Magnesium Stearate, Hypothesis, Nocebo and Adverse ‘Halo Effect’ – a Critical Review.

Reading Time: 18 minutes

Michael Ash BSc DO ND Dip ION reviews the use of magnesium stearate in food supplements and discusses the science and chemistry in terms of alleged risk and its benefits.

Overview

A small number of clinicians, manufacturers and health care activists hypothesise that magnesium stearate, safely used by the food supplement and pharmaceutical industry for over 50 years is a detrimental and unnecessary component. Further, the detractors suggest that it may have immunologically adverse consequences, adversely alter the bacterial communities in our digestive tract and compromises GI function and nutrient absorption.

“Attack articles” which unfairly portray excipients or otherwise stretch the boundaries between truth and falsehood do not serve the public interest.

Of course, a hypothesis needs to be substantiated. After all, a hypothesis is simply an explanation for a phenomenon which can be tested in some way which ideally either proves or disproves the hypothesis. For the duration of testing, the hypothesis is taken to be true, and the goal of the researcher is to rigorously test the terms of the hypothesis.

The suggestions that magnesium stearate presents a problem for human health should be based on substantive, reproducible and testable explanations. At the very least they need to be relational – that is observations and explanations should have scientific plausibility. A hypothesis should be a plausible, probable explanation of some process, event or entity – but not all hypotheses of course are valid, or correct.

However, opinion leaders[1] may attract unqualified support for their hypothesis based on the ‘halo effect’; this is the phenomenon whereby we assume that because people are good at doing A they will be good at doing B, C and D (or the reverse—because they are bad at doing A they will be bad at doing B, C and D).

The negative opinions which state alleged problems of including magnesium stearate in food and pharmaceutical products are so well distributed in the internet arena that they are now responsible for a ‘nocebo’ effect. Nocebo effects are adverse events produced by negative expectations and represent the negative side of placebo effects. As with their placebo counterpart, nocebo responses demonstrate the powerful interaction between the therapeutic context and the patient’s mind-brain interaction.[2]

It is well recognised that nocebo effects exist and operate during routine treatments, negatively affecting clinical outcomes even when placebos are not administered. The nocebo effects and placebo effects that have genuine impact on the functionality of the patient are the direct result of the psychosocial context or therapeutic environment on a patient’s mind, brain, and body. Both phenomena can be produced and amplified by multiple factors, such as written opinion, verbal suggestions and past experience.[3] These not only have relevance in clinical management but also complicate perceptions of validity when emotionally connected to unsubstantiated hypotheses.

To this extent, a balance must exist between communicating important nutrient information and ensuring that every attempt is made to minimise unsubstantiated negative instructions and diminish negative therapeutic context. This fine balance must take into consideration the patient’s or consumer’s autonomy to make a decision based on all relevant information, whilst reframing the information in a non-deceptive, yet reassuring way. I hope that the following information is received in this context.

First let me explain a little of the chemistry

For over 40 years magnesium stearate, also known as octadecanoic acid and magnesium salt, has been used in the manufacture of food and pharmaceutical tablets and capsules. It has the chemical formula Mg (C18H35O2)2.

It is a salt containing two equivalents of stearate (the negatively charged anion of stearic acid) and one positively charged magnesium cation (Mg2+). This means magnesium stearate is a new compound formed when the positive ions from stearic acid are combined with magnesium.

In most food supplement manufacturing, especially from the better quality companies, it is used in very small quantities, less than 1% of the finished food supplements. It is used by companies along with other flow agents to aid accurate mixing of multiple ingredients and to reduce adhesion and flow complications. Pharmaceutical magnesium stearate should always be used to ensure cGMP analysis is complied with in both the food and pharmaceutical industry.

How does it work?

