Research News
October 2010
Melatonin and sleep-related problems in children with intractable epilepsy
Sleep disturbances are common in epilepsy. To investigate the effect of melatonin on children who suffer from seizures, 23 children with intractable epilepsy and 14 children with controlled seizures were evaluated by psychometric sleep assessment and assay of diurnal and nocturnal melatonin levels. Children with intractable epilepsy received oral melatonin before bedtime and were reassessed after 3 months. Children with intractable epilepsy had higher scores for each category of sleep walking, forcible teeth grinding, and sleep apnea. At the end of therapeutic trial, patients with intractable epilepsy exhibited significant improvement in bedtime resistance, sleep duration, sleep latency, frequent nocturnal arousal, sleep walking, excessive daytime sleepiness, nocturnal enuresis, forcible teeth grinding, sleep apnea, and Epworth sleepiness scores. There was also a significant reduction in seizure severity. The use of melatonin in patients with intractable seizures was associated with improvement of many sleep-related phenomena and the severity of seizures. (Pediatr Neurol. 2010 Apr;42(4):249-54.)
Hair cortisol and the risk for acute MI in adult men
Researchers at The University of Western Ontario have provided the first direct evidence using a biological marker, to show chronic stress plays an important role in heart attacks. A prospective case-control study included 56 patients admitted to hospital with acute MI and 56 control patients, admitted to internal medicine wards for other indications. An enzyme immunoassay technique was used to measure cortisol in the most proximal 3 cm of hair, considered to represent the most recent 3 months of exposure. Median hair cortisol contents (range) were 295.3 (105.4-809.3) ng/g in acute MI patients and 224.9 (76.58-949.9)ng/g in controls (p = 0.006, Mann-Whitney U-test). After controlling for other risk factors for acute MI using multiple logistic regression, log-transformed hair cortisol content remained the strongest predictor (OR 17.4, 95% CI 2.15-140.5; p = 0.007). The researchers concluded that chronic stress, as assessed by increased hair cortisol in the 3 months prior to the event, maybe a contributing factor for AMI. (Stress. 2010 Sep 2 [Epub ahead of print].)
Variety in Fruit and Vegetable Intake Linked to Lower Lung Cancer Risk in Smokers
After a mean follow-up of 8.7 years in the European Prospective Investigation into Cancer and Nutrition study, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables. With increasing variety in vegetable subgroups, risk of lung cancer decreases (HR, 0.77; 95% CI, 0.64-0.94 highest versus lowest quartile; P trend = 0.02). This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97). Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk. (Cancer Epidemiol Biomarkers Prev; 19(9); 2278-86.)
Effect of exercise on oxidative stress
173 overweight or obese, postmenopausal, sedentary women were randomized either to an aerobic exercise intervention (60%–75% observed maximal HR) for ≥45 min·d−1, 5 d·wk−1 (n = 87), or to a stretching control group (n = 86), on an intent-to-treat basis. Baseline and 12-month measures included urinary F2-isoprostane (marker of oxidative stress), maximal O2 uptake, body weight, body fat percentage, waist circumference, and intra-abdominal fat surface area. During the 12-month study, exercisers increased maximal O2 uptake (+13.6%; P 15% decreased F2-isoprostane by 14.1% (P = 0.005 vs controls). These findings suggest that aerobic exercise, when accompanied by relatively marked gains in aerobic fitness, decreases oxidative stress among previously sedentary older women and that these effects occur with minimal change in mass or body composition. (Med Sci Sports Exerc. 2010 Aug;42(8):1448-53.)
Shortened nighttime sleep duration in early life and subsequent childhood obesity
In a prospective cohort study of subjects aged 0 to 13 years (n = 1930), a short duration of nighttime sleep at baseline was strongly associated with increased risk of subsequent overweight or obesity (odds ratio = 1.80; 95% confidence interval, 1.16-2.80) in children aged 0-4 years at baseline. For older children (aged 5-13 years), baseline sleep was not associated with subsequent weight status; however, contemporaneous sleep was inversely associated. Daytime sleep had little effect on subsequent obesity in either group. Shortened sleep duration in early life is a modifiable risk factor with important implications for obesity prevention and treatment. Insufficient nighttime sleep among infants and preschool-aged children may be a lasting risk factor for subsequent obesity. Napping does not appear to be a substitute for nighttime sleep in terms of obesity prevention. Limitations of this study include collection of sleep data for only 2 days in a year, lack of baseline BMI data for the younger children, potential confounding by physical activity and diet, and reliance on parental report for baseline weight. (Arch Pediatr Adolesc Med. 2010 Sep;164(9):840-5.)
