Whey Protein Allergy & Intolerance (Sensitivity): Symptoms & Causes

Whey protein supplements serve as an extremely efficient way to get quality, highly-bioavailable protein in your diet without excessive calories (great protein-to-calorie ratio).

That said, not everyone tolerates whey protein well – some individuals have whey allergies and sensitivities such that whey protein is unsafe or unhealthy to continue using.

Whey protein, a component of cow milk, consists primarily of the components alpha-lactalbumin and beta-lactoglobulin – of which the latter tends to be more allergenic.

For reference, cow milk allergy (CMA) is relatively common in children and adults with an estimated prevalence from 0.5% to 3%. (R1, R2)

The prevalence of whey protein allergy remains unknown, however, it is likely extremely rare as an isolated diagnostic entity (e.g. whey allergy without cow milk allergy).

Adult-onset whey allergy (e.g. no prior allergy but newly developed as an adult) has an estimated prevalence under 0.6%. (R)

Table of Contents

What causes whey allergy? (Possible mechanisms)

Put simply, whey allergy is caused by the immune system reacting to the ingestion of whey protein.

As Sousa et al. stated, “defects in oral tolerance are thought to be the root cause of food allergy.”

The exact reason(s) for which a whey protein allergy occurs may vary among individuals with whey protein allergy.

Genetics & epigenetics

There are likely genetic and epigenetic factors that influence both immune activity (specifics) and perhaps odds of developing a reaction to whey protein.

Immunological profile

Immune function can be influenced by a variety of genetic, epigenetic, and environmental variables.

Specific immunological signatures might predispose one to a whey allergy relative to other immunological signatures.

Atopic predisposition correlates strongly with various food allergies.

Sensitization

While most pediatrics with cow milk allergy (CMA) and whey allergy will outgrow this within a few years – select individuals might actually develop a whey protein allergy as a result of “sensitization” via non-ingestion exposures.

Powder inhalation

One potential modality of sensitization is inhalation of airborne whey protein powder particulates during preparation (e.g. while scooping & mixing).

Whey protein particles then enter the nasal cavity – which might cause the immune system to perceive whey as an invading pathogen, such that it continues to manufacture antibodies.

(Read: Snorting Whey Protein)

Gastrointestinal mechanisms

Large amounts of cow milk protein introduced to the GI tract may increase antigenic load.

If paired with exercise, this could increase intestinal permeability due to exercise-related movements.

The combination of increased antigenic load and intestinal permeability could theoretically cause whey to leak outside of the gut and induce sensitization in a subset of individuals – as anti-allergy mechanisms may become dysfunctional.

Immune signature in cow milk allergy (CMA)…

The duration of clinical reactivity in cow’s milk allergy is associated with levels of specific immunoglobulin G4 (IgG4) and immunoglobulin A (IgA) antibodies to beta-lactoglobulin in pediatrics. (R)

This is supported by data from a study by Savilahti et al. in which immune markers of 83 patients with IgE-mediated CMA were compared to 6209 patients without CMA.

Persistent CMA is associated with high CM-specific IgE levels, lower serum IgA levels to beta-lactoglobulin at diagnosis, and lower IgG4 levels to beta-lactoglobulin and alpha-casein at follow-up.

Development of tolerance to CM is associated with elevated concentrations of beta-lactoglobulin-specific serum IgA at time of diagnosis and later increasing specific IgG4 levels to beta-lactoglobulin and alpha-casein.

Ruiter et al. found that maintenance of tolerance to cow’s milk (i.e. no allergy) in atopic children and adults without CMA is associated with elevated levels of specific IgG4 and low specific IgE. (R)

Types of whey protein allergies (hypersensitivity)

IgE-mediated

IgE-mediated whey allergy is an allergy to whey that’s caused by IgE antibodies with activation of mast cells and basophils.

  • Typically occurs within minutes of ingesting the allergenic food.
  • Classic representations of food allergy with hypersensitivity response.
  • Common symptoms: hives, skin redness, vomiting, and possibly anaphylaxis.

Non-IgE-mediated

Non-IgE-mediated whey allergy is an allergy to whey that’s caused by components of the immune system separate from IgE antibodies.

  • Does not appear immediately after the ingestion of the allergenic food.
  • Usually occurs at least 2 hours after consumption of whey
  • Usually related to reactions in the GI tract such as vomiting, bloating, diarrhea, etc.
  • Rarely life threatening because these do not induce anaphylaxis.
  • Allergic proctocolitis, food protein-induced enteropathy, celiac disease, Heiner syndrome, cow’s milk protein-induced iron deficiency anemia, eosinophilic esophagitis, etc.

Mixed (IgE + non-IgE)

Mixed whey allergy is an allergy to whey that’s caused by both IgE antibodies and non-IgE components of the immune system.

  • Includes symptoms characteristic of IgE-mediated and non-IgE-mediated food allergy.

