In 2001, the Medicines Control Agency (MCA), which oversees drug products in the United Kingdom, licensed evening primrose oil (EPO) products for the symptomatic relief of atopic eczema and the relief of breast pain. But in 2002, the MCA concluded that there was not enough evidence that they are effective and withdrew the authorization . In December 2003, an editorial in the British Medical Journal wondered why the products had been licensed in the first place and charged that negative findings had been suppressed .. Since supplement promoters often accuse drug companies and the “medical establishment” of suppressing their work, I find it amusing that the opposite appears to have happened. This article desribes what I observed about EPO marketing in the 1980s.
In 1989, the U.S. Food and Drug Administration asked me to examine the marketing of evening primrose oil and borage oil products by Efamol Ltd. and its principal American distributors. U.S. Federal laws required that products marketed for the prevention, cure, mitigation or treatment of disease be “generally recognized by experts as safe and effective” recognized as safe and effective for their intended purposes. The health-food industry markets thousands of such products, but in most cases the intended purpose is not printed on the product label, where it could render the manufacturer an easy target for government regulators. Instead, this information is transmitted through other channels of communication that are less obvious or may not be subject to regulation. The documents I reviewed outlined the most elaborate marketing scheme I have seen in which a “dietary supplement” company promoted claims through other channels that would not be legal in labeling or advertising.
PO’s primary promoter was David Horrobin, M.D., Ph.D. (1939-2003), a Canadian medical professor who decided to commercialize research he had been doing for several years into gamma-linolenic acid (GLA), which is EPO’s active ingedient. In 1977, he and his wife (Sherri Clarkson) founded the Efamol Company for that purpose . The following year, Efamol joined Agricultural Holdings, a large British manufacturer that had been breeding evening primrose plants, moved to East London, and began making its first products. In 1981, the company’s Canadian division, Efamol Research, Inc. moved to Nova Scotia, and the manufacturing division, Efamol Ltd., relocated to Guildford, England. The company later changed its name to Scotia, became listed on the London Stock Exchange, and made Horrobin one of the 100 richest people in England. In 1997, he left Scotia and set up a new company, Laxdale Ltd, to develop pharmaceuticals for psychiatric and neurodegenerative disorders [4,5].
During the early 1980s, Efamol’s EPO was marketed in the United States as Evening Primrose Oil from England(tm) by Health From the Sun Products, Inc., of Dover, Massachusetts. The company advertised in trade magazines that EPO was “the biggest sales opportunity since vitamin C . . . . because there is more authoritative medical and nutritional evidence behind Evening Primrose Oil than any other product ever introduced into the health food industry.” Horrobin’s picture and endorsement of Efamol EPO appeared in this ad with no mention that he was president and managing director of the company that produced it. The ad made no health claims, but retailers who responded were sent multiple copies of customer handouts in which such claims appeared. One was a flyer which claimed that EPO enables weight loss without dieting, slows down the aging process, is effective against PMS, lowers cholesterol as effectively as drugs, lowers blood pressure, can help most people with mild or moderate rheumatoid arthritis, helps hyperactive children, and slows down the progress of multiple sclerosis. Another handout was a magazine article entitled “Evening Primrose Oil-Miracle Worker of the Eighties,” written by Horrobin. It stated that half of the people who took 2 to 4 grams of EPO lost weight without a conscious effort to diet and that EPO had significantly improved eczema in adults and children, produced dramatic improvement in women with premenstrual syndrome (PMS), and helped women with painful, lumpy breasts.
By the mid-1980s, Efamol’s products were sold in the United States and more than 25 other countries. During this period, although Efamol “officially” maintained that its EPO products were foods or “dietary supplements,” therapeutic claims for them were disseminated by the company and a succession of American distributors.