Magnesium stearate exists as “plate-like” crystals (or lamellae) stacked together like a deck of cards. As the blending of food ingredients or drugs proceeds, plates continuously shear off and coat adjacent particles of ingredients. The higher the concentration of magnesium stearate used or the longer this blending continues, the more complete this coating of the adjacent particles will become. For effective lubrication, you do not need and, in fact, you do not want to coat everything too completely with the lubricant as it alters the speed at which the tablet and capsule contents are made bioavailable. So the 1% or so of the total contents of the pill or capsule used by magnesium stearate is not only safe but produces an effective and bioavailable food supplement. As with all professional food supplements concentration, grade and mixing parameters must be carefully controlled and respective food supplement companies will apply their own ethos to these as well as meeting good manufacturing compliance.

Bioavailability issues

Studies have shown that magnesium stearate may affect the release time of the active ingredients in tablets, etc., but not that it reduces the overall bioavailability of those ingredients.[4] Trillions of supplements and medicines are consumed on a daily basis that contains magnesium stearate; some of these may have actually been formulated with slightly higher volumes of magnesium stearate than the typical 1% to deliberately delay the release of the ingredients.

Stearic acid

Stearic acid (also called octadecanoic acid) is one of the most common long-chain fatty acids, found in both natural animal and vegetable fats, known also by its structural description of being an 18-carbon chain fatty acid (C18:0) with a chemical structure of C36H70MgO4. It may also be used as a lubricant in the manufacture of food and pharmaceutical products.

Whilst it is classified as a saturated fatty acid (SFA), both biochemically and for purposes of nutrition labelling and dietary recommendations, data accumulated during the past 50 years indicate that stearic acid is unique among the SFAs in the food supply.[5] Stearic acid is found in numerous foods consumed on a daily basis – such as meat, coconut oil and chocolate, but evidence suggests that it is enzymatically converted into oleic acid during digestion (CH3(CH2)7CH=CH(CH2)7COOH) , neutralising any perceived negative risk related to cholesterol levels.[6]

Stearic acid is well absorbed by the gut being transported in chylomicrons and remnant particles before being metabolised by the liver. In the liver, any excess stearic acid is converted to the 18-carbon monounsaturated oleic acid via a desaturasing enzyme in the liver and then recirculates in lipoprotein complexes as oleic acid, which is not hypercholesterolaemic.[7] As described it is proposed, this conversion to oleic acid may explain why stearic acid does not elevate plasma cholesterol concentrations.[8]

Magnesium

Magnesium (Mg) is an essential mineral for human life and is combined with stearic acid to produce safe magnesium stearate. Production methods used can provide stearic acid without any of the hydrogenation processes that may introduce trans-fat by-products.

The British Pharmacopoeia 2011 describes magnesium stearate as a compound of magnesium with a mixture of solid organic acids (stearic acid and palmitic acid), and consists chiefly of variable proportions of magnesium stearate and magnesium palmitate. The fatty acids are derived from edible sources (in the food supplement industry these are vegetable unless otherwise stated). It contains not less than 4.0% and not more than 5.0% of Mg, calculated on the dried basis.

Magnesium stearate is not blackboard chalk

One of the many unsubstantiated statements made by some magnesium stearate critics is that it is the same as blackboard chalk. This is a chemical impossibility; whilst blackboard chalk was historically primarily made of natural chalk composed of calcite and described as calcium carbonate (CaCO3), today it is often made from gypsum or calcium sulphate (CaSO4·2H2O) and both forms are very different than that found in magnesium stearate.

Safety

In the USA the Food and Drug Administration (FDA) is the responsible agency tasked to rule on food ingredients in terms of their ‘generally recognised as safe’ status (GRAS). The FDA states: magnesium stearate is generally considered safe for human consumption at levels below 2,500 mg/kg per day.[9]

The FDA report as referenced above, goes on to state: …… leads to the opinion that none of the available evidence suggests any probable hazard when any of the GRAS compounds of magnesium is used as a food ingredient. In view of the foregoing, The Select Committee concludes that:

There is no evidence in the available information on magnesium carbonate, magnesium chloride, magnesium sulphate, magnesium hydroxide, magnesium oxide, magnesium stearate, dibasic magnesium phosphate and tribasic magnesium phosphate that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when they are used at levels that are now current and in the manner now practiced, or which might reasonably be expected in the future.

