Naturopathic Medical Research Dragon's Medical Bulletin July Aug 2010

Objective: The present study was to further examine the mechanisms underlying the beneficial effects of hyperbaric oxygen (HBO2) on experimental spinal cord injury (SCI). Rats were divided into three major groups: (1) sham operation (laminectomy only); (2) laminectomy + SCI+ normobaric air (NBA; 21% O2 at 1 ATA); and (3) laminectomy + SCI + HBO2 (100% O2 at 2.5 ATA for two hours).

Spinal cord injury was induced by compressing the spinal cord for one minute with an aneurysm clip calibrated to a closing pressure of 55 g. HBO2 therapy was adopted immediately after SCI. Behavioral tests of hind limb motor function measured by Basso, Beattie, Bresnahan locomotor scale was conducted at day 1 to 7 after SCI. The triphenyltetrazolium chloride staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling assay were also conducted after SCI to evaluate spinal cord infarction and apoptosis respectively.

Both glial cell lines derived neurotrophic nerve growth factor (GDNF) and vascular endothelial growth factor (VEGF) positive cells and cytokines in the injured spinal cord were assayed by immunofluorescence and commercial kits, respectively. It was found that HBO2 therapy significantly attenuated the SCI-induced hind limb dysfunction, spinal cord infarction and apoptosis, and overproduction of spinal cord interleukin-1beta and tumor necrosis factor-alpha. In contrast, the numbers of both GDNF-positive and VEGF-positive cells and production of spinal cord interleukin-10 during SCI were all significantly increased by HBO2. Data suggested that HBO2 may have attenuated experimental SCI by stimulating production of GDNF, VEGF and interleukin-10.

Tai PA, et al. Attenuating of Experimental Spinal Cord Injury by Hyperbaric Oxygen: Stimulating Production of Vasculoendothelial and Glial Cell Lines Derived Neurotrophic Growth Factors and Interleukin-10. J Neurotrauma. 2010 Jun;27(6):1121-7.

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2. Optimizing Vitamin D Level May Prevent Old Age Urinary Incontinence

Objective: To estimate the prevalence of vitamin D deficiency in women with pelvic floor disorders and to evaluate possible associations between vitamin D levels and pelvic floor disorders.

Methods: Using 2005–2006 National Health and Nutrition Examination Survey data, we performed a cross-sectional analysis of nonpregnant women older than 20 years of age with data on both pelvic floor disorders and vitamin D measurements (n=1,881). Vitamin D levels lower than 30 ng/mL were considered insufficient. The prevalence of demographic factors, pelvic floor disorders, and vitamin D levels were determined, accounting for the multi-stage sampling design; odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate associations between vitamin D levels and pelvic floor disorders with control for known risk factors.

Results: One or more pelvic floor disorders were reported by 23% of women. Mean vitamin D levels were significantly lower for women reporting at least one pelvic floor disorder and for those with urinary incontinence, irrespective of age. In adjusted logistic regression models, we observed significantly decreased risks of one or more pelvic floor disorders with increasing vitamin D levels in all women aged 20 or older (OR, 0.94; 95% CI, 0.88–0.99) and in the subset of women 50 years and older (OR, 0.92; 95% CI, 0.85–0.99). Additionally, the likelihood of urinary incontinence was significantly reduced in women 50 and older with vitamin D levels 30 ng/mL or higher (OR, 0.55; 95% CI, 0.34–0.91).

Conclusion: Higher vitamin D levels are associated with a decreased risk of pelvic floor disorders in women.

Badalian SS, et al. Vitamin D and Pelvic Floor Disorders in Women: Results From the National Health and Nutrition Examination Survey. Obstet Gynecol. 2010 Apr;115(4):795-803.

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3. More Evidence Shows Importance of Magnesium in Asthma Management

Background: Epidemiological data shows low dietary magnesium (Mg) may be related to incidence and progression of asthma.

Objective: To determine if long term (6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma.

Subjects: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute (NHLBI) and Asthma Education and Prevention Program (NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids (ICS) as asthma medications were enrolled.