Note: A whey protein “intolerance” means that non-immune mechanisms are causing the reactions (e.g. gastrointestinal discomfort).

Whey protein allergy symptoms & reactions

Included below symptoms that may result from whey protein allergy.

Keep in mind that these lists may not contain every single symptom that someone might experience with whey allergy… the aim here is to give readers a general idea.

IgE-mediated whey allergy

Included below are some of the symptoms one might observe following an IgE-mediated whey protein allergy.

These symptoms typically emerge within minutes following exposure or ingestion of whey protein.

  • Anaphylaxis: This is a potentially life-threatening allergic reaction to whey that can cause a state of shock accompanied by low blood pressure, difficulty breathing (airway constriction, narrowing, blockage), vomiting, weak or rapid pulse, and hives. Requires immediate epinephrine.
  • Blood pressure changes: Someone might experience significant changes in blood pressure – typically hypotension (low blood pressure) which might trigger syncope (fainting) episodes.
  • Convulsions: Sudden irregular movements of the body caused by involuntary musculoskeletal contractions might occur in select cases of whey allergy.
  • Difficulty breathing: This may be a sign of anaphylaxis which requires urgent medical attention (and epinephrine administration).
  • Dizziness: Due to a combination of immune-mediated systemic changes following allergen ingestion, some individuals become extremely dizzy (this could be a sign of hypotension). (Read: Dizziness After Whey Protein).
  • Eye tearing, redness, itching: One’s eyes may generate significant more tears, become red, and/or itch as the result of a whey allergy.
  • Heart rate changes: Normal pulse ranges from 60-100 BPM. In the event of a whey allergy, this may change drastically.
  • Itching: Itching may occur on the skin (such as with hives) or within the eyes, nose, or throat areas.
  • Loss of consciousness: Individuals with severe whey allergy could lose consciousness within minutes of whey exposure.
  • Nasal discharge & congestion: May be accompanied by increased mucus production in the nasopharynx, globus sensation, and/or postnasal drip following whey intake.
  • Mental status changes: Agitation, anxiety, depression, brain fog, cognitive impairment, etc. could potentially occur as a result of a severe allergy.
  • Hives (skin rash): Red blotches or welts that itch may surface across certain areas of the skin.
  • Nausea & Vomiting: Nausea and vomiting are extremely common reactions to those with whey protein allergy.
  • Sneezing: Someone with a whey allergy may have sneezing fits after ingesting whey.
  • Swelling (edema): Lips, tongue, throat, airways may swell up as a result of a whey allergy.

Non-IgE-mediated whey allergy

Non-IgE-mediated allergies are commonly misclassified as “intolerance” due to significant overlap in symptom manifestations (primarily affecting the GI tract).

The difference? Non-IgE-mediated allergies involve the immune system reacting to whey (typically in delayed manner ~1-2+ hours after exposure) and intolerance has zero immune involvement.

Symptoms of non-IgE-mediated food allergies typically cease within 2-4 weeks of completely removing the offending food (e.g. whey) from one’s diet.

  • Blood or mucus in stool: Individuals with non-IgE-mediated whey allergy might notice the presence of blood or mucus in stool – or just generally atypical stool shape/appearance.
  • Chronic reflux: Due to a combination of gastrointestinal manifestations and increased mucus production – some individuals might develop chronic acid reflux conditions (e.g. GERD, LPR, etc.) until the allergenic agents are completely removed from the diet for at least 2-4 weeks.
  • Constipation: Non-IgE-allergies can sometimes interfere with normative digestive processes and gastrointestinal motility such as to cause constipation.
  • Diarrhea: A subset of individuals with whey allergy may experience significant digestive distress and diarrhea.
  • Dizziness: This may emerge within 1-2 hours of consuming whey and might persist for a significant duration until whey is fully eliminated from the diet. Likely related to a combination of lower blood pressure and inflammation.
  • Esophagitis: Some individuals with whey allergy may develop esophagitis – or inflammation of the esophagus wherein it becomes difficult to swallow and painful burning is experienced throughout the esophagus. May also cause vomiting or choking episodes. (Eosinophilic esophagitis is an example of a non-IgE manifestation of food allergy.)
  • Esophageal dysfunction: In addition to generalized esophageal inflammation (esophagitis) – various components of the esophagus may become dysfunctional (e.g. upper/lower esophageal sphincters) in response to allergy such that chronic esophageal motility disorders and/or reflux conditions develop.
  • Fatigue & lethargy: Feeling extremely fatigued, lethargic, tired, etc. after consuming whey might be a symptom of a non-IgE-related whey allergy. When the immune system reacts to a specific food – this can cause inflammation which in turn causes fatigue.
  • Low blood pressure: Those with non-IgE whey allergy might experience low blood pressure after ingestion of whey. This may be accompanied by significant dizziness and possibly even fainting spells (depending on the significance of the hypotension).
  • Mucus production: A non-IgE-mediated allergy to whey may involve postnasal drip, phlegm in the throat, or increased mucus production in the nasopharynx. This could result in “globus sensation” and potentially urge to frequently swallow.
  • Stomach, abdominal, chest pains: Many individuals experience pain in the stomach, abdomen, or chest – within 1-2 hours of whey ingestion. Although this could be a sign of general intolerance – it might also indicate an allergy.

