Literature Review & Commentary

by Alan R. Gaby, MD

Borage-seed oil for rheumatoid arthritis

Fifty-six patients with active rheumatoid arthritis were randomly assigned to receive, in double-blind fashion, 2.8 g/day of gamma-linolenic acid (GLA; from a concentrate prepared from borage-seed oil) or placebo (sunflower oil) for six months. Subsequently, all patients received GLA, in single-blind fashion, for an additional six months. After the first six months, the improvements in the following parameters were significantly greater in the GLA group than in the placebo group: swollen joint count, tender joint count, tender joint score, pain, and Health Assessment Questionnaire score. Meaningful clinical improvement (at least 25% improvement in four measures) occurred in fourteen (63.6%) of twenty-two patients in the GLA group, compared with four (21.1%) of nineteen patients in the placebo group (p = 0.015). During the second six months, both groups showed improvement in disease activity. Of the twenty-one patients who received GLA for twelve months, sixteen (76.2%) showed meaningful improvement at twelve months, compared with baseline. Adverse reactions included belching (three in the GLA group, two in the placebo group) and diarrhea (four in the GLA group, one in the placebo group).

COMMENT: This study demonstrates that borage-seed oil is a well-tolerated and effective treatment for active rheumatoid arthritis. The results of this study were similar to those from a previous trial with a lower dose of borage-seed oil (1.4 g/day of GLA). The additional finding in the present study was that continued treatment beyond six months resulted in further improvement. Although it is not known how borage-seed oil works against rheumatoid arthritis, GLA is believed to stimulate the synthesis of prostaglandin E1, which might, in turn, enhance the production of suppressor T cells.

Zurier RB, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum 1996;39:1808-1817.


Environmental pollution and autoimmune disease

The prevalence and incidence of systemic lupus erythematosus (SLE) was investigated in an African-American community in Gainesville, Georgia, that had been exposed to industrial emissions for a long period of time. The prevalence of SLE was 300 cases per 100,000 population, and the incidence was 63.7 cases per 100,000 person-years. These numbers were six-fold and nine-fold higher than the highest previously reported prevalence and incidence, respectively, of SLE.

COMMENT: Sixty years ago, SLE was an uncommon disorder, affecting an estimated 3-4 individuals per 100,000. Today the estimated prevalence of this disease has increased by about 4-15-fold. Some of this increase may be due to more reliable diagnostic tests; however, it is also possible that more people are developing the disease today than in years past. The present study suggests that environmental pollution plays an important role in the etiology of SLE. I propose an intervention trial: we clean up the environment around Gainesville, Georgia and then see what happens to the incidence of SLE over the next thirty years. Better still, let’s do a multi-center trial and clean up the whole planet.

Kardestuncer T, Frumkin H. Systemic lupus erythematosus in relation to environmental pollution: an investigation in an African-American community in North Georgia. Arch Environ Health 1997;52:85-90.


Amoebic infections and rheumatoid disease

According to the author, amoebae of the genus Naegleria have been demonstrated in all human tissues, particularly in those taken from patients with various types of rheumatoid disease. These organisms can be killed in vitro by metronidazole, clotrimazole and other nitroimidazole drugs. Treatment of active cases of rheumatoid disease by any of these anti-amoebic drugs has resulted either in cessation of the disease or a temporary exacerbation of symptoms, followed by their lessening or disappearance (Herxheimer reaction).

COMMENT: It is generally accepted that protozoal infections can cause “reactive arthritis”; however, the observations of the late Dr. Wyburn-Mason have never been taken seriously by conventional medicine. I have administered a course of metronidazole to approximately 40 patients with various rheumatoid disease (including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis); nearly half of these patients experienced marked and long-lasting benefit. The most impressive case was that of a middle-aged man with a ten-year history of moderately severe psoriatic arthritis that never fluctuated in intensity. Within five days of starting metronidazole, the arthritic symptoms disappeared and did not return over a five-year follow-up period. The work of Wyburn-Mason was the basis for the formation of the Rheumatoid Disease Foundation, now called Arthritis Trust, PO Box 8949, Topeka, KS, 66608-8949.

Wyburn-Mason R. The Naeglerial causation of rheumatoid disease and many human cancers: a new concept in medicine. Med Hypotheses 1979;5:1237-1249.