Design: Subjects were randomly assigned to consume 340 mg (170 mg twice a day) of Mg or a placebo for 6.5 months.

Measurements: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. Markers of asthma control were: methacholine challenge test (MCCT) and pulmonary function test (PFT) results. Subjective validated questionnaires on asthma quality of life (AQLQ) and control (ACQ) were completed by participants. Markers of inflammation, including c-reactive protein (CRP) and exhaled nitric oxide (eNO) were determined.

Results: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute (FEV(1)) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate (PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units (P <0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status.

Conclusion: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

Kazaks AG, et al. Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial. J Asthma. 2010 Feb;47(1):83-92.

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4. Diabetics on Metformin Should be Supplemented with Vitamin B12 to Minimize the Risk of Peripheral Neuropathy

Objective: The severity of peripheral neuropathy in diabetic patients varies for unclear reasons. Long-term use of metformin is associated with malabsorption of vitamin B(12) (cobalamin [Cbl]) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. The intent of this study was to clarify the relationship among metformin exposure, levels of Cbl, Hcy, and MMA, and severity of peripheral neuropathy in diabetic patients. We hypothesized that metformin exposure would be associated with lower Cbl levels, elevated Hcy and MMA levels, and more severe peripheral neuropathy.

Research Design and Methods: This was a prospective case-control study of patients with type 2 diabetes and concurrent symptomatic peripheral neuropathy, comparing those who had received > six months of metformin therapy (n = 59) with those without metformin exposure (n = 63). Comparisons were made using clinical (Toronto Clinical Scoring System and Neuropathy Impairment Score), laboratory (serum Cbl, fasting Hcy, and fasting MMA), and electrophysiological measures (nerve conduction studies).

Results: Metformin-treated patients had depressed Cbl levels and elevated fasting MMA and Hcy levels. Clinical and electrophysiological measures identified more severe peripheral neuropathy in these patients; the cumulative metformin dose correlated strongly with these clinical and paraclinical group differences.

Conclusions: Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy.

Wile DJ, et al. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care. 2010 Jan;33(1):156-61.

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5. DHA Oil Supplementation Prevents LDL Cholesterol Oxidation

Objective: To determine the effect of supplementation with increasing doses of docosahexaenoic acid (DHA), as the only n-3 polyunsaturated fatty acid (PUFA), on low-density lipoprotein (LDL) redox status and oxidizability.

Methods: Twelve healthy men aged 53-65 years ingested consecutive doses of DHA (200, 400, 800 and 1600 mg/day), each dose for two weeks.

Results: The proportions of DHA increased dose-dependently in LDL phospholipids and cholesteryl esters, even after two weeks of supplementation with 200mg/day DHA. The daily intake of 200, 400 and 800 mg DHA resulted in increased alpha-tocopherol concentrations, decreased MDA concentrations, and a longer lag time for copper-induced LDL oxidation. Supplementation with 1600 mg/day DHA had no effect on the above parameters. In plasma, concentrations of 4-hydroxy-hexenal, specifically derived from the peroxidation of n-3 fatty acids, significantly increased after 800 and 1600 mg DHA, representing 0.01% of plasma n-3 PUFAs, while 4-hydroxy-nonenal concentrations, derived from the peroxidation of n-6 fatty acids, did not change.

Conclusion: Our results clearly show that an intake of 200-800 mg/day DHA may have protective and antioxidant effects on LDL and could represent optimal doses for cardiovascular disease prevention in a healthy population.

Calzada C, et al. Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men. Atherosclerosis. 2010 Feb;208(2):467-72. Epub 2009 Aug 3.

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6. Tart Cherry Juice Might Help Muscle Function Recovery After Strenuous Exercise

Abstract: This investigation determined the efficacy of a tart cherry juice in aiding recovery and reducing muscle damage, inflammation and oxidative stress.Twenty recreational marathon runners assigned to either consumed cherry juice or placebo for five days before, the day of and for 48 hours following a Marathon run.

