Literature Review and Commentary

by Alan R. Gaby, MD

Probiotic for Diverticular Disease

Two hundred ten patients (median age, 62 years) with symptomatic, uncomplicated diverticular disease in remission were randomly assigned to receive, in double-blind fashion, 1600 mg per day of mesalazine, Lactobacillus casei subsp. DG (24 billion organisms per day), both treatments, or placebo. The treatments were administered the first 10 days of each month for 12 months. A recurrence was defined as the reappearance of abdominal pain with a rating of at least 5 on a scale of 10, with higher numbers indicating worse symptoms. The proportion of patients who had a recurrence was 0% with combination therapy, 13.7% with mesalazine, 14.5% with the probiotic, and 46% with placebo (p < 0.001 for probiotic vs. placebo; p < 0.01 for mesalazine plus probiotic vs. mesalazine alone). Acute diverticulitis occurred in 6 patients receiving placebo and in 1 patient receiving the probiotic (p = 0.003).

Comment

: Patients with diverticular disease have been found to have a decrease in healthy colonic bacterial flora and an increase in the number of pathogenic bacteria. It has been suggested that these changes may promote inflammation and an increase in epithelial cell proliferation in the colonic mucosa. These results of the present study indicate that L. casei subsp. DG was effective for maintaining remission of symptomatic, uncomplicated diverticular disease, and that the combination of the probiotic and mesalazine was more effective than the probiotic by itself.

Tursi A et al. Randomised clinical trial: mesalazine and/or probiotics in maintaining remission of symptomatic uncomplicated diverticular disease – a double-blind, randomised, placebo-controlled study. Aliment Pharmacol Ther. 2013;38:741–751.

Probiotic Prevents Dental Caries and Gingivitis

One hundred thirteen mother-child pairs were randomly assigned to receive, in single-blind fashion, the probiotic Lactobacillus reuteri strain ATCC 55730 (derived from breast milk) or placebo. The mothers received 5 drops of oil daily (containing 10⁸ colony-forming units) during the last month of gestation, and the children received the same daily dose during the first year of life. At 9 years of age, the proportion of children who were free of dental caries was significantly higher in the probiotic group than in the placebo group (82% vs. 58%; p < 0.01). In addition, there were fewer sites with gingivitis in the probiotic group than in the placebo group (p < 0.05). There was no difference between groups in the concentration of Streptococcus mutans (an organism that promotes the development of dental caries).

Comment

: These results demonstrate that daily administration of L. reuteri strain ATCC 55730 during the last 4 weeks of pregnancy and the first year of the child’s life resulted in a decrease in caries prevalence and less gingivitis at 9 years of age. The probiotic presumably worked by altering the oral flora, although it did not influence the concentration of S. mutans. Studies using xylitol gum have shown that the best results are obtained when treatment is begun before the child’s teeth have erupted. If that is also the case with probiotics, then treatment should be started early in life, as was done in the present study.

Stensson M et al. Oral administration of Lactobacillus reuteri during the first year of life reduces caries prevalence in the primary dentition at 9 years of age. Caries Res. 2014;48:111–117.

Pantethine Lowers Serum Cholesterol

Thirty-two patients (mean age, 51 years) at low-to-moderate cardiovascular disease risk who were eligible for statin therapy according to the National Cholesterol Education Program guidelines were randomly assigned to receive, in double-blind fashion, pantethine (300 mg twice a day for 8 weeks, then 300 mg 3 times per day for 8 weeks) or placebo. The mean serum LDL-cholesterol level decreased by 11% after 16 weeks in the pantethine group and increased by 3% in the placebo group (p = 0.01 for the difference in the change between groups). The decrease in LDL-cholesterol levels compared with placebo was also significant in the pantethine group after 8 weeks (p < 0.03).

Comment

: Pantethine is the stable disulfide form of pantetheine, a biologically active form of pantothenic acid. As a precursor to coenzyme A, pantethine plays a role in fat metabolism. Pantethine also inhibited HMG-CoA reductase activity in isolated rat hepatocytes, an effect that mirrors that of statin drugs (Cighetti G et al. Effects of pantethine on cholesterol synthesis from mevalonate in isolated rat hepatocytes. Atherosclerosis. 1986;60:67–77). Several previous studies, mostly uncontrolled, have shown that pantethine supplementation can lower LDL-cholesterol levels, a finding that was confirmed in the present randomized controlled trial. Pantethine has also been reported previously to decrease triglyceride levels and to increase HDL-cholesterol levels. Pantethine is generally well tolerated and has not been reported to cause serious side effects. However, unlike with statin drugs, there have been no long-term studies to determine whether lowering lipid levels with pantethine decreases the incidence of cardiovascular disease. Pantothenic acid, despite being structurally similar to pantethine, has no effect on lipid levels.

Evans M et al. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation. Vasc Health Risk Manag. 2014;10:89–100.

Human Milk for Diaper Rash

One hundred forty-one Iranian infants (mean age, 4.6 months) with mild-to-moderate acute diaper dermatitis were randomly assigned to apply sparingly 1% hydrocortisone ointment or human breast milk twice a day for 7 days. The breast milk used was the hind milk (the milk at the end of the feed that is higher in fat content). Marked improvement was seen in both groups, and improvement was similar between groups.

Comment

: This study demonstrates that topical application of human breast milk is as effective as topical hydrocortisone for the treatment for diaper rash in infants. The mechanism of action is not known.

Farahani LA et al. Comparison of the effect of human milk and topical hydrocortisone 1% on diaper dermatitis. Pediatr Dermatol. 2013;30:725–729.

N-Acetylcysteine Prevents Exacerbations in Chronic Obstructive Pulmonary Disease

One thousand and six Chinese patients (mean age, 66 years) with moderate-to-severe chronic obstructive pulmonary disease (COPD) were randomly assigned to receive, in double-blind fashion, 600 mg of N-acetylcysteine (NAC) twice a day or placebo for 1 year. The mean number of exacerbations per patient was significantly lower in the NAC group than in the placebo group (1.16 vs. vs. 1.49; 22% decrease; p = 0.001).

Comment

: NAC is a precursor to glutathione, one of the major antioxidants in lung tissue. NAC also functions as a mucolytic agent when given by inhalation. The extent to which this effect occurs after oral administration is not clear, although orally administered NAC has been shown to enhance the clearance of mucus by the pulmonary cilia. The results of the present study demonstrate that treatment with NAC can prevent disease exacerbations in patients with moderate-to-severe COPD. Most, but not all, previous research has found a similar effect of NAC.

Zheng JP et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014;2:187–194.

Interpreting Negative Research

One hundred sixty adults with recurrent aphthous ulcers (canker sores) were randomly assigned to receive, in double-blind fashion, a daily multivitamin providing the US reference daily intake for vitamins A, B complex, C, D, and E or placebo for 1 year. The mean number of new episodes of aphthous ulcerations was nonsignificantly lower by 9% in the multivitamin group than in the placebo group (4.19 vs. 4.60 episodes; p = 0.69). The mean duration of new episodes was also nonsignificantly lower by 3.7% in the multivitamin group than in the placebo group (8.66 vs. 8.99 days; p = 0.60). The authors concluded that supplementation with a daily multivitamin did not decrease the number or duration of recurrent aphthous stomatitis episodes.

Comment

: Many low-potency multivitamin supplements on the market contain artificial coloring agents and other additives to which some individuals are allergic or sensitive. I wrote to the author of this study, to ask what additives were present in the multivitamin used in the study. He replied that the multivitamin contained artificial coloring agents, whereas the placebo was pure lactose. According to some investigators and to my clinical experience, food allergy is one of the most common triggering factors for aphthous ulcers. The presence of allergens in the multivitamin may therefore have masked a beneficial effect of the vitamins. Previous research suggests that several different nutrients, including B vitamins and iron, can reduce the recurrence rate of aphthous ulcers.

Lalla RV et al. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012;143:370–376.

Iron Depletion Improves Nonalcoholic Fatty Liver Disease

Thirty-eight patients (mean age, 54 years) with severe nonalcoholic fatty liver disease and elevated serum ferritin levels (250 ng/ml or higher) were randomly assigned to lifestyle changes plus iron depletion by phlebotomy (n = 21) or to lifestyle changes alone (control group; n = 17). Iron depletion was achieved by removing 350 ml of blood every 10-15 days according to baseline hemoglobin values and venesection tolerance, until the ferritin level was less than 30 ng/ml and/or transferrin saturation was less than 25%. Among the 21 patients who followed the program, the proportion of patients who had histological improvement was higher (67% vs. 22%; p < 0.04) and the degree of improvement in steatosis grade was greater (p = 0.02) in the iron-depletion group than in the control group. Among the 35 patients who were followed up at 2 years, serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase) were lower in iron-depleted than in control patients (p < 0.05).

Comment

: Elevated serum ferritin levels with mild hepatic iron accumulation is seen in 20% to 30% of patients with nonalcoholic fatty liver disease who are referred to specialty clinics. Iron overload directly induces liver damage and plays a role in the pathogenesis of metabolic syndrome by promoting insulin resistance. The results of the present study suggest that iron depletion by phlebotomy enhances the beneficial effects of lifestyle changes in patients with nonalcoholic fatty liver disease and iron overload (as indicated by elevated serum ferritin levels). Other, less invasive, ways to decrease iron overload are to avoid red meat and to consume foods and beverages that inhibit iron absorption (such as coffee, tea, and soy products).

Valenti L et al. A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia. World J Gastroenterol. 2014;20:3002–3010.

Another Benefit of Chewing Your Food

Forty-five volunteers (aged 18–45 years) were asked to attend 3 test sessions to eat pizza for lunch until comfortably full by chewing each portion of food either 100%, 150%, or 200% of their usual number of chews before swallowing. Food intake in the sessions with 150% and 200% of the usual number of chews was reduced significantly, by 9.5% and 14.8%, respectively, compared with the 100% session. Increasing the number of chews also prolonged meal duration and reduced the eating rate.

Comment

: These results suggest that increasing the number of chews before swallowing may reduce food intake and potentially help prevent obesity. Chewing food thoroughly also stimulates the secretion of saliva, which contains factors that help prevent the development of dental caries and other factors that help protect the esophagus from the deleterious effects of acid reflux. There is truth to the old saying that “Nature will castigate those who do not masticate.”

Zhu Y, Hollis JH. Increasing the number of chews before swallowing reduces meal size in normal-weight, overweight, and obese adults. J Acad Nutr Diet. 2014;114:926–931.