Forty-nine patients with severe sinusitis (48 acute, 1 chronic) were randomly assigned to receive, in double-blind fashion, bromelain (Ananase®; 2 tablets 4 times a day) or a placebo for six days, in addition to antibiotics and other standard medications. Eighty percent of the patients receiving bromelain had good-to-excellent improvement, compared with 50% of those given the placebo. Bromelain was significantly more effective than placebo in relieving nasal discomfort, breathing difficulty, and pain. Compared with placebo, bromelain also significantly reduced the mean duration of standard therapy (16 days vs. 10 days).

Comment: Bromelain is an extract of the stems of pineapples that has anti-inflammatory activity. It also appears to increase the permeability and reduce the viscosity of inflammatory exudates, thereby promoting normal drainage and enhancing access of antibacterial agents (e.g., antibiotics, antibodies, and other components of the system) to the site of an infection. The results of this study indicate that bromelain can increase the response to conventional therapy in patients with sinusitis. In some studies of people with other types of infections, bromelain was beneficial even when administered without antibiotics.

The product used in this study was an enteric-coated preparation that is no longer commercially available. Most of the bromelain products currently on the market are not enteric-coated, so it is possible that a substantial proportion of the biological activity of these products is destroyed by gastric juices after oral administration. Ananase contained 20 mg of bromelain per tablet, whereas modern products usually contain substantially larger amounts. There is little or no published research on the effectiveness of non-enteric-coated bromelain products.

Seltzer AP. Adjunctive use of bromelains in sinusitis: a controlled study. EENT Monthly 1967;46:1281-1288.

Two hundred-ten consecutive patients with chronic sinusitis, of whom 101 were treated surgically, were studied. Fungal cultures of nasal secretions were positive in 202 (96%) of the patients. Candida albicans was cultured in 15.4% of patients, Alternaria in 44.3%, Penicillium in 43.3%, Cladosporium in 39%, and Aspergillus spp. in 29.5%; a wide range of other organisms were cultured less frequently. Allergic mucin (containing clusters or sheets of degenerating eosinophils) was found in 97 (96%) of the 101 surgical cases. Fungal elements (hyphae, destroyed hyphae, conidiae, and spores) were found histologically in 82 (81%) of the 101 surgical specimens. Allergic fungal sinusitis was diagnosed in 94 (93%) of the 101 surgical cases, based on histopathologic findings and culture results. An elevated IgE level to at least one fungal species was found in only 28% of 95 patients tested, and skin-prick tests were positive to at least one fungal allergen in only 25% of 179 patients tested.

Comment: The results of this study suggest that, among patients with chronic sinusitis, allergy to common airborne fungi appeared to be a causative factor in at least 93% of cases. Conventional tests for fungal allergy (e.g., IgE levels and skin-prick tests) failed to detect fungal allergy in the majority of patients with allergic fungal sinusitis. The research group that performed this study subsequently demonstrated that patients with chronic sinusitis have an exaggerated immune response to airborne fungi (J Allergy Clin Immunol 2004;114:1369-1375). They have also reported, in open (J Allergy Clin Immunol 2002;110:862-866) and double-blind (J Allergy Clin Immunol 2005;115:125-131) trials, that intranasal administration of the antifungal drug amphotericin B resulted in clinical improvement and a reduction in mucosal thickening. In the open trial, of 51 patients treated, 75% improved and 35% became disease-free.

In my experience, some patients with chronic sinusitis show marked improvement after identifying and avoiding allergenic foods. A few patients have shown a dramatic response to intravenous nutrient therapy (the Myers' cocktail; see Altern Med Rev 2002;7:389-403).

Ponikau JU, et al. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc 1999;74:877-884.

Nineteen patients (aged 6-19 years) with cystic fibrosis were randomly assigned to receive, in double-blind fashion, inhaled, buffered reduced glutathione (GSH) or placebo (sodium chloride with a hint of quinine) for 8 weeks. The treatments were administered 4 times a day (3 to 4 hours apart), for a total daily GSH dose of approximately 66 mg/kg of body weight. Primary outcomes were forced expiratory volume in 1 second (FEV1), forced vital capacity, forced expiratory flow at 25-75% of vital capacity, and peak flow; secondary outcomes were body mass index, 6-minute walk distance, and self-reported cough frequency, mucus production, wellness, improvement, and stamina. The mean change for peak flow was -6.5 L/min with placebo and +33.7 L/min with GSH (p = 0.04). Self-reported mean improvement on a scale from 1 to 5 (1 being much worse and 5 being much better) was 2.8 for placebo and 4.7 for GSH (p = 0.004). Of the 13 primary and secondary outcomes examined, 11 favored the treatment group over the placebo group (p = 0.002), indicating a general tendency of improvement in the GSH group. No significant side effects of GSH were reported.