In 1985, Nature’s Way of Springville, Utah, took over as Efamol’s exclusive American distributor. Like its predecessor, Nature’s Way made few health claims in its magazine ads but transmitted many through other channels. Its May/June 1985 newsletter for retailers, for example, stated that Nature’s Way Evening Primrose Oil “assists the body in expelling waste by strengthening the body’s immune system, and helping circulation. It is also valuable in fighting skin problems, and helping faulty tear ducts and salivary glands.” The Efamol Corporate Video, distributed in November 1985, contained the following ideas:
- The company is “pioneering research into natural sources of new medicines.”
- Various disorders might be caused by a “metabolic block” in fatty acid metabolism that prevents formation of adequate amounts of prostaglandin.
- Efamol Ltd. has actively encouraged and coordinated independent research using EPO into a variety of disorders, “including dermatological disease, gynecological problems, and cardiovascular diseases in which possible deficiency of prostaglandins has been implicated.”
- “Efamol products are currently marketed as foods and dietary supplements and are not licensed for clinical usage other than in approved clinical trials.”
In 1986, Nature’s Way announced that it was starting a library of videotapes that retailers could borrow, free of charge, to help train their staff. The first such video contained a lecture Dr. Horrobin gave earlier that year on “The Role of Essential Fatty Acids and Prostaglandins in Health.” The lecture was given at a trade show in Anaheim, California, where Horrobin was introduced by Ken Murdock, president of Nature’s Way. During the lecture, Horrobin said that although virtually all Americans get abundant amounts of essential fatty acids in their diet, 20% “may have flaws in the body” that limit their full use. Thus, he asserted, there occurs a functional deficiency of a metabolite called gamma linolenic acid (GLA), which is needed to produce prostaglandins. Horrobin’s solution, of course, was to consume Efamol EPO, which is rich in GLA.
Throughout his lecture, Horrobin stressed that he and his company were deeply committed to research and had generated more than a hundred clinical studies. He said that he was particularly proud of studies with negative results (for weight-reduction, for example) because their existence added credibility to the positive ones. In discussing some of the studies, he showed slides of the dosages used. Thus retailers who attended the lecture, as well as those who viewed the videotape, could tell precisely how to “prescribe” the products to their customers. An undercover investigator who borrowed the tape in 1988 “to show a customer with PMS” was told that ten copies were circulating.
During the same period, dozens of articles in Bestways Let’s Live, Better Nutrition, Today’s Living, Total Health, Medical Self-Care, and other magazines that habitually promoted dubious nutrition ideas recommended EPO for PMS and other conditions. Some of these articles mentioned Efamol by name and a few cited Horrobin’s work. Ads for Efamol EPO and/or other EPO products appeared in almost every issue containing an article about evening primrose oil.
The December 1983 issue of the British magazine She described a study in which three hundred of its readers took Efamol EPO for premenstrual syndrome. She’s article, entitled “The Efamol Verdict,” called the results “dramatic” and said that 78% showed improvement in depression, 87% in irritability, 72% in headaches, 75% in pain/tenderness, and 71% in joint swelling. Soon afterward, an Efamol news bulletin advised: “Perhaps you can organize a similar study in your market. The results to PMS sufferers as well as to sales can only be dramatic.”
In October 1985, one Efamol bulletin included a “Training Manual,” the front cover of which stated “strictly for internal use and readership only.” Its introduction stated, “If you are to be involved in actually selling Efamol products then you will soon extract the information you require to perform your task efficiently. . . . The manual should be retained of course, for reference purposes for the day when a customer asks that very question you knew the answer to but can’t remember.” Section 6 of the manual referred readers to several publications that promote the use of Efamol products. The manual stated that one of these publications was “a useful Public Relations tool,” while another “considers different medical applications of Efamol.”
In March 1987, Efamol Ltd. distributed copies of women’s magazine articles reporting that Efamol’s EPO had helped its readers with PMS. The accompanying bulletin indicated that the articles “represent another excellent example of the valuable role played by PR in supporting the marketing of Efamol.” Another bulletin stated: “Dr. Horrobin has recently written the enclosed review of PMS for a consumer magazine aimed at young mothers in the U.S.A.” The article gave specific directions for using Efamol EPO for PMS and stated, “For most women, PMS can now be a thing of the past.”
