Study Analyzes "Hypoallergenic" Cow's Milk Formulas for Allergenic Activity
By Jacquelyn K. Beals, PhD
Medscape Medical News
December 14, 2009 (Buenos Aires, Argentina) — Hypoallergenic formulas based on hydrolyzed cow's milk or combinations of amino acids have considerable variation in their biochemical and immunologic characteristics. The degree to which a given formulation is hypoallergenic can be identified and measured with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), mass spectrometry, and the immunoglobulin (Ig)E reactivity of each formula.
During their first year, 2% to 3% of infants develop hypersensitivity to cow's milk. This is frequently associated with early exposure to cow's milk. Formulas that lack allergenic activity and do not lead to harmful cytokine production are useful for preventing cow's milk sensitization and allergy in potentially sensitive children, according to Heidrun Hochwallner, a PhD candidate at the Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, in Austria, who presented her team's research here at the World Allergy Organization XXI World Allergy Congress.
Scientists have investigated milk proteins for nearly 50 years, and note that sensitivity is more likely to occur in children with early exposure to cow's milk. Because more than half of allergic children have no family history of allergy, an effective way to prevent milk allergies might be to use hydrolyzed milk protein for all children who require breast milk supplements.
The current study investigated 16 cow's milk formulas to determine their respective allergenic activity. The IgE reactivity of each formula was tested in sera from 22 patients with a cow's milk allergy; T-cell proliferation and cytokine secretion were examined in cultures of peripheral blood mononuclear cells from patients with cow's milk allergy and from people with IgG antibodies specific to cow's milk.
Among the 16 formulas tested, "the amino acid formulations showed the lowest IgE-binding activity, low T-cell reactivity, and low allergenic activity," Ms. Hochwallner told Medscape Allergy and Immunology. In contrast, "the formulas with intact proteins, complete proteins, showed high levels of IgE-binding activity, T-cell reactivity, and allergenic activity," she said.
"We could also see a difference in the induction of cytokine levels, so we could kind of identify formulas that induce lower levels than others of interferon-γ, interferon-α, and [interleukin] IL-6.?.?.?. And we could see formulas that induced lower levels of the Th2-driving cytokines IL-5 and IL-13," said Ms. Hochwallner.
As summarized in the meeting abstract: "We could rank the various formulas regarding allergenic activity. Most interestingly, we could demonstrate that certain formulas did not stimulate a potential detrimental cytokine pattern, indicating that these formulas not only lack IgE-related inflammatory and sensitizing activity, but also do not induce harmful cytokine production."
Is it odd that the standards for "hypoallergenic cow's milk formulas" are so varied? It is "somewhat surprising, but not really, because the manufacturing process varies from one manufacturer to another," session comoderator Sami Bahna, MD, DrPH, professor of pediatrics and medicine, chief of allergy and immunology, and director of the Allergy and Immunology Training Program, Louisiana State University Health Sciences Center, in Shreveport, told Medscape Allergy and Immunology.
"The molecules or the peptides that are remaining can vary widely — for example, the extensively hydrolyzed whey. You may find casein in it, because the whey came from the whole milk," said Dr. Bahna. "Casein-derived formulas can have whey in them, but generally, they are hypoallergenic. Only about 3% to 5% of children who are allergic to cow's milk are allergic to the extensively hydrolyzed formula."
"On the other hand, partially hydrolyzed formulas have larger peptides and can cause allergy. So although they are useful as?.?.?. prophylaxis, they are not indicated. In fact, they are contraindicated for children who are already allergic," Dr. Bahna said. A person who is truly allergic to cow's milk or milk formula has to go to extensively hydrolyzed formula, and probably more than 95% of the formula on the market would be tolerated well. "If it's not tolerated, then they go to amino acid formulas," added Dr. Bahna.
"Also, it depends on the availability, the society, the community, and the prices," explained Dr. Bahna. "The majority of cow's-milk-allergic children would tolerate soy formula, which is similar in price, and it's easily available and the taste is reasonable also. We have to individualize," Dr. Bahna said. "If a person is highly allergic, we may have to go to the very expensive or the amino acid formulas?.?.?. so the individualization will be good for the family."
In closing, the presenters noted that some formulas lack IgE-related inflammatory and sensitizing activity and do not induce production of harmful cytokines. The authors suggest that other types of inflammatory disease — inflammatory bowel disease, for example — might benefit from these noninflammatory milk formulations.
Ms. Hochwallner and Dr. Bahna have disclosed no relevant financial relationships.
World Allergy Organization XXI World Allergy Congress (WAC): Abstract?471. Presented December?7, 2009.