Comment: Glutathione is a major antioxidant in lung tissue. Patients with cystic fibrosis have markedly decreased concentrations of total (oxidized plus reduced) glutathione in the epithelial lining fluid of the lung. Anecdotal reports suggest that nebulized glutathione administered by aerosol can relieve symptoms and improve clinical outcome in patients with chronic obstructive pulmonary disease. The results of the present study indicate that glutathione is also beneficial for the chronic lung disease that occurs in patients with cystic fibrosis.

Bishop C, et al. A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis. Chest 2005;127:308-317.

Twenty-one HIV-negative adults with newly diagnosed pulmonary tuberculosis were hospitalized for 8 weeks and randomly assigned to receive a cholesterol-rich diet (800 mg/day of cholesterol) or a normal diet (250 mg/day of cholesterol). The extra amount of cholesterol in the high-cholesterol diet was derived from butter, beef liver, egg yolk, and milk products. All patients received the same 4-drug antitubercular regimen (isoniazid, rifampin, pyrazinamide, and ethambutol) and no patient had a drug-resistant strain of Mycobacterium tuberculosis. After 2 weeks, sputum cultures had become negative in 80% of patients receiving the high-cholesterol diet and in 9% of those receiving the normal diet (p < 0.002). In addition, the bacillary population (p = 0.0002) and sputum production (p < 0.05) decreased faster in the high-cholesterol group than in the normal-diet group.

Comment: Hypocholesterolemia is common among tuberculous patients and is associated with mortality in miliary cases. Some in vitro studies have shown that cholesterol is necessary for the functioning of macrophages and lymphocytes, which play a role in the immune response to infection. The results of the present study demonstrate that a cholesterol-rich diet accelerates recovery in patients with pulmonary tuberculosis. Such patients are often generally malnourished, so it is possible that other nutrients present in egg yolk, beef liver, and milk (such as protein and B vitamins) also contributed to their recovery.

Perez-Guzman C, et al. A cholesterol-rich diet accelerates bacteriologic sterilization in pulmonary tuberculosis. Chest 2005;127:643-651.

A meta-analysis was performed of 5 randomized double-blind trials (n = 9,292) of vitamin D3 supplementation for hip fracture prevention and 7 randomized double-blind trials (n = 9,820) of vitamin D3 supplementation for prevention of non-vertebral fractures. All participants were at least 60 years of age. A dose of 700 to 800 IU/day reduced the relative risk (RR) of hip fracture by 26% (3 trials with 5,572 persons; pooled RR = 0.74; 95% confidence interval [CI], 0.61-0.88) and any non-vertebral fracture by 23% (5 trials with 6,098 persons; pooled RR = 0.77; 95% CI, 0.68-0.87) vs. calcium or placebo. No significant benefit was observed with 400 IU/day of vitamin D (2 trials with 3,722 persons; pooled RR for hip fracture = 1.15; 95% CI, 0.88-1.50; and pooled RR for any non-vertebral fracture = 1.03; 95% CI, 0.86-1.24).

Comment: Vitamin D plays a role in calcium absorption, and vitamin D deficiency causes bone abnormalities including osteoporosis or osteomalacia. In addition, vitamin D deficiency can result in poor balance and proximal muscle weakness, both of which increase the risk of falling. Several clinical trials have shown that supplementation of elderly people with 800 IU/day of vitamin D reduced the number of falls by nearly 50%. The reduction in fracture risk associated with vitamin D supplementation is probably due to a combination of stronger bones and less falling.

The Adequate Intake for vitamin D, as established by the Institute of Medicine of the National Academy of Sciences, is 400 IU/day for adults aged 51-70, and 600 IU/day for people aged 71 and older. Vitamin D requirements tend to increase with advancing age, because the capacity of the skin to synthesize vitamin D decreases as people get older. In addition, many elderly people are housebound, and fail to obtain adequate amounts of sunlight to protect against vitamin D deficiency. The results of the present study suggest that 400 IU/day of vitamin D is insufficient for elderly people, and that a dose of 800 IU/day is more effective for fracture prevention. The Institute of Medicine has set the "safe upper limit" for vitamin D at 2,000 IU/day, but some research suggests that as much as 4,000 IU/day is safe for the average person.

Bischoff-Ferrari HA, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005;293:2257-2264.