Other documents described how Efamol Ltd. had used public relations as a marketing tool. For example, a 1983 bulletin said that the main objective of a news conference held in New York by Horrobin in 1982 “was to make known as widely as possible the new discovery of the benefits to eczema sufferers of EFAMOL capsules taken orally. Media used: Newspapers, Magazines, Radio, TV, News Agencies.” The letter was accompanied by a list of more than one hundred press outlets that carried stories. In August 1983, Efamol Ltd. distributed copies of a Redbook magazine article recommending evening primrose oil for PMS. The article described Dr. Horrobin’s work and stated that “the usual dosage is six to eight 500-mg capsules daily.” Multiple reprints of the Redbook article were distributed to health-food retailers throughout the United States by Health From the Sun, described by Efamol Ltd. as the major subdistributor of Efamol in the United States at that time. In October 1985, Efamol Ltd. distributed multiple copies of an article from Current Therapeutics, which it said would “be of great value in your PR activities.”
In November 1986, Efamol Ltd. distributed an article from Rodale’s Allergy Relief Newsletter which suggested evening primrose oil for eczema. In a sidebar, Horrobin advised readers to stick to name brands, such as Efamol or Naudicelle. The company advised its distributors that the article “may be particularly interesting to any local eczema societies you may have.”
In March 1987, Efamol Ltd. distributed a news bulletin headlined “American PMS Self-Help Group Publishes Article by Dr. Horrobin.” The article stated that “a relatively minor problem of [essential fatty acid] nutrition is the commonest cause of PMS. This can be corrected by lifestyle changes and/or by direct supplementation with GLA in the form of evening primrose oil.” The published article was introduced with a note that readers could write directly to Dr. Horrobin “to request reprints of this and other articles describing his research.”
In October 1987, Efamol Ltd. distributed an article from a British magazine which stated: “Any misconception that Efamol is a company producing mere dietary supplements and dabbling on the fringe of the medical scene are quickly dispelled by Horrobin. He has always thought of the Efamol essential fatty acids as pharmaceuticals, he says, but marketing them originally as nutritional supplements has provided the means to generate cash to fund continuing research.” The article also states that product licenses had been applied for in the United Kingdom, Germany, Sweden, Norway, New Zealand, and Canada for the treatment of atopic eczema with an EPO product, while approval for the same product as an over-the-counter supplement for PMS had already been granted in Finland and was pending in France.
Efamol’s EPO products were also marketed to health professionals through many channels.
- In November 1986, Dr. Horrobin sent a memo to Nature’s Way suggesting an “Efamol Good Health Program” that would include specified dosages of four EPO products for eczema, diabetes, arthritis, coronary heart disease, high blood pressure, asthma, allergies, psoriasis and PMS. In 1987, Murdock Pharmaceuticals (a Nature’s Way subsidiary) distributed much of this information-almost word-for-word-to its physician customers.
- The listing in the 1986 Physicians’ Desk Reference for Nonprescription Drugs included dosage and stated: “Indications: For the relief of symptoms of premenstrual syndrome, such as mood changes (anxiety, irritability, nervous tension and depression), water retention (swelling), abdominal bloating, breast pain and tenderness, and fatigue.” The same information appeared in the 1987 edition of this book under Murdock Pharmaceuticals instead of Nature’s Way.
- A January 1987 memo from Murdock Pharmaceuticals to Horrobin related how Murdock had exhibited at a convention of the American College of Advancement in Medicine (a group of physicians engaged in such unscientific practices as chelation therapy for atherosclerosis). The memo also mentioned that ads have been placed in Complementary Medicine magazine and the Physicians’ Desk Reference for Nonprescription Drugs. Ads in the Nov./Dec. 1986 and Jan./Feb. 1987 issues of Complementary Medicine contained no therapeutic claims but invited doctors to contact Murdock Pharmaceuticals for further information. The earlier ad, shown on the following page, pictured the hands of a doctor writing a prescription for Efamol products.
