formula. [Kido: 2015]
    • Indications for use: May be tolerated by some infants with cow milk protein intolerance. Insufficient evidence for use in prevention of asthma, eczema, food allergies, and rhinitis, although possibly helpful to prevent eczema in infants at high risk. [Vandenplas: 2016] [Cabana: 2017] Insufficient evidence for use to manage gastroesophageal reflux, [Vandenplas: 2016] [Savino: 2014] constipation, or colic in infants.
    • Contraindications: Milk allergy [Carolyn: 2012]
    • Examples of partially hydrolyzed formulas: Similac Total Comfort, Enfamil LIPIL, Gerber Good Start products, and store brand Gentle formulas
  • Extensively hydrolyzed protein. Through a heat and enzymatic process, casein is broken into small portions (peptides and amino acids), which are then generally not recognized by the body as an allergen. Taste and cost can be a limiting factor for use.
    • Indications for use: Infants diagnosed with allergy to cow milk protein, with significant protein-induced enteropathy or enterocolitis [Jatinder: 2008] or failure to thrive. [Mousan: 2016] Weak evidence for use in prevention of allergies. [Vandenplas: 2014] [Lifschitz: 2015] Lack of evidence for use in preventing asthma and allergic rhinitis, although possibly helpful to prevent eczema in infants at high risk. [Vandenplas: 2016] [Cabana: 2017] Insufficient evidence for use to manage gastroesophageal reflux, [Vandenplas: 2016] [Savino: 2014] constipation, or colic in term infants. Weak evidence for use in preterm infants to manage gastroesophageal reflux, [Vandenplas: 2016] [Savino: 2014] and lack of evidence to prevent necrotizing enterocolitis or feeding intolerance in preterm infants. [Ng: 2017]
    • Examples of extensively hydrolyzed formulas: Alimentum, Gerber Extensively HA, Nutramigen
  • Amino acid based protein (aka Elemental). Taste and cost can be a limiting factor for use.
    • Indications for use: When extensively hydrolyzed formulas are not tolerated and there is extreme protein hypersensitivity or anaphylaxis to cow milk protein. [Meyer: 2018] [Mousan: 2016] May be used for severe enteropathy including severe rectal bleeding, growth failure, and eosinophilic esophagitis, particularly for those infants with multiple symptoms. [Meyer: 2018]
    • Examples of amino acid/elemental formulas: Alfamino, EleCare, Neocate, PurAmino

Fat

Typically almost half of the calories in cow milk based formulas are from fat that is formulated to provide an appropriate and absorbable blend of essential fatty acids. The fat is usually derived from vegetable oils such as palm olein, soy, coconut, high-oleic sunflower or safflower, plus occasionally animal fats. [Committee: 2013] Many formulas include added long-chain poly-unsaturated ARA and DHA omega fatty acids. The sources of these are single cell organisms.
  • Medium chain triglycerides. More readily digestible than long chain.
    • Indications for use: For fat malabsorption, such as in short bowel syndrome, cystic fibrosis, and intractable diarrhea
    • Example: Pregestimil
  • Long chain triglycerides (ketogenic). Provides 3-4 grams of fat for every 1 gram of carbohydrate and protein. See Ketogenic Diet for more information.
    • Indications for use: For children whose seizures have not responded to several different seizure medicines: Only for use in close consultation with a neurologist. [Epilepsy: 2014]
    • Examples: Nutricia KetoCal
  • Polyunsaturated fatty acids (PUFAs). Added to emulate composition of breast milk, but may lead to deterioration of the product unless antioxidants are also added. [Zou: 2016]
    • Indications for use: Lack of evidence currently that adding PUFAs help prevent allergies. [Schindler: 2016] Insufficient evidence of risks or benefits of using PUFAs for preterm infants for visual acuity, growth, and neurodevelopment. [Moon: 2016]
    • Example: DHA (docosahexaenoic acid) and ARA (arachidonic acid)