In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for the oversight of food ingredients and medicines and in turn are supported by the Food Standards Agency (FSA). The British Pharmacopoeia  is the leading collection of standards for UK medicinal products and pharmaceutical substances and all recognise magnesium stearate as suitable, safe and approved for human consumption. In the EU, the European Food Standards Agency is responsible for oversight of food additives and ingredients, and once again provides approval for its use in food supplements and medicines.

Immune issues

The immune system is a vital part of our ability to survive and function. One of the most elaborate areas of human biology, this very complexity has been used by some opinion leaders to imply and infer a dubious impact of magnesium stearate on immune function. References are often made to a 1990 paper published in the journal Immunology by people wishing to suggest a related immunological risk.[10]

Natural killer cells are often implicated in the context of this denigration, inferences suggest they are compromised or suppressed in the face of magnesium stearate and ergo, taking food supplements or medicines that contain this excipient will result in immune suppression. NK cells are an important part of our immediate defence – we inherit them already to function, and as such they are considered as protypical innate immune cells and although similar to adaptive T cells whose response is driven by prior exposure they are not the same. NK cells represent the third lymphocyte population in addition to T and B cells.[11]

The link to this paper and the associated claims about magnesium stearate are at best spurious and at worst suggest a failure to understand or interpret research. The Immunology Journal article refers to the use of isolated stearic acid – this is not the same as magnesium stearate, being applied to mouse derived T and B cells in vitro. The cells are stimulated by exogenous mediators and then doused in stearic acid. Due to an inherent enzyme deficiency in T cells the stearic acid is taken into the cell membrane, but B cells reject it. The end result after 6-8 hours saturation is T cell wall collapse.

The authors state – “This does not prove a cause an effect relationship between membrane lipid changes and disruption of the membrane potential”.

They do suggest that subject to further trials this mechanism may be utilised to prevent organ transplant rejection, and for the suppression of autoimmune activity, as it would have similar effect to cyclosporine but without any of the side effects. However, no further papers on this model have been published suggesting that its role as a clinical tool in organ rejection is unlikely to appear in the near future.

The key points are:

  • The model used was ‘in vitro’ – a notoriously unreliable indicator for human health related investigations
  • The agent was pure stearic acid not magnesium stearate
  • The cells were mice derived
  • The outcome was seen as being positive (from the perspective of the researchers)
  • The cells selected were the adaptive immune T cells, not the innate NK cells, and whilst membranes are similar these cells are not the same

Magnesium stearate is not the same thing as stearic acid, but a compound that is derived from it. Stearic acid is a saturated fatty acid found in all vegetable, seed, nut, and animal oils. Although stearic acid can be derived from several sources, including bovine, the most common source for food supplements is vegetable stearic acid primarily from coconut and palm oils. Stearic acid has actually been demonstrated in human studies to demonstrate healthy outcomes.[12],[13]

Biofilms

Some commentators suggest that magnesium stearate can cause the development of biofilms in the human intestine based on effects seen with vegetable stearate on baths and sinks. The so called ‘scum ring’ seen on baths, sinks and some toilets is constructed from minerals from the water, dirt, body oils, sloughed off skin and bacteria.

This association once again is stretching scientific plausibility to breaking point; there is no research suggesting or proving biofilms occur in humans with ingestion of magnesium stearate. In fact, there are no human studies that imply or confirm risk of consumption of magnesium stearate at all.

Biofilms are the tight-knit communities that some bacteria form on surfaces to protect themselves from antimicrobial attack. Biofilms contribute to the ability of bacteria to communicate and behave as a group for social interactions like a multi-cellular organism and has provided significant benefits to bacteria in host colonisation, defence against competitors, and adaptation to changing environments. The understanding that biofilms can and are vital to our human microbiota is sometimes lost in the popular hysteria that all biofilms are bad.[14]

The large intestine in humans is the site most heavily colonised by micro-organisms in the GI tract. While the colonic microbiota is usually thought of as being a homogeneous entity, this is an over simplification, because the bacteria exist in a multiplicity of different microhabitats and metabolic niches in the mucus layer lining the gut, the mucosa and on the surfaces of digestive residues in the gut lumen. These microcosms are continually changing, as nutrients are consumed or new resources become available. Environmental and nutritional factors, the chemical composition of the substratum and host defensive mechanisms associated with the innate and adaptive immune systems all play a role in biofilm development and deconstruction. The surface area of the gastric lumen is modifiable through food selection and diet; prebiotics, probiotics and antibiotics are likely the most significant exogenous modifiers of bacterial communities[15],[16],[17]. The suggestion that the ingestion of magnesium stearate, is on its own sufficient to create a detrimental biofilm, shows a poor comprehension of the complex dynamics of bacteria and yeasts in the gut lumen.

Contamination

The raw materials for vegetable stearate are derived from plants, in particular palm trees. Suggestions are made that as some plant sources are treated with pesticides, that contamination issues are not only possible, but present a health risk. Others suggest that because of a single incident of magnesium stearate contamination, (which, by the way, had no health related adverse outcomes)[18] that this ‘risk’ invalidates all supplements that use this ingredient to facilitate manufacturing quality and consistency.

This cannot be substantiated and is a highly tenuous proposal. Most plants used in the manufacture of food supplements draw minerals and contaminants from the ground or air – and most of us eat these each day, even if we select organic foods. Exposurerisk must be placed in context. Toxic chemicals enter the body not only from exogenous sources (air, water, diet, drugs, and radiation) but also from endogenous processes, including inflammation, lipid peroxidation, oxidative stress, existing diseases, infections, and gut flora. We possess a highly adaptive set of homeostatic management systems to manage these.

Magnesium stearate used in food supplements is a non-hydrogenated plant based fatty acid and magnesium combination, consumed globally by billions of people each day, with no identified or scientifically recorded adverse health effects. Nocebo effects, however, may have been generated by inappropriate and unsubstantiated emphasis on risk by opinion leaders.

There are many genuinely concerning contaminants that exist in our diets and environment that not only act as independent mediators of our health, but also operate collectively. The model now described as the ‘exposome’’ – representing the totality of exposures from gestation onwards is gaining momentum in environmental health science and helping us to develop better clinical care.[19] Proponents of the exposome concept distinguish this approach as being a broad-based assessment of exposures, as opposed to the traditionally parochial approach of environmental scientists and activists looking at one toxin or class of exposures at a time.[20]

Concluding statement

Magnesium stearate has no known risk for humans when consumed as designed; in very small quantities in food supplements and medicines. No detractor’s web site supplies any substantive evidence that this is an incorrect statement; neither do the online medical libraries PubMed or Medline.

Personal opinion may still be to avoid food supplements and medicines that utilise this lubricant; however, this will ultimately be an emotional decision rather than one based on weight of valid evidence.

References


[1] Opinion leaders are individuals who obtain more media coverage than others and are especially educated on a certain issue. They seek the acceptance of others and are especially motivated to enhance their social status. (Rose p, Kim JH. Current Psychology. Volume 30, Number 3 (2011), 203-214, DOI: 10.1007/s12144-011-9114-1 View Abstract )

[2] Brody H, Miller FG. Lessons from recent research about the placebo effect–from art to science. JAMA. 2011 Dec 21;306(23):2612-3. No Abstract Available

[3] Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet. 2010 Feb 20;375(9715):686-95. Review. View Abstract

[4] Uzunović A, Vranić E. Effect of magnesium stearate concentration on dissolution properties of ranitidine hydrochloride coated tablets. Bosn J Basic Med Sci. 2007 Aug;7(3):279-83. View Abstract

