February 9, 2010

Re: False Information about Stearic Acid and Magnesium Stearate Disseminated By Ultra Laboratories

Dear Jarrow Formulas Customer: Whom It May Concern:

It has come to our attention that a supplement marketer, Ultra Laboratories, has been enclosing in their shipments a notice entitled “INGREDIENT WARNING, Stearic Acid/Magnesium Stearate.”  The statement contains false and misleading statements regarding the compounds stearic acid and magnesium stearate.  These statements create confusion among retailers and consumers and also result in damage to the reputation and business operations of many nutraceutical and pharmaceutical companies, including Jarrow Formulas, Inc.

As colleagues in the nutrition industry, we are disappointed by this type of unprofessional conduct.  The statements in question are without scientific merit.

The publications Ultra Laboratories cite do not support their claim of potential toxicity of stearic acid and magnesium stearate.  In fact, stearic acid is a normal part of the human diet.

Stearic acid is a naturally occurring fatty acid that is found in both animal and plant fats (Table 1).  In the body, stearic acid is converted into oleic acid, an important fatty acid that is also commonly found in olive oil and other naturally occurring fats.  A number of recent clinical studies have shown that this conversion into oleic acid results in recirculation of lipo-protein complexes in the form of oleic acid1.  Thus, intake of stearic acid does not increase the concentration of plasma cholesterol 1-6 .  A growing number of studies have even shown its association with reduced LDL, speculating the effect of stearic acid on the reduced uptake of cholesterol and the increased release of endogenous cholesterol7-8.   There have been no adverse effects reported in these high stearic acid dietary studies, as long as the levels are under the recommended daily fatty acid consumption level6,9-10. These data collectively suggest this fatty acid is less unhealthy than many other fatty acids that we consume as food and product ingredients. 

Table 1

Stearic acid is a waxy substance that is usually combined with the essential mineral magnesium (magnesium stearate). Production of magnesium stearate can provide stearic acid without any of the hydrogenation processes that may introduce trans-fat by-products. Magnesium stearate contains between 6.8-8.3% of magnesium oxide, which in a typical supplement amounts to only 1/10,000 of the recommended daily magnesium intake, and it is well accepted as evidenced by the Generally Recognized As Safe (GRAS)15 designation. The FDA has confirmed its safety and suitability for foods and food preparations in accordance with GMP16.

Magnesium stearate is often used as a lubricant during capsule filling and is also used as a binder in tablets to hold other ingredients together. However, the level of magnesium stearate never reaches more than 2% of the product weight in dietary supplements, and is usually much less or negligible.  In such small amounts (0.5mg or less), it is orders of magnitude below the labeling requirement of any fats (0.5g). 

The studies that are cited on Ultra Laboratories’ misleading “warning” are irrelevant to the safety of stearic acid/magnesium stearate in supplements for the following reasons.

Am. J. Med. Sci. 1999;318(1):15-21
This article discusses an association between high levels of saturated fatty acids and increased apoptosis in post-ischemic or post-surgical cardiac tissues.  The author begins the article with the statement that abnormal levels of fatty aids in the blood only occur with pathologies including chronic diabetes, obesity, and hyperlipidemia.  Acutely, fatty acids are elevated in people with myocardial ischemia and cardiac surgery. Thus, in healthy people, ingested fatty acids are metabolized and do not cause a sustained increase in circulating levels. The findings in this article include 1) that high levels of fatty acids lead to fatty acid oxidation and delayed recovery in post-ischemic hearts and 2) failed transfer and metabolism of fatty acid (eg. Failed CPT-I) results in mitochondria-mediated apoptosis. In post-ischemic or post-surgical hearts, many changes occur, including immunologic and metabolic abnormalities.  Oxygen supply is limited in these hearts, and thus, in order to efficiently supply energy without using too much oxygen, normal glucose vs. fatty acid metabolism (30-40% vs. 60-70%) is shifted toward glucose-dominant metabolism 17-18.  This may cause an accumulation of fatty acid, and subsequent fatty acid oxidation can consume the available oxygen supply, aggravating hypoxia and extending injury.  If these fatty acids are not transported into mitochondria via transferase enzymes (eg. CPT-I), they could accumulate and induce mitochondria-dependent apoptosis as the author reported.  The article concludes that additional studies are required to gain further understanding of the association, and these findings may only “partially explain the link between the high levels of circulating fatty acids and heart disease”.  This study is interesting, but it is completely out of context for determining any toxicity of dietary stearic acid as an excipient in the microgram range.  This level of stearic acid would never reach the levels that these studies examined, and the system in this study is so complex and non-physiologic that it is impossible to conclude anything about the effect of stearic acid when used as an excipient.

Journal of Neurochemistry, 2003;84 (4): 655-668
This article is similar to the one above, discussing the association between increased saturated fatty acid levels and apoptosis in traumatic neural injury in the CNS and PNS.  Again, this study was conducted in an artificially enriched pheochromocytoma cell culture system that was stimulated with high concentrations of growth factor and saturated fatty acids (300μM).  Brain injury results in hypoxia-ischemia with increased concentrations of fatty acids due to the breakdown of damaged membranes.  Such traumatic injury can stimulate altered gene expression and modulate various signaling pathways. As in the previous study, the system in which these effects are reported and the levels of saturated fatty acids studied are exceptionally unique and irrelevant to the physiological effects of the miniscule levels of stearic acid that are consumed with dietary supplements.    

Immunology 1990; 70:379-384
Proc. Natl. Acad. Sci. USA 1989; 86: 6133-6137
Biochemistry Immunology 1985; 56:659-666
Immunology 1984; 53:507-514
The goal of each of these four studies was to investigate different metabolic functions of stearic acid in B and T cell responses.  These studies are conducted in “highly enriched B- and T-cell populations” isolated from mice that were artificially stimulated with high concentrations of different mitogens and also treated with abnormally high concentrations of stearic acid (50μM and 160 μM – many thousand-fold higher than the normal total serum fatty acid level of 10nM, of which stearic acid comprises only a fraction).  The species disparity, as well as the very specialized study environments may not be appropriate for drawing conclusions regarding the toxicity of stearic acid in humans. Interestingly, some of the conclusions of these studies with this controlled environment include 1) that T-cells have little or no desaturase activity and thus, they cannot metabolize stearic acid, leading to accumulation of saturated fatty acids, loss of membrane fluidity, and ultimately, cell death, but 2) this inhibitory effect can be reversed when cells were co-supplemented with oleic acid.  The authors state that it unclear if T-cell proliferation is dependent on the B-cells’ ability to metabolize stearic acid in a physiologic environment, and if so, this may play a role in the cross-talk between B- and T-cells and in downstream immune responses. In healthy individuals, stearic acid is readily converted into oleic acid, and thus, the inhibitory effect of stearic acid on T-cell proliferation may be minimal under normal conditions.  Generally speaking, the human immune system is extremely complex, and we only know very little about it. It is possible that the inhibitory effect that was observed may be a protective mechanism that contributes to the maintenance of a well-balanced immune system. 

In conclusion, there have been no reported adverse effects of stearic acid/magnesium stearate in humans at the concentrations that are used in foods and product ingredients.  Interestingly, an increasing number of studies have been reporting beneficial effects of stearic acid on cardiovascular health when used as a substitute for other fatty acids19-30 .

Jarrow Formulas uses USP grade magnesium stearate at minuscule concentrations when needed to formulate our dietary supplements.  All of our manufacturing is carried out in GMP/NSF compliant facilities that are strictly monitored by us and third-party regulatory organizations.  Thus, we take pride in our products and their quality and safety. 

The statements published by Ultra Laboratories are false, reckless, and damaging to the image of the dietary supplement industry as a responsible industry.  It is misleading to consumers. We are demanding that Ultra laboratories cease and desist from their false, defamatory and misleading campaign or we will be compelled to take the matter to the proper division of the Federal Trade Commission and the National Advertising Division of the Better Business Bureau. 
Lastly, the statement by Ultra Laboratories that stearic acid or magnesium stearate have “clearly been shown to be an allergen” is simply completely false.  For one, allergens are generally protein related.

Very truly yours,

Jarrow L. Rogovin
President
Jarrow Formulas, Inc.
1824 S. Robertson Blvd.
Los Angeles, CA 90035
Phone: 310-204-6930

Kaori Shimazaki, Ph.D.
Technical Support & Education
Jarrow Formulas, Inc.
1824 S. Robertson Blvd.
Los Angeles, CA 90035
Phone: 310-204-6930 X109

References:

1. 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;58:174-9.

2. Snook JT, Park S, Williams G, Tsai Y-H, Lee N. Effect of synthetic triglycerides of myristic, palmitic, and stearic acid on serum lipoprotein metabolism. Eur J Clin Nutr. 1999;53:597-605.

3. Meijer GW, Weststrate JA. Interesterification of fats in margarine: Effect on blood lipids, blood enzymes, and hemostasis parameters. Eur J Clin Nutr. 1997;51:527-534.

4. Nestel PJ, Pomeroy S, Kay S, Sasahara T, Yamashita T. Effect of a stearic acid-rich, structured triacylglycerol on plasma lipid concentrations. Am J Clin Nutr. 1998;68:1196-1201.

5. Zock PL, de Vries JHM, de Fouw NJ, Katan MB. Positional distribution of fatty acids in dietary triglycerides: Effects on fasting blood lipoprotein concentrations in humans. Am J Clin Nutr. 1995;61:48-55.

6. Zampelas A, Williams CM, Morgan LM, Wright J, Quinlan PT. The effect of triacylglycerol fatty acid positional distribution on postprandial plasma metabolite and hormone responses in normal adult men. Br J Nutr. 1994;71:401-410.

7. Hunter, J. Edward; Zhang, Jun; Kris-Etherton, Penny M. (January 2010). "Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review". Am. J. Clinical Nutrition (American Society for Nutrition) 91 (1): 46–63

8. Schneider CL, et al. Dietary stearic acid reduces cholesterol absorption and increases endogenous cholesterol excretion in hamsters fed cereal-based diets. J Nutr. 2000 May;130(5):1232-8. PMID: 10801924

9. Meijer GW, Weststrate JA. Interesterification of fats in margarine: Effect on blood lipids, blood enzymes, and hemostasis parameters. Eur J Clin Nutr. 1997;51:527-534.

10.  Louheranta AM, Turpeinen AK, Schwab US, Vidgren HM, Parviainen MT, Uusitupa MIJ. A high-stearic acid diet does not impair glucose tolerance and insulin sensitivity in healthy women. Metabolism. 1998;47:529-534.

11.USDA Nutrient Database for Standard Reference, Release 19, 2006 (7).

12. The Hershey Company Website. www.hersheys.com/nutrition/fat.asp. Downloaded 02/03/2010.

13. Denke MA. Role of beef and beef tallow, an enriched source of stearic acid, in a cholesterol-lowering diet. Am J Clin Nutr. 1994 Dec;60(6 Suppl):1044S-1049S. Review. PMID: 7977148

14. Effects of cocoa butter on serum lipids in humans: historical highlights. Am J Clin Nutr. 1994 Dec;60(6 Suppl):1014S-1016S. Review. PMID: 7977142

15.FDA Center for Food Safety and Applied Nutrition. Database of Select Committee on GRAS Substances (SCOGS) Reviews. CFSAN/Office of Food Additive Safety. October 2006

16. Code of Federal Regulations. Title 21, Volume 3. Revised as of April 1, 2006. CITE: 21CFR184.1090 [48 FR 52445, Nov. 18, 1983, as amended at 50 FR 49536, Dec. 3, 1985; 69 FR 24512, May 4, 2004]

17. Taegtmeyer H. Energy substrate metabolism as target for pharmacotherapy in ischemic and reperfused heart muscle. Heart Metab 1998; 1: 5–9.

18. Opie LH. Glycolytic rates control cell viability in ischemia. J Appl Cardiol 19xx; 3: 407–414.3  "stearic acid." Encyclopædia Britannica. 2006. Encyclopædia Britannica Online. 18 Dec. 2006 

19. Kris-Etherton, P.M., Griel, A.E., Psota, T.L., et al. Dietary stearic acid and risk of cardiovascular disease: intake, sources, digestion, and absorption. Lipids 40: 1193-1200, 2005.

20. Haumann, B.F. Stearic acid: a ‘different’ saturated fatty acid. INFORM (American Oil Chemists’ Society) 9(3): 202-208, 1998.

21. Grundy, S.M. Influence of stearic acid on cholesterol metabolism relative to other long-chain fatty acids. Am. J. Clin. Nutr. 60(suppl): 986s-990s, 1994.

22. Mensink, R.P. Effects of stearic acid on plasma lipid and lipoproteins in humans. Lipids 40: 1201-1205, 2005.

23. Mensink, R.P., Zock, P.L., Kester, A.D.M., et al. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am. J. Clin. Nutr. 77: 1146-1155, 2003.

24. Nicolosi, R.J. Dietary fat saturation effects on low-density-lipoprotein concentrations and metabolism in various animal models. Am. J. Clin. Nutr. 65 (suppl): 1617s-1627s, 1997.

25. Hassel, C.A., Mensing, E.A., Gallaher, D.D. Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters. J. Nutr. 127: 1148-1155, 1997.

26. Tholstrup, T., Marckmann, P., Jespersen, J., et al. Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids. Am.J. Clin. Nutr. 59: 371-377, 1994.

27. Kelly, F.D., Sinclair, A.J., Mann, N.J., et al. A stearic acid-rich diet improves thrombogenic and atherogenic risk factor profiles in healthy males. Eur. J. Clin. Nutr. 55: 88-96, 2001.

28. Kelly, F.D., Sinclair, A.J., Mann, N.J., et al. Short-term diets enriched in stearic or palmitic acids do not alter plasma lipids, platelet aggregation or platelet activation status. Eur. J. Clin. Nutr. 56: 490-499, 2002.

29. Judd, J.T., Baer, D.J., Clevidence, B.A., et al. Dietary cis and trans monounsaturated and saturated FA and plasma lipids and lipoproteins in men. Lipids 37: 123-131, 2002.
Tholstrup, T. Influence of stearic acid on hemostatic risk factors in humans. Lipids 40: 1229-1235, 2005.

30.Thijssen, M.A., Hornstra, G., Mensink, R.P. Stearic, oleic, and linoleic acids have comparable effects on markers of thrombotic tendency in healthy human subjects. J. Nutr. 135: 2805-2811, 2005.