Curing lupus with “witchcraft”

A 28-year-old Phillipine-American female developed weakness, hepatomegaly, lymphadenopathy, and albuminuria. Laboratory tests were diagnostic of systemic lupus erythematosus (SLE). Around the same time she developed hypothyroidism and was placed on L-thyroxine. Although the patient’s SLE responded for awhile to prednisone (which caused numerous side effects), she subsequently developed lupus nephritis which failed to respond to a combination of prednisone and azathioprine. A renal biopsy showed membranous and focal glomerulonephritis and immune complex disease. When high-dose, sustained prednisone and cyclophosphamide were recommended, the patient chose instead to return to the remote Phillipine village of her birth. Much to the surprise of her physicians, she returned three weeks later without any clinical evidence of SLE. She declined further treatment with prednisone or thyroid hormone and refused further testing of blood and urine, as directed by the village witch doctor, who had removed the curse placed on her by a previous suitor. Two years later she remained well and insisted that her SLE had been cured by removal of the “evil spirit” that had caused her original symptoms.

COMMENT: According to the author of this report, it is unlikely that this patient’s SLE “burned out.” The mechanism by which an Asian medicine man can cure active lupus nephritis, change myxedema into euthyroidism, and allow precipitous withdrawal from corticosteroid treatment without triggering adrenal failure is unknown.

Kirkpatrick RA. Witchcraft and lupus erythematosus. JAMA 1981;245:1937.


Milk allergy and lupus

An infant with recurrent upper respiratory symptoms and pulmonary infiltrates was found to have LE cells, tart cells, and milk-precipitating antibodies in serum. Symptoms resolved after elimination of cow’s milk from the diet, but recurred on two occasions after ingestion of milk. The appearance of tart cells (which result from phagocytosis by polymorphonuclear leukocytes of dead nuclei) appeared to be related to ingestion of milk and to the change in milk antibody titers. This case is consistent with a diagnosis of atypical SLE due to milk allergy.

COMMENT: The relationship between food allergy and autoimmune disease has not been studied extensively, although there are some reports of food allergy as a triggering factor for rheumatoid arthritis (Lancet 1986;1:236-238.) and some other less common rheumatological conditions. It has been demonstrated that antigenic macromolecules from food can be absorbed intact from the gastrointestinal tract. These molecules can trigger the production of antibodies which, depending on a person’s genetic makeup, might initiate an autoimmune process. Although additional research is needed, the clinical response to an allergy-elimination diet is often gratifying.

Anderson JA, et al. Hyperreactivity to cow's milk in an infant with LE and tart cell phenomenon. J Pediatr 1974;84:59-67.


Treatment of lupus with acupuncture

Twenty-five patients with systemic lupus erythematosus (SLE) were treated with acupuncture. Ten of these patients had not received previous glucocorticoid therapy and were treated with acupuncture alone. The others, who had failed to respond to treatment with glucocorticoids for at least five months, were treated with acupuncture and gradually decreased their steroid dosages. A well-matched control group was also followed for comparison. Acupuncture treatment was associated with considerable improvements in symptoms, signs and laboratory findings.

COMMENT: Because there was no placebo group in this study, one cannot rule out the possibility that some of the reported benefit was due to a placebo effect. Of course, acupuncture is a safe treatment and SLE can be a serious disease, so patients have little to lose by trying this treatment. One way to perform a double-blind study of acupuncture is to randomly assign patients to receive appropriate acupuncture or sham acupuncture and then have the needles placed by someone who does not know whether the points are real or sham.

Shu-fang F, et al. Treatment of systemic lupus erythematosus by acupuncture. A preliminary report of 25 cases. Chin Med J 1985;98:171-176.


Alfalfa exacerbates lupus

Two patients are reported with clinically and serologically quiescent systemic lupus erythematosus (SLE) who experienced reactivation of their disease in association with ingestion of alfalfa tablets. One patient, whose disease had been inactive for at least four years, had an exacerbation after ingesting 15 alfalfa tablets per day for nine months. The other patient showed a progressive exacerbation of her disease over an 18-month period; she had been ingesting eight alfalfa tablets per day for 2.5 years. Analysis of the alfalfa tablets revealed the presence of L-canavanine.

COMMENT: Administration of L-canavanine has been shown to exacerbate the severity of kidney damage and to increase antinuclear antibody titers in NZB and (NZB x NZW) F1 mice (animal models of SLE). In addition, a lupus-like syndrome developed in monkeys fed a diet containing 40% dried alfalfa sprouts. It is not known whether ingesting small amounts of alfalfa sprouts could cause problems in individuals with autoimmune disease. Alfalfa meal (as opposed to the seeds) has not been found to contain L-canavanine and has not been reported to be associated with autoimmune disease.

Roberts JL, et al. Exacerbation of SLE associated with alfalfa ingestion. N Engl J Med 1983;308:1361.

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Press Release -- Lupus and Autoimmune Disease
August/September 1999 Issue of Townsend Letter for Doctors and Patients
Literature Review

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