Markers of muscle damage (creatine kinase, lactate dehydrogenase, muscle soreness and isometric strength), inflammation [interleukin-6 (IL-6), C-reactive protein (CRP) and uric acid], total antioxidant status (TAS) and oxidative stress [thiobarbituric acid reactive species (TBARS) and protein carbonyls] were examined before and following the race. Isometric strength recovered significantly faster (P=0.024) in the cherry juice group. No other damage indices were significantly different. Inflammation was reduced in the cherry juice group (IL-6, P<0.001; CRP, P<0.01; uric acid, P<0.05).

TAS was approximately 10% greater in the cherry juice than the placebo group for all post-supplementation measures (P<0.05). Protein carbonyls was not different; however, TBARS was lower in the cherry juice than the placebo at 48 h (P<0.05). The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function.

Howatson G, et al. Influence of tart cherry juice on indices of recovery following marathon running. Scand J Med Sci Sports. 2009 Oct 21. [Epub ahead of print]

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7. Young African-American Asthmatics Have Higher Rate of Vitamin D Deficiency

Objective: The goal of this study was to examine the prevalence of vitamin D insufficiency and deficiency among urban African-American (AA) youth with asthma compared with control subjects without asthma.

Study Design: A cross-sectional case-control study was conducted at an urban pediatric medical center. Total 25-hydroxyvitamin D insufficiency (<30 ng/mL) and deficiency (<20 ng/mL) were assessed in urban self-reported AA patients, aged 6 to 20 years, with (n = 92) and without (n = 21) physician-diagnosed asthma.

Results: Blood samples were available for 85 (92%) cases. The prevalence of vitamin D insufficiency and deficiency were significantly greater among cases than control subjects (73/85 [86%] vs 4/21 [19%], adjusted odds ratio = 42 [95% confidence interval: 4.4 to 399] for insufficiency and 46/85 [54%] vs 1/21 [5%], adjusted odds ratio = 20 [95% confidence interval: 1.4 to 272] for deficiency).

Conclusions: Most of this sample of urban AA youth with persistent asthma were vitamin D deficient or insufficient. Given the emerging associations between low vitamin D levels and asthma, strong consideration should be given to routine vitamin D testing in urban AA youth, particularly those with asthma.

Freishtat RJ, et al. High prevalence of vitamin D deficiency among inner-city African American youth with asthma in Washington, DC. J Pediatr. 2010 Jun;156(6):948-52. Epub 2010 Mar 16.

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8. Extended-Release Niacin Could Help Manage Hyperphosphatemia in Renal Failure Patients

Background and Objectives: Niacin administration lowers the marked hyperphosphatemia that is characteristic of renal failure. We examined whether niacin administration also reduces serum phosphorus concentrations in patients who have dyslipidemia and are free of advanced renal disease.

Design, Setting, Participants, and Measurements: We performed a post hoc data analysis of serum phosphorus concentrations that had been determined serially (at baseline and weeks 4, 8, 12, 18, and 24) among 1,547 patients who had dyslipidemia and were randomly assigned in a 3:2:1 ratio to treatment with extended release niacin (ERN; 1 g/d for four weeks and dose advanced to 2 g/d for 20 weeks) combined with the selective prostaglandin D2 receptor subtype 1 inhibitor laropiprant (L; n = 761), ERN alone (n = 518), or placebo (n = 268).

Results: Repeated measures analysis revealed that ERN-L treatment resulted in a net mean (95% confidence interval) serum phosphorus change comparing ERN-L with placebo treatment of −0.13 mmol/L (−0.15 to −0.13 mmol/L; −0.41 mg/dl [−0.46 to −0.37 mg/dl]). These results were consistent across the subgroups defined by estimated GFR of <60 or >/=60 ml/min per 1.73 m(2), a serum phosphorus of >1.13 mmol/L (3.5 mg/dl) versus

Conclusions: We have provided definitive evidence that once-daily ERN-L treatment causes a sustained 0.13-mmol/L (0.4-mg/dl) reduction in serum phosphorus concentrations, approximately 10% from baseline, which is unaffected by estimated GFR ranging from 30 to >/=90 ml/min per 1.73 m(2) (i.e., stages 1 through 3 chronic kidney disease).

Maccubbin D. Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. Clin J Am Soc Nephrol. 2010 Apr;5(4):582-9. Epub 2010 Mar 18.

