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Literature review & commentary.

Selenium for Recurrent Hyperthyroidism

Forty-one patients with recurrent Graves' disease who had been receiving antithyroid medication (methimazole) for at least two years were randomly assigned to receive selenium (100 [micro]g twice a day as sodium selenite) or no selenium (controls) for six months. Patients treated with radioactive iodine or thyroidectomy were excluded. At two months, mean values for free thyroxine and free triiodothyronine had decreased to a significantly greater extent, and the mean TSH value had increased to a significantly greater extent, in the selenium group than in the control group. At six months, the proportion of patients who had normal anti-TSH-receptor antibody levels was significantly higher in the selenium group than in the control group (19% vs. 0%; p < 0.02). During a median follow-up period of 19.5 months, the remission rate was higher in the selenium group than in the control group (52% vs. 25%; p = 0.07).

Comment: Selenium has been reported to have a number of different beneficial effects on thyroid disease. In some, but not all studies, selenium supplementation decreased anti-thyroid peroxidase antibody levels in patients with autoimmune thyroiditis. In addition, selenium supplementation improved quality of life, reduced ocular involvement (orbitopathy), and slowed disease progression in euthyroid patients with mild Graves' orbitopathy (Marcocci C, et al. Selenium and the course of mild Graves' orbitopathy. N Engl J Med. 2011;364:1920-1931.) In the present study, selenium supplementation enhanced the effect of antithyroid drugs in patients with recurrent Graves' disease.

Wang L, et al. Effect of selenium supplementation on recurrent hyperthyroidism caused by Graves' disease: a prospective pilot study. Harm Metab Res. 2016;48:559-564.

N-Acetylcysteine for Obsessive-Compulsive Disorder

Forty-four patients (mean age, 33 years) with moderate-to-severe obsessive-compulsive disorder (OCD) were treated with 200 mg per day of fluvoxamine and were randomly assigned to receive, in double-blind fashion, 2,000 mg per day of N-acetylcysteine (NAC) or placebo for 10 weeks. Compared with placebo, NAC significantly improved the mean total score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (p = 0.012) and the mean score on the Y-BOCS obsession subscale (p = 0.011).

Comment: Hyperactivity of glutamatergic neurotransmission has been implicated in the pathogenesis of OCD. NAC is believed to reduce glutamatergic activity. In previous case reports and double-blind trials, NAC was beneficial in the treatment of OCD, including patients with trichotillomania (hair-pulling disorder). The results of the present study demonstrate that NAC is beneficial as an adjunct to fluvoxamine in the treatment of moderate-to-severe OCD.

Paydary K, et al. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther. 2016;41:214-219.

Vitamin D for Autistic Children

One hundred nine Egyptian children (aged 3-10 years) with autism spectrum disorder were randomly assigned to receive, in double-blind fashion, vitamin [D.sub.3] (300 IU per kg of body weight per day, with a maximum of 5,000 IU per day) or placebo for four months. Autism severity and social maturity were assessed by the Childhood Autism Rating Scale, Aberrant Behavior Checklist, Social Responsiveness Scale, and Autism Treatment Evaluation Checklist. The mean serum 25-hydroxyvitamin D level prior to treatment was 27 ng/ml. Compared with placebo, vitamin D significantly improved symptoms of autism, including irritability, hyperactivity, social withdrawal, inappropriate speech, stereotypical behavior, and communication. No significant side effects occurred.

Comment: In this study, vitamin D supplementation improved symptoms of autism in Egyptian children. Prior to vitamin D supplementation, the mean serum 25-hydroxyvitamin D level was 27 ng/ml. The appropriate 25-hydroxyvitamin D cut-off level for diagnosing vitamin D deficiency, and the reliability of serum 25-hydroxyvitamin D as an indicator of vitamin D status remain controversial. However, it appears that it is not necessary for autistic children to have severe vitamin D deficiency in order for them to benefit from vitamin D supplementation. Further research is needed to confirm the safety and efficacy of the relatively large dose of vitamin D used in this study.

Saad K, et al. Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. J Child Psychol Psychiatry. 2016 Nov 21 [Epub ahead of print].

Mediterranean Diet Improves Sexual Function in People with Type 2 Diabetes

Two hundred fifteen men and women (mean age, 52 years) with newly diagnosed type 2 diabetes were randomly assigned to consume a Mediterranean diet or a low-fat diet. The primary outcome measures were changes of erectile function according to the International Index of Erectile Function (IIEF) in men, and changes in female sexual function according to the Female Sexual Function Index (FSFI) in women. During a total follow-up of 8.1 years, sexual function decreased slightly in both sexes with both diets. The mean decline in the IIEF score was significantly less by 1.22 points (p = 0.024) and the mean decline in the FSFI score was significantly less by 1.18 points (p < 0.02) with the Mediterranean diet than with the low-fat diet.

Comment: The "Mediterranean diet" refers to the diet of olive-growing regions of the Mediterranean. In addition to olive oil, the diet emphasizes salads, legumes, wheat, fruit, nuts, and garlic. In Italy, a lot of pasta is consumed; whereas in Spain, fish consumption is high. Fat intake is around 30-40% of total energy. The results of the present study suggest that consumption of a Mediterranean diet can decrease the deterioration of sexual function in both men and women with newly diagnosed type 2 diabetes. While the mechanism of action is not certain, a Mediterranean diet may help preserve sexual function by improving cardiovascular function and overall health.

Maiorino Ml, et al. Effects of Mediterranean diet on sexual function in people with newly diagnosed type 2 diabetes: The MEDITA trial. J Diabetes Complications. 2016;30:1519-1524.

