Literature Review and Commentary

by Alan R. Gaby, MD

Probiotic to Prevent Respiratory Infections

Three hundred fifteen children (aged 3–12 years) who had a household member with symptoms of an acute respiratory infection (ARI) were randomly assigned to receive, in double-blind fashion, a probiotic preparation or placebo. The probiotic (Up4-Junior) was started on the first day the household member became ill and was continued for 2 weeks. It contained Lactobacillus acidophilus DDS-1 (NCIMB 30333) and Bifidobacterium lactis UABLA-12 (NCIMB 30334) in a proportion of 1:4, at a dose of 5 billion colony-forming units per day, with 50 mg of fructooligosaccharides. The proportion of children who developed an ARI was nonsignificantly lower by 12% (57% vs. 65%; p = 0.26), the median duration of illness was significantly lower by 29% (5.0 vs. 7.0 days; p < 0.001) and the median severity of ARIs was significantly lower by 54% (p < 0.001) in the probiotic group than in the placebo group.

Comment

: In this study, supplementation of children with a probiotic preparation at the first sign of illness of a household member nonsignificantly decreased the incidence and significantly decreased the duration and severity of secondary acute respiratory infections. Probiotic organisms may help eradicate or prevent the growth of pathogenic organisms by competing with them for nutrients and colonization sites, producing antimicrobial compounds, and enhancing the immune function of the host. The results of this study are consistent with other research showing that various probiotics can prevent infections.

Gerasimov SV et al. Role of short-term use of L. acidophilus DDS-1 and B. lactis UABLA-12 in acute respiratory infections in children: a randomized controlled trial. Eur J Clin Nutr. Epub 2015 Oct 14.

Fish Oil Prevents Seizures

Seventy children (aged 4–12 years) with epilepsy resistant to anticonvulsant medication were randomly assigned to receive, in single-blind fashion, 1200 mg per day of fish oil (providing 360 mg of eicosapentaenoic acid and 240 mg of docosahexaenoic acid) or placebo (corn oil) for 3 months, while continuing their medication. At the end of the third month, the proportion of children who were free of seizures was 57% in the fish oil group and 3% in the placebo group.

Comment

: Omega-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models of epilepsy. In the present study, fish oil, when given as an adjunct to anticonvulsant medication, markedly decreased seizure activity in children with treatment-resistant epilepsy. The results of previous research suggest that there is a “therapeutic window” for fish oil in the treatment of epilepsy, such that both lower doses and higher doses are less effective than the optimal dose. Considering the strong positive results in this study, a fish oil dosage of around 1200 mg per day could be recommended for children in the age range of 4 to 12 years.

Reda DM et al. Fish oil intake and seizure control in children with medically resistant epilepsy. N Am J Med Sci. 2015;7:317–321.

Probiotic Prevents Surgical Complications

One hundred sixty-four patients undergoing colorectal surgery for cancer were randomly assigned to receive, in double-blind fashion, 1 capsule twice a day of a probiotic preparation or placebo, beginning on the day of surgery and continuing for a total of 15 days. If the patient was intubated, the treatment was given through a nasogastric tube. The probiotic preparation (LactoLevure; UniPharma, Athens, Greece) consisted of (colony-forming units per capsule) Lactobacillus acidophilus LA-5 (1.75 × 10⁹), L. plantarum (0.5 × 10⁹), Bifidobacterium lactis BB-12 (1.75 × 10⁹), and Saccharomyces boulardii (1.5 × 10⁹). The primary outcome was the development of postoperative complications in the first 30 days. The study was stopped prematurely due to efficacy in the probiotic group. Compared with placebo, the probiotic significantly decreased the incidence of all major postoperative complications (28.6% vs. 48.8%; p = 0.01), postoperative pneumonia (2.4% vs. 11.3%; p < 0.03), surgical site infections (7.1% vs. 20.0%; p = 0.02), and anastomotic leakage (1.2% vs. 8.8%; p = 0.03).

Comment

: In this study, administration of a multistrain probiotic preparation prevented postoperative complications in patients undergoing colorectal surgery for cancer. Probiotics may work by enhancing immune function and by promoting earlier postoperative recovery of bowel function (thereby decreasing translocation of bacteria from the gut).

Kotzampassi K et al. A four-probiotics regimen reduces postoperative complications after colorectal surgery: a randomized, double-blind, placebo-controlled study. World J Surg. 2015;39:2776–2783.

Quercetin Lowers Uric Acid Levels

Twenty-two healthy males (aged 19–60 years) with a plasma uric acid level in the high-normal range were randomly assigned to receive, in double-blind fashion, 500 mg of quercetin or placebo once a day for 4 weeks. After a 4-week washout period, each person received the alternate treatment for an additional 4 weeks. Compared with baseline, the mean plasma uric acid level fell by 7.9% with quercetin (p < 0.01) and increased by 1.6% with placebo.

Comment

: Xanthine oxidase is an enzyme that plays a role in the biosynthesis of uric acid. Quercetin has been found to inhibit bovine xanthine oxidase in vitro, with an apparent Km of 3.2 µmol/L. That concentration is only about twice as high as the plasma quercetin level attained when healthy volunteers ingested 220 g per day of onions (providing 114 mg per day of quercetin) for 7 days. Thus, the dosage of quercetin used in the present study (500 mg per day) might produce a plasma quercetin concentration high enough to decrease uric acid production. Although the decrease in plasma uric acid levels observed in this study was only modest, quercetin supplementation could be a useful adjunct to dietary modifications for people with elevated uric acid levels. The possibility that larger doses of quercetin would have a greater effect warrants investigation.

Shi Y, Williamson G. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial. Br J Nutr. 2016;115:800–806.

Pruning Bone Loss

Forty-eight women (aged 65–79 years) with osteopenia were randomly assigned to receive 50 g per day of dried plums (equivalent to 5 or 6 dried plums), 100 g per day of dried plums (equivalent to 10 to 12 dried plums), or no plums (control group) for 6 months. Compared with the control group, both groups receiving dried plums had significantly less total body bone loss, although the effects at specific sites (lumbar spine and hip) were not significant. The lower dose of dried plums appeared to be as effective as the higher dose. Both doses of dried plums decreased a marker of bone resorption.

Comment

: Dried plums (prunes) have previously been shown to prevent bone loss in an animal model of osteoporosis and at a dose of 100 g per day in humans. The results of the present study indicate that 50 g of dried plums per day is as effective as 100 g per day. Inflammation plays a role in bone resorption, and it is thought that dried plums decrease bone resorption by inhibiting inflammation. In addition, dried plums are rich in nutrients such as vitamin K, magnesium, and boron, all of which play a role in promoting bone health.

Hooshmand S et al. The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial. Osteoporos Int. Epub 2016 Feb 22.

Cocoa Flavanols Improve Skin Wrinkles

Sixty-two Korean women (aged 43–86 years) with moderately photoaged skin and visible facial wrinkles were randomly assigned to receive, in double-blind fashion, a daily cocoa beverage that contained 320 mg of cocoa flavanols or a placebo beverage for 24 weeks. At 24 weeks, the mean improvements in wrinkles and skin elasticity were significantly greater in the cocoa group than in the placebo group.

Comment

: In this study, regular consumption of cocoa flavanols had a positive effect on facial wrinkles and skin elasticity in Korean women. That amount of cocoa flavanols would be present in 50 to 340 g per day of dark chocolate, depending on the type of dark chocolate. Milk chocolate would not be expected to be as effective as dark chocolate, because the presence of milk may inhibit the absorption of cocoa flavanols.

Yoon HS et al. Cocoa flavanol supplementation influences skin conditions of photo-aged women: a 24-week double-blind, randomized, controlled trial. J Nutr. 2016;146:46–50.

Does Niacin Cause Diabetes?

A meta-analysis was conducted on 11 randomized controlled trials (including a total of 26,340 nondiabetic participants) that examined the effect of niacin therapy (1–4 g per day) on the incidence of diabetes. All of the studies enrolled patients who either had or were at increased risk of developing cardiovascular disease. During a mean follow-up period of 3.6 years, niacin therapy was associated with a significant 34% increase in incidence of diabetes. This equated to 1 additional case of diabetes per 43 initially nondiabetic individuals treated with niacin for 5 years. Results were consistent regardless of whether participants received statin therapy.

Comment

: Niacin has been used to decrease serum cholesterol levels in patients at risk of developing cardiovascular disease. It is unpopular with patients, because it frequently causes an uncomfortable skin flush. In addition, a recent study found that the addition of extended-release niacin to statin therapy increased the risk of ischemic stroke in patients with cardiovascular disease, low HDL cholesterol, and high triglycerides. The results of the new meta-analysis indicate that niacin also increases the incidence of diabetes in patients who have or are at increased risk of developing cardiovascular disease. For these and other reasons, niacin is no longer widely used to prevent heart disease.

However, niacin may also have value in the treatment of schizophrenia, senile dementia, and some other conditions. It is not known whether niacin increases the risk of diabetes in patients with these conditions, but blood glucose levels should be monitored in patients being treated with large doses of niacin. Niacinamide, which is reportedly beneficial in the treatment of osteoarthritis, anxiety, type 2 diabetes, schizophrenia, and various skin conditions, does not appear to increase the risk of developing diabetes.

Goldie C et al. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials. Heart. 2016;102:198–203.

Vitamin D, Asthma, and Colds: Caution with African Americans

Four hundred eight adults with mild-to-moderate asthma, a plasma 25-hydroxyvitamin D (25[OH]D) level less than 30 ng/ml, and asthma symptoms despite treatment with an inhaled glucocorticoid were randomly assigned to receive, in double-blind fashion, vitamin D3 (100,000 IU as a bolus, followed by 4,000 IU per day) or placebo for 28 weeks, while tapering the inhaled glucocorticoid. Two hundred three participants experienced at least one cold during the study. Despite achieving a mean 25(OH)D level of 41.9 ng/ml, vitamin D supplementation had no effect on scores on the Wisconsin Upper Respiratory Symptom Survey. The rate of colds was nonsignificantly higher in the vitamin D group than in the placebo group (1.48 vs. 1.24 colds per person per year; p = 0.15). Among African Americans, the rate of colds was significantly higher by 70% in the vitamin D group than in the placebo group (p = 0.02).

Comment

: These findings indicate that supplementation with relatively large doses of vitamin D did not prevent colds in patients with poorly controlled asthma. To the contrary, colds tended to occur more frequently in patients receiving vitamin D than those receiving placebo. Among African Americans, this increase in frequency of colds was statistically significant. Previous research has shown that vitamin D metabolism and vitamin D requirements may differ between blacks and whites. In addition, a 25(OH)D concentration that indicates vitamin D deficiency in whites may indicate normal vitamin D status in blacks, because of differences between whites and blacks in concentrations of vitamin D-binding protein. The results of the present study support previous research suggesting that aggressive vitamin D supplementation may do more harm than good in African Americans.

Denlinger LC et al. Vitamin D supplementation and the risk of colds in patients with asthma. Am J Respir Crit Care Med. 2016;193:634–641.