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9.Intravenous Omega-3 Fatty Acids Helps Rheumatoid Arthritis

Background: The present study investigated the efficacy and safety of parenteral omega-3 fatty acids (omega-3 FA) in patients with active rheumatoid arthritis (RA).

Methods: We performed a double-blind, randomized, placebo-controlled study in 23 patients with moderate to severe RA. Patients received either 0.2 g of fish oil emulsion/kg (active) or 0.9% saline (placebo) infusion intravenously for 14 consecutive days, followed by 20 weeks of 0.05 g of fish oil/kg (active) or paraffin wax (placebo) ingested orally as capsules. A decrease in swollen and tender joint counts was the primary efficacy measure.

Results: At baseline, both swollen and tender joint counts were not significantly different between patients in the treatment and placebo groups. Twenty patients completed the infusion portion of the study, and 13 completed the oral portion. Swollen joint count was significantly lower in the omega-3 FA group compared with the placebo group after one week of infusion (P = .002) as well as after two weeks of infusion (P = .046). Tender joint count also tended to be lower in the omega-3 FA group, although this did not reach statistical significance. Both swollen and tender joint counts were significantly lower in the omega-3 FA group compared with the placebo group during and at the end of oral treatment.

Conclusion: Our pilot study indicates that parenteral omega-3 FAs are well tolerated and improve clinical symptoms of RA. Subsequent oral administration of omega-3 FAs may prolong the beneficial effects of the infusion therapy. These results warrant validation in larger multicenter studies.

Bahadori B, et al. Omega-3 Fatty acids infusions as adjuvant therapy in rheumatoid arthritis. JPEN J Parenter Enteral Nutr. 2010 Mar-Apr;34(2):151-5.

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10. Probiotic Streptococcus Thermophilus Fermented Milk Might Help Aspirin Induced Chronic Gastritis

Aim: To investigate the potential therapeutic effect of exopolysaccharide (EPS)-producing Streptococcus thermophilus (S. thermophilus) CRL 1190 fermented milk on chronic gastritis in Balb/c mice.

Methods: Balb/c mice were fed with the fermented milk for seven days after inducing gastritis with acetyl-salicylic acid (ASA, 400 mg/kg body weight per day for ten days). Omeprazole was included in this study as a positive therapeutic control. The gastric inflammatory activity was evaluated from gastric histology and inflammation score, number of interleukin-10 (IL-10), interferon-γ (INFγ) and tumor necrosis factor-α (TNF-α) cytokine-producing cells in the gastric mucosa, and thickness of the mucus layer.

Results: Animals receiving treatment with the EPS-producing S. thermophilus CRL 1190 fermented milk showed a conserved gastric mucosa structure similar to that of healthy animals. Inflammation scores of the fermented milk-treated mice were lower than those of mice in the gastritis group (0.2 ± 0.03 vs 2.0 ± 0.6, P < 0.05). A marked decrease in INFγ+ (15 ± 1.0 vs 28 ± 1.2, P < 0.05) and TNF-α+ (16 ± 3.0 vs 33 ± 3.0, P < 0.05) cells and an increase in IL-10+ (28 ± 1.5 vs 14 ± 1.3, P < 0.05) cells compared to the gastritis group, was observed. Also, an increase in the thickness of the mucus gel layer (2.2 ± 0.6 vs 1.0 ± 0.3; 5.1 ± 0.8 vs 1.5 ± 0.4 in the corpus and antrum mucosa, respectively, P < 0.05) compared with the gastritis group was noted. A milk suspension of the purified EPS from S. thermophilus CRL1190 was also effective as therapy for gastritis.

Conclusion: This study suggests that fermented milk with S. thermophilus CRL 1190 and/or its EPS could be used in novel functional foods as an alternative natural therapy for chronic gastritis induced by ASA.

Rodriguez C, et al. Therapeutic effect of Streptococcus thermophilus CRL 1190-fermented milk on chronic gastritis. World J Gastroenterol. 2010 Apr 7;16(13):1622-30.

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11. Intranasal Oxytocin Looks Promising for Autistic Kids

Background: A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems.

