Literature review & commentary.
Subject: Weight loss (Methods)
Melatonin (Health aspects)
Delirium (Care and treatment)
Enterocolitis, Neonatal necrotizing (Prevention)
Enterocolitis, Pseudomembranous (Prevention)
Probiotics (Health aspects)
Author: Gaby, Alan R.
Pub Date: 02/01/2012
Publication: Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464
Issue: Date: Feb-March, 2012 Source Issue: 343-344
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 282825216
Full Text: Alpha-Lipoic Acid Promotes Weight Loss

Three hundred sixty obese individuals (mean age, 41 years; mean body mass index, 33.2 kg/[m.sub.2]) were randomly assigned to receive, in double-blind fashion, alpha-lipoic acid (ALA; 1200 or 1800 mg per day) or placebo for 20 weeks. Among the 228 individuals who completed the trial, mean weight loss was 0.94 kg (1.03% of body weight) with placebo, 1.49 kg (1.65% of body weight) with 1200 mg per day of ALA, and 2.76 kg (3.04% of body weight) with 1800 mg per day of ALA (p < 0.05 for 1800 mg of ALA vs. placebo). Percent loss of fat mass in the 3 groups paralleled percent loss of body weight, which suggests that weight loss was due largely to loss of fat mass. Urticaria and itching sensation (usually mild and transient) occurred in 3% to 8% of patients receiving ALA.

Comment: ALA is a cofactor for mitochondrial respiratory enzymes, and improves mitochondrial function. In previous research, ALA prevented the development of obesity in rodents by reducing food intake and increasing energy expenditure. The results of the present study indicate that treatment with ALA results in a modest amount of weight loss in obese people.

Koh EH etal. Effects of alphd-lipoic acid on body weight in obese subjects. Am I Med. 2011; 124:85. e1-85.e8.

Melatonin for Delirium

One hundred forty-five elderly patients (mean age, 84.5 years) who were admitted to a hospital medical unit through the emergency department were randomly assigned to receive, in double-blind fashion, 0.5 mg of melatonin or placebo every night for 14 days or until discharge. The primary outcome measure was the occurrence of delirium, as determined by Confusion Assessment Method (CAM) criteria. The proportion of patients who experienced delirium during hospitalization was significantly lower in the melatonin group than in the placebo group (12% vs. 31%; p = 0.014). Results were similar after exclusion of the 14 patients who had delirium at the time of admission.

Comment: Delirium complicates hospitalization in at least 20% of patients aged 65 years or older. It is associated with increased morbidity and mortality and increased health-care costs. While the cause of delirium is multifactorial, most cases are associated with an imbalance of neurotransmitters. In this study, administration of low-dose melatonin prevented the development of delirium in elderly hospitalized patients.

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Al-Aama T et al. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2011; 26:687-694.

Probiotics Prevent Necrotizing Enterocolitis in Very-Low-Birth-Weight Premature Infants

Two hundred thirty-one preterm infants weighing 750 to 1499 g at birth were randomly assigned to receive, in double-blind fashion, human milk with Lactobacillus casei and Bifidobacterium breve (3.5 x [10.sub.7] to 3.5 x [10.sub.9] colony-forming units once a day) or human milk alone. The treatment was begun on the second day of life and was continued until day 30. The primary outcome measure was the occurrence of necrotizing enterocolitis (NEC) stage 2 or greater, as defined by Bell's modified criteria. Four cases of NEC stage 2 or greater occurred in the control group, as compared with no cases in the active-treatment group (p = 0.05). The time until the infants achieved full enteral feeding was faster in the active-treatment group than in the control group (p = 0.02).

Comment: NEC is a serious gastrointestinal disease seen mainly in premature, very-low-birth-weight infants, and occasionally in term babies. It is characterized by necrosis of part of the intestine, which can lead to life-threatening complications. While the cause is unknown, it appears to be related to intestinal ischemia and to the presence of abnormal intestinal flora. Conventional treatments include parenteral nutrition to rest the bowel, antibiotics, and surgery. Without treatment, the mortality rate is high, especially in infants weighing less than 1500 g. Even with appropriate treatment, some infants die of the disease. The results of the present study indicate that supplementation with L. casei and B. breve can prevent NEC in very-low-birth-weight premature infants.

Braga TD et al. Efficacy of Bifidobacte.rium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birth-weight pretenn infants: a double-blind, randomized, controlled trial. Am J Clln Mar. 2011;93:81-86.

Probiotics Prevent Radiation-Induced Diarrhea

Sixty-three women undergoing pelvic radiotherapy and cisplatin treatment for cervical cancer were randomly assigned to receive, in double-blind fashion, a probiotic preparation or placebo, beginning 7 days before the start of radiotherapy and continuing daily until the end of radiotherapy. The preparation contained 2 x [10.sup.9] units of Lactobacillus acidophilus plus Bifidobacterium bifidurn per dose (equivalent to 2 capsules); 2 doses were administered per day, before breakfast and dinner. The incidence of grade 2 or 3 diarrhea was significantly lower in the active treatment group than in the placebo group (9% vs. 45%; p = 0.002). The need for antidiarrheal medication use was also significantly less in the active-treatment group than in the placebo group (p = 0.03). In addition, active treatment improved stool consistency compared with placebo (p < 0.001).

Comment: Radiation-induced diarrhea frequently occurs during pelvic radiotherapy. The results of the present study indicate that treatment with a specific probiotic preparation reduced the incidence of radiation-induced diarrhea and the need for antidiarrheal medication and improved stool consistency in women undergoing radiation therapy for cervical cancer.

