By Kevin She
8 Jan 2016
It’s 2016, Happy New Year! We were recently baffled when a friend of ours expressed dire concern that we were even considering allowing the possibility of including magnesium stearate as an excipient in one of our products.
The first few pages of a google search for “magnesium stearate” this morning returned an alarming number of pages vilifying magnesium stearate based on a massive misunderstanding … many of which then went on to try to sell their products or services to the reader.
Magnesium stearate, especially in the amounts commonly used (very little), is completely benign. It is registered in the United States FDA as Generally Recognized as Safe (GRAS), is a permitted food additive by Health Canada, and is allowed in Europe with no specified maximum level.
What is magnesium stearate and why is it used?
Magnesium stearate has been used for over 80 years in the production of food supplements and in the manufacture of tablets and capsules. It is estimated that it is in about 70% of all food supplement tablets worldwide and is commonly used to make candies and is an ingredient in baby formulas.
Stearate is the salt of stearic acid, much the same as the chloride part in sodium chloride (table salt). While the name comes from the Greek work “stéar” (or στέαρ) which means tallow (rendered beef or mutton fat), it is also abundant in cocoa and shea butters and coconut oil. Many manufacturers specify vegetable stearate for their products, similar to the situation of specifying vegetable cellulose capsules instead of gelatin capsules. At room temperature, pure magnesium stearate is a slippery light white powder.
When making compressed tablets and when filling capsules, magnesium stearate is sometimes added to the powdered raw materials for its lubricating properties. This is primarily to help the ingredients not stick to itself or to the manufacturing equipment; this helps to make sure that exactly the same amount of ingredients are in each and every tablet or capsule.
Why the vilification?
Many of these alarmist pages, if they provide any evidence at all, point to this research article published in 1990 “Molecular basis for the immunosuppressive action of stearic acid on T cells” by P.W. Tebbey and T.M. Buttke.
It sounds scary, but the study has nothing to do with dietary magnesium stearate. The basic scientific question that the study sought to answer was why the cell membrane (which is made up of lots of different fatty acids), of one kind of immune cell respond to a certain kind of fatty acid differently than another kind of immune cell.
But let us be generous and explore the study further. To summarize the study two different kinds of immune cells, B cells and T cells, were isolated from mice and grown separately in petri dishes. Mitogen, substances that forces these cells to grow and divide, was added to these cells with or without stearic acid and allowed to grow for eight hours. The cells were then looked at to see how many were still alive and also to see what the amounts of different fatty acids were in their cell membrane before and after treatment. It was found that T cells weren’t happy when stearic acid was around while B cells were just fine. The mechanism for this difference was that B cells have an enzyme that can turn stearic acid into a form more useful for making healthy membranes, whereas T cells lack this enzyme and in this very artificial system they are forced to incorporate stearic acid as-is into their membranes, resulting in more rigid and fragile cell membranes.
The study is in laboratory mice. Sometimes animal studies are useful for informing human biology, sometimes they’re not. In this case, while mouse T cells lack the enzyme in question (stearoyl-CoA desaturase), human T cells naturally make this enzyme (Robichaud &al., 2013) and would not have had a problem in this experiment.
The experiments were carried out in vitro – experiments performed outside of their normal biological context, or “test tube experiments” – which, again, is sometimes useful for informing human biology, sometimes they’re not. The immune cells involved in this study were forced to use stearic acid; immune cells in the body would have access to the different fatty acids they need in order to support healthy membranes after cell division.
Have studies been performed to test the safety of dietary magnesium stearate? Certainly. In order to receive GRAS status from the FDA and to be recognized as safe by Health Canada requires a lot of strong supporting evidence. One early study published in 1980 by Sondergaard &al. fed rats up to 20% magnesium stearate in their diet for three months. The conclusion is that the no-effect-level is estimated to be 5% of the total diet. Although rat studies in general only loosely correlate with human responses, the study means an average Canadian weighing 80kg (177lbs) can eat up to 200 grams (7 ounces) of magnesium stearate every day with no effect. It would be incredibly difficult to convince healthy human volunteers to eat that much magnesium stearate every day for three months to test this, though.
For reference, when used, magnesium stearate makes up only 0.25 – 5% of the capsule weight, typically at 1%. If a person consuming 20 capsules each weighing 500mg with 5% magnesium stearate, that’s still only 0.5 grams (0.018 ounces) total.