Lycopene in treatment of high-grade gliomas: a pilot study
The therapeutic benefit of lycopene is well established for prostate carcinoma in various clinical trials and has been proposed for other malignancies including high-grade gliomas. In a randomized placebo control study, fifty patients with high-grade gliomas were treated with surgery followed by adjuvant radiotherapy and concomitant paclitaxel. Patients were then randomized to receive either oral lycopene (Group A) 8 mg daily with radiotherapy or placebo (Group B). Pre-and post-radiotherapy plasma lycopene levels were measured using high-precision liquid chromatography. Patients were followed up at three-monthly intervals with clinical examinations for 1 year. Primary endpoint was response at six months post radiotherapy. The commonest histology was glioblastoma multiforme (n = 32). Pre- and post-treatment plasma lycopene levels in the patients in Group A was 152 ng/ml and 316 ng/ml and in the patients in Group B were 93 ng/ml and 98 ng/ml (P = 0.009). The follow-up duration was significantly higher for Group A than Group B (66.29 vs. 38.71 weeks, P = 0.05). The authors conclude that the addition of nutrition supplements such as lycopene may have potential therapeutic benefit in the adjuvant management of high-grade gliomas. (Neurol India. 2010 Jan-Feb;58(1):20-3.)
A water-soluble extract of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas
A water-soluble extract of Ganoderma lucidum mycelia (MAK) is one of the G. lucidum extracts that has been reported to exhibit cancer-preventive effects in animal studies. To confirm cancer-preventive effects of MAK, a no-treatment concurrent controlled trial on patients with colorectal adenomas was performed. Patients who were determined to be carrying colorectal adenomas by colonoscopy were enrolled. Patients in the MAK group took MAK (1.5g/day) for 12 months. Follow-up colonoscopy was performed after 12 months, and the colonoscopists recorded the size and site of all adenomas. Among 123 patients who enrolled in the MAK group, 96 eligible patients completed the trial. The 102 eligible patients in the no-treatment control group were selected randomly from the department’s patients. The changes in the number of adenomas up to 12 months increased to 0.66 +/- 0.10 (mean +/- SE) in the control group, while decreasing in the MAK group to -0.42 +/- 0.10 (p < 0.01). The total size of adenomas increased to 1.73 +/- 0.28 mm in the control group and decreased to -1.40 +/- 0.64 mm in the MAK group (p < 0.01). The results suggest that MAK suppresses the development of colorectal adenomas. (Hiroshima J Med Sci. 2010 Mar;59(1):1-6.)
A diet based on high-heat-treated foods promotes risk factors for DM & CVD
The aim of this study was to determine whether high-heat-treated foods pose a risk for healthy subjects. A randomized, crossover, diet-controlled intervention trial with 62 volunteers was divided into two groups, one based on mild steam cooking and another based on high-temperature cooking. These 2 diets differed mainly in their contents of Maillard reaction products (MRPs). MRPs were assessed in the diet and in subjects’ feces, blood, and urine samples, with N(epsilon)-carboxymethyllysine as an indicator of MRPs. Biological indicators of glucose and lipid metabolism as well as oxidative stress were analyzed in subjects after 1 month. In comparison with the steamed diet, 1 month of consuming the high-heat-treated diet induced significantly lower insulin sensitivity and plasma concentrations of omega-3 fatty acids, vitamins C, and E [-17% (P<0.002), -13% (P<0.0001), and -8% (P<0.01), respectively]. However, concentrations of plasma cholesterol and triglycerides increased [+5% (P<0.01) and +9% (P<0.01), respectively]. Conclusion: A diet that is based on high-heat-treated foods increases markers associated with an enhanced risk of type 2 diabetes and cardiovascular diseases in healthy people. (Am J Clin Nutr. 2010 May;91(5):1220-6.)
Antioxidant micronutrients and biomarkers of oxidative stress and inflammation in colorectal adenoma patients
Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), the effects of an antioxidant micronutrient combination (800mg dl-alpha-tocopherol acetate, 24mg beta-carotene, 1.0g vitamin C, 200microg l-selenomethionine, 7.2mg riboflavin, 80mg niacin, 60mg zinc, 5mg manganese) was given daily over 4 months and oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma was accessed. Plasma TNF-alpha, IL-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (p=0.002), and CySS decreased by 19% (P=0.03); however, IL-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status. (Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):850-8.)