Chitapanarux I et al. Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bilidurn in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radial Oncoi. 2010;5:31.

Higher Iodine Intake Associated with Thyroid Disorders

A population-based cross-sectional study was conducted among 3813 individuals in two areas of China in which iodine intake differs (Rongxing: medium urinary iodine [MUI] excretion, 261 [micro]g/L; Chengshan: MUI excretion, 145 [micro]g/L). Both communities consumed iodized salt. The difference in iodine intake was due mainly to differences in the iodine concentration of drinking water The prevalence of subclinical hypothyroidism (TSH > 4.8 mU/L with normal free T4) was significantly higher in Rongxing than in Chengshan (5.0% vs. 2.0%; p < 0.001). The prevalence of thyroperoxidase (TPO) antibodies and antithyroglobulin (Tg) antibodies was also significantly higher in Rongxing than in Chengshan (TPO: 10.6 vs. 8.4%; p = 0.02; Tg: 10.27 vs. 7.93%; p = 0.01).

Comment: In this study, higher dietary iodine intake was associated with a higher prevalence of both subclinical hypothyroidism and autoimmune thyroiditis in certain areas of China. A number of previous observational studies have reported similar findings. While observational studies cannot prove causation, the results of the new study are consistent with the clinical observation that a small proportion of patients develop thyroid disease after treatment with high doses of iodine.

Teng X et al. More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels. Eur f Endocrinol. 2011;164:943-950.

Soy Phytoestrogens May Lead to Hypothyroidism

Sixty patients (mean age, 57 years) with subclinical hypothyroidism (TSH between 5 and 15 mU/L with a normal free T4 level) were randomly assigned to receive, in double-blind fashion, 30 g per day of soy protein that contained either 2 mg of phytoestrogens (representative of a Western diet) or 16 mg of phytoestrogens (representative of a vegetarian diet) for 8 weeks. After an 8-week washout period, each patient received the alternate treatment for an additional 8 weeks. Six of the 52 females in the study progressed to overt hypothyroidism while receiving 16 mg per day of phytoestrogens, whereas no patient progressed to overt hypothyroidism while receiving 2 mg per day of phytoestrogens (p < 0.05).

Comment: The results of this study demonstrate that high-isoflavone soy protein can promote the development of overt hypothyroidism in women with subclinical hypothyroidism. Previous studies have shown that soy products have an antithyroid effect in a small proportion of the population. This antithyroid effect is due at least in part to 2 soy isoflavones (genistein and daidzein) and may be more pronounced in people with iodine deficiency than in those with normal iodine status.

Sathyapalan T et al. The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab. 2011; 96:1442-1449.

Acetyl-L-Carnitine Therapy for Hepatic Encephalopathy

One hundred twenty-one patients with overt hepatic encephalopathy (61 with HE1 [mild grade] and 60 with HE2 [moderate grade]) were randomly assigned to receive, in double-blind fashion, 2 g of ALC or placebo twice a day for 90 days. In the HE1 group, compared with placebo, ALC significantly improved mental fatigue (p < 0.05), fatigue severity (p < 0.001), the 7-day Physical Activity Recall questionnaire score (p < 0.001), and Short Physical Performance Battery (p < 0.001). In the HE2 group, compared with placebo, ALC significantly improved fatigue severity (p < 0.001) and the 6-minute walk test (p < 0.05). The mean serum ammonia concentration decreased to a significantly greater extent in both active-treatment groups than in the respective placebo groups (p < 0.001).

Comment: Hepatic encephalopathy is characterized by various neuropsychiatry symptoms, and is a complication of cirrhosis of the liver. Patients with hepatic encephalopathy frequently experience fatigue, possibly due to hyperammonemia. Acetyl-L-carnitine (ALC) may have a neuroprotective effect and, as a source of carnitine, may improve mitochondrial energy production. In the present study, supplementation with ALC decreased the severity of both mental and physical fatigue, increased physical activity, and decreased serum ammonia concentrations in patients with both mild and moderately severe hepatic encephalopathy.

Malaguarnera M et at. Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr. 2011; 93:799-808.

Vitamin D Prevents Drug-Induced Musculoskeletal Symptoms

Fifty-eight women with breast cancer, who had musculoskeletal symptoms due to treatment with anastrozole (an aromatase inhibitor), were stratified according to their baseline 25-hydroxyvitamin D level and were randomly assigned to receive, in double-blind fashion, vitamin D2 or placebo for 6 months. Group A (25-hydroxyvitamin D level of 20-29 ng/ml) received 50,000 IU of vitamin D2 once a week for 8 weeks, then once a month for 4 months. Group B (25-hydroxyvitamin D level of 10-19 ng/ml) received 50,000 IU once a week for 16 weeks, then once a month for 2 months. Musculoskeletal symptoms were assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). At 2 months, FIQ pain (p < 0.005), BPI worst-pain (p = 0.04), BPI average-pain (p < 0.007), BPI pain-severity (p = 0.04), and BPI interference (p = 0.034) scores were better with vitamin D2 than with placebo. The positive effect of vitamin D2 was stronger in Group B than in Group A.

Comment: Musculoskeletal symptoms occur frequently as a side effect in patients receiving aromatase inhibitors. The results of the present study indicate that vitamin D supplementation can prevent anastrozole-induced musculoskeletal symptoms, and that the effect is more pronounced in women with 25-hydroxyvitamin D levels less than 20 ng/ml than in those with levels of 20 ng/ml or higher.

Rastelli AL et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomised trial. Breast Cancer Res Treat. 2011;129:107-116.

by Alan R. Gaby, MD drgaby@earthlink.net
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