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From the Townsend Letter for Doctors & Patients
August/September 2002

Literature Review and Comment
by Alan R. Gaby, MD


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Problem with American Heart Association "Step 1" diet

     The American Heart Association (AHA) recommends the so-called "Step 1" diet to reduce elevated serum cholesterol levels. This diet allows a maximum of 30% of energy from fat (with less than 10% of total energy from saturated fat) and is high in carbohydrates. To assess the effect of this diet, 55 overweight, sedentary postmenopausal women (mean age, 59 years) were prescribed it for a period of 10 weeks. During the study period, the percent of energy from total fat and saturated fat and the intake of cholesterol decreased significantly, while the percent of energy from complex carbohydrates and simple carbohydrates increased. Mean body weight fell by 2%, total cholesterol fell by 8%, LDL cholesterol fell by 6%, and HDL cholesterol fell by 16%. The only dietary change that predicted a decrease in HDL cholesterol concentration was an increase in the proportion of energy from simple sugars (e.g., glucose, sucrose, fructose, lactose, and maltose) (p < 0.05).

     Comment: Although the AHA Step 1 diet decreased total and LDL cholesterol levels in this group of women, it decreased HDL cholesterol by an even greater proportion. In women, a low HDL cholesterol concentration is a stronger independent predictor of cardiovascular disease risk than is elevated total cholesterol or LDL cholesterol. Therefore, women who follow AHA guidelines for lowering their serum cholesterol may actually be increasing their risk of heart disease. Statistical analysis suggested that the increase in intake of simple sugars was responsible for the reduction in HDL cholesterol levels. That observation is consistent with other studies showing that increasing intake of refined sugar lowers HDL cholesterol. Therefore, while a low-fat, high-carbohydrate diet may be beneficial, complex carbohydrates should be emphasized, such as whole grains, legumes, fruits, vegetables, nuts, and seeds.

Bunyard LB, et al. Dietary intake and changes in lipoprotein lipids in obese, postmenopausal women placed on an American Heart Association Step 1 diet. J Am Diet Assoc 2002;102:52-57.

Can food allergy trigger myocardial infarction?
     Seventy-six patients who had experienced a myocardial infarction before age 45 (mean age, 39 years) were studied. Fourteen of these patients (18%) had increased levels of circulating immune complexes (CICs) at least three years after the acute event. In contrast, only 5% of age-matched healthy controls had CICs. In half of the 14 patients with elevated CICs, these complexes were found to contain antibodies against food proteins, as well as the corresponding antigens. The food proteins involved were bovine serum albumin (n = 6), gliadin (n = 5), and ovalbumin (n = 1). Four patients with CICs to bovine serum albumin underwent a two-week elimination diet, followed by a single challenge with cow's milk. The milk challenge resulted in a rise in CICs, as well as signs of activation of the classical complement pathway.

     Comment: There is considerable evidence in both animals and humans that CICs may promote the development of atherosclerosis, even in the absence of classical risk factors. The results of this study indicate that, in susceptible individuals, ingestion of certain foods results in the formation of CICs, which may predispose to myocardial infarction at a young age, possibly by triggering an inflammatory process. I have seen three patients over the years who experienced food-induced angina; these patients would develop symptoms only after the consumption of specific foods to which they were sensitive. Dr. William Rea has demonstrated that chest pain and cardiac arrhythmias can be triggered in susceptible individuals by exposure to foods or common inhalants (Ann Allergy 1978;40:243-251). The importance of allergy in the pathogenesis of cardiovascular disease deserves closer attention, particularly in patients whose medical history is suggestive of food allergy (i.e., history of otitis media, asthma, rhinitis, eczema, migraine, irritable bowel syndrome, hyperactivity, etc.).

Mustafa A, et al. Circulating immune complexes induced by food proteins implicated in precocious myocardial infarction. Ann Med 2001;33:103-112.

