Common medicines contain hidden gluten and soy, study finds

Common medicines contain hidden gluten and soy, study finds

Researchers show that widely used pain and fever medications may harbor undeclared gluten or soy ingredients - concerns for millions with allergies or sensitivities.

A study recently published in the journalScientific reportsevaluated the presence of soy- and gluten-derived excipients in medical products approved in Portugal.

Food allergies are a major public health problem and their prevalence has increased in recent decades. Gluten is a protein found in barley, rye and wheat and can cause adverse reactions in those with gluten sensitivity. Gluten ingestion causes three clinical disorders: celiac disease (CD), wheat allergy and non-celiac gluten sensitivity, which have different symptoms and characteristics.

Over 60% of gluten-containing antipyretics were found in these common pill formats that rarely disclose starch sources.

Some excipients are used in various pharmaceutical forms, including sodium starch glycolate, starch, and pregelatinized starch, while others are derived from sources such as rye, barley, oats, and wheat. Potato starch and cornstarch are also used because they are gluten-free and they are safe for those with gluten-related disorders. A common ingredient, starch is a major source of gluten. However, when “starch” is listed without a specific botanical origin, it complicates allergen identification because it may come from wheat or gluten-free sources.

In addition, soy is one of the top food allergens and often causes allergic reactions in children. Soy contains several different proteins with different risks for severe reactions. Additionally, soy allergies can manifest as urticaria, oral allergy syndrome, asthma, angioedema, and anaphylaxis. Currently, soy or gluten allergies lack a definitive cure, and the best treatment is to avoid these allergens in diet and medical products altogether. However, analyzes on the presence of gluten or soy in medical products are scarce.

Even trace amounts of allergens in excipients such as soy lecithin or wheat starches can be clinically relevant despite their low protein content.

About the study

Inhalers emerged as allergy-safe alternatives: all 115 anti-asthmatic and bronchodilator inhalers analyzed were free of soy and gluten, likely due to simpler formulations.

In the present study, researchers examined the prevalence of soy- and gluten-derived excipients in medical products in Portugal. First, the SMPC (Summary of Product Characteristics) database for human drugs was searched to identify soy- and gluten-derived adjuvants. They focused on therapeutic classes most commonly prescribed for adults and children, including nonsteroidal anti-inflammatory drugs (NSAIDs), antipyretics and analgesics, as well as anti-asthmatics and bronchodilators.

Paracetamol and ibuprofen were selected due to their high national sales volume, making the study relevant to public health priorities in Portugal.

All medical products authorized for marketing in Portugal with a linked SMPC in the online database (infomed) were eligible for inclusion. Branded and generic products, excluding injectable products, were included in all formulations and dosages. Because the dose or amount of allergen in the SMPC was not specified, the team focused on determining whether gluten, soy and related substances were present.

The medicinal products were classified based on the presence of xanthan gum, oats, starch, glucose syrup, wheat, rye, semolina, bran, barley, malt, sodium carboxymethyl starch, gelatinized starch, and pregelatinized starch. Similarly, products were classified as not soy-free if they contained soy, lecithin, tocopherols, phytosterols or xanthan gum.

Xanthan gum was treated as a risk factor for both allergens due to its potential production from soy or gluten-containing sources and was therefore included in both classifications according to the precautionary principle.

In addition, Fisher's exact and chi-square tests were performed to evaluate the associations between the presence of excipients and pharmacotherapeutic groups.

Results

Syrups carried hidden soy risks: Liquid NSAIDs and analgesics had the highest soy content, with syrups containing soy-derived thickeners such as xanthan gum in 60% of cases.

A total of 308 medical products were analyzed. These included 108 antipyretics and analgesics, 115 bronchodilators and anti-asthmatics, and 85 NSAIDs. Sodium carboxymethyl starch and pregelatinized starch were the predominant gluten excipients, while xanthan gum and soy were the most common soy-derived excipients. Xanthan gum and soy were almost exclusively present in NSAIDs, antipyretics and analgesics.

Pharmacotherapeutic groups were significantly associated with the presence of soy- or gluten-derived excipients. Gluten excipients were more common in antipyretics and analgesics than in NSAIDs, while soy excipients were more common in NSAIDs than in antipyretics and analgesics.

None of the 115 antiasthmatic and bronchodilator inhalation products contained all soy or gluten adjuvants.

Among paracetamol-based antipyretics and analgesics, 51.2% of solid oral forms and 40% of oral liquid forms were not gluten-free, with gluten most commonly found in film-coated tablets (61.1%) and regular tablets (60%).

In contrast, only 4.4% of solid oral NSAIDs contained gluten, and gluten was found primarily in their liquid oral forms (26.7%).

Prevalence of gluten and soy allergens in different dosage forms (%).

Soy-derived excipients were found in 30% of liquid oral formulations and 33.3% of rectal suppositories of antipyretics and analgesics.

In the NSAID group, 11.8% of solid oral forms and 26.7% of oral liquid forms contained soy, with soft capsules and film-coated tablets being important contributors.

Furthermore, there was no correlation between the presence of gluten and the classification of medications as brand or generic.

However, a significant association was found between brand or generic classification and the presence of soy-derived excipients (p < 0.05), reflecting formulation differences between manufacturers.

None of the solid oral forms of antipyretics and analgesics contained soy, while 30% of the oral liquid forms, particularly syrups (60%), did. Among NSAIDs, nearly 12% of solid oral forms and 27% of oral liquid forms contained soy.

Conclusions

Undescribed starches dominate: 74% of starch-containing products could not specify their origin (e.g. wheat versus corn), leaving patients guessing about hidden gluten risks.

The results show different prevalences of soy and gluten in medications between dosage forms and therapeutic classes. These findings have significant safety implications for vulnerable consumers. Individuals with gluten sensitivity or celiac disease (CD) should exercise caution when using solid oral antipyretics and analgesics. People with soy allergies should exercise caution when using liquid oral formulations and suppositories.

Liquid formulations and rectal acids may offer safer alternatives for those with gluten sensitivity, while solid oral NSAIDs may be a low-risk option for those sensitive to gluten.

Additionally, health care providers should be aware of the possible presence of these allergens and counsel individuals with sensitivities accordingly.

The study authors highlight the need for clearer allergen labeling for medical products and caution that reliance on SMPCs alone may not fully reveal hidden allergen sources. They also note that possible cross-contamination during manufacturing cannot be ruled out without direct confirmation from the manufacturers, which is an important limitation of the study.

Additionally, manufacturers should clearly label the presence of these allergens to inform consumers and healthcare providers and to investigate formulations that eliminate or minimize their presence. In particular, the study emphasizes that the excipients listed as “starch” should be accompanied by the declared botanical source such as wheat, corn or potatoes to enable safe selection for allergic individuals.

Proper labeling and increased awareness can help mitigate risks and ensure safer medications for people with gluten and soy sensitivities.

Overall, the results underline the need for more transparency regarding excipients in medications.

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