Examples of medical conditions attributable to non-IgE-mediated allergies: Allergic proctocolitis, food protein-induced enteropathy, celiac disease, Heiner syndrome, cow’s milk protein-induced iron deficiency anemia, eosinophilic esophagitis.

Note: Some individuals may exhibit “mixed” allergy to whey such as a combination of IgE-mediated and non-IgE-mediated reactions.

  • Mixed reactions might be rarer simply due to the fact that once the allergy is identified – individuals typically stop consuming the offending agent (which resolves the non-IgE allergy).

Whey intolerance (sensitivity) symptoms

There may be overlap between intolerance symptoms and normative symptoms associated with digestion of whey protein.

The difference between a true intolerance and normative digestion is likely the consistency of symptoms (do they occur every time?) and magnitude of impairment (e.g. severe stomach pain) following ingestion.

  • Acid reflux & heartburn
  • Bloating
  • Constipation
  • Diarrhea
  • Flatulence (gas)
  • Gastrointestinal distress
  • Gurgling noises from stomach
  • Postnasal drip, throat mucus, etc.
  • Stomach & abdominal pains

Note: It’s possible to have both an allergy AND an intolerance to whey protein such that a subset of symptoms are immune-mediated and others are not.

Whey protein allergy (Scientific Literature)

Included below are studies and/or discussions of whey protein allergy in the scientific literature.

Bodybuilding Protein Supplements & Cow Milk Allergy in Adult (2018) (Sousa et al.) (R)

  • A healthy 24-year-old male with 3-month history of GI symptoms (abdominal discomfort, nausea during exercise, worsening of abdominal pain, and vomiting).
  • GI symptoms occurred during exercise and also a few minutes following ingestion of cow milk without exercise.
  • Reactions initially occurred exclusively at the gym and would significantly improve without medication within several hours after gym sessions.
  • None of the reactions were associated with cutaneous, respiratory, or cardiovascular reactions – and the patient never attended the emergency department or had previously sought medical care.
  • This individual eventually noticed that his symptoms were replicated after ingestion of cow milk (which he previously tolerated fine) without exercise – and consulted a medical doctor (allergist/immunologist).
  • This individual had no previous history of allergy or intolerance to foods or drugs – and no other atopic history (e.g. rhinitis, asthma, dermatitis).
  • When asked about food ingestion around the time of exercise, he reported ingestion of a blend of hydrolyzed whey and casein proteins for bodybuilding over the last 2 years.
  • Despite usage of this supplement for ~2 years, in the 2 most recent months prior to allergist consultation, the patient developed moderate rhino-conjunctivitis (nasal congestion, runny nose, postnasal drip, sneezing, red eyes) while preparing/mixing the protein.
  • Chemical analysis of his protein supplements revealed the following:
    • Supplement #1: High concentration of hydrolyzed whey protein isolates (mixture of mostly beta-lactoglobulin and alpha-lactalbumin) within 24 grams of whey per dose (30.4 g of supplement)
    • Supplement #2: Casein (25 grams of casein protein per dose & 31 g of supplement).
  • In-vivo tests revealed IgE-mediated allergy to cow milk, alpha-lactalbumin, beta-lactoglobulin, and casein extracts, and the specific protein supplement.
  • The patient was NOT lactose intolerant (as determined by a negative hydrogen breath test).
  • Authors theorized that the presentation of large amounts of proteins in the GI tract could trigger sensitization and adult-onset allergy to whey, casein, and cow milk/dairy.
  • This individual switched to a 100% vegetable protein supplement and tolerated it fine – with no further allergy symptoms.
  • A few weeks later the individual tried consuming yogurt and cheese but he experienced oral allergy and thus began avoiding all dairy products.

What did the authors of this study state in the discussion?

Authors stated that adult-onset cow milk allergy is rarely reported and this is the first case possibly related to bodybuilding supplements.

Because the patient had no history of food allergy – this makes authors assume that true adult-onset cow milk allergy (CMA) was developed.

According to authors, cow milk allergy (CMA) in adults is likely to be severe and persistent – and that “spontaneous tolerance” is rare. (In other words: if you have cow milk allergy as an adult – it’s unlikely the allergy will ever resolve.)

Immunological mechanisms by which adult-onset cow milk allergy occurs remain unknown.

Authors hypothesize that, in this specific case: transient dysfunction of the protective mechanisms may have triggered “sensitization” and subsequent allergy permanence.

Transient dysfunction of protective mechanisms may have occurred from:

  • Large quantities of cow milk proteins introduced to GI tract (increases antigenic load)
  • Exercise (increases intestinal permeability)

Note: Increased antigenic load plus atopic predisposition may initiate an abnormal mucosal immune response as well – but didn’t apply in this specific case.