Methods: In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger's Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition.

Results: In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose.

Conclusions: This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders.

Guastella AJ, et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010 Apr 1; 67(7):692-4. Epub 2009 Nov 7.

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12. Lutein Supplementation Slows Vision Loss in Retinitis Pigmentosa

Objective: To determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A.

Design: Randomized, controlled, double-masked trial of 225 non-smoking patients, aged 18 to 60 years, evaluated over a four-year interval. Patients received 12 mg of lutein or a control tablet daily. All were given 15,000 IU/d of vitamin A palmitate. Randomization took into account genetic type and baseline serum lutein level.

Main Outcome Measures: The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program; prespecified secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Retinopathy Study acuity.

Results: No significant difference in rate of decline was found between the lutein plus vitamin A and control plus vitamin A groups over a four-year interval for the HFA 30-2 program. For the HFA 60-4 program, a decrease in mean rate of sensitivity loss was observed in the lutein plus vitamin A group (P = .05). Mean decline with the 60-4 program was slower among those with the highest serum lutein level or with the highest increase in macular pigment optical density at follow-up (P = .01 and P = .006, respectively). Those with the highest increase in macular pigment optical density also had the slowest decline in HFA 30-2 and 60-4 combined field sensitivity (P = .005). No significant toxic effects of lutein supplementation were observed.

Conclusion: Lutein supplementation of 12 mg/d slowed loss of midperipheral visual field on average among nonsmoking adults with retinitis pigmentosa taking vitamin A. Application to Clinical Practice Data are presented that support use of 12 mg/d of lutein to slow visual field loss among nonsmoking adults with retinitis pigmentosa taking vitamin A.

Berson E, et al. Clinical Trial of Lutein in Patients With Retinitis Pigmentosa Receiving Vitamin A. Arch Ophthalmol. 2010;128(4):403-411.

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13. Higher Blood Viscosity Might Contribute to Cognitive Decline in Type 2 Diabetics

Background: the association between the rheological factors haematocrit and plasma viscosity and cognitive ability has not been extensively studied. It is possible that blood viscosity affects cerebral blood flow and cognitive function. This study tested the contemporaneous associations between these two markers of rheology and cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.

Methods: a cross-sectional cohort of 1,066 men and women with type 2 diabetes (Edinburgh Type 2 Diabetes Study) was used for the analysis. Plasma viscosity and haematocrit were measured in venous blood samples at baseline. Contemporaneously, a battery of seven cognitive tests was administered to all participants. These data were used to derive a general intelligence factor, g. A vocabulary-based test was also administered as an estimate of prior intelligence, and adjustment for scores on this test was used to estimate lifetime cognitive decline.

Results: increased plasma viscosity was associated with poorer age- and sex-adjusted scores on the cognitive domains of processing speed, mental flexibility and general intelligence, g, with standardised regression coefficients -0.092 (P < 0.01), -0.077 (P < 0.05) and -0.093 (P < 0.01), respectively. After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes and glycaemic control, the associations remained significant for the measure of processing speed and g, with standardised regression coefficients -0.059 (P < 0.05) and -0.051 (P < 0.05). Increased haematocrit was significantly associated with better age- and sex-adjusted cognitive scores on the majority of the tests and with g. However, significant associations were not retained after adjustments for additional covariates.

Conclusions: increased plasma viscosity is associated with decreased cognitive ability and increased estimated lifetime cognitive decline. The relationship between haematocrit and cognitive ability requires further study.

Marioni RE, et al. Blood rheology and cognition in the Edinburgh Type 2 Diabetes Study. Age Ageing. 2010 May;39(3):354-9. Epub 2010 Mar 2.

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14.Korean Red Ginseng Could Improve the Sex Life of Peri-Menopausal Women

Introduction: Many menopausal women experience climacteric symptoms including impairment of sexual function. Recent reports have suggested that Korean red ginseng (KRG) has a relaxing effect on the clitoral cavernosal muscle and vaginal smooth muscle in rats.

Aim: We assessed whether KRG extracts would improve sexual function in menopausal women.

