True or False:
Allergens are Present
in Breast Milk for Weeks
The standard response from medical professionals to women who are starting elimination diets is that it takes two weeks for ingested allergens to leave their breast milk. With this advice, the infant is commonly placed on hypoallergenic formula for two weeks while the mother adjusts her diet. This can be problematic for her supply as well as reduce the likelihood that the infant will return to breastfeeding. Additionally, this means that once the woman has begun her allergen free diet, she cannot go back. If it truly takes two weeks for allergens to not be found in breast milk, then there are no “cheat meals” to speak of. Mothers cannot enjoy even a single regular cookie on the very rare occasion because it may plague their milk for weeks on end. So, lets dig deeper into this theory by looking into the current research available.
How is Protein Transferred to Human Milk?
Most human milk proteins are synthesized by mammary epithelial cells, transported through the secretory pathway, packaged in secretory vesicles, and released by exocytotic fusion [1]. Additional proteins are transported to the mammary gland by transcytosis from blood plasma [2]. Many nonhuman proteins transferred through this mechanism have been detected via immunoassays, including those originating from peanuts, wheat, eggs, and cow’s milk.
Peanuts
In this study, 23 women ingested 50 grams of peanuts and had their breast milk collected every hour. For the peanut proteins they were studying, the researchers found that only 11 of the 23 had detectable levels of peanut in their breast milk. Of those 11 women, most showed peak levels in their breast milk after 1-2 hours. The study shows that peanuts did not enter the breast milk of several women. For those women who did test positive for peanut proteins, all but one indicated that it was no longer detectable after 8 hours [3].
Egg
Scientists gave one group of women a daily muffin containing an egg while providing an egg-free muffin to the other group. They found that daily consumption did not result in an accumulation of egg protein in breast milk over time [4]. In other words, the egg protein would have been eliminated from the breast milk within 24 hours before the mother ingested another egg. If the egg protein had stayed in the mother’s breast milk, there would be a concentration accumulation with each passing day. The same lab also found that breast milk concentration of egg protein was higher after cooked egg consumption compared to raw egg. The amount of egg consumed directly correlated with breast milk concentration which peaked within 8 hours of consumption [4].
Milk
Cow’s milk protein allergy (CMPA) is an immunologically mediated response to cow’s milk antigens [5]. While the symptoms suggestive of CMPA are found in up to 15% of infants, there is no diagnostic laboratory test [6]. CMPA may develop in formula fed or breast-fed babies [7]. Exclusively breast-fed CMPA is believed to be due to β-lactoglobulin found in human milk 4-6 hours post maternal cow’s
milk consumption. However, a 2019 human milk proteomic analysis discovered additional peptides/proteins originating from bovine milk products [8]. These dominant nonhuman proteins included bovine caseins (α-S1-, α-S2-, β-, and κ-caseins) in addition to β-lactoglobulin which were not detected in milk from mothers on a dairy-free diet.
Cow’s milk protein is the most analyzed nonhuman protein analysis in human milk to date. The Zhu study discussed above utilized in-gel separation of the milk proteins and "shotgun proteomics" to identify 1577 human proteins and 36 nonhuman proteins [8]. The dominant source of these nonhuman proteins was that of bovine origination. It is not clear how intact proteins transfer from the gastrointestinal system to mammary glands or why bovine proteins were more prevalent. It is hypothesized that certain bovine proteins, such as caseins, may undergo incomplete proteolysis due to their distinctive and protective property of coagulation at acidic pH. These and many other collaborating studies show the relationship between nonhuman proteins found in human milk and material dietary intake.
Using the same methods, another lab designed a dietary intervention and milk expression time point study. In other words, women were asked to be dairy-free prior to being given a serving of cow's milk followed by milk expression every hour for 6 hours. Using mass spectrometer ion intensity (incredibly accurate) testing, they found cow's milk proteins peaked at 2 hours post-ingestion and were undetectable at 6 hours [9].
*Milk Update 5/8/2020
A 2017 study titled "Detection of β-lactoglobulin in human breast-milk 7 days after cow milk ingestion" was purposefully not covered in the original version of this article [12]. Researchers found β-lactoglobulin increased in concentration from 0.580 ng/ml baseline (after a 7 day CMP-free diet) to 1.15 ng/ml and 1.08 ng/ml at days 3 and 7, respectively. While the study is factual in that there was detectable CMP 7 days post-ingestion, the author fails to accurately correlate this to breastfeeding and food intolerance/allergy. CMP reactivity typically occurs at 611 ng/ml or higher [13]. This means that even at the highest concentration found throughout the study (one sample was 3.7 ng/ml at 24 hours) the amount of β-lactoglobulin was still 200x less than what would elicit a response. Unfortunately, the researchers also did not have a control group of women who had not consumed CMP to prove their methodology was correct and that the results were in fact from mother's ingestion of cow's milk.
