The author of this report has found amebas of the genus Naegleria in synovial tissue and other tissues of patients with rheumatoid disease. These amebas have also been found to a lesser extent in tissues of healthy humans. Treatment of active rheumatoid disease with any of various antiamebic drugs (such as metronidazole, clotrimazole, or tinidazole) typically resulted in remission of the disease, both in the joints and in other affected tissues. Remission was sometimes preceded by a temporary exacerbation of symptoms (Herxheimer reaction). Based on these observations, the author concluded that Naegleria may be a source of constant antigenic stimulation in people who are genetically susceptible to the organism, and that the presence of this ameba in affected tissues is the cause of many cases of rheumatoid disease.

Comment: Although it is well known that certain types of infections or parasitic infestations can cause a "reactive arthritis" that mimics rheumatoid disease, the idea that infection is a common cause of rheumatoid disease is not accepted in the general medical community. Some investigators have argued that what Wyburn-Mason thought were amebas in various tissues were really just macrophages.

I have used metronidazole or other antiamebic drugs in approximately 40 patients who suffered from rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. In approximately one-third of these cases, the response was dramatic and long-lasting. One man had a 10-year history of moderately severe psoriatic arthritis that rarely fluctuated in severity. Within 5 days of starting anti-amebic treatment, his arthritic symptoms disappeared and did not return over a 5-year follow-up period. Because metronidazole therapy is not without risk, I usually reserve this treatment for patients who have not responded adequately to an allergy-elimination diet and other natural remedies.

Other doctors have used a combination of metronidazole and allopurinol, because allopurinol is said to interfere with the enzyme systems of the ameba. The reported success rates with that approach are higher than what I have seen using metronidazole alone. Additional information on anti-amebic therapy is available at http://www.garynull.com/documents/arthritis/antiamoebic_treatment.htm.

Other investigators have had some success using tetracycline or minocycline to treat rheumatoid arthritis. That treatment is based on the theory that the disease is caused by a mycoplasma infection.

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

Forty-six healthy, hyperlipidemic men and women (mean age, 59 years) were randomly assigned to one of three weight-maintaining diets for one month: 1) a diet very low in saturated fat, based on milled whole-wheat cereals and low-fat dairy foods (control diet); 2) the same diet plus lovastatin (20 mg/day); or 3) a dietary portfolio high in plant sterols (1.0 g/1,000 kcal, from a plant sterol ester-enriched margarine), soy protein (21.4 g/1,000 kcal, from soy milk and soy meat analogs), viscous fibers (9.8 g/1,000 kcal, from oats, barley, eggplant, okra, and psyllium), and almonds (14 g/1,000 kcal). The control, lovastatin, and dietary portfolio groups had mean decreases in LDL cholesterol of 8.0%, 30.9%, and 28.6%, respectively. Reductions in C-reactive protein levels were 10.0%, 33.3%, and 28.2%, respectively. The changes in the statin and dietary portfolio groups were all significantly different from the changes in the control group, but did not differ significantly from each other. The authors concluded that using a combination of cholesterol-lowering dietary interventions increased the effectiveness of diet as a treatment for hypercholesterolemia. Moreover, this diet decreased LDL cholesterol and C-reactive protein levels to a similar extent as lovastatin.

Comment: Statins have become the standard of care for people who have, or are at risk of developing, cardiovascular disease. While some of the benefit of these drugs is presumably due to lowering of LDL-cholesterol levels, the anti-inflammatory effect of statins (as reflected by a reduction in C-reactive protein levels) may be at least as important as the cholesterol-lowering effect. A growing body of evidence indicates that C-reactive protein is an independent risk factor for heart disease.

The results of the present study demonstrate that a comprehensive dietary program can be as effective as a statin drug in reducing both LDL-cholesterol and C-reactive protein levels. For motivated people, dietary modification seems like a viable alternative to statin drugs.

Jenkins DJA, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA 2003;290:502-510.

Eleven patients with diabetes participated in a crossover study (2 weeks on each of 2 different diets), and 13 other patients with diabetes participated in a 6-week randomized trial of the same diets. The two diets had a similar content of protein, carbohydrate, and fat, but differed by approximately five-fold in their content of advanced glycation endproducts (AGEs), which was achieved by varying the cooking time and temperature. After two weeks on the high-AGE diet, the serum concentration of AGEs increased by 64.5% (p = 0.02) and on the low-AGE diet decreased by 30% (p = 0.02); the values at six weeks were +28.2% (p = 0.06) and -40% (p = 0.02), respectively. After six weeks, the mean C-reactive protein concentration increased by 35% relative to baseline on the high-AGE diet and decreased by 20% relative to baseline on the low-AGE diet (p = 0.014).

