Common Chemicals Found in Supplements: What Are Their Health Effects?

By
 Lauren Fang

Supplements provide a convenient way to bolster vitamin, mineral, and general nutrient consumption. But walk into any Whole Foods, GNC, Vitamin Shoppe, or Edmond’s, and it is easy to see that supplement nutrition labels contain various chemical additives besides the active ingredient. These additives are known as excipients. While excipients help to stabilize tablets to prevent degradation, they can also harm human health. For instance, many pills and tablets contain additives that are toxic to the body when large doses are ingested. Three common excipients found in capsules and pills are magnesium stearate, silicon dioxide, and titanium dioxide, each of which can potentially exert toxic effects on different organ systems. 

Magnesium Stearate 

What Is Magnesium Stearate?

Magnesium stearate is the most commonly used lubricant for tablets. It prevents ingredients from sticking to manufacturing equipment and repels water, which can cause clumping. This excipient also acts as a binder, just as a baking recipe might use eggs to help bind flour into a dough or batter. Although the food and pharmaceutical industries widely employ magnesium stearate, healthcare professionals and consumers have repeatedly questioned its safety. 

Toxicity Studies

Some research has analyzed magnesium stearate’s short-term toxicity. A three-month study examined a group of rats receiving magnesium stearate at 0%, 5%, 10%, or 20% of their diet. Several rats developed kidney stones in the bladder or urinary tract. In the high-dose group (20%), stone formation caused four male rats to die within the first two months. Moreover, the rats’ livers exhibited increased iron levels. 

It is worth noting that if iron was chronically elevated in humans as it was in these rats, liver damage would occur. Such conditions would also produce excessive reactive oxygen species (oxygen atoms that have lost an electron and that rip electrons from other surrounding molecules such as DNA, lipids, and proteins). Research indicates that reactive oxygen species (ROS) can disrupt cell cycle progression and dysregulate cell growth. Put another way, if ROS interacted with genetic material such as DNA, they could provoke harmful, cancer-causing mutations.

Therefore, how much magnesium stearate is actually safe? Ultimately, researchers concluded that a diet containing 5% magnesium stearate, equivalent to 2500 mg/kg body weight per day, is the highest innocuous dose. The average US woman and man weighs 170.8 lbs (77.47 kg) and 199.8 lbs (90.63 kg), respectively, and thus can safely consume 194,000 mg and 227,000 mg of magnesium stearate daily. A capsule typically contains .25% to 5% magnesium stearate by weight, so a 500 mg supplement would contain between 1.25 to 25 mg of magnesium stearate. Additionally, because the body metabolizes magnesium stearate, the chemical does not accumulate. 

Regarding the excipient’s long-term effects, few studies exist. One experiment involved researchers’ implanting magnesium stearate pellets into mice urinary bladders to assess the chemical’s carcinogenicity (ability to cause cancer). Out of 41 mice tested, only two developed tumors (one benign, the other malignant) during the 30-week study. Moreover, Japanese researchers conducted another noteworthy study indicating that magnesium stearate does not directly damage cellular genetic information nor increase cancer risk.

The Verdict

In the US, magnesium stearate is classified as “generally recognized as safe” or GRAS. The aforementioned research suggests that magnesium stearate is safe in small quantities. Animal studies show that when magnesium stearate represents greater than 5% of the diet, short-term adverse effects can occur. 

Silicon Dioxide

What Is Silicon Dioxide? 

Supplement manufacturers utilize silicon dioxide (silica) as an anti-caking agent and excipient. Natural events release crystalline silica into the environment; consequently, soil and beach sand contain trace amounts and such incidental environmental exposure is not problematic. On the other hand, frequent occupational exposure to inhalable-sized silica particles (less than 10 microns in diameter) is dangerous—it is well known that miners’ constant inhalation of respirable silica can cause lung damage and disease. Comparatively, food and pharmaceutical grade silicon dioxide exists as smaller nanoparticles; nevertheless, despite their smaller size and the decreased synthetic material that they contain, their enhanced chemical reactivity can still trigger noxious effects.

Toxicity Studies

A recent study published in Nanotoxicology investigated silicon dioxide’s impact on gastrointestinal (GI) function. Researchers exposed human intestinal epithelial cells (the layer of cells that compose the surface of the small and large intestines) to 30 nanometer (nm) silicon dioxide nanoparticles, which corresponds to the approximate daily adult silicon dioxide nanoparticle intake. Intestinal epithelial cell functionality changed significantly, and cellular inflammation occurred. The GI tract epithelium normally functions as a selective barrier, allowing certain essential nutrients, water, and electrolytes to pass into circulation while filtering out other harmful substances. Acute and chronic silicon dioxide exposure visibly and drastically decreased the GI tract’s surface area available for nutrient absorption. This substantially reduced zinc and iron transport across the cell barrier. Such impaired transport can weaken the immune system, slow wound healing, hamper growth and development, and inhibit hemoglobin production, which is needed to transport oxygen to cells. 

Silicon dioxide nanoparticles’ effects extend beyond the GI system. They can also affect immune cells. After swallowing a pill that contains silicon dioxide, macrophages (a type of white blood cell that engulfs harmful bacteria and other foreign microorganisms) and T-lymphocytes (a type of immune cell) respond, uptaking and processing silicon dioxide nanoparticles immediately. Exposure to these nanoparticles actually reprograms the immune cells metabolically and creates inflammatory chemicals, which can facilitate cell dysfunction and death. 

Many mouse and human cell studies as well as live animal studies evince silicon dioxide nanoparticle toxicity on tissues and organs. In the liver, IV-injected silicon dioxide nanoparticles can produce granulomas or localized clusters of inflamed cells, typically non-cancerous. Additionally, IV-administered silica nanoparticles demonstrate the ability to cause cardiac inflammation. Upon entering blood cells, these nanoparticles can activate cellular clean-up (autophagy) and death (apoptosis), processes that if unregulated possess the potential to trigger abnormal bodily responses and initiate pathways that generate disease.  

The Verdict

Silicon dioxide is an FDA approved food additive. Both the World Health Organization and the European Food Safety Authority have evaluated silicon dioxide and established the acceptable daily intake as “not specified,” which generally refers to substances of very low toxicity; though, this may also indicate insufficient human data to determine a threshold. While health regulatory authorities grant approval for substances whose benefits outweigh the risks, the studies above exemplify several health risks associated with ingesting silicon dioxide.

Titanium Dioxide

What Is Titanium Dioxide? 

Titanium dioxide is used as a coloring agent, creating the opaque whiteness characteristic of various tablets, and a protective coating on capsules. As a pharmaceutical excipient, titanium dioxide helps prevent premature capsule degradation; however, does it simultaneously undermine consumers’ health? 

Toxicity Studies

A particular mouse study involved orally administering a single dose of 25nm, 80nm and 155nm diameter nanoparticles of titanium dioxide. Results indicated that all rodent spleens and brains retained the chemical. Furthermore, the female rodents’ livers and kidneys within the smallest nm diameter cluster displayed signs of potential inflammation and chemical accumulation, respectively, while all mice in the 80nm experimental group showed kidney and liver swelling, dead liver cells, and small brain lesions. Although the liver (the body’s main detoxifier) and kidneys normally excrete compounds such as titanium dioxide, the 25 and 80 nm particles precluded this and instead titanium dioxide accrued and induced organ damage. 

Titanium dioxide exposure can also injure the GI tract, causing intestinal epithelial (intestinal surface layer) cell damage, as one research study showed. Although cell death did not occur, microvilli (finger-like projections on the surface of the small intestine) were absent, shortened, or fell to their sides, thereby preventing intestinal nutrient absorption and secretion. 

No acceptable daily intake limit currently exists for titanium dioxide, making it essential to monitor its ingestion given its known adverse effects. Titanium dioxide’s nanoparticle size is critical to consider, as size is not uniformly distributed throughout pharmaceutical products and nanoparticles with diameters less than or equal to 30 nm possess enhanced chemical reactivity that can increase the excipient’s toxic potential. Unfortunately, nutrition labels do not specify nanoparticle size; therefore, ascertaining titanium dioxide’s chemical reactivity once consumed is nearly impossible.  

The excipient’s concentration in various pills is better understood and quantified, however. According to scientific estimates, tablets contain .01% to 1% titanium dioxide by mass while capsules consist of slightly more at 2%. This means that a 500 mg multivitamin contains 5 mg of titanium dioxide. Some researchers extrapolated maximum human daily intake from rodent study data and calculated the safe range for the excipient’s consumption to be between 0.4 and 5 mg/kg body weight per day.   For the average US woman and man who weighs 170.8 lbs (77.47 kg) and 199.8 lbs (90.63 kg), respectively,  this theoretically amounts to 387 mg and 453 mg of safe titanium dioxide intake daily.

The Verdict

If ingested infrequently, titanium dioxide is not lethal, but this does not necessarily green light daily consumption, particularly due to unknown nanoparticle sizes. Research reveals that titanium dioxide negatively impacts cell and organ function, including producing oxidative stress and tissue inflammation. The FDA lists titanium dioxide as safe for use in food additives and pharmaceutical excipients, but animal studies and human in vitro experiments demonstrate titanium dioxide’s adverse effects.  

Bottom Line

Is it safe to consume pharmaceutical excipients like magnesium stearate, silicon dioxide, and titanium dioxide? Research shows that such additives act as health hazards to varying degrees and none are risk-free. Therefore, it is best to avoid synthetic chemicals and compounds when possible.  Remember that there are dietary supplements, vitamins, and minerals available sans fillers and binders. Check nutrition labels carefully.   

Medically Reviewed: Meaning, Purpose, and Intent
THE provides research-based, leading-edge health and wellness news and insights to help readers prevent and reverse chronic and acute maladies so as to live a disease-free, vital life. To that end, original content is medically reviewed by a medical (MD or DO) or naturopathic doctor (ND, NMD, or DNM) or a doctor of philosophy (PhD) for authenticity, validity, and accuracy, ensuring that THE’s content reflects relevant and reliable information. Please click the Medical Reviewer’s name to review his/her credentials.

Larry

Dr. Nikisha Richards

After graduating cum laude with a Bachelor of Science degree in biology from LeMoyne-Owen College, the only historically black college in Memphis, TN, Nikisha Richards completed medical school at Wayne State University School of Medicine and her internship at Michigan State University. She went on to complete her ophthalmology residency at Howard University Hospital and an ophthalmic plastic reconstructive and aesthetic surgery fellowship at the University of Pittsburgh Medical Center. Dr. Richards is a diplomate of the American Board of Ophthalmology and is currently on faculty as an assistant professor of ophthalmology at Virginia Commonwealth University Health System as well as the school of medicine. She has several publications in medical science journals, has written four medical-surgical book chapters, and has served as an editor for other publications. She excels in teaching both medical students and residents and is the recipient of the 2016-2017 ophthalmology instructor of the year award at Virginia Commonwealth University. Dr. Richards is a member of the greatest sorority, Delta Sigma Theta Sorority, Inc and she loves jazz.

Lauren Fang
Lauren Fang holds a Bachelor of Science degree in biomedical engineering from Johns Hopkins University. She is passionate about educating the public on health and wellness and making medical research accessible to all. Lauren has worked in the biopharmaceutical industry and volunteers as a rare disease patient advocate. Follow her on Instagram @lauren_fang8.

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