Food allergies affect one in ten people, and lactose intolerance affects as many as 75% of the world's population. It is understandable that patients make great efforts to avoid consuming problematic ingredients due to the unpleasant immune and gastrointestinal (GI) reactions that can occur as a result of eating foods to which they are hypersensitive, some of which can be life-threatening.

This problem extends beyond food. The medications that a person has been given can sometimes also cause unanticipated intolerances and allergies.

US Propylene Market  it was thought that the product's active pharmaceutical ingredient (API) was to blame for these side effects.
However, gastroenterologists at Harvard Medical School and Massachusetts Institute of Technology (MIT) conducted research that was published last year found  that the majority of the pill's excipients, which serve as fillers and contribute to adverse reactions in patients, are to blame. This occurs despite the fact that regulators have assessed their toxicity and safety and declared them to be inactive.

Giovanni Traverso, a gastroenterologist at Brigham and Women's Hospital and an engineering professor at MIT, is one of the study's lead authors. He says: Inactive ingredients make up approximately three quarters of every pill, tablet, or capsule.

The report found that the average tablet or capsule contains 280 milligrams of inactive ingredients and only 160 milligrams of active pharmaceutical ingredient (API) based on data from PillBox and Gelbe Liste, two drug databases in the United States and Germany, respectively.

According to Traverso, "there are more than 30,000 different ingredients that can be classified as an inactive ingredient, and there are on average eight [inactive ingredients] in every pill." For the 18 medications that are prescribed most frequently in the United States, there are approximately 82.5 alternative formulations for each active pharmaceutical ingredient.

It is concerning to note that only 12% of APIsS are not accompanied by inactive ingredients that have been found to cause allergic reactions, and almost 93% of oral pills contain at least one potential allergen.
Risks associated with medication adherence and polypharmacy According to Traverso, "[Although] the quantities of allergen we are taking about are low, for people taking many medications – known as polypharmacy – the amounts could add up and actually have a negative effect, such as GI upset."

If a patient took ten prescription medications per day, they would consume approximately 28 grams of inactive ingredients per day, which is more than enough for many patients to experience side effects.

Considering that the focus is on drug-to-drug interactions for polypharmacy patients, it is concerning that little is known about interactions between APIs and inactive ingredients.

Not only are the adverse events and their effect on patients' well-being a concern, but the Harvard/MIT report also says that they could cause people to stop taking their medications, which "directly affects the potential to intervene [positively] to mitigate someone's disease."

People mistakenly believe that the API is to blame for side effects, necessitating complete discontinuation of the medication. However, the study demonstrates that the inactive ingredient most likely contributes to the allergy or intolerance's aggravation. As a result, the adverse reaction issue could be resolved by simply altering the medication's formulation.

IBS spotlight: when medicines harm, irritable bowel syndrome (IBS) is a particularly alarming example, according to the MIT and Harvard Medical School study. Patients are encouraged to reduce their intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS) as a means of managing this condition. Disaccharide examples include lactose.

However, the researchers discovered that 55% of all medications contain at least one FODMAP sugar—45% contain lactose alone and 5% contain more than one—and that the amounts of the sugars could exceed 500 milligrams, which would cause IBS patients to consume more FODMAPs and experience significant adverse GI symptoms.

Worse still, significant amounts of allergens and FODMAPs were found in the inactive ingredients of IBS-management medications. As a result, medications that are supposed to improve a patient's well-being might actually make their symptoms and quality of life worse. Rifaximin, which contains propylene glycol, is one example.

According to the article's conclusion, there were FODMAP-free alternatives for every class of IBS medication investigated, requiring "appropriate selection of not only the API, but also the formulation as a whole to help mitigate adverse reactions or improve symptom control."

Awareness of the dangers posed by inactive ingredients The researchers from MIT and Harvard Medical School have established without a doubt that inactive ingredients play a crucial role in drug formulations; They can support drug absorption through the gastrointestinal tract, stabilize the molecule, make the pill easier to swallow, and serve as a filler.

They are absolutely necessary, but more people need to be aware that they can be quite active. According to Traverso, the purpose of this study was to determine the causes of the adverse events that patients had reported to him and his fellow gastroenterologists. In order to "ensure that everyone – patients and healthcare providers – start to appreciate the complexity of adverse events," the researchers wanted to raise awareness of the findings.

Traverso adds, "We need to understand the potential impact on their health because anyone who takes a drug is ingesting these inactive materials." He mentions that since this paper was published a year ago, he has occasionally received emails and phone calls from patients expressing gratitude for increased awareness of what causes their adverse events.

However, increasing people's access to information about these ingredients is the only way to increase this awareness. Better tools are needed, according to Traverso, so that hypersensitive patients and their doctors can identify drug ingredients that might affect them.

Who is in charge of finding a solution to this problem?
The fact that "the mass content of individual inactive ingredients in pills or capsules is largely not reported by manufacturers" is mentioned in the report, which makes it difficult for patients and physicians to obtain accurate information regarding the medications.

However, Traverso makes it abundantly clear that pharmaceutical companies should not bear all of the blame. He asks for better labeling from pharmacies from regulators; Although medications may include a list of side effects related to the active pharmaceutical ingredient (API), this list typically does not include a similar list for the inactive ingredients.

In addition, he advocates for additional academic and pharmaceutical research into the general problem of allergens in inactive ingredients, with patient safety as the top priority.