Literature Review and Commentary

by Alan R. Gaby, MD

Some People Are Especially Susceptible to Vitamin D Toxicity

Six infants with idiopathic hypercalcemia were found to have recessive mutations in the CYP24A1 gene, which encodes 25-hydroxyvitamin D 24-hydroxylase, the key enzyme involved in the degradation of 1,25-dihydroxyvitamin D. CYP24A1 mutations were also identified in a second cohort of infants in whom severe hypercalcemia had developed after supplementation with a bolus dose of vitamin D. All CYP24A1 mutations that were identified resulted in complete loss of function of the vitamin D-metabolizing enzyme.

Comment

: About 200 cases of idiopathic infantile hypercalcemia were reported in Britain in the 1950s during a period of high vitamin D supplementation (up to 4000 IU per day) in fortified milk products. Manifestations included failure to thrive, vomiting, dehydration, fever, and nephrocalcinosis. However, most infants receiving high-dose vitamin D had no adverse effects. Idiopathic infantile hypercalcemia appears to be inherited as an autosomal recessive trait. The results of the present study suggest that otherwise healthy infants with CYP24A1 mutations have increased susceptibility to vitamin D toxicity. Several months ago in this column, I reviewed a report from Pediatrics, in which 3 children developed hypercalcemia and an elevated 25-hydroxyvitamin D concentration after receiving vitamin D in doses that were within accepted guidelines and believed to be safe. Although only a small proportion of the population is at increased risk of developing vitamin D toxicity, practitioners prescribing vitamin D should be aware of its potential to cause harm.

Schlingmann KP et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365:410–421.

Saw Palmetto Improves Sexual Function in Men with BPH

Eighty-two men with benign prostatic hyperplasia (BPH) received, in open-label fashion, 320 mg per day of a saw palmetto extract (containing 86% fatty acids) for 8 weeks. Compared with baseline, the mean International Prostate Symptom Score improved by 52% (p < 0.0001). In addition, the mean score on the brief Sexual Function Inventory (a measure of sexual dysfunction) improved significantly (p < 0.0001). A correlation was observed between improved BPH symptoms and reduced sexual dysfunction.

Comment

: In elderly men, BPH is a major risk factor for sexual dysfunction. Moreover, standard treatments for BPH symptoms, such as alpha blockers and 5alpha-reductase inhibitors, can cause sexual dysfunction. Saw palmetto extracts have been used for many years to treat BPH symptoms. While the results of research have been conflicting, most studies have shown a beneficial effect. One advantage of saw palmetto over prescription drugs is that the former does not cause sexual dysfunction, and may actually improve sexual function. Controlled trials are needed to rule out the possibility that the improvement in sexual function observed in the present study was due to a placebo effect.

Suter A et al. Improving BPH symptoms and sexual dysfunctions with a saw palmetto preparation? Results from a pilot trial. Phytother Res. Epub 2012 Apr 23.

Probiotic Gum for Bad Breath

Twenty-five healthy young adults with self-reported malodorous morning breath were randomly assigned, in double-blind fashion, to chew 1 piece of gum in the morning and 1 in the evening containing either 2 strains of probiotic lactobacilli (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289, each at a concentration of 10⁸ colony-forming per piece) or placebo for 2 weeks. After a 3-week washout period, each subject chewed the other gum for an additional 2 weeks. The gum was chewed for 10 minutes, at least 1 hour after food intake. Malodor was assessed by certified organoleptic judges. After 14 days, malodor was significantly less with probiotics than with placebo (p < 0.05). The effect size was modest.

Comment

: The results of this study indicate that chewing a probiotic-containing gum had a beneficial effect on morning bad breath. The mechanism of action was not determined, but it is presumably due to a change in the oral bacterial flora. Further research is needed to determine whether other probiotic strains would have a similar effect.

Keller MK et al. Effect of chewing gums containing the probiotic bacterium Lactobacillus reuteri on oral malodour. Acta Odontol Scand. 2012;70:246–250.

Magnesium Lozenges Prevent Postoperative Sore Throat

Seventy patients undergoing orthopedic surgery were randomly assigned to receive, in double-blind fashion, a placebo or magnesium lozenge 30 minutes preoperatively. The lozenge contained 100 mg of magnesium (as magnesium citrate) and was dissolved in the mouth. The incidence of sore throat at 2 hours (23% vs. 57%; p = 0.007) and at 4 hours (14% vs. 40%; p = 0.032) postoperatively was significantly lower in the magnesium group than in the placebo group. The severity of sore throat was also significantly lower in the magnesium group than in the placebo group at 0 hours and 2 hours postoperatively, and was nonsignificantly lower at 4 hours.

Comment

: Postoperative sore throat is a complication of orotracheal intubation. Magnesium is a noncompetitive N-methyl-D-aspartate receptor antagonist that is thought to be involved in the modulation of pain. The results of the present study demonstrate that the administration of a magnesium lozenge 30 minutes preoperatively can reduce the incidence and severity of sore throat in the immediate postoperative period.

Borazan H et al. Oral magnesium lozenge reduces postoperative sore throat: a randomized, prospective, placebo-controlled study. Anesthesiology. 2012;117:512–518.

Omega-3 Fatty Acids for Tourette’s Syndrome

Thirty-three children and adolescents (aged 6–18 years) with Tourette’s syndrome were randomly assigned to receive, in double-blind fashion, omega-3 fatty acids (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA] in a 2:1 ratio) or placebo (olive oil) for 20 weeks. The initial dosage of EPA + DHA was 500 mg per day; this was increased gradually, according to clinical response and tolerance, to a potential maximum of 6 g per day. A response for tic symptoms was defined as an improvement of 30% or more on the primary Yale Global Tic Severity Scale (YGTSS)-Tic and secondary YGTSS-Global and YGTSS-Impairment scores. After 20 weeks, the response rate according to YGTSS-Tic score was nonsignificantly higher in the active-treatment group than in the placebo group (53% vs. 38%; p > 0.1), whereas the response rates according to the YGTSS-Global measure (53% vs. 31%; p = 0.05) and YGTSS-Impairment measure (59% vs. 25%; p < 0.05) were significantly higher in the active-treatment group than in the placebo group.