[5] Kris-Etherton PM, Griel AE, Psota TL, Gebauer SK, Zhang J, Etherton TD. Dietary stearic acid and risk of cardiovascular disease: intake, sources, digestion, and absorption. Lipids. 2005 Dec;40(12):1193-200. Review. View Abstract

[6] Cohn JS, Kamili A, Wat E, Chung RW, Tandy S. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications. Atheroscler Suppl. 2010 Jun;11(1):45-8. Epub 2010 May 2. Review. View Abstract

[7] Lin DS, Connor WE, Spenler CW. Are dietary saturated, monounsaturated, and polyunsaturated fatty acids deposited to the same extent in adipose tissue of rabbits? Am J Clin Nutr. 1993 Aug;58(2):174-9. View Abstract

[8] Cohn JS, Kamili A, Wat E, Chung RW, Tandy S. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications. Atheroscler Suppl. 2010 Jun;11(1):45-8. Epub 2010 May 2. Review. View Abstract

[9] http://www.accessdata.fda.gov/scripts/fcn/fcnDetailNavigation.cfm?rpt=scogsListing&id=198

[10] Tebbey PW, Buttke TM. Molecular basis for the immunosuppressive action of stearic acid on T cells. Immunology. 1990 Jul;70(3):379-84. Erratum in: Immunology 1990 Oct;71(2):306. View Abstract

[11] Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S. Innate or adaptive immunity? The example of natural killer cells. Science. 2011 Jan 7;331(6013):44-9. Review. View Abstract

[12] Kelly FD, Sinclair AJ, Mann NJ, Turner AH, Abedin L, Li D. A stearic acid-rich diet improves thrombogenic and atherogenic risk factor profiles in healthy males. Eur J Clin Nutr. 2001 Feb;55(2):88-96. View Abstract

[13] Storm H, Thomsen C, Pedersen E, Rasmussen O, Christiansen C, Hermansen K. Comparison of a carbohydrate-rich diet and diets rich in stearic or palmitic acid in NIDDM patients. Effects on lipids, glycemic control, and diurnal blood pressure. Diabetes Care. 1997 Dec;20(12):1807-13. View Abstract

[14] Elias S, Banin E. Multi-species biofilms: living with friendly neighbors. FEMS Microbiol Rev. 2012 Jan 9. doi: 10.1111/j.1574-6976.2012.00325.x. [Epub ahead of print] View Abstract

[15] Macfarlane S, Dillon JF. Microbial biofilms in the human gastrointestinal tract. J Appl Microbiol. 2007 May;102(5):1187-96. Review. View Abstract

[16] Macfarlane S, Bahrami B, Macfarlane GT. Mucosal biofilm communities in the human intestinal tract. Adv Appl Microbiol. 2011;75:111-43. View Abstract

[17] Van Wey AS, Cookson AL, Roy NC, McNabb WC, Soboleva TK, Shorten PR. Bacterial biofilms associated with food particles in the human large bowel. Mol Nutr Food Res. 2011 Jul;55(7):969-78. doi: 10.1002/mnfr.201000589.  Epub 2011 Jun 3. Review. View Abstract

[18] http://apps.who.int/prequal/info_press/documents/Mg-Stearate_InformationNote_Dec2011.pdf

[19] Rappaport SM. Discovering environmental causes of disease. J Epidemiol Community Health. 2012 Feb;66(2):99-102. View Abstract

[20] C.P. Wild. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev, 14 (2005), pp. 1847–1850 View Abstract

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9 Comments. Leave new

  • Please see well referenced article by Dr Mercola that Magnesium Stearate is a dangerous ingredient: “previous research has shown that stearic acid suppresses T cells—your natural killer cells—which are a key component of your immune systemi. According to that study, stearic acid causes the collapse of cell membrane integrity—an effect that was found to be time and dose dependent—which, ultimately, can destroy cell function.”

    Reply
    • Michael Ash
      July 9, 2012 2:47 pm

      Hello Mariette

      I am not sure – but did you read the article in full – mine I mean, as I specifically refer to the same papers described in your post. The paper published in Immunology is a perfectly decent research paper – but it has nothing to do with magnesium stearate and therefore is, I regret, an example of unsuitable and incorrect association. Mg stearate when mixed properly at 1% or less of the volume of a food supplement or medicine is not only perfectly safe but is consumed by trillions of people every day.

      If a company was to add say 5% weight and over mix, then slow dissolution would occur, but there is still no evidence that it has any adverse effect on the cells of the immune system.

      Reply
    • RAGHUNADH M
      June 2, 2017 11:56 am

      Query received from FDA regarding minor change in excipient ( Magnesium stearate) with respect to innovator formulation of Antibiotic tablet. Magnesium stearate is absent in Innovator formulation.

      FDA wants to prove that addition of this Magnesium stearate have no effect on antimicrobial effect of antibiotic…….can you please suggest how we can prove that the difference between formulation with and without this Magnesium stearate have same antimicrobial activity… As per my knowledge MIC studies are done with pure antibiotics/ API….in formulation is it possible…?

      Reply
  • Do you have access to any other research regarding Magnesiuim Stearate? I seem to be allergic to it.

    I have Autoimmune Hepatitis and require an Immunosuppressant. I am unable to find one without Magnesium Stearate, but this substance causes breathlessness, for which I have required 2 hospital admissions, but despite intensive tests, they wre unable to find a cause.

    No I’ve discovered that Magnesium Stearate has a recorded side effect of breathlessness and is the only ingredients each of the medications have in common.

    I’d like ot find out more information, as I cannot be the only person to have this reaction. Many thanks, June

    Reply
    • Hello June
      Thanks for your e mail. I am not sure if you read all of the article, but Mg Stearate will not cause an allergic reaction, and I am unaware of any published data that describes any breathlessness associated with it. Stearic acid is present in many commonly eaten foods in much higher quantities than that found in supplements, and if you were to experience a breathlessness it would occur from meat and chocolate ingestion, to name just 2.

      Autoimmune Hepatitis will mean that cytochrome P450 enzymes used by you to metabolise medications amongst others, will be altered in their functionality and the subsequent production of antibodies and other agents are likely to be the cause of your reactivity.

      best wishes

      Reply
  • Chemistry question. If magnesium is safe and stearic acid is safe….does that really make magnesium stearate safe by association via it’s respective components, even though when things are combined it creates a different molecular structure? In this instance…the stearic acid become stearate. A different structure.

    Reply
    • Michael Ash
      April 8, 2013 4:45 pm

      Hello Janice

      Stearic acid is the saturated fatty acid with an 18 carbon chain and has the more technical name octadecanoic acid. It is a waxy solid, and its chemical formula is CH3(CH2)16CO2H. Its name comes from the Greek word στέαρ “stéar”, which means tallow. The salts and esters of stearic acid are called stearates. Stearic acid is one of the most common saturated fatty acids found in nature following palmitic acid.

      Magnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance, powder which becomes solid at room temperature. It has the chemical formula Mg(C18H35O2)2. It is a salt containing two equivalents of stearate (the anion of stearic acid) and one magnesium cation (Mg2+).
      Whilst you are correct that the addition of a salt changes the chemical structure, the two components are not changed except by virtue of a bond. This increases their carbon chain from 16-18 but neither component becomes adversely altered and each are split during digestion to their original state. Both of which are harmless and quite likely beneficial.

      I hope that helps

      Reply
  • Just curious: I never see a quantity listed for either magnesium stearate or stearic acid on the supplement bottles. So how would we know if we are exceeding the safe limit in a day if we need to take multiple supplements?

    Reply
    • Hi Jan, the ingredients listed in the small text at the bottom of a Nutrition Facts label are too small in percentage terms to be given their own line. But as supplements that use MgStearate as a flow agent use less than 1% by weight, a 2000mg tablet would typically contain 20mg or less of Mg Stearate. This is less than 1% of the recognised safe level of ingestion of 2,500mg daily. The image above provides some further comparisons.

      Reply

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