One other study that has been cited as an argument that magnesium stearate is less than benign is the alarmingly titled 2012 article “Magnesium stearate: an underestimated allergen” published in the “Journal of Biological Regulators and Homeostatic Agents” (this journal’s impact factor, a measure of how often articles in that journal are cited by other academic work, is 0.0 in 2012 – i.e. terrible) by Tammaro &al. It is also interesting to note that the article body doesn’t appear to be available, even for purchase.
This is additionally, by the author’s admission, the first report (and as of today, the last) of a case of urticarial manifestation (hives) in response to magnesium stearate. Without access to the body of the article, no analysis or conclusions can be made. Perhaps something was lost in translation with the title of the report?
Another criticism of magnesium stearate might stem from another misconception. Soap scum, the residue that can build up in the shower and sink, contains magnesium and calcium stearates. Some on the internet have made claims that dietary magnesium stearate intake promotes the formation of “harmful biofilms in the intestine.”
The intestine and a porcelain sink or glass shower door are vastly different; the intestine is a biological and constantly active surface with passive and active transporters whereas solid surfaces are passive and dissolved salts can build up over time as the water carrying them evaporates.
Moreover, biofilms are nothing like soap scum; in general, biofilms are a term to describe groups of microorganisms that stick to one another. Biofilms typically form on hard surfaces, such as on teeth, and accumulate over time as the microorganisms grow or new microorganisms colonize the surface. Many microorganisms that form biofilms actively secrete extracellular polymeric substances that are primarily made up of long chain sugars and proteins and may also include DNA and lipids from dead and dying cells. Rest assured that magnesium stearate will not form biofilms – anywhere.
One further criticism that is sometimes used is that magnesium stearate “inhibits nutrient absorption” or that it causes pills to not dissolve. These criticisms might be from the 2007 article by Uzunovic and Vranic where they find that a higher amount of magnesium stearate slows down the dissolution of coated tablets in artificial stomach acid. However, the authors themselves conclude that even with the higher amounts of magnesium stearate that the pills still dissolved adequately and satisfies pharmacopoeial requirements for tablets. Furthermore, the authors caveat the in vivo (in people) experiments should be conducted.
Indeed, in vivo tests have been done; for example, one in 1996 by Rekhi &al., and one in 1998 by Eddington &al., showed that the bioavailability of drug, as demonstrated by serum levels after ingestion, is not affected by the presence or increased amount of magnesium stearate.
Magnesium stearate has been extensively shown to be safe and is an important ingredient to help ensure the uniformity of dosing, which contributes to the efficacy and safety of pharmaceuticals and natural health products. However, science is an ongoing process and evidence should continually be evaluated in a rational manner. After 80 years of extensive use, the body of evidence strongly indicates that the small amounts present in natural health products shouldn’t be a problem for a vast majority of the population.
Eddington, ND., Ashra, M., Augsburger, LL., Leslie, JL., Fossler, MJ., Lesko, LJ., Shah, VP., & Rekhi, GS. Identification of formulation and manufacturing variables that influence in vitro dissolution and in vivo bioavailability of propranolol hydrochloride tablets. Pharm. Dev. Tech. 3(4); 535-47
Rekhi, GS., Eddington, ND., Fossler, MJ., Schwartz, P., Lesko, LJ., & Augsburger, LL. 1996 Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate-release tablet formulations. Pharm. Dev. Tech. 2(1); 11-24
Robichaud, PP., Boulay, K., Munganyiki, JE., & Surette, ME. 2013 Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells. J. Lipid Res. 54(10): 2665-77
Songergaard, D., Meyer, O., & Wurtzen, G. 1980 Magnesium stearate given perorally to rats. A short term study. Toxicology. 17(1):51-5
Tammaro, A., Abruzzese, C., Narcisi, A., Cortesi, G., Persechino, F., Parisella, FR., & Persechino, S. 2012 Magnesium stearate: an underestimated allergen. J. Biol.. Regul. Homeost. Agents. 26(4):783-4
Uzunovic, A & Vranic, E. 2007 Effect of magnesium stearate concentration on dissolution properties of ranitidine hydrochloride coated tablets. Bosnian J. Basic Med. Sci. 7(3); 279-83