Literature Review and Commentary

by Alan R. Gaby, MD

Compounds in Green Tea Prevent Influenza

One hundred ninety-seven health-care workers in Japan were randomly assigned to receive, in double-blind fashion, capsules providing daily 378 mg of green tea catechins and 210 mg of theanine or placebo for 5 months, from November to April. The incidence of clinically defined influenza infection was significantly lower by 69% in the active-treatment group than in the placebo group (4.1% vs. 13.1%; p = 0.022). The incidence of laboratory-confirmed influenza infection was nonsignificantly lower by 80% in the active-treatment group than in the placebo group (1% vs. 5.1%; p = 0.11).

Comment

: Catechins and theanine (an amino acid) are components of green tea. In previous studies, gargling with an aqueous solution of green tea catechins 3 times per day reduced the incidence of influenza in elderly nursing home residents. In a double-blind trial, administration of a proprietary green tea extract reduced the number of days with cold or flu symptoms by 36%, compared with placebo, in healthy volunteers. Like the earlier research, the results of the present study indicate that green tea constituents can prevent influenza.

Matsumoto K et al. Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial. BMC Complement Altern Med. 2011;11:15.

Omega-3 Fatty Acids Beneficial for Cardiomyopathy

One hundred thirty-three patients (mean age, 62.5 years) with nonischemic dilated cardiomyopathy who had minimal symptoms while on conventional therapy were randomly assigned to receive, in double-blind fashion, omega-3 fatty acids (OMACOR) or placebo (olive oil) for 12 months. The dosage was 5 g/day for 1 month, then 2 g/day. Each gram of OMACOR contained 850 to 882 mg of EPA and DHA ethyl esters in the average ratio of 0.9:1.5. After 12 months, mean left ventricular ejection fraction increased by 10.4% in the active-treatment group and decreased by 5% in the placebo group (p < 0.001 for the difference in the change between groups). Compared with placebo, active treatment significantly improved exercise capacity (p < 0.002) and New York Heart Association (NYHA) functional class (p < 0.001). NYHA functional class improved in 26.9% of the patients receiving active treatment and remained the same in the other 73.1%. The hospitalization rate for heart failure was significantly lower by 80.5% in the active-treatment group than in the placebo group (5.9% vs. 30.3%; p = 0.0002).

Comment

: This study demonstrates that, in patients with nonischemic dilated cardiomyopathy and minimal symptoms while on conventional therapy, administration of omega-3 fatty acids increased left ventricular systolic function and functional capacity and reduced hospitalizations for heart failure. While omega-3 fatty acids have numerous beneficial effects on the cardiovascular system, the mechanism by which they ameliorate heart failure in patients with dilated cardiomyopathy is not known.

Nodari S et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2011;57:870–879.

Probiotic/Prebiotic Effective for Atopic Dermatitis

Ninety children (aged 1–3 years) with moderate to severe atopic dermatitis were randomly assigned to receive, in double-blind fashion, a mixture of Lactobacillus acidophilus DDS-1, Bifidobacterium lactis UABLA-12, and fructooligosaccharides or placebo for 8 weeks. Active treatment provided 5 billion colony-forming units of viable bacteria twice a day. After 8 weeks, the mean improvement in the Scoring of Atopic Dermatitis (SCORAD) score was significantly greater in the active-treatment group than in the placebo group (33.7% vs. 19.4%; p = 0.001).

Comment

: In this study, a combination probiotic/prebiotic preparation was effective in the treatment of atopic dermatitis in children. Previous studies on the use of probiotics in children with atopic dermatitis have produced conflicting results. Further research is needed to determine which probiotic strains are most effective, and whether the addition of a prebiotic enhances the effect of the probiotic. Milk-allergic children should not use probiotic products that have been grown on casein or on other milk proteins.

Gerasimov SV et al. Probiotic supplement reduces atopic dermatitis in preschool children: a randomized, double-blind, placebo-controlled, clinical trial. Am J Clin Dermatol. 2010;11:351–361.

Vitamin D and Mortality: A U-Shaped Curve

In a prospective cohort study of 1194 elderly men (mean age, 71 years), during a median follow-up period of 12.7 years, there was a U-shaped association between plasma 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (< 46 nmol/L) and the highest 5% (> 98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was higher by more than 2-fold at both low and high plasma concentrations of 25(OH)D. Increased rates of cardiovascular death were also seen at both low and high 25(OH)D levels, but the association was statistically significant only for low concentrations.

Comment

: In recent years, a number of investigators have recommended aggressive vitamin D supplement in order to increase serum 25(OH)D levels to 90 to 100 nmol/L. The main basis of this recommendation is that some observational studies have found that individuals with these high 25(OH)D levels have lower rates of cancer, fractures, and other health conditions, when compared with people who have lower 25(OH)D levels. However, many of these observational studies failed to control for factors that influence 25(OH)D concentrations, such as age, body mass index, and comorbidities. The results of the present study are consistent with the possibility that both high and low 25(OH)D levels can have negative health consequences. While observational studies do not prove cause and effect, the present study does not support the routine use of high doses of vitamin D for the sole purpose of increasing the 25(OH)D level to 90 to 100 nmol/L.

Michaelsson K et al. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr. 2010;92:841–848.

Vitamin E for Nonalcoholic Fatty Liver Disease

One hundred seventy-three children (aged 8–17 years) with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were randomly assigned to receive, in double-blind fashion, 800 IU per day of vitamin E, 1000 mg per day of metformin, or placebo for 96 weeks. The primary outcome was a sustained reduction in the alanine aminotransferase (ALT) level, defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Secondary outcomes were improvements in histological features of NAFLD and resolution of nonalcoholic steatohepatitis (NASH; i.e., improvement from NASH or borderline NASH to not having NASH). A sustained reduction in ALT level was seen in 26% of patients receiving vitamin E, 16% of those receiving metformin, and 17% of those receiving placebo (differences not significant). However, the reduction in ALT levels was significantly greater in the vitamin E group than in the placebo group up to week 48, and the reduction remained nonsignificantly greater in the vitamin E group for the remainder of the study. The blunting in the difference in ALT levels between the vitamin E and placebo group after week 48 was due mainly to continued improvement in ALT levels in the placebo group (presumably because of continued adherence to diet and exercise recommendations). The mean improvement in the NAFLD activity score was significantly greater in the vitamin E group (but not in the metformin group) than in the placebo group (p = 0.02). The proportion of patients who had a resolution of NASH was 58% with vitamin E, 41% with metformin, and 28% with placebo (p = 0.006 for vitamin E. vs. placebo).

Comment

: The results of this study suggest that vitamin E can produce clinical improvements in patients with NAFLD, including an improvement in the level of liver enzymes, a reduction in the severity of fatty liver, and an improvement in steatohepatitis. Surprisingly, the authors concluded in the abstract that vitamin E was not effective, because it failed to achieve the primary outcome measure of a sustained reduction in ALT levels. However, the data clearly demonstrated a beneficial effect.

Lavine JE et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305:1659–1668.

Ginger Prevents Chemotherapy Side Effect

Sixty children and young adults (aged 8–21 years) with bone sarcoma who were undergoing 3-day chemotherapy cycles with cisplatin/doxorubicin were randomly assigned to receive, in double-blind fashion, 5 or 6 capsules per day of ginger powder or placebo, in addition to conventional antiemetic therapy (ondensetron and dexamethasone). Patients weighing 20 to 40 kg received 1000 mg per day of ginger in 3 divided doses (1 hour before the start of the chemotherapy infusion, 3 hours after the start of chemotherapy, and 8 hours after the start of chemotherapy). Patients weighing 40 to 60 kg received 2000 mg per day of ginger (800 mg 1 hour before the start of the chemotherapy, 800 mg 3 hours after the start of chemotherapy, and 400 mg 8 hours after the start of chemotherapy). Acute chemotherapy-induced nausea and vomiting (CINV) was defined as nausea and vomiting occurring within 24 hours of the start of chemotherapy (days 1–4) and delayed CINV as that occurring at least 24 hours after the completion of chemotherapy (days 5–10). The incidence of acute chemotherapy-induced nausea was 100% in both groups. Acute moderate to severe nausea occurred after 55.6% of chemotherapy cycles in the active-treatment group and in 93.3% of cycles in the placebo group (p = 0.003). For acute moderate to severe vomiting, the respective percentages were 33.3% and 76.7% (p = 0.002). For delayed moderate-to-severe nausea, the respective percentages were 25.9% and 73.3% (p < 0.001). For delayed moderate-to-severe vomiting, the respective percentages were 14.8% and 46.7% (p = 0.022).

Comment

: Ginger has been found to be effective for the prevention of postoperative nausea and vomiting. The results of the present study indicate that ginger can also reduce the incidence and/or severity of both acute and delayed chemotherapy-induced nausea and vomiting.

Pillai AK et al. Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy. Pediatr Blood Cancer. 2011;56:234–238.

Chromium Helpful for Overweight Children

Twenty-four overweight children (aged 9–12 years) were randomly assigned to receive, in double-blind fashion, 400 mcg per day of chromium chloride or placebo for 6 weeks. It was not specified whether the dosage referred to elemental chromium or to the chromium salt. All children participated in a program of nutritional education and 90 minutes of aerobic activity 3 times a week. Compared with placebo, chromium treatment resulted in a significant improvement in insulin sensitivity (as determined by homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index). In addition, compared with placebo, chromium significantly increased lean body mass (mean, 2.43 kg vs. 1.36 kg; p = 0.02) and significantly decreased percentage body fat (mean, −3.32% vs. +0.65%; p = 0.04). There was no significant difference between groups in body mass index.

Comment

: In this study, chromium supplementation improved insulin sensitivity and body composition in overweight children. Thus, chromium supplementation should be included as part of a comprehensive program of diet and exercise for overweight children. Previous research suggests that chromium works by enhancing the binding of insulin to its receptor.

Kim CW et al. Effects of short-term chromium supplementation on insulin sensitivity and body composition in overweight children: randomized, double-blind, placebo-controlled study. J Nutr Biochem. Epub 2011;Jan 7.

Bisphosphonates Aren’t So Dangerous … Or Are They?

In Sweden, 12,777 women aged 55 years or older sustained a fracture of the femur in 2008. Radiographs were reviewed from 1234 of the 1271 women who had a subtrochanteric or shaft fracture. Of those, 59 patients had atypical fractures. The age-adjusted relative risk of atypical fracture associated with bisphosphonate use was 47.3 (95% confidence interval, 25.6–87.3). The increase in absolute risk was 5 cases per 10,000 patient-years. The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses = 1.3). After drug withdrawal, the risk diminished by 72% per year from the time of the last use. The authors concluded that these findings “may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small.”

Comment

: A few years ago, reports began to appear that linked bisphosphonate use to atypical fractures of the femoral shaft and to osteonecrosis of the jaw. According to the present study, people who took bisphosphonates were 47 times more likely to suffer an atypical femoral-shaft fracture than were people who did not take bisphosphonates. The risk of sustaining such a fracture increased with increasing duration of bisphosphonate use. As noted by the authors, the absolute risk of having a drug-induced fracture was small. However, there is something disconcerting about the fact that drugs used to treat osteoporosis actually cause fractures, no matter how small the risk. The fact that bisphosphonates prevent many more fractures than they cause should not necessarily be “reassuring,” considering that there are many other osteoporosis treatments that do not cause any fractures. These include DHEA, progesterone (data are conflicting regarding efficacy), strontium, various other micronutrients (e.g., magnesium, manganese, zinc, copper, folic acid, silicon, and vitamin K), and weight-bearing exercise.

Schilcher J et al. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med. 2011;364:1728–1737.