It was explained that: the gut has developed non-specific mechanisms (both immunological and non-immunological) such as producing: (A) secretory IgA and (B) antigen interaction associated with GALT (gut-associated lymphoid tissue) – to prevent unselective immunization secondary to the absorption of foreign antigens.

Authors stated:

“In those without allergy, antigen presenting cells (mostly dendritic cells) process food antigens and present them on a major histocompatibility complex class II receptor to T cells resulting in a status of immunologic homeostasis known as oral tolerance – characterized by deletion of antigen-specific T cells and production of T regulatory (Treg) cells that suppress inflammatory responses to antigens.”

Defects in oral tolerance are thought to be the root cause of food allergy. A decreased immune response toward foreign antigens resulting in dysfunction of Treg cellular activity likely sets the stage for both IgE-mediated and non-IgE-mediated cow milk allergy.

GI symptoms in food allergy result from abnormalities in transport across intestinal walls (increased secretory and/or decreased absorptive function), increased permeability, and mobility of the intestine.

The following was concluded: Widespread administration of “protein supplements” may contribute to an increase in the prevalence of adult-onset cow milk allergy.

Cow’s Milk Allergy in Adults is Rare but Severe: Both Casein & Whey Proteins Are Involved (2008) (Lam et al.) (R)

  • Adult cow milk allergy (CMA) patients were evaluated via questionnaires; skin prick tests; specific IgE tests for CM allergens (18 patients) and a double-blind, placebo-controlled food challenge (N=10).
  • A control group of cow milk-sensitized, but tolerant adults was included (N=25).
  • Results? 67% (20/30 CMA patients) reported severe symptoms.
    • All patients (N=10) in the double-blind placebo-controlled food challenge had confirmed CMA.
    • Eliciting doses for subjective symptoms were significantly lower than for objective signs.
    • Severity of CMA by history and eliciting dose was NOT correlated with SPT (skin prick test) or IgE results.
    • Patients exhibited higher SPT reactivity than controls for cow milk, alpha-lactalbumin and beta-lactoglobulin – but not for casein.
    • Specific IgE to CM was higher and IgE to casein was higher in patients with CMA relative to controls.
    • No differences were found for IgE to alpha-lactalbumin and beta-lactoglobulin.
  • Conclusion: Adult CMA is severe in nature. Eliciting doses are low (starting at just 0.3 mg CM protein).

Xu et al. (2020): Covalent attachment of polysaccharides to proteins via glycation (Maillard reaction) blocks some IgE-binding epitopes on protein allergen. A small study was conducted to determine whether enzymatic hydrolysis plus glycation might reduce IgE binding for people with CMA protein allergy. (R)

  • Whey protein isolate was hydrolyzed via immobilized trypsin and chymotrypsin to degree of hydrolysis values of 17-27%.
  • Immobilized enzymes were used to avoid heat-treatment of hydrolysate (heating might affect IgE binding affinity).
  • Resulting whey protein isolate hydrolysates (WPIH) were glycated with 10-kDa dextran (DX) in aqueous solutions at 62 degrees Celsius for 24 hours.
  • Blood sera was obtained from 8 patients with confirmed cow milk allergy (CMA) and a composite serum was used for IgE binding analysis.
  • Result? WPIH-DX glycates had significantly reduced WPI-specific IgE binding capacity compared to whey protein isolate and unglycated WPIH. The reduction in IgE binding for WPIH-DX glycate was reduced by ~99%.
  • Conclusion: Hydrolysis of whey protein isolate followed by glycation with DX significantly reduces the allergenicity of whey proteins.

Halken et al. (1993): Evaluated an ultrafiltered whey hydrolysate infant formula called Profylac in children with confirmed cow milk protein allergy/intolerance. (R)

  • 66 children with cow milk protein allergy/intolerance were test subjects
  • 35 children had IgE-mediated reactions (cow milk protein allergy)
  • 61 children had at least 2 different symptoms and 31 had allergies beyond cow milk
  • All 66 children underwent Profylac challenge
    • 64 had it daily for at least 3 months
    • 58 had it daily for at least 6 months
  • Result? No side effects occurred. However, 2/35 (6%) with IgE CMA ahd positive skin prick tests and 3/28 and specific IgE class 2 responses to Profylac.
  • This study indicates that extensively hydrolyzed whey may not be a problem for a subset of individuals with preexisting whey or cow milk allergy.

Businco et al. (1989): Hydrolyzed whey protein is sometimes administered to babies with cow milk allergy because it is less allergenic, unlikely to induce passive cutaneous anaphylaxis, and antibodies to beta-lactoglobulin (BLG) do not occur. (R)

  • 5 infants (ages 3-8 months) with IgE-mediated cow milk allergy (CMA) experienced allergic reactions to hydrolyzed whey protein.
  • This report demonstrates that cow milk whey protein trypsin hydrolysate can trigger severe allergic reactions in children with cow milk allergy (CMA) and should be utilized with significant caution as a dietary alternative.