- Murdock’s “Efamol PMS Promotion Campaign” included advertisements to pharmacists; letters to physicians, pharmacists and “PMS sufferers”; and a “PMS Symptom and Treatment Chart.” The ad to pharmacists (in California Pharmacist, Sept. 1987) said Efamol PMS was “the primary constituent in a recommended PMS program.” The letter to pharmacists mentioned that the product was listed in the Physicians’ Desk Reference for Nonprescription Drugs.
- In May 1987, a Murdock vice-president wrote to the Arthritis Foundation to suggest that the Foundation distribute information that Efamol products were an alternative in treating arthritis for those who suffer side effects from nonsteroidal antiinflammatory drugs (NSAIDS).
In 1989, after reviewing more than a thousand pages of documents, I advised the FDA:
- It is clear that Efamol Ltd. has been engaged in a continuous and systematic campaign to establish in the public mind that Efamol EPO is useful against PMS and various other diseases and conditions.
- Any restraint shown in the claims is related to the knowledge that they may be illegal in labeling.
- It is self-evident that consumers won’t buy products unless they perceive a need for them. It is also obvious that a product claimed to be effective in a troublesome condition (such as PMS) will sell much better than one advertised to relieve a supposed deficiency of a chemical (gamma-linolenic acid).
- Although Dr. Horrobin has claimed to have done sufficient research to establish that evening primrose oil is safe and effective against PMS and eczema, he has not gained FDA approval for marketing evening primrose oil products as drugs in the United States. Marketing them as “food supplements” is a transparent attempt to evade the food and drug laws.
å Regulatory Actions
In 1979, the FDA had notified Efamol representatives that EPO could not be imported into the United States unless the company sought and obtained approval by filing an appropriate food additive petition or new drug application. Efamol agreed not to export EPO to the United States, but in 1985 it began shipping it in bulk to California for encapsulation. The capsules would then be shipped to distributors who would market them as dietary supplements through health-food stores or by mail-order. In 1985, the FDA issued an Import Alert to detain EPO labeled for food use because the agency considered it an unsafe food additive.
In 1984, General Nutrition, Inc., three of its officers, and two of its retail store managers were charged with conspiring to defraud the FDA and violating provisions of the Food, Drug, and Cosmetic Act which require that drug products be approved by the FDA as safe and effective prior to marketing. The indictment alleged:
- Between 1980 and 1981, General Nutrition, its president (Gary Daum), and two vice-presidents conspired to purchase EPO from Efamol Ltd. and to promote and sell it under the name Gammaprim for the prevention and treatment of high blood pressure, arthritis, multiple sclerosis, and other ailments.
- In 1980, one of the defendants received a letter from Horrobin suggesting that Efamol products be marketed without FDA approval. Referring to EPO’s supposed beneficial effects, the letter stated, “Obviously you could not advertise Efamol for these purposes but equally obviously there are ways of getting the information across.” Subsequent company memos described an elaborate promotional scheme that included newspaper articles, radio talk shows, and publications for use in General Nutrition’s retail stores. In addition, oral claims were made by retail employees to prospective customers. FDA investigators posing as customers at various stores in western New York State were told that Gammaprim would be better for treatment of high blood pressure than the prescription drugs Nitrostat or Diuril, and that it was good for arthritis as well.
- By virtue of these claims, Gammaprim became a drug within the meaning of the law. However, rather than submitting the product to the FDA for premarket evaluation, defendants sought to disguise it as a food supplement, thereby attempting to defraud the FDA .