Does vitamin K deficiency cause arteries to calcify?
     The relationship between vitamin K status and coronary artery calcification (determined by electron-beam computed tomography) was assessed in 600 men (aged 50-70 years) who had no symptoms of atherosclerosis. There was no linear relationship between vitamin K status and coronary calcification. However, men in the bottom 10 percentile with respect to vitamin K status (determined by the percent of undercarboxylated osteocalcin in serum) had significantly more coronary artery calcification than did those with better vitamin K status, After adjustment for blood pressure and lipid levels, poor vitamin K status was associated with a 2.7-fold increase in the risk of severe coronary artery calcification, an increase that is comparable to that associated with smoking.

     Comment: Vitamin K plays a role in normal calcification of bone. It is conceivable that vitamin K deficiency could lead to abnormal calcification processes in the body, such as coronary artery calcification; however, such a possibility has not been previously studied. Rats given warfarin (a vitamin K antagonist) develop extensive arterial calcification. The present study suggests that vitamin K deficiency may cause similar problems in humans. Of course, low vitamin K intake could be merely a marker for low intake of other nutrients known to play a role in atherosclerosis prevention (such as vitamin C, folic acid, and flavonoids). Nevertheless, this study provides yet another reason for people to consume dark green vegetables (the main dietary source of vitamin K).

Jancin B. Low vitamin K linked to coronary calcification risk. Fam Pract News 2002;32(1):1-2.

Soy isoflavones relieve menopausal symptoms and improve lipid levels
     Eighty women (aged 45-55 years) with menopausal symptoms were randomly assigned to receive, in double-blind fashion, 100 mg/day of soy isoflavones in three divided doses or placebo for four months. After four months, there was a significant decrease in menopausal symptoms (as determined by the Kupperman index), compared with baseline (p < 0.01) and compared with the change in the placebo group (p < 0.01). Total cholesterol and LDL cholesterol decreased significantly in the isoflavone group compared with baseline (p < 0.001) and compared with the change in the placebo group (p < 0.01). There were no significant changes in levels of HDL cholesterol, triglycerides, or blood pressure.

     Comment: Previous studies have shown that ingestion of soy protein can relieve menopausal symptoms and reduce serum cholesterol levels. Although these beneficial effects have been attributed to the isoflavones in soy, the possibility that other components have biological activity has not been ruled out. The present study confirms that the "medicinal" value of soy is, indeed, due in large part to its isoflavone content. However, that does not mean that taking an isoflavone pill would provide all of the benefits of eating soy. In addition to isoflavones, soy contains lecithin (which can raise HDL cholesterol levels), protein of relatively high biological value, phytate (which may prevent cancer, but also appears to inhibit absorption of some minerals), essential fatty acids, and moderate amounts of vitamins E and K.

Han KK, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002;99:389-394.

Soy does not relieve menopausal symptoms: bad treatment or bad research?
     One hundred twenty-three postmenopausal women with breast cancer and moderate hot flashes were randomly assigned to receive, in double-blind fashion, 250 ml twice daily of a soy beverage (providing 90 mg/day of isoflavones) or an isoflavone-free placebo beverage for 12 weeks. Both groups experienced significant reductions in the mean frequency of hot flashes (25.3% reduction for soy, 33.7% reduction for placebo), and significant improvements in the mean hot-flash score, determined by the frequency multiplied by the intensity of hot flashes (30% reduction for soy, 39.6% reduction for placebo). However, there were no significant differences between groups, with respect to the mean number of hot flashes or the mean hot-flash scores. The authors concluded that the soy beverage was no more effective than placebo as a treatment for hot flashes in postmenopausal women with breast cancer.

     Comment: The results of this study contradict those of the other study cited above, and are inconsistent with a fairly large body of research showing that soy helps relieve menopausal symptoms. Surprisingly, the placebo used in the negative study was a rice beverage. Rice contains gamma-oryzanol, which, according to studies from Japan, is an effective treatment for menopausal hot flashes. The use of an "active" placebo makes the treatment being studied appear less effective than it really is. In designing controlled studies, researchers should choose a "placebo" that is unlikely to mimic the effects of the treatment being studied.

Van Patten CL, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 2002;20:1449-1455.

Fungus allergy as a cause of sinusitis
     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%, 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 96% and fungal elements (hyphae, destroyed hyphae, conidiae, and spores) were found histologically in 81% of the 101 surgical specimens. Allergic fungal sinusitis was diagnosed in 93% of the surgical cases, based on histopathologic findings and culture results. An elevated IgE level to at least 1 fungal species was found in only 28% of 95 patients tested, and skin-prick tests were positive to at least 1 fungal allergen in only 25% of 179 patients tested.