An international trial of antioxidants in the prevention of pre-eclampsia (INTAPP)
Objective: To investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. Study design: In a multi-center randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1g vitamin C and 400IU alpha-tocopherol) or placebo. The primary outcome was GH and its adverse conditions. Results: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or peri-natal death (non-prespecified) as well as preterm pre-labor rupture of membranes. Conclusions: Vitamin C and E supplementation did not reduce the rate of pre-eclampsia or GH, but increased the risk of fetal loss or peri-natal death and preterm pre-labor rupture of membranes. (Am J Obstet Gynecol. 2010 Mar;202(3):239.)
Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo
Meta-analyses of the trials suggested that antidepressants are only marginally efficacious compared to placebos and documented profound publication bias that inflated their apparent efficacy. The analysis also documented a second form of bias in which researchers failed to report the negative results for the pre-specified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure as though it was their primary measure of interest. The STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. In one trial, it was found that out of 4041 patients started on citalopram, 370 dropped out within 2 weeks. Of the 1,854 remitted patients, 670 (36.7%) dropped out within 1 month of their remission and only 108 (5.8%) survived continuing care and took the final assessment without relapsing and/or dropping out. The reviewed findings argue for a reappraisal of the current recommended standard of care of depression. (Psychother Psychosom. 2010;79(5):267-79.)
Fatty acid supplements improve respiratory, inflammatory and nutritional parameters in adults with cystic fibrosis
Chronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. The aim of the study was to examine the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation, pulmonary status, quality of life and anthropometric parameters. Seventeen adult subjects with CF received 324mg of eicosapentaenoic, 216mg of docosahexaenoic, 480mg of linoleic and 258mg of gammalinolenic acid daily. Inflammation markers, spirometry parameters, number and severity of respiratory exacerbations, antibiotic consumption, quality of life, anthropometric parameters and serum phospholipid fatty acid composition were assessed. At the end of the treatment period TNF alpha levels, IgG and IgM anti-oxidized LDL antibodies fell significantly. Spirometry improved significantly. Annual respiratory exacerbations and days of antibiotic treatment fell significantly. The improvement in QoL was not significant. Serum levels of docosahexaenoic, total omega-3 and linoleic acid rose significantly. The fat-free mass and hand grip dynamometry improved significantly. The authors concluded that low-dose supplements of n-3 and gammalinolenic fatty acids over a long period (one year) appears to improve pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), inflammatory and anthropometric parameters in adults with CF. (Arch Bronconeumol. 2010 Feb;46(2):70-7.)
Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study
25-hydroxyvitamin D levels were measured in sera collected from 1024 children with mild-to-moderate asthma in a multi-center clinical trial randomized to receive as-needed beta-agonists or placebo. Using multi-variable modeling, the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial were examined. Thirty-five percent of all subjects were vitamin D insufficient (< 30 ng/mL 25-hydroxyvitamin D). Mean vitamin D levels were lowest in African American subjects and highest in white subjects. After adjusting for age, sex, body mass index, income, and treatment group, insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit (odds ratio, 1.5; 95% CI, 1.1-1.9; P = .01). The authors conclude that vitamin D insufficiency is common in this population of children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period. (J Allergy Clin Immunol. 2010 Jul;126(1):52-8.e5.)
Nutritional intervention in patients with DM2 who are hyperglycaemic despite optimized drug treatment
93 participants < 70 years with type 2 diabetes and a HbA1c of more than 7% despite optimized drug treatments plus at least two of overweight or obesity, hypertension, and dyslipidaemia were examined in this randomized controlled trial. Intensive individualized dietary advice for six months; both the intervention and control participants continued with their usual medical surveillance. HbA1c was the primary outcome. Secondary outcomes included measures of adiposity, blood pressure, and lipid profile. After adjustment for age, sex, and baseline measurements, differences in HbA1c between the intervention and control groups at six months (-0.4%, 95% confidence interval -0.7% to -0.1%) was highly statistically significant (P=0.007), as were the decreases in weight (-1.3 kg, -2.4 to -0.1 kg; P=0.032), body mass index (-0.5, -0.9 to -0.1; P=0.026), and waist circumference (-1.6 cm, -2.7 to -0.5 cm; P=0.005). A decrease in saturated fat (-1.9% total energy, -3.3% to -0.6%; P=0.006) and an increase in protein (1.6% total energy, 0.04% to 3.1%; P=0.045) in the intervention group were the most striking differences in nutritional intake between the two groups. (BMJ. 2010 Jul 20;341:c3337.)
Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis
A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little studied. A prospective cohort study of 145 participants with relapsing-remitting MS from 2002 to 2005 were investigated to examine whether higher levels of serum 25-hydroxyvitamin D (25-OH-D) were associated with a lower risk of relapses in MS patients. Serum 25-OH-D levels were measured biannually, and the hazard of relapse was assessed using survival analysis. An inverse linear relationship existed between 25-OH-D levels and the hazard of relapse over the subsequent 6 months, with hazard ratio (HR) 0.91 (95% CI: 0.85-0.97) per 10nmol/l increase in 25-OH-D level (p= 0.006). 25-OH-D at monthly intervals were estimated, resulting in a slightly enhanced association, with HR 0.88 (95% CI, 0.82-0.95) per 10nmol/l increase (p= 0.001). Adjusting for potential confounders did not alter these findings. Higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50nmol/l could halve the hazard of a relapse. (Ann Neurol. 2010 Aug;68(2):193-203.)
Genistein aglycone does not affect thyroid function
The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. A sub-cohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone daily (n = 71) or placebo (n = 67), plus calcium and vitamin D3 at therapeutic doses. Circulating thyroid hormones (TSH, free T(3), free T(4)) and autoantibodies (thyroid peroxidase, thyroglobulin, and thyroid microsomal antigen) were assessed in 40 genistein and 37 placebo subjects who completed 3 years. Thyroid hormone receptor (THRalpha and THRbeta) and retinoid receptor (RARalpha, RARgamma, and RXRalpha) expression from peripheral blood monocytes was also evaluated at baseline, 12, 24, and 36 months in all 3-yr completers. Genistein administration over 3 years did not affect serum thyroid hormones or autoantibodies. In addition, there were no differences in THRalpha, THRbeta, RARalpha, RARgamma, or RXRalpha mRNA expression between groups. The data suggests that genistein aglycone intake does not significantly increase the risk of clinical or subclinical hypothyroidism at the dose of 54 mg/d. (J Clin Endocrinol Metab. 2010 Jun;95(6):3067-72.)
Inhibition of Streptolysin O by allicin, an active component of garlic
Streptolysin O (SLO) is a potent cytolytic toxin produced by almost all strains of group A streptococci and is considered an important virulence factor for this organism. This study investigated the effect of allicin and aqueous garlic extract on the haemolytic activity of SLO. All tested materials potentially inhibited the SLO haemolytic activity. Allicin neutralized SLO in a dose- and time-dependent manner. Fifteen minute incubation of SLO with 35 mug concentration of allicin totally inhibited haemolytic activity of SLO (IC50 = 5.97 mug). The inhibitory activity of old extract of garlic was equipotent as pure allicin (IC50 = 6.27 mug; p < 0.05). In contrast fresh extract of garlic inhibits the SLO haemolytic activity at lower concentrations (IC50 = 1.59 mul; 1.9 mug allicin). The inhibitory effect of the allicin was restored by addition of reducing agent DTT at 2 mM, suggesting that allicin likely inhibits the SLO by binding to cysteinyl residue in the binding site. These results indicate a new activity for allicin and may be proposed as an alternative drug against streptococcal diseases. (J Med Microbiol. 2010 Jun 10. [Epub ahead of print].)
Study shows breastfeeding HIV-positive women should not receive vitamin A supplements
Supplementation in lactating HIV-1-infected women with preformed vitamin A and beta-carotene (VA/BC) increased the risk of mother-to-child transmission of HIV through breastfeeding. The aim of the study evaluated the effect of VA/BC or multivitamin (B complex, vitamin C, and vitamin E) supplementation of HIV-infected women on HIV shedding in breast milk during the first 2 y postpartum. Viral (cell-free) and proviral (cell-associated) HIV loads were quantified in breast-milk samples, and were collected /=6 months postpartum (relative risk: 1.34; 95% CI: 1.04, 1.73). No associations with pro-viral load were observed. The multivitamin had no effects. In observational analyses, beta-carotene but not retinol breast-milk concentrations were significantly associated with an increased viral load in milk. (Am J Clin Nutr. 2010 Aug 25. [Epub ahead of print].)