Mediterranean Diet for Fracture Prevention?

The association between consumption of a Mediterranean diet and incidence of hip fracture was examined in two Swedish cohort studies consisting of 37,903 men and 33,403 women who were free of cardiovascular disease and cancer and who answered a food-frequency questionnaire in 1997. A modified Mediterranean diet score (mMED; range, 0-8 points) was created based on high consumption of fruits and vegetables, legumes and nuts, whole grains, fermented dairy products, fish, and olive/rapeseed oil; moderate intake of alcohol; and low intake of red and processed meat. During a 15-year follow-up period, 3,175 hip fractures occurred at a median age of 73.3 years. A 1-unit increase in the mMED score was associated with a 6% lower hip fracture rate (adjusted hazard ratio = 0.94; 95% confidence interval [CI], 0.92-0.96). Comparing the highest quintile of adherence to the mMED (6-8 points) with the lowest quintile (0-2 points), the adjusted hazard ratio of hip fracture was 0.78 (95% CI, 0.69-0.89), indicating a 22% reduction in fracture incidence. Results were similar in men and women.

Comment: Although observational studies cannot prove causation, this study raises the possibility that adherence to a Mediterranean diet can decrease the risk of hip fracture in both men and women. Mediterranean diets contain abundant amounts of micronutrients that play a role in promoting bone health, including magnesium, B vitamins, boron, and vitamin K.

Byberg L, et al. Mediterranean diet and hip fracture in Swedish men and women. J Bone Miner Res. 2016;31:2098-2105.

Whole Grains, Heart Disease, Cancer, and Mortality

A meta-analysis was conducted on 14 prospective cohort studies (including a total of 786,076 participants) that examined the association between intake of whole grains and mortality from all causes, cardiovascular disease, and cancer. Pooled relative risks comparing the highest and lowest categories of whole grain intake were 0.84 (p < 0.001) for total mortality, 0.82 (p < 0.001) for cardiovascular disease mortality, and 0.88 (p < 0.001) for cancer mortality. For each 16-g per day increase in intake of whole grains (about 1 serving per day), relative risks for total, cardiovascular disease, and cancer mortality were 0.93 (p < 0.001), 0.91 (p < 0.001), and 0.95 (p < 0.001), respectively.

Comment: This meta-analysis of observational studies found that increasing intake of whole grains was associated with lower overall mortality and a lower incidence of death from cardiovascular disease and cancer. Substances present in whole grains that might decrease the risk of heart disease, cancer, or both, include fiber, magnesium, vitamin E (mixed tocopherols), betaine, and B vitamins. A substantial proportion of each of these substances is lost when whole grains are refined to white flour.

Zong G, et al. Whole grain intake and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies. Circulation. 2016; 133:2370-2380.

Melatonin for Premedication Prior to Anesthesia

Ninety-two children (aged 5-14 years) scheduled for elective surgery were randomly assigned to receive, in double-blind fashion, premedication with oral melatonin (0.5 mg per kg) or oral midazolam (0.5 mg per kg), 40 minutes before induction of anesthesia with propofol. Compared with midazolam, melatonin significantly decreased the dose of propofol required to induce anesthesia. No significant difference was found between groups with respect to pre- and post-anesthesia sedation, which suggests that melatonin is as effective as midazolam.

Comment: Midazolam is widely used prior to induction of anesthesia in both adults and children. Midazolam has a number of side effects including paradoxical reactions, interactions with opioids, variable bioavailability and elimination half-life, excessive sedation, disorientation, impaired psychomotor performance, and amnesia. Melatonin is recognized as an effective alternative to midazolam in adults, but data regarding its use in children are conflicting. The results of the present study demonstrate that premedication with melatonin can increase the potency of propofol, and that melatonin is an effective alternative to midazolam in children undergoing elective surgery. Use of melatonin as premedication instead of midazolam could decrease the number of adverse reactions in patients undergoing anesthesia.

Gitto E, et al. Melatonin versus midazolam premedication in children undergoing surgery: A pilot study. J Paediatr Child Health. 2016;52:291-295.

Vitamins B6 and B12 Decrease the Concentration of Unmetabolized Folic Acid

Fifty-eight elderly individuals (mean age, 82 years) were randomly assigned to receive, in single-blind fashion, 400 [micro]g per day of folic acid or folic acid plus 8 mg per day of pyridoxine and 10 [micro]g per day of vitamin B12 for a median duration of 23 days. After supplementation, the median concentration of unmetabolized folic acid was significantly lower by 72% in the group receiving all three B vitamins than in those receiving folic acid alone (0.17 vs. 0.61 nmol/L; p = 0.001). The proportion of individuals who had an unmetabolized folic acid concentration of 0.21 nmol/L or greater was lower in the group receiving all three B vitamins than in those receiving folic acid alone (33% vs. 76%; p value not stated).

Comment: Unmetabolized folic acid is frequently present in the serum of people taking folic acid supplements and in elderly people receiving folic acid-fortified foods or supplements. Concerns have been raised that unmetabolized folic acid could have deleterious effects on health. However, there is as yet no convincing evidence that unmetabolized folic acid is harmful. The results of the present study suggest that the metabolism of folic acid depends on the presence of adequate amounts of other B vitamins. The clinical significance of these findings remains to be determined.

Obeid R, et al. Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial. Eur J Nutr. 2016;55:1021-1028.


by Alan R. Gaby, MD
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Title Annotation:treating hyperthyroidism with selenium; treating obsessive compulsive disorder with N-acetylcysteine; and managing autism with vitamin D
Author:Gaby, Alan R.
Publication:Townsend Letter
Date:Jun 1, 2017
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