Comment: AGEs form during the heating of common foods. They result from reactions between reducing sugars and proteins or lipids. In contrast to the AGEs that are formed in vivo, dietary AGEs form much more rapidly in the presence of heat and in far greater concentrations. The infusion of AGEs into rabbits results in the formation of atheroma-like lesions. Approximately 10% of ingested AGEs are absorbed; of that 10%, two-thirds is retained in tissues in reactive forms. The results of the present study suggest that dietary AGEs (or some other substances that are formed along with AGEs during cooking) cause an inflammatory reaction in the body, and may contribute to the pathogenesis of cardiovascular disease.

The formation of AGEs in foods can be minimized by emphasizing certain methods of cooking (e.g., boiling or poaching, as opposed to grilling or frying). In addition, heating a protein in the presence of a reducing sugar (fructose, lactose, or glucose) accelerates the formation of AGEs. Eating as many raw foods as possible is probably the best way to reduce the AGE content of the diet. For additional information on the AGE content of foods, see J Am Diet Assoc 2004;104:1287-1291.

Vlassara H, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci 2002;99:15596-15601

Forty-five children (mean age, 7.3 years; range, 3.2-10.6 years) experiencing a mean of 6.6 sleep terror episodes per month were randomly assigned to receive L-5-hydroxytryptophan (5-HTP) (n = 31) or to serve as an untreated control group (n = 14). The dose of 5-HTP was 2 mg/kg of body weight at bedtime for 20 days. At the one-month follow-up visit, the sleep terrors had completely disappeared in 51.6% of the children receiving 5-HTP, and there was a greater-than-50% reduction in an additional 41.9% of cases, for a positive response rate of 93.5%. In the control group, the episodes disappeared in 28.6%, while 71.4% showed no change. After 6 months, 83.9% of children treated with 5-HTP and 28.6% of controls were free of sleep terrors.

Comment: Sleep terrors are characterized by sudden waking from slow wave sleep with persistent fear or terror, screaming, sweating, confusion, and increased heart rate. People with sleep terrors usually do not report dreams or nightmares, but might have a vague sense of frightening images. The prevalence of sleep terrors ranges from 1% to 7.5%, with peak prevalence between ages 5 and 7 years. It has been suggested that sleep terrors are associated with a dysfunction of the serotonergic system. The results of the present study suggest that short-term treatment with 5HTP (the precursor to serotonin) results in a long-term improvement in sleep terrors.

Bruni O, et al. L-5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr 2004;163:402-407.

Forty-nine patients with a witnessed out-of-hospital cardiac arrest of presumed cardiac origin, who were in a coma after cardiopulmonary resuscitation (CPR) despite restored spontaneous blood flow, were treated with hypothermia and were randomly assigned to receive, in double-blind fashion, coenzyme Q10 (CoQ10) or placebo. The dose of CoQ10 was 250 mg in liquid form, followed by 150 mg 3 times a day for 5 days, administered through a nasogastric tube. The 3-month survival rate was 68% in the CoQ10 group (17 of 25) and 29% (7 of 24) in the placebo group (p = 0.0413). A good neurological outcome (Glasgow Outcome Scale of 4 or 5) occurred in 9 (36%) of 25 patients in the CoQ10 group and 5 (21%) of 24 in the placebo group (p value not stated).

Comment: Of people who receive CPR after out-of-hospital sudden cardiac arrest, only about 12% are discharged alive from the hospital. More than 90% of survivors are unable to return to their previous lifestyles, mainly because of brain damage. Neuronal death occurs both during ischemia and after reperfusion. Mitochondrial dysfunction and oxidative stress have been implicated in delayed neuronal injury. Therapeutic hypothermia has been shown to improve survival after CPR.

The results of the present study demonstrate that the beneficial effect of hypothermia can be further increased by treatment with CoQ10, which presumably works by enhancing mitochondrial function and reducing oxidative stress. The addition of CoQ10 more than doubled the survival rate and nearly doubled the proportion of people who retained good neurological function.

Future research should investigate the effect of other nutrients that play a key role in mitochondrial function, such as magnesium, niacinamide, and riboflavin. In a previous study, hypomagnesemia was present in 23% of 22 patients after cardiac arrest, and 41% were hypermagnesemic. All patients with abnormal serum magnesium concentrations died, whereas 5 of 8 patients with a normal serum magnesium concentration were successfully resuscitated. That finding suggests that patients who are hypomagnesemic after cardiac arrest might benefit from magnesium therapy.

Damian MS, et al. Coenzyme CoQ10 combined with mild hypothermia after cardiac arrest: a preliminary study. Circulation 2004;110:3011-3016.

Two potato meals containing 50 g of carbohydrate were fed to 9 subjects with varied insulin sensitivity, at mean temperatures of 83.6 degrees C for hot potato and 26.0 degrees C for cooled potato. Cooled potato resulted in a significantly lower mean postprandial blood glucose level, area under the glucose curve, glycemic index, and serum triglyceride concentration, compared with hot potato (p < 0.05).

Comment: This study demonstrates that the temperature at which a starchy food is consumed influences its glycemic index and its effect on postprandial triglyceride levels. It is possible that cooling a cooked food changes the chemical structure of the starch, thereby slowing the rate at which it is digested. Diabetics who have difficulty controlling their glucose levels with the usual dietary approaches might benefit from chilling their starchy foods before eating them.

Najjar N, et al. Glycemic and insulinemic responses to hot vs cooled potato in males with varied insulin sensitivity. Nutr Res 2004;24:993-1004.

One hundred-three patients with painful episodes of osteoarthritis of the knee were randomly assigned to receive, in double-blind fashion, an oral enzyme-flavonoid preparation (Phlogenzym; Mucos Pharma, Geretsried, Germany) or diclofenac sodium (50 mg twice a day) for 6 weeks. Each enteric-coated tablet of Phlogenzym contained 90 mg of bromelain, 48 mg of trypsin, and 100 mg of rutosid (a flavonoid similar to rutin); the dose was 1 tablet 3 times a day. The primary outcome variables were Lequesne's Algofunctional Index (LFI) and a "complaint index", including pain at rest, pain on motion and restricted function. Both treatments resulted in clear improvements. The mean value of the LFI decreased (improved) from 13.0 to 9.4 in the Phlogenzym group and from 12.5 to 9.4 in the diclofenac group. Significant improvements were also seen in the complaint index, with a slight tendency towards superiority of Phlogenzym. According to the physician's global judgment of efficacy, the results were rated as good or better for 51.4% of the Phlogenzym patients, and for 37.2% of the diclofenac patients. Most patients in each group rated tolerability very good or good.

Comment: The results of this study indicate that an oral enzyme-flavonoid combination was at least as effective as a standard non-steroidal anti-inflammatory drug (NSAID) in the treatment of osteoarthritis of the knee. While this product probably does not influence the progression of the disease (like glucosamine sulfate and chondroitin sulfate do), it appears to be useful for symptom relief. Given the currently available choices of rotting your heart with COX-2 inhibitors, rotting your intestines or kidneys with other NSAIDS, or rotting your liver with acetaminophen, it is encouraging to have a simple alternative that does not seem to rot anything.

Akhtar NM, et al. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee - a double-blind prospective randomized study. Clin Rheumatol 2004;23:410-415.

Mice were fed hazelnut extract with or without prior administration of omeprazole (a proton-pump inhibitor) or concurrent administration of sulcrafate (which has antacid activity). The doses of the drugs were equivalent to what would be given to humans, on a body-weight basis. Mice given the antiulcer drugs, but not the other mice, formed anaphylactogenic IgG1 toward hazelnut and developed type I skin reactivity to hazelnut extract. In a second study, 153 patients (mean age, 65.9 years) from a gastroenterology clinic who had been taking H2-blockers or proton pump inhibitors for 3 months because of dyspepsia or chronic gastritis were screened for specific IgE to hazelnut and inhalant allergens. Five patients (3.3%) had hazelnut-specific IgE, 4 of the 5 showed specific skin reactivity, 3 of the 5 had a positive reaction to oral provocation, and 2 of the 5 had a food allergy to hazelnut. None of these 5 patients showed sensitization to pollens that cross-react with hazelnut. Of 50 other patients from the same clinic who were not receiving antiulcer drugs, none showed evidence of sensitization to hazelnut allergens. The researchers concluded that the use of antiulcer drugs may lead to the development of immediate-type hypersensitivity toward hazelnut.

Comment: Hazelnut is the most frequent cause of IgE-mediated food allergy, with a prevalence of 21-53% in patients with food allergies in Europe. In approximately 5% of nut-allergic patients, severe systemic reactions (including asthma and hypotension) have been reported. While hazelnut allergy typically results from sensitization to cross-reacting pollen, severe allergic reactions to hazelnuts can occur without associated pollen allergy. Oral sensitization to hazelnut could presumably occur if antigens reach the intestinal mucosa intact. However, most of the major allergens in hazelnut extracts are not resistant to gastric and pancreatic digestion and, therefore, do not act as classic food allergens. On the other hand, such antigens might survive the digestive process intact, if the gastric acid secretion is blocked or neutralized.

Scholl I, et al. Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans. Am J Clin Nutr 2005;81:154-160.