*Milk Update 8/20/2020
The above information and our overview of healing timelines found here align with the Spanish Pediatric GI, Primary Care, and Immunology Societies [14]: "When CMPA is suspected in a young child based on the clinical history, CMP should be eliminated from the diet. Elimination leads to improvement and resolution of symptoms in a variable period of time, which may be of 1 to 5 days in acute forms (acute FPIES, vomiting), 1–2 weeks in cases of eczema or rectal bleeding, and up to 2–4 weeks in patients with constipation, diarrhea and/or growth faltering."
Similar information can be found through several other sources. For example, the Journal of Pediatric Gastroenterology & Nutrition states [15]: "If the history suggests an immediate reaction, then the maternal elimination diet needs to be maintained for only 3 to 6 days. If delayed reactions are suspected (eg, allergic proctocolitis), then the diet should be continued for up to 14 days. If there is no improvement, then it is likely that diagnoses other than CMPA are the cause of the symptoms and the child should be further evaluated."
As outlined above, if CMP continued to linger in breast milk for weeks post-ingestion then acute reactions would continue past a few days and chronic reactions would take longer than 4 weeks to fully improve. These recommendations follow the scientific studies showing that concentration will peak a few hours after ingestion and steadily decreases from there. This quick peak and clearance explains why acute reactions occur then improve within 72 hours and chronic within a few weeks, exactly like direct introduction.
Wheat
Of 53 lactating women given 20 grams of wheat, 41 of them tested positive for gliadin. Maximum levels were found 2-4 hours after ingestion [10]. Another study of 49 women with unrestricted diets all expressed breast milk containing gliadin. Six of these women were put on a 3-day wheat free diet which resulted in undetectable gliadin levels [11], indicating that the 3-day period was sufficient time to clear breast milk of wheat proteins. It is important to know that the time to clear wheat may be significantly less than 3 days, unfortunately there aren't any known studies with a closer time point (YET).
These studies, as well as several others, indicate two important takeaways:
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Ingested proteins associated with food sensitivities do not always enter the mothers breast milk
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When the protein was detected in breast milk, it was typically cleared in 6-8 hours for a single serving
*More research is needed to fully understand how allergen proteins both enter and leave breast milk.
References:
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Franke, Werner W., et al. "Involvement of vesicle coat material in casein secretion and surface regeneration." The Journal of cell biology 69.1 (1976): 173-195.
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Ollivier-Bousquet, Michele. "Transferrin and prolactin transcytosis in the lactating mammary epithelial cell." Journal of mammary gland biology and neoplasia 3.3 (1998): 303-313.
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Vadas, Peter, et al. "Detection of peanut allergens in breast milk of lactating women." Jama 285.13 (2001): 1746-1748.
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Palmer, D. J., M. S. Gold, and M. Makrides. "Effect of maternal egg consumption on breast milk ovalbumin concentration." Clinical & Experimental Allergy 38.7 (2008): 1186-1191.
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Walker‐Smith, J. A. "Diagnostic criteria for gastrointestinal food allergy in childhood." Clinical & Experimental Allergy 25 (1995): 20-22.
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Host, Arne, and Susanne Halken. "Cow’s milk allergy: where have we come from and where are we going?." Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 14.1 (2014): 2-8.
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Kilshaw, Peter J., and Andrew J. Cant. "The passage of maternal dietary proteins into human breast milk." International Archives of Allergy and Immunology 75.1 (1984): 8-15.
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Zhu, Jing, et al. "Discovery and quantification of nonhuman proteins in human milk." Journal of proteome research 18.1 (2018): 225-238.
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Picariello, Gianluca, et al. "Excretion of dietary cow’s milk derived peptides into breast milk." Frontiers in Nutrition 6 (2019): 25.
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Troncone, R., et al. "Passage of Gliadin Into Human Breast Milk." Pediatric Research 20.7 (1986): 696.
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Chirdo, F. G., et al. "Presence of high levels of non-degraded gliadin in breast milk from healthy mothers." Scandinavian journal of gastroenterology 33.11 (1998): 1186-1192.
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Matangkasombut, Ponpan, et al. "Detection of β-lactoglobulin in human breast-milk 7 days after cow milk ingestion." Paediatrics and international child health 37.3 (2017): 199-203.
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Allen, Katrina J., et al. "Allergen reference doses for precautionary labeling (VITAL 2.0): clinical implications." Journal of allergy and clinical immunology 133.1 (2014): 156-164.
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Jaime, Beatriz Espín, et al. "Non-IgE-mediated cow's milk allergy: consensus document of the spanish society of paediatric gastroenterology, hepatology, and nutrition (SEGHNP), the spanish association of paediatric primary care (AEPAP), the spanish society of extra-hospital paediatrics and primary health care (SEPEAP), and the spanish society of paediatric clinical immunology, allergy, and asthma (SEICAP)." Anales de Pediatría (English Edition) 90.3 (2019): 193-e1.
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Koletzko, S., et al. "Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines." Journal of pediatric gastroenterology and nutrition 55.2 (2012): 221-229.