Methods: Thirty-two menopausal women participated in a placebo-controlled, double-blind, crossover clinical study with administration of either three capsules of ginseng (1 g per capsule) or placebo daily. After completing the KRG or placebo arm, the participants were crossed over to the other arm after a two-week washout period. The efficacy and safety of the KRG extracts were measured by using questionnaires.

Main Outcome Measures: Female Sexual Function Index (FSFI) and Global Assessment Questionnaire (GAQ).

Results: Twenty-eight women completed the study. They were, on average, 51.2 +/- 4.1 years old, and their mean menopausal state was for a duration of 37.4 +/- 2.9 months. Few carryover effects were noted in either study arm. The ginseng extract significantly improved scores on the FSFI from 3.10 +/- 0.87 to 3.50 +/- 0.72 in the sexual arousal domain (P = 0.006). The GAQ was more significantly affected by ginseng extracts than by placebo (P = 0.046). There were no severe adverse events in the KRG group, although two cases of vaginal bleeding occurred during KRG treatment.

Conclusions: Oral administration of KRG extracts improved sexual arousal in menopausal women. Red ginseng extracts might be used as an alternative medicine in menopausal women to improve their sexual life.

Oh KJ, et al. Effects of Korean red ginseng on sexual arousal in menopausal women: placebo-controlled, double-blind crossover clinical study. J Sex Med. 2010 Apr;7(4 Pt 1):1469-77. Epub 2010 Feb 5.

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15. Niacin’s Cardio-Protective Effects Go Beyond Simply Improving Lipid Profiles

Objective: To determine if niacin can confer cardiovascular benefit by inhibiting vascular inflammation and improving endothelial function independent of changes in plasma lipid and lipoprotein levels.

Methods and Results: New Zealand white rabbits received normal chow or chow supplemented with 0.6% or 1.2% (wt/wt) niacin. This regimen had no effect on plasma cholesterol, triglyceride, or high-density lipoprotein levels. Acute vascular inflammation and endothelial dysfunction were induced in the animals with a periarterial carotid collar. At the 24-hour postcollar implantation, the endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1 was markedly decreased in the niacin-supplemented animals compared with controls. Niacin also inhibited intima-media neutrophil recruitment and myeloperoxidase accumulation, enhanced endothelial-dependent vasorelaxation and cyclic guanosine monophosphate production, increased vascular reduced glutathione content, and protected against hypochlorous acid-induced endothelial dysfunction and tumor necrosis factor alpha-induced vascular inflammation.

Conclusion: Previous human intervention studies have demonstrated that niacin inhibits coronary artery disease. This benefit is thought to be because of its ability to reduce low-density lipoprotein and plasma triglyceride levels and increase high-density lipoprotein levels. The present study showed that niacin inhibits vascular inflammation and protects against endothelial dysfunction independent of these changes in plasma lipid levels.

Wu B, et al. Evidence That Niacin Inhibits Acute Vascular Inflammation and Improves Endothelial Dysfunction Independent of Changes in Plasma Lipids. Arterioscler Thromb Vasc Biol. 2010 May;30(5):968-75. Epub 2010 Feb 18.

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16.Coffee and Tea Enhances Fat Metabolism at Different Times

Objectives: Drinking green tea is associated with many health benefits, including increased fat oxidation. We tested the hypothesis that epigallocatechin-3-gallate (EGCG), the main green tea catechin, increases fat oxidation in obese men.

Methods: Ten healthy overweight/obese males (body mass index 31.3+/-0.8 kg/m(2)) were studied in a randomized, placebo-controlled, double-blind crossover trial. Study supplements were low EGCG (300 mg), high EGCG (600 mg), caffeine (200 mg), EGCG/caffeine (300 mg/200 mg) or placebo and were taken orally for three days. At the third day of supplementation, O(2) consumption and CO(2) production was measured by indirect calorimetry to assess energy expenditure and fat oxidation over four hours each after overnight fasting and after a standardized test meal.