In motions to stop the prosecution, the defendants claimed: (a) their right to free speech was being violated, (b) the prosecution was unfair because many other companies making health claims in advertising had not been criminally prosecuted, (c) Gammaprim should not be considered a drug because it is not inherently toxic, and (d) the laws under which they were being prosecuted were too vague. In 1986, these motions were dismissed by a federal judge who noted that the defendants were aware, or should have been aware, that they were breaking the law. A few months later, General Nutrition pled guilty to four counts of misbranding a drug and agreed to pay $10,000 to the government as reimbursement for costs of prosecution. Daum (who was no longer its president) pled guilty to one count of misbranding and was fined $1,000. The remaining charges against other employees were dismissed. Horrobin was not prosecuted ifor his role in the alleged conspiracy, but I believe he could have been.
In 1988, he FDA ordereed Wilner Chemists, a drugstore in New York City, to stop distributing EPO products because the agency considered EPO to be an unsafe food additive .
During 1988, FDA investigators who visited one pharmacy and several health-food stores were told by a salesperson that EPO was effective for PMS, arthritis, and/or eczema. The investigators were shown magazine articles or other literature containing claims of this type. During the same year, at the FDA’s request, a U.S. marshal seized 21 barrels containing EPO and vitamin E, plus quantities of five Efamol products. In 1989, forty-five more barrels of EPO were seized en route to California for encapsulation. In both cases, the FDA charged that Efamol Ltd. was marketing an unapproved food additive. With respect to the products, the FDA also charged that they were unapproved new drugs and misbranded. Federal district judges agreed with the FDA and ordered the seized materials destroyed. Efamol’s appeals all the way to the U.S. Supreme Court were unsuccessful.
During these proceedings, Efamol Ltd. was compelled to produce documents which showed how it had spread therapeutic claims through press conferences, news releases, “news bulletins” to distributors, and many other channels of communication. Between 1983 and 1989, the company had issued more than 60 bulletins reporting on EPO research and other developments. Many were accompanied by reprints from scientific journals, newspapers, or magazines. A few were accompanied by a television transcript, booklet, or book. These materials promoted EPO for treating PMS, alcoholism, pregnancy-induced hypertension, atopic eczema, elevated cholesterol levels, hypertension, scleroderma, multiple sclerosis, rheumatoid arthritis, mastalgia (breast pain) and other problems. The bulletins encouraged use of the information for public relations purposes. The company also published and distributed bibliographies of scientific publications relevant to EPO to health-food retailers throughout the United States. Some of the references in these bibliographies were emphasized by highlighted quotes — including some from Dr. Horrobin’s paper — which made explicit therapeutic claims for Efamol’s EPO. Some of the bulletins included a statement like, “The way in which this information is used must, of course, be consistent with local regulations which generally do not permit direct medical claims in advertisements, etc.” Most of these documents were included in the materials the FDA gave me to review.
At the time I did my FDA review, it appeared to me that more commercially-sponsored research had been done on evening primrose oil than on any other dietary supplement. But the situation also struck me as peculiar. If EPO were genuinely useful, why weren’t there lots of independent studies? I also wondered whether any of the Horrobin’s data were faked. Although I had no evidence that they were, his marketing strategies made me question his honesty. Distribution of his videotaped lecture to retailers about EPO was a criminal act, and his memo to GNC about “obvious way of getting the message across” made it clear that he clearly understood the law. Would someone that contemptuous of the law have any qualms about faking data? One instance of probable fraud in the early 1990s came to light when the British General Medical Counsel concluded that a neurophysiologist who studied the use of Efamol in diabetics had falsified data and been promised a royalty if the product were approved for drug use. However, the Council’s report made no mention of Horrobin and concluded that this was an isolated incident that was motivated by misguided belief rather than financial considerations .