Carbohydrate

Lactose is the main carbohydrate in human milk as well as in many formulas. It breaks down to glucose and galactose. Almost all infants are able to tolerate lactose, even when they have cow milk protein allergy. [Heine: 2017] Corn maltodextrin is sometimes used as a secondary source of carbohydrate in formula. One study found that many infant formulas’ calories are more than 20% from sugar. [Walker: 2015] Complex carbohydrates, also known as starches, are used in some formulas as thickeners to help with gastroesophageal reflux.
  • Alternatives to lactose. These include sucrose, corn syrups, tapioca starch, maltodextrins, and other modified starches. Reduced lactose formulas exist as well.
    • Indications for use: Congenital lactase deficiency, which is rare, and lactose intolerance (not a common infant condition)
    • Examples of lactose free formulas: Enfamil ProSobee, Gerber Good Start Soy, Similac for Diarrhea, store brand Soy
    • Examples of reduced lactose formulas: Gerber Good Start Soothe, Honest Co. Organic Sensitive, Similac Sensitive, store brand Gentle and Sensitivity
  • Added starch. Typically contains added rice starch
    • Indications for use: Gastroesophageal reflux
    • Examples: Enfamil A.R., Similac for Spit-Up, store brand Added Rice Starch

Electrolytes, Minerals, and Vitamins

These include major and trace (FDA-regulated) minerals and vitamins.
  • Iron: Quantities vary in different types of formulas to adjust for absorption. Standard infant formulas contain 10-12 mg/L. Low-iron formulas contain 4-6 mg/L and are not routinely recommended. Caregivers may be concerned that the iron upsets their infant's stomach or causes constipation, but no scientific evidence demonstrates this effect. [Committee: 2013]
    • Indications for use of low-iron formulas: Neonatal hemochromatosis (rare), impaired renal function
    • Example: Similac PM 60/40
  • Aluminum: Although the aluminum content of human milk is 4-65 ng/mL, soy protein based formula is 600-1300 ng/mL. [Jatinder: 2008] Because aluminum competes with calcium for absorption, increased amounts of dietary aluminum from isolated soy protein based formula may contribute to the reduced skeletal mineralization (osteopenia) observed in preterm infants and infants with intrauterine growth retardation. [Jatinder: 2008] Term infants with normal renal function do not seem to be at substantial risk of developing aluminum toxicity from soy protein based formulas. [Jatinder: 2008]

Other Nutrients

Emerging research on formulas using combinations of interventions including synbiotics (both probiotics and prebiotics), low-lactose content, hydrolyzed proteins, magnesium, and/or other components suggests opportunities for improvement of infant colic, spitting up, constipation, allergies, and intestinal health as well as potential health benefits for premature infants such as prevention of necrotizing enterocolitis. Safety and efficacy studies are ongoing. [Xinias: 2017] [Xinias: 2018] [Radke: 2017] [Vandenplas: 2017] Additional components added to infant formula to more closely emulate breast milk may include taurine [Verner: 2007], lutein, choline, carnitine [Kumar: 2004], nucleotides [Singhal: 2010], Vitamin E, and others.
  • Probiotics: Probiotics are supplements containing organisms that change the microflora of the host. These organisms are typically Lactobacillus, Bifidobacterium, and Streptococcus species. The addition of probiotics to powdered infant formula has not been proven harmful to healthy term infants. A 2018 AAP meta-analysis supports use of Lactobacillus reuteri to treat infant colic in breast-fed babies, but the evidence is still lacking for its use in formula. [Sung: 2018]
    • Examples of Formulas Containing Probiotics: Gerber Good Start, Good Start Gentle, Good Start Grow for Toddlers, and Pure Bliss by Similac
  • Prebiotics: Prebiotics are supplements containing a nondigestible ingredient, usually in the form of oligosaccharides, which selectively stimulates the favorable growth or activity of indigenous probiotic bacteria. Human milk contains substantial quantities of prebiotics. Use of prebiotics in infant formula is undergoing extensive study but is not thought to be harmful. [Vandenplas: 2017] Almost all infant formulas and many older child formulas include prebiotics.

Authors & Reviewers

Last update/revision: August 2018
Current Authors and Reviewers:
Author: Jennifer Goldman-Luthy, MD, MRP, FAAP

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