Results: Energy expenditure was not affected by any supplementation, neither after overnight fasting nor after the test meal. During the first two hours after overnight fasting, fat oxidation increased by 7.7 (not significant, NS), 15.2 (NS), 26.3 (P<0.05 vs placebo) and 35.4% (P<0.01 vs placebo and low EGCG), for low EGCG, high EGCG, caffeine and EGCG/caffeine, respectively. During the first two hours after the meal, the mean increase in fat oxidation was 33.3 (P<0.05 vs placebo), 20.2 (NS), 34.5 (P<0.05 vs placebo) and 49.4% (P<0.05 vs placebo) for low EGCG, high EGCG, caffeine and EGCG/caffeine, respectively.

Conclusions: Low EGCG increases postprandial fat oxidation in obese men and this to the same extent as 200 mg caffeine, whereas high EGCG does not exert this effect. Fasting fat oxidation is increased only by caffeine (with or without EGCG). There is no synergism of low EGCG and 200 mg caffeine. Energy expenditure is not affected by EGCG.

Thielecke F, et al. Epigallocatechin-3-gallate and postprandial fat oxidation in overweight/obese male volunteers: a pilot study. Eur J Clin Nutr. 2010 Jul;64(7):704-13. Epub 2010 Apr 7.

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17. Check and Treat High Ferritin in Patients with Nonalcoholic Fatty Liver Disease

Background and Aims: Increased ferritin and body iron stores are frequently observed in nonalcoholic fatty liver disease (NAFLD), associated with heightened susceptibility to vascular damage. Conflicting data have been reported on the role of iron in atherosclerosis, with recent data suggesting that excess iron induces vascular damage by increasing levels of the hormone hepcidin, which would determine iron trapping into macrophages, oxidative stress, and promotion of transformation into foam cells. Aim of this study was to investigate the relationship between iron status and cardiovascular damage in NAFLD.

Methods and Results: Vascular damage was evaluated by common carotid arteries intima-media thickness (CC-IMT) measurement and plaque detection by ecocolor-doppler ultrasonography in 506 patients with clinical and ultrasonographic diagnosis of NAFLD, hemochromatosis gene (HFE) mutations by restriction analysis in 342 patients. Serum hepcidin-25 was measured by time-of-flight mass spectrometry in 143 patients. At multivariate analysis CC-IMT was associated with systolic blood pressure, glucose, LDL cholesterol, abdominal circumference, age, and ferritin (p=0.048).

Carotid plaques were independently associated with age, ferritin, glucose, and hypertension. Ferritin reflected iron stores and metabolic syndrome components, but not inflammation or liver damage. Hyperferritinemia was associated with increased vascular damage only in patients with HFE genotypes associated with hepcidin upregulation by iron stores (p<0.0001), and serum hepcidin-25 was independently associated with carotid plaques (p=0.05).

Conclusion: Ferritin levels, reflecting iron stores, are independent predictors of vascular damage in NAFLD. The mechanism may involve upregulation of hepcidin by increased iron stores in patients not carrying HFE mutations, and iron compartmentalization into macrophages.

Valenti L, et al. Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2010 Apr 12. [Epub ahead of print]

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18. Heart Transplant Patients Could Benefit From L-Arginine Supplementation

Background: Endothelial dysfunction is associated with the decreased exercise capacity observed in heart-transplant (HTx) recipients. l-Arginine supplementation (LAS) stimulates the nitric oxide (NO) pathway and restores endothelial function.

Objective: We compared exercise capacity in healthy subjects and HTx patients and investigated whether chronic LAS might improve exercise capacity and NO/endothelin balance after an HTx.

Design: Clinical, echocardiographic, and exercise characteristics were measured in 11 control subjects and 22 HTx recipients. In a prospective, double-blind study, the 22 HTx recipients performed a 6-min exercise [6-min-walk test (6MWT)] and a maximal bicycle exercise test before and after a 6-wk period of placebo intake or LAS. Endothelial function was measured by analyzing blood NO metabolites, endothelin, and the resulting NO/endothelin balance.

Results: Exercise capacity decreased after transplantation. Unlike with the placebo intake, a six-week LAS improved quality of life in HTx recipients (mean +/- SEM Minnesota Score: from 15.3 +/- 1.3 to 10.6 +/- 1.1; P < 0.001) and their submaximal exercise capacity. The distