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The Discovery of Cetyl Myristoleate

A Unique Natural Compound Valuable in Arthritis Conditions
A Sponsored Article by
Dr. Charles Cochran and Dr. Raymond Dent


Introduction

Arthritis is a disease of epidemic proportions, but it has been around for so many centuries that it is considered by most people as a part of growing old or a consequence of physical injury. Arthritis is in fact a far more complex disease than is generally known. For instance, Dorland's Medical Dictionary describes 27 different types of arthritis, and that does not include such diverse conditions as systemic lupus erythematosus, scleroderma, fibromyalgia, and numerous other conditions which some authorities consider to be types of arthritis. One authority states that there are approximately 100 causes for arthritis.

Arthritis is thought to affect more than 50 million Americans, and is generally accepted to be the leading cause of movement limitation and disability. It deserves and receives a great deal of research and medical attention. There are hundreds of drugs, procedures, and medical aids and devices directed at coping with the many manifestations of the disease. Given this degree of complexity, certainly no one agent alone could ever be expected to manage or cure "arthritis" in its entirety. New agents take their place in the spectrum and make a contribution. Now there is a relatively new discovery of a natural substance, cetyl myristoleate, which shows promise of making a great contribution in non-infective types of arthritis.


Cetyl Myristoleate

Cetyl myristoleate was discovered and isolated by one person, working alone, on a quest to find a cure for arthritis. Harry W. Diehl, while employed by the National Institute of Arthritis, Metabolism, and Digestive Diseases, specialized in sugar chemistry. He used his chemical knowledge and research instincts to great advantage, identifying and characterizing over 500 compounds, several of which were patented by the National Institutes of Health (NIH). His most significant discovery before cetyl myristoleate was a method of synthesizing 2-deoxydextroribose, a sugar used in the preparation of oral polio vaccine by Dr. Jonas Salk.

Diehl's interest in discovering a way to help victims of arthritis began over 40 years ago when his friend and next door neighbor, a carpenter, developed severe rheumatoid arthritis. His condition deteriorated over time until he became disabled. The neighbor had a family to support, but his arthritis made that impossible. Diehl is a deeply religious man whose feelings overwhelmed him as his friend's condition worsened. Harry thought, "Here I am working at the National Institutes of Health, and I have never seen anything that was good for curing arthritis."4 He decided to establish a laboratory in his home and embark on a search for something to relieve the pain and disability of his neighbor and the millions of people who suffer from arthritis. Unfortunately, he was too late to help the neighbor, but Diehl's research did lead to the discovery of cetyl myristoleate, which may someday be hailed as one of the significant nutritional discoveries of the 20th century.


The Quest

As a researcher, Diehl knew that finding a cure for arthritis first meant inducing the disease experimentally in research animals. He started with mice, and quickly realized that he was unable to induce arthritis in them. Diehl said he tried every way he could to give those mice arthritis, but they just would not get it. Then, he contacted a researcher in California who wrote to him, "If you or anyone else can give mice arthritis, I want to know about it, because mice are 100% immune to arthritis."5 At that moment, Diehl's research instincts told him that what he wanted was already somewhere in those mice.

It was a long, tedious job, working on his own in his spare time, but Diehl finally found the factor - cetyl myristoleate - that protected mice from arthritis. As Diehl said, "It didn't come on a silver platter to me, but after years of chemical sleuthing and just old-fashioned chemical cooking, I found it!" On thin layer chromatography of methylene chloride extract from macerated mice, Diehl noticed a mysterious compound, which was subsequently identified as cetyl myristoleate. As Diehl was to prove, cetyl myristoleate circulates in the blood of mice and makes them immune to arthritis.

Cetyl myristoleate is now known to exist in sperm whale oil and in a small gland in the male beaver. At this time no other sources in nature are known to contain cetyl myristoleate. While the first amounts of cetyl myristoleate for experimentation were extracted from mice, Diehl quickly developed a method for making cetyl myristoleate in the lab by the esterification of myristoleic acid.


Chemistry

Cetyl myristoleate, an oil, is the hexadecyl ester of the unsaturated fatty acid cis-9-tetradecenoic acid. The common name for the acid is myristoleic acid. Myristoleic acid is found commonly in fish oils, whale oils, dairy butter, and kombo butter. The chemical formula for cetyl myristoleate is (Z)-ROCO(CH2)7CH=CH(CH2)3CH3. Cetyl myristoleate was unrecorded in chemical literature until Diehl's discovery was reported. The current Merck Index of Chemicals does not list cetyl myristoleate. A search of Chemical Abstracts lists Diehl's method of extracting cetyl myristoleate from mice but contains no reference to cetyl myristoleate prior to his 1977 patent.

Experimentation

To test his theory that mice are immune to arthritis because of cetyl myristoleate, Diehl began to experiment on laboratory rats. This research was reported in an article written in conjunction with one of his colleagues at NIH in the Journal of Pharmaceutical Sciences.6 In summary, this paper reports that ten normal mice were injected in the tail with Freund's Adjuvant (heat-killed desiccated Mycobacterium butyricum) to which rats and certain other rodents are susceptible. In a period of 10-20 days, no noticeable swelling developed in the legs or paws. Mice in a second group were injected in the left hind paw. Again, after 10-20 days, no swelling was detected as determined by comparison of the measurements of paws at the time of injection.

Then, a group of rats was injected with cetyl myristoleate, and 48 hours later, they were given the arthritis-inducing Freund's adjuvant. A control group of rats was given Freund's adjuvant only. Both groups of rats were observed for a total of 58 days with respect to weight change, hind and front leg swelling, and general well-being. All rats receiving only Freund's adjuvant developed severe swelling of the front and hind legs, lagged in weight gain, and were lethargic and morbid. Those receiving cetyl myristoleate before receiving Freund's adjuvant grew an average of 5.7 times as much as the control group and had little if any evidence of swelling or other symptoms of polyarthritis.

The authors concluded that it was apparent that cetyl myristoleate gave virtually complete protection against adjuvant-induced arthritis in rats. Furthermore, a 1:1 mixture of cetyl myristoleate and a homologue, cetyl oleate, gave results not significantly different from administering cetyl myristoleate alone.


A Hiatus

Diehl patented his discovery in 1977, receiving a use patent for rheumatoid arthritis. He then sought pharmaceutical companies to conduct human trials with cetyl myristoleate, but none were interested in his discovery. Perhaps the lack of interest was because cetyl myristoleate was a natural substance and could not be granted a product patent, or maybe because drug companies know they will have to run through 25,000 to 35,000 substances before they find one that makes it to market. Diehl had made a major nutritional discovery, and no one was interested! Being a scientist, not a marketing expert, Diehl let his discovery lay dormant for about 15 years.

Correspondence:

Dr. Charles L. Cochran
226 Lake Court
Aptos, California 95003

Dr. Raymond Dent
RR 1, Box 169 Lymington Road
Limmerick, Maine 04048

USA References

1) Dorland's Medical Dictionary, 25th Ed.

2) Shils, Olson, and Shike. Modern Nutrition in Health and Disease. Lea & Febigen, 1994. Philadelphia, PA. p. 1480

3) Diehl, H. W. and Fletcher, H. G., A Simplified Preparation of 2-Deoxy-D-ribose Based on Treatment of a-D- Glucose Monohydrate with Solid Calcium Hydroxide, Archives of Biochemistry and Biophysics, Vol. 78, No. 2, Dec. 1958

4) Wright, M.D., J., and Gaby, M.D., A, Nutrition and Healing, August, 1996, Vol.3, Issue 8, paraphrase from page 5.

5) Private correspondence to H. W. Diehl, Rockville, Md. from Dr. Fay Wood, Univ. of Cal., Berkeley, 1969

6) Diehl, H. W. and May, E. L., Cetyl Myristoleate Isolated from Swiss Albino Mice: An Apparent Protective Agent against Adjuvant Arthritis in Rats. Jour. of Pharmaceutical Sciences, Vol. 83, No. 3, Mar, 94 pp296-299.

7) Murray, M. T. Encyclopedia of Nutritional Supplements, Prima Publishing, Rocklin, CA 1996 p. 237

8) Sobel, D. and Klein, A. C.. Arthritis: What Works. St. Martins Press, New York, NY. pp. 221-225

9) Shils, Olson, and Shike. Ibid. pg. 550.

10) Setnikar, I., et al., Pharmacokinetics of glucosamine in man. Arztneim Forsch 43 (10), 1109-1113, 1993

11) Setnikar, I., et al., Pharmacokinetics of glucosamine in the dog and man. Arztneim Forsch 36(4), 729-735, 1986.

12) Morrison, M., Therapeutic applications of chrondroitin-4-sulfate, appraisal of biologic properties. Folia Angiol 25, 225-232, 1977.

13) Leberco Testing, Inc., Jan. 22, 1996, private correspondence to EHP Products, Inc.



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