Comment

: Tourette’s syndrome is characterized by motor and vocal tics. It typically begins during childhood and improves spontaneously when the child becomes an adult. People with this condition also frequently suffer from obsessive-compulsive disorder and attention deficit disorder. The cause of Tourette’s syndrome is unknown. Conventional therapy includes neuroleptic drugs such as haloperidol or pimozide. The results of the present study suggest that omega-3 fatty acids can improve tic-related problems in children and adolescents with this difficult-to-treat condition.

Gabbay V et al. A double-blind, placebo-controlled trial of omega-3 fatty acids in Tourette’s disorder. Pediatrics. 2012;129:e1493–e1500.

Vitamins C and E Improve Helicobacter Eradication Rate

Two hundred Turkish patients with Helicobacter pylori infection received standard triple therapy (30 mg of lansoprazole, 1000 mg of amoxicillin, and 500 mg of clarithromycin, each twice a day for 14 days). In addition, the patients were randomly assigned to receive, in open-label fashion, in a 4:1 ratio, 500 mg of vitamin C and 200 IU of vitamin E, each twice a day for 30 days (n = 160), or no vitamin C and E (control group; n = 40). H. pylori eradication was defined as a negative urea breath test 4 to 6 weeks after the completion of therapy. In intent-to-treat analysis, the eradication rate was significantly higher in the vitamin group than in the control group (82.5% vs. 45%; p < 0.05).

Comment

: Eradication rates with currently accepted triple therapy regimens vary between geographic locations and do not exceed 70% to 80%. Eradication rates are much lower in locations such as Turkey, where there is widespread antibiotic use. The results of the present study demonstrate that adding vitamins C and E to standard triple therapy can increase the eradication rate in a population with a relatively low success rate with conventional therapy. Previous research has shown that vitamin C at a dosage of 5 g per day can inhibit H. pylori growth. Whether the mechanism of action of vitamin C and vitamin E in the present study is related to a direct effect on H. pylori or to an interaction with conventional therapy is not clear.

Sezikli M et al. Supplementing vitamins C and E to standard triple therapy for the eradication of Helicobacter pylori. J Clin Pharm Ther. 2012;37:282–285.

Omega-3 Fatty Acids for Sickle Cell Disease

One hundred forty patients in Sudan who had sickle cell disease were randomly assigned to receive, in double-blind fashion, 1 (aged 2–4 years), 2 (aged 5–10 years), 3 (aged 11–16 years), or 4 (age 17 years or older) capsules per day of omega-3 fatty acids, each capsule containing 278 mg of docosahexaenoic acid (DHA) and 39 mg of eicosapentaenoic acid (EPA), or placebo for 1 year. In intent-to-treat analysis, compared with placebo, omega-3 fatty acids decreased the median number of vasoocclusive events per year (0 vs. with 1.0; p < 0.0001), the incidence of severe anemia (3.2% vs. 16.4%; p < 0.05), and the proportion of patients who required blood transfusions (4.5% vs. 16.4%; p < 0.05). Omega-3 fatty acids also decreased by 60% the number of patients who were unable to attend school at least once during the study because of illness related to the disease (p < 0.05).

Comment

: Blood cell aggregation and adherence to vascular endothelium and inflammation play a central role in vasoocclusive crises in sickle cell disease. Omega-3 fatty acids (DHA and EPA) have antiaggregatory, antiadhesive, anti-inflammatory, and vasodilatory actions. The concentrations of DHA and EPA in red cells, platelets, and mononuclear cells are low in people with sickle cell disease. The results of the present study suggest that omega-3 fatty acids are beneficial for patients with this disease.

Daak AA et al. Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2013;97:37–44.

Aged Garlic Extract for Colds and Influenza

One hundred twenty healthy volunteers (mean age, 26.5 years) were randomly assigned to receive, in double-blind fashion, 2.56 g per day of aged garlic extract powder (Wakanuga of America, Mission Viejo, CA) or placebo for 90 days. The incidence of colds and influenza (45% vs. 55%; p = 0.442) and the total number of days with symptoms (317 vs. 358; p = 0.132) were nonsignificantly lower in the aged garlic extract group than in the placebo group. The total number of days on which subjects felt too ill to function was significantly lower by 58% in the aged garlic extract group than in the placebo group (53 vs. 126; p < 0.001). In addition, compared with placebo, aged garlic extract improved certain measures of immune function.

Comment

: In earlier research, various garlic preparations demonstrated antiviral, antibacterial, and antifungal activity, and also enhanced immune function. In the present study, administration of aged garlic extract decreased the severity of colds and influenza in healthy volunteers. The chemical composition of aged garlic extract differs from that of fresh garlic, because the aging process results in the conversion of naturally occurring sulfur-containing compounds into other sulfur-containing compounds. Allicin, which is present in relatively high concentrations in fresh garlic extracts, has been reported to kill human rhinovirus in vitro. In a previous double-blind trial, a garlic preparation with a high allicin content decreased the incidence of the common cold by about two-thirds. Aged garlic extracts contain relatively low amounts of allicin, so it is presumed that other compounds formed during the aging process exerted a beneficial effect. Further research is needed to determine which garlic preparations are most effective for preventing and treating colds and influenza.

Nantz MP et al. Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention. Clin Nutr. 2012;31:337–344.