Twenty-one obese nondiabetic women (aged 23-53 years) were randomly assigned to consume for 16 weeks a low-calorie diet that was either 1) high in carbohydrate (60% of energy) and low in fat (20% of energy) (HC/LF) or 2) low in carbohydrate (40% of energy) and high in fat (40% of energy) (LC/HF). The women were classified as either insulin-sensitive (fasting insulin < 10 microU/ml; n = 12) or insulin-resistant (fasting insulin > 15 microU/ml; n = 9). Insulin-sensitive women on the HC/LF diet lost a mean of 13.5% of their initial body weight, whereas those on the LC/HF diet lost 6.8 % (p < 0.002 for the difference in the change between groups). In contrast, among insulin-resistant women, those on the LC/HF diet lost a mean of 13.4% of their initial body weight, whereas those on the HC/LF diet lost 8.5% (p < 0.04 for the difference in the change between groups). These differences could not be explained by changes in resting metabolic rate, activity, or food intake. Overall, changes in insulin sensitivity were associated with the degree of weight loss (r = -0.57; p < 0.05).

Comment: The results of this study suggest that the ideal weight-loss diet for an obese woman depends on her state of insulin sensitivity. Women who are insulin-sensitive lose weight more rapidly with a high-carbohydrate diet than with a low-carbohydrate diet. In contrast, a low-carbohydrate diet is more effective for women who are insulin-resistant. In both groups of women, weight loss resulted in improved insulin sensitivity. Diets high in complex carbohydrates, which contain abundant amounts of plant foods, are generally more healthful than low-carbohydrate diets, which usually contain more animal foods. Obese insulin-resistant women might fare best if they start on a low-carbohydrate diet and then switch to a high-complex-carbohydrate diet after their insulin sensitivity improves.

Cornier MA, et al. Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women. Obes Res 2005;13:703-709.

A 40-year-old woman with multiple 1- to 2-mm gallstones documented by ultrasound underwent a "liver cleansing" regimen at the advice of an herbalist. The regimen consisted of free intake of apple and vegetable juice until 6 p.m., but no food, followed by consumption of 600 ml of olive oil and 300 ml of lemon juice over several hours. Early the next morning, multiple semi-solid green "stones" were passed per rectum. Analysis of the stones revealed that they contained no cholesterol, bilirubin, or calcium, but were made up of 75% fatty acids. Experimentation revealed that mixing equal volumes of oleic acid (the main component of olive oil) and lemon juice produced semi-solid white balls after the addition of a small amount of potassium hydroxide. The authors concluded that the green "stones" passed by this woman resulted from the action of gastric lipases on the triglycerides that make up olive oil, yielding long-chain carboxylic acids (mainly oleic acid). This process was followed by saponification into large insoluble micelles of potassium carboxylates (lemon juice contains a high concentration of potassium) or "soap stones." The cholesterol stones observed on ultrasound were removed surgically.

Comment: Variations of the regimen described above are frequently mentioned by herbalists and nutritionists as a method of promoting the passage of gallstones. Some patients claim to have passed numerous gallstones after undergoing a "gallbladder flush" similar to this one. None of the patients, however, had their "stones" analyzed, and none had before-and-after gallbladder sonograms to document the passage of gallstones. Thus, it appears that most or all of these patients were merely passing "soap stones." The gallbladder flush may not be entirely worthless, however; there is one case report in which treatment with olive oil and lemon juice resulted in the passage of numerous gallstones, as demonstrated by ultrasound examination (Br J Surg 1992;79:168).

Sies CW, Brooker J. Could these be gallstones? Lancet 2005;365:1388.

Forty-two patients (mean age, 38.7 years) with recurrent migraines were randomly assigned to receive, in double-blind fashion, 100 mg of coenzyme Q10 (CoQ10) 3 times a day or a placebo for 4 months. The primary outcome measure was the change in attack frequency in month 4 compared with baseline. At baseline, the mean attack frequency in both groups was 4.4 per month. The proportion of patients who had a 50%-or-greater reduction in attack frequency in month 4 was 47.6% for CoQ10 and 14.4% for placebo. The mean reduction in attack frequency was 27.1% in the CoQ10 group and 2.1% in the placebo group (p < 0.05 for the difference in the change between groups). The mean duration and severity of migraines did not differ between groups. No significant side effects were reported.

Comment: Previous studies have demonstrated that migraine patients have impaired mitochondrial function, resulting in a reduction in energy production, in brain tissue. Nutrients essential for mitochondrial energy production include magnesium, riboflavin, niacinamide, and CoQ10. Controlled trials have demonstrated that supplementing with either magnesium or riboflavin can reduce the attack rate in migraine sufferers. Niacinamide has not been studied for migraine prophylaxis. While there is a single case report in which niacin reduced the recurrence rate of migraines (Mayo Clin Proc 2003;78:770-771), the effectiveness of niacin may have been due to its vasodilatory action, which is not shared by niacinamide. An earlier uncontrolled trial showed a beneficial effect of CoQ10, and those results have now been confirmed in this double-blind trial.

Sandor PS, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 2005;64:713-715.