     Comment: These findings suggest that fungal allergy is extremely common in patients with chronic sinusitis. However, conventional tests (IgE levels and skin-prick tests) fail to detect fungal allergy in the majority of patients with allergic fungal sinusitis. Why so many patients with sinusitis have a localized fungal infection is not clear, although repeated use of antibiotics may play a role. Some doctors have anecdotally reported good results by having patients inhale small amounts of nystatin powder through the nose, or by using antifungal herbs in a nasal wash. However, clinical trials are needed to demonstrate the safety and effectiveness of such an approach. Considering how common chronic sinusitis is, and how difficult it is to treat with conventional approaches, further investigation of the role of fungus infection/allergy is urgently needed.

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

Wheat grass juice for ulcerative colitis
     Twenty-three patients (mean age, 35.3 years) with active distal ulcerative colitis were randomly assigned to receive, in double-blind fashion, wheat grass (Triticum aestivum) juice or placebo (matched with wheat grass juice for appearance, but not for taste or smell) for 1 month. The wheat grass juice was prepared fresh each day and consumed within an hour of extraction. The initial dose was 20 ml/day; this was increased by 20 ml/day every day to a maximum dose of 100 ml/day. Efficacy of treatment was assessed by a disease activity index that included rectal bleeding, number of bowel movements per day, sigmoidoscopic evaluation, and global assessment by a physician. Nineteen patients completed the trial. Compared with placebo, wheat grass juice significantly reduced (improved) the overall disease activity index score (p < 0.04) and the severity of rectal bleeding (p < 0.03) and abdominal pain (p < 0.02). Improvement on sigmoidoscopic examination was seen in 7 (78%) of 9 patients receiving wheat grass juice and in 3 (30%) of 10 patients receiving placebo (p = 0.13). No serious side effects were seen. Nausea occurred in 33% of patients receiving active treatment; however, 41% of those receiving active treatment reported the positive side effect of increased vitality.

     Comment: In this study, wheat grass juice appeared to be beneficial in the treatment of active distal ulcerative colitis. Wheat grass is produced by sprouting and planting the seeds of the common wheat plant (Triticum aestivum). The difference between wheat grass and what most of us recognize as edible wheat is that the former is harvested much earlier in its life cycle. The use of wheat grass juice for therapeutic purposes was developed by Dr. Ann Wigmore. Although it has been recommended for nearly 50 years as a treatment for various diseases (including chronic inflammatory conditions and cancer), until now it has not been tested in clinical trials. Perhaps this report will spur researchers to investigate some of the other claims that have been made for wheat grass juice.

Ben-Arye E, et al. Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial. Scand J Gastroenterol 2002;37:444-449.

Diet and exercise improves hepatitis C
     Nineteen obese patients with hepatitis C participated in a 12-week diet and exercise program with the goal of achieving weight loss of 0.5 kg per week. After 12 weeks, there was a mean weight loss of 5.9 kg. In 16 of the 19 patients, serum ALT levels fell progressively during the study. Of the 10 patients who had a liver biopsy prior to and 3-6 months after the intervention, 9 showed a reduction in steatosis (fatty degeneration). In these patients, the median fibrosis score decreased (improved) from 3 to 1 (p = 0.01). Patients who maintained their weight loss over the following 6-12 months had sustained improvement in their liver function tests, despite persistence of the virus.

     Comment: Hepatic steatosis is found in 60% of patients with hepatitis C and is strongly associated with more severe fibrosis. Steatohepatitis is also a relatively common condition among obese individuals, even if they do not drink alcohol and are not infected with a hepatitis virus. Previous studies have shown that weight loss results in biochemical and histological improvement in patients with non-alcohol steatohepatitis. The present study suggests that similar improvements may be seen in obese patients with chronic hepatitis C who undertake a weight-loss program.

Hickman I, et al. Weight reduction improves biochemistry and histology in patients with chronic hepatitis C. Am J Clin Nutr 2002;75(Suppl):339S.


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