Assuming that the research was all legitimate, was it reasonable to conclude that EPO safe and effective for any of its intended purposes or that EPO worked by correcting a “GLA deficiency”? In the early 1990s, Purdue University’s Varro E. Tyler, Ph.D., a leading authority on plant medicines, looked very carefully at Horrobin’s writings and concluded:
[Horrobin’s theories] would be valid only if all of the specified conditions are favorably influenced by additional production in the body of prostaglandin E1 and if a deficiency of GLA is the single factor responsible for limited prostaglandin production. Both of these factors remain unproven. If they are not true, then [assuming] that evening primrose oil [is effective] in such conditions is somewhat like assuming one’s car will run better if the gas tank is completely full instead of half full. Some clinical evidence exists supporting the possible efficacy of evening primrose oil in the treatment of . . . PMS . . . sore breasts, multiple sclerosis, atopic eczema, various diabetes-associated problems, cardiovascular disease, and several other conditions. . . .However, the validity of some of the reports has been refuted or at least questioned. An Australian study . . . of evening primrose oil in treating women with moderate PMS concluded that the improvement was solely a placebo effect. . . . Furthermore, there are no data to support the safety of long-term consumption .
In 1993 and 2000, other reviewers looked at studies of evening primrose oil or borage oil (which contains higher concentrations of GLA) for eczema concluded that the largest and best of them did not show convincing evidence of any benefit [10,11]. In December 2003, the British Medical Journal reported a well-designed study of 140 eczema patients who took either a high dose of GLA or a placebo for 12 weeks showed no difference between the two groups . The report was accompanied by an editorial  which stated that:
- Horrobin co-authored a 1989 meta-analysis that praised research sponsored by his company and unjustifiably criticized a large independent study that showed negative results.
- The authors of negative study were unable to achieve publication of a well-reasoned defense of their study.
- A subsequent review with negative conclusions did not get published because Scotia threatened to sue if it were.
- In 1995, the British Department of Health commissioned a meta-analysis of 20 studies, which included 10 unpublished studies held by the company. Although the report produced a relatively clear conclusion, the authors were not permitted to make it public.
- The Health Technology Assessment systematic review published in 2000 provided an opportunity for the company to hand over its unpublished studies for inclusion in that report, but it did not do so.
In April 2003, the British Medical Journal published an obituary of Horrobin which charged that “evening primrose oil . . . may go down in history as the remedy for which there is no disease, and David Horrobin . . . may prove to be the greatest snake oil salesman of his age.” The editorial triggered more than 100 angry responses from Horrobin’s family, former business associates, scientists who described how Horrobin had been extremely kind and helpful to them, and others who said they had not known Horrobin but thought that the obituary showed extremely poor taste. None of the critics mentioned the improper marketing activities I have described in this report.
- What’s new: Epogam and Efamast (gamolenic acid)—withdrawal of marketing authorisations, MCA Web site, Sept 13, 2002]
- Williams HC. Evening primrose oil for atopic dermatitis: Time to say goodnight. British Medical Journal 327:1358-1359, 2004.
- Efamol: Leaders in Nutritional Health. Medical Marijuana Mission Web site, accessed January 29, 2004.
- McGoldrick S. In response to David Horrobin’s obituary. BMJ rapid responses, April 25, 2003.
- Oranski I David F. Horrobin (obituary). Lancet 361:1395, 2003.
- Indictment in USA vs. General Nutrition, Incorporated, Gary A. Daum, David E. Walsh, George E. McTurk, Ilene M. Fenicchia, and Jessie M. Copia. In the Western District of New York, January 1984 Session.
- Faline JJ. Regulatory letter to Irving Willner. Feb 2, 1988.
- Dyer O. GMC reprimands doctor for research fraud. Briish Medical Journal 326:730, 2003.
- Tyler VE: The Honest Herbal. Philadelphia: George F. Stickley Company, 1993.
- Berth-Jones and others. Placebo controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet 341(8860): 1557-1560, 1993.
- Hoare C and others. Systematic review of treatments for atopic eczema. Health Technology Assessment 4:37, 2000.
- Takwale A and others. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. British Medical Journal 327:1385-1388, 2003.
- Richmond C. Obituary: David Horrobin, founder of Scotia Pharmaceuticals and the journal Medical Hypotheses, and passonate promoter of evening primrose oil. British Journal of Medicine 326:885, 2003.
This article was posted in January 1, 2004.