Risk factors for whey protein allergy

Included below are risk factors for “cow milk allergy” which encompasses whey.

  • Family history of whey allergy (or cow milk & dairy allergy)
  • Environmental factors
  • Formula feeding (with intact protein)
  • Shorter duration of breastfeeding
  • Older maternal age
  • Higher parity
  • Prematurity
  • C-section delivery

Preventing cow milk allergy?

Included below is the Middle-East Consensus recommendation for prevention of cow milk allergy in pediatrics. (R)

  1. Exclusive breastfeeding up to 6 months for every infant.
  2. If breastfeeding is not possible or breast milk is unavailable – partially hydrolyzed whey formula with documented safety & efficacy should be recommended for those at risk of food allergy.
  3. Not all partially hydrolyzed whey formulas are the same – so be cognizant that this can affect outcomes.
  4. When breastfeeding is not possible or breast milk unavailable – partially hydrolyzed whey formula with documented safety & efficacy could be considered for all infants.

Other possible modes of prevention (not specific to infants)

  • Lowe et al. (2011) found “no evidence to support recommending partially hydrolyzed whey at weaning for the prevention of allergic disease in high-risk infants.” (R)
  • Bavaro et al. (2019) suggest that it might be possible to reduce milk allergenicity in young children via baking milk in the oven at 180 degrees Celsius for 10 minutes (within muffins). (R)
  • Abbring et al. (2019): Raw cow’s milk (though not recommended due to possible contamination with pathogens) may have allergy-protective effects. (R)
  • Graversen et al. (2020): State that heat-treatment in the production of cow milk protein-based products might help prevent and treat cow milk allergy. (R)

Reversing Cow Milk Protein Allergy (?)

Included below is a step-down approach that can be considered for managing children with cow milk protein allergy.

  1. Strict avoidance of intact cow milk protein (CMP).
  2. Replace CMP with extensively hydrolyzed formula (eHF) or amino acid formula (AAF) in case of severe symptoms.
  3. The diagnosis is confirmed with a positive challenge test.
  4. A Middle-East Step-Down Consensus meeting (10 leading experts from Saudi Arabia, UAE, Lebanon, Jordan, Kuwait) recommends using partially hydrolyzed whey formula as a “bridge” between extensively hydrolyzed whey formula or AAF and intact CMP.
  5. CMP is eventually reintroduced when tolerated after a successful challenge.
  6. In brief: (1) avoid cow milk and use eHF or AAF; (2) eventually transition to partially hydrolyzed whey (as a “bridge”); and finally (3) switch to intact cow milk after a successful challenge.

Other findings related to CMPA reversal

  • Zhao et al. (2021): Dietary selenium (Se) inhibits whey-induced food allergy in an animal research model. (R)
  • Liu et al. (2022): Oral pre-exposure of mice to 2 beta-lactoglobulin-derived peptides loaded with PLGA nanoparticles induced a dose-related partial prevention of cow milk allergy symptoms upon challenge to whole whey protein and silenced whey-specific immune response.

Animal research of whey allergy

Preliminary evidence that should not be extrapolated to humans.

Kim et al. (2018)

Compared the anti-allergic effects of whey protein concentrate and whey protein hydrolysate in rat cells.

The result? Enzymatically prepared whey protein hydrolysate reduced allergenic response relative to whey protein concentrate (evidenced by dose-dependent reductions in TNF-alpha, IL-1B, IL-4, and IL-13). (R)

Gomes-Santos et al. (2015)

BALB/c mice sensitized with alum-adsorbed beta-lactoglobulin. Mice orally challenged with either whey protein or whey hydrolysate.

Whey protein caused IgE elevation and weight loss – with gut inflammation, enhanced sIgA and IL-5, and lower IL-4 and IL-10 in the intestine.

Whey hydrolysate maintained normal IgE, IL-4, and IL-5 without causing gut inflammation. (R)

Is it really a whey protein allergy? (Considerations)

It is important to consider other possible causes for allergy/sensitivity symptoms following ingestion of whey protein supplements.

Some people may mistakenly assume that they’re allergic to “whey protein” – when in fact these individuals are allergic other components/additives within a specific whey product – or are merely “intolerant” (non-immune-mediated, non-allergic reactions).

Other additives & components

Most whey protein supplements contain ingredients beyond “whey protein.”

It is possible that you could be allergic to components within the supplement that are distinct from whey protein.

Protein intolerance

Some individuals have a condition called “protein intolerance” wherein they are unable to efficiently digest or break down amino acids.

When food proteins aren’t adequately digested – this can trigger food protein allergies.

  • Protein intolerance can occur with any type of protein.
  • Select individuals may have an intolerance to one type of protein (e.g. dairy) but not another (e.g. wheat).
  • Protein intolerance may have both dose-related and time-related effects wherein intolerance symptoms only occur if a certain quantity is consumed within a specific duration (e.g. 40+ grams of protein in under 10 minutes).

Contaminants (?)

Some whey protein products may contain contaminants (e.g. heavy metals) that are triggering some sort of an allergic response.

The way to avoid this is to only purchase whey from a reputable source that’s been randomly audited for purity by an independent third-party.

(I’d guess that contaminants are unlikely the cause for most individuals – but it warrants a mention.)

Is whey protein allergy dose-dependent and/or time-dependent?

In some cases, yes. Interestingly, select individuals exhibit whey allergy only if they: (A) consume a quantity of whey that exceeds a specific threshold – (B) within a specific time duration.

Select individuals with whey allergy might display zero signs/symptoms if small amounts are ingested (e.g. 5-10 grams) over an extended duration (e.g. 24-hour period).

These same individuals might have significant signs/symptoms (e.g. vomiting, hives, nausea, etc.) if large amounts are ingested (e.g. 40 grams) within a limited duration (e.g. 10 minutes).

It’s further possible that the same dose-dependent and time-dependent effects could apply to select individuals with delayed, non-IgE-mediated whey allergies/sensitivities.

In those with delayed allergy (non-IgE-mediated), administration of: (1) a small amount of whey each day or (2) a moderate or large amount of whey infrequently (e.g. once a week) – might trigger no significant allergic reaction.

However, these same individuals (non-IgE-mediated allergies) might find that: (1) a large amount of whey each day and/or (2) regular/daily ingestion of whey – causes a significant (albeit delayed) allergy (appearing hours, days, or weeks after exposure).

Questions to ask yourself (if suspected whey allergy)…

Included below are a list of questions you may want to ask yourself if you think you have a whey allergy.

Obviously if you want rapid confirmation as to whether you have a whey allergy – an allergist/immunologist (MD) could conduct skin & blood testing (but this would only reveal IgE-mediated allergies).

  1. Dairy/cow milk allergy (?): If you have a preexisting dairy allergy or sensitivity, you shouldn’t have whey because whey is a component of dairy (to which you are allergic). This is relatively obvious.
  2. Specific whey product (?): Have you considered that the specific whey product you’re using contains added ingredients and/or contaminants that may be triggering your allergic reaction? The easiest way to test this is to switch to a completely different brand from a reputable company. Consider going with a product that contains zero additives/fillers.
  3. Whey concentrate vs. whey isolate vs. whey hydrolysate (?): Whey concentrate contains a small amount of lactose (which shouldn’t be problematic in most cases even among those with lactose intolerance) whereas whey isolate and hydrolyzed whey contain zero lactose and are your best bets for minimizing odds of allergy.
  4. 100% pure hydrolyzed whey (?): Have you tested a whey protein supplement containing ONLY 100% pure hydrolyzed whey (zero additional ingredients) to verify that you are reacting badly to whey? I recommend pure hydrolyzed whey – as this contains zero lactose and is the least likely to cause allergy.
  5. Protein intolerance (?): Have you considered that you may have an intolerance to large quantities of protein – regardless of type? (This would be a reaction to amino acids/biogenic amines from insufficient protein degradation such that a histamine response is generated.) The reason to consider protein intolerance is that most whey users are getting a large protein dose in a short duration (e.g. 20-40 grams in a protein shake consumed within 5-10 minutes) whereas standard feeding may not have ever provided this large dose of protein (such that protein intolerance may have gone unrecognized until the whey was introduced).
  6. Threshold allergy (dose & time) (?): Have you considered that your allergy to whey might be contingent upon both dosage and time? Some individuals have a “threshold” allergic response wherein low doses (e.g. 20 mg or less) and/or infrequent administration (e.g. once or twice a week) cause zero reaction – but if a “threshold” is exceeded perhaps within a certain timespan – significant allergies manifest.
  7. Non-ingestion exposures (?): It is theoretically possible that non-ingestion exposures (e.g. chronic inadvertent inhalation of whey powder during preparations) result in “sensitization” in a subset of individuals. (This has been documented in adults taking oat baths and inhaling flour, etc.). Sensitization causes the immune system to produce antibodies (defensive proteins) in response to the substance (in this case whey).
  8. Whey allergy vs. whey intolerance (?): Many people confuse the terms allergy and intolerance. An allergy to whey is a cellular immune-mediated reaction (can be immediate via IgE, delayed via non-IgE aspects, or mixed). An intolerance to whey affects the digestive system (e.g. bloating, gas, cramps, heartburn) with no immune involvement.

Whey allergy without cow milk allergy (CMA): Is this possible? If so, how?

Yes. On the American Academy of Allergy Asthma & Immunology (AAAAI) website, a case is presented by a medical doctor (MD) who reports: (R)

  • A 30-year-old male patient who experienced 3 distinct episodes of: violent vomiting (without any other symptoms) after having a whey protein shake and/or a whey protein bar.
  • This patient tolerated milk fine – with no significant allergic or adverse reaction to milk ingestion.
  • Skin testing for 2 different whey protein powders revealed “high positive” reactions but cow’s milk reaction was “negative.”
  • Systemic IgE reaction to whey was elevated at 7.06.

The allergist (Dennis Ledford) questioned the AAAAI how this is possible and Scott Sicherer (MD) replied.

Sicherer stated that it is first necessary to confirm that there was no other possible allergenic trigger in these whey products that may have caused the reaction besides the actual whey.

(A better test on this patient likely would’ve been to use pure whey without any additives due to the fact that many whey protein products contain a plethora of additional ingredients.)

Assuming that this patient was NOT allergic to any other component of the whey protein products besides the “whey” itself – positive skin testing and positive whey sIgE indicates an isolated allergy to whey protein.

Sicherer noted that it is possible that there is a dose-related effect that would explain why milk and other milk products are tolerated but concentrated whey protein causes allergy.

This is plausible considering that one dose of whey protein supplements contain ~8-fold the amount of protein in cow’s milk (3-3.5 grams). (R)

Sicherer further acknowledged that there are examples of allergic reactions attributable to specific proteins within foods – which might explain this particular allergy case.

Sicherer states that adult-onset cow milk allergy is rare which raises a question of academic interest about the means of sensitization & loss of tolerance.

Sicherer wonders whether this individual had: (1) a childhood milk allergy that resolved and/or (2) a high threshold that was exceeded after ingestion of concentrated whey protein products.

Sicherer also wonders whether this individual had a type of non-ingestion exposure (e.g. inhaling some of the powder while preparing his drinks) which could increase sensitization.

Non-ingestion exposure has been documented as a source of adult-onset food allergy (e.g. from individuals taking oat baths, inhaling wheat flour powder, etc.).

Sicherer further referenced a case report by Sousa et al. (2018) in which a previously healthy 24-year-old developed a casein allergy – suspected to be induced via sensitization by the high protein content within the supplement.

Sicherer and colleagues at Jaffe Food Allergy Institute had never seen a case like this. This indicates that specific allergy to a component within cow milk (e.g. whey) is probably extremely rare/uncommon.

What can you do if you have a whey protein allergy?

If you have a whey protein allergy – it’s not really that big of a deal.

Yes, you’re going to miss out on arguably the best tasting form of protein shake, but there are still a variety of other quality and delicious protein sources that can be utilized for maintaining/supporting muscle and a healthy weight.

  1. Alternative protein sources
  2. Protein from non-dairy foods

What are some good alternatives to whey protein?

Whey is a convenient, highly-bioavailable protein source that’s generally easy for the body to digest and assimilate – which is why it’s become a mainstay supplement in fitness, weight loss, and health industries.

However, just because you cannot tolerate whey doesn’t mean it’s the end of the world.

There are other sources of protein for shakes such as: casein, pea, brown rice, soy, wheat, etc.

Although many are concerned about vegan protein sources being mechanistically estrogenic – there’s no quality data to substantiate this claim.

They are less bioavailable (this is true) but if you get enough daily protein – it won’t matter to a significant extent.

Solid foods can be consumed such as: eggs, chicken, beans, lentils, fish, tofu, select cheeses, nutritional yeast, etc.

Although consuming solid foods is less convenient if pressed for time – most people find consuming solid foods more satisfying.

How common are whey protein allergies?

It is known that dairy/cow milk allergy occurs in 0.5% to 3% of individuals.

It is more common among children – and most (~75%) will outgrow this allergy by adulthood.

Self-reports from adults indicate that dairy/cow milk allergy occurs in between 1-3%.

However, it is unclear as to whether these self-reports are diagnostically accurate (as many other conditions e.g. lactose intolerance may be conflated with a true allergy).

Knowing that dairy/cow milk allergy is relatively uncommon – a specific allergy to whey in the absence of allergy to other components of cow milk is even rarer.

If you have a dairy/cow milk allergy (CMA) can you tolerate whey?

Not usually – but it’s possible in rare cases. Most experts recommend avoiding whey protein if you have a confirmed cow milk/dairy allergy.

I did find one case report by Lee et al. (2016) in which a 7-month-old female with milk allergy [confirmed by an allergist and symptoms (dry cough, vomiting, hives over 90% of body)] – ended up tolerating a partially hydrolyzed whey formula without an allergic response. (R)

Lee et al. noted that “some patients may be sensitized to individual milk proteins only.”

In this case, the patient had a casein-specific allergy and was able to tolerate partially hydrolyzed whey.

However, Egan et al. (2018) emphasize the following: “Partially hydrolyzed whey should NOT be recommended for individuals with cow milk allergy. Prevalence of partially hydrolyzed whey tolerance is far lower than previously reported in European studies.” (R)

If you have a whey allergy can you tolerate cow’s milk?

Not usually – but it’s possible in rare cases. Some individuals may be allergic to the specific proteins concentrated within whey protein (alpha-lactalbumin & beta-lactoglobulin).

Although these proteins are present in milk – their concentrations are substantially lower relative to standalone whey protein.

There can be a dose-dependent allergy such that low amounts of “whey proteins” (present in a glass of milk) won’t trigger an allergy – but high concentrations (as would be found in a scoop of whey protein concentrate) cause noticeable allergy.

Whey allergy (hypersensitivity) vs. whey intolerance? (Differentiation)

The terms allergy, hypersensitivity, sensitivity and intolerance are commonly used incorrectly – and can be somewhat confusing. Let’s quick break down the differences.

  • Whey allergy (hypersensitivity): An immune-mediated reaction to the ingestion of whey protein.
  • Whey intolerance (sensitivity): Characterized by non-immune-mediated reactions to the presence of whey. Whey intolerance may involve the inability to efficiently digest whey or its byproducts. Intolerance is most commonly associated with gastrointestinal reactions.

Can you have a whey allergy without casein allergy? (Whey vs. Casein)

This would be relatively uncommon. There are medical case reports in which individuals are allergic to whey but not casein – and others who are allergic to casein but not whey.

Individuals with cow milk (dairy) allergy are generally recommended to avoid both whey and casein – because these are both specific components of cow milk.

Is there lactose in whey protein? Could this explain the reaction?

Most people who are lactose intolerant can still tolerate some lactose and should have no major issues with any form of whey protein.

  • Whey concentrate contains a small amount of lactose.
  • Whey isolate contains zero lactose.
  • Whey hydrolysate (hydrolyzed whey) contains no lactose, no carbs, no fats.

If lactose is an issue even in tiny concentrations – then simply using whey isolate or whey hydrolysate ensures that zero lactose was ingested.

Concerned about whey in milk so avoid milk?

Dixit et al. (2012): In cow milk allergic children and adults – buffalo milk may be a good substitute for cow milk without any change in nutritional quality. (R)

In other words, buffalo milk may be a decent alternative if a person wants a different form of non-vegan milk.

Can a doctor test for a whey protein allergy?

Yes. You can test for a whey protein allergy by consulting an allergist/immunologist (MD).

These specialists can perform “skin prick” type tests – as well as bloodwork following controlled whey exposure to determine whether your immune system is reacting strongly to whey protein.

Can you determine whether you have a whey allergy without an allergist?

Disclaimer: I am NOT recommending or endorsing self-testing. Allergic reactions can be serious and possibly fatal. Therefore, I recommend talking to a doctor to confirm hypothesized safety of a self-test before you consider it.

Probably. If you buy plain whey protein (zero additives) and consistently experience adverse effects (e.g. vomiting) after ingestion – then it’s likely that you have a whey allergy.

However, if your whey is full of additives – then it could be that an additive is triggering your reaction and NOT the whey.

The only way to do a true whey protein allergy test is to administer plain whey (zero additional components/ingredients/additives).

What about the dose of protein at once? It’s possible that some people might be intolerant to a certain quantity of protein at once.

Obviously there can be a dose-response curve specific to whey protein allergy – but there may be a dose-response curve for dietary protein in general for some people.

The way to parse out this effect would be to consume protein from a completely different source in a large bolus (e.g. soy protein, wheat protein, egg protein, etc.) and determine whether the same quantity of protein ingested rapidly causes an allergic reaction.

If you experience adverse reactions (e.g. vomiting) after a variety of other foods – then you probably have another medical condition (e.g. gastroesophageal disorder) that warrants evaluation.

Have you ever experienced a whey protein allergy?

If you’ve experienced a whey protein allergy or sensitivity – feel free to describe your experience in the comments.

Include details that may be helpful including:

  • History of cow milk allergy (CMA)
  • Possible inhalation of whey protein powder
  • Whether likely IgE-mediated vs. non-IgE-mediated vs. mixed
  • Specific symptoms of your whey protein allergy/sensitivity
  • Whether you tested pure whey protein (to ensure the allergy isn’t to other components within the whey protein supplement)
  • Whether the allergy has a dose-response threshold (such that it doesn’t occur with 20 grams but occurs with a 40-gram bolus OR such that it doesn’t occur when you have whey once a week – but occurs if you have whey every day for a week, etc.)
  • Whether you’re also allergic to casein
  • Whether you’ve always had a whey protein allergy
  • Any difference between whey concentrate & whey isolate & whey hydrolysate?
  • Medications you take & medical conditions that may have contributed or increased susceptibility to the allergy/sensitivity

Endnotes…

Reflecting upon this article: My initial intention was to investigate “whey protein allergy” presentation in adults – not infants/children.

However, researching this led down many rabbit holes and I figured I should include information/findings associated with non-adults as well.

Moreover, because whey is a component of cow’s milk – much of the scientific research is focused on “cow milk” as a whole rather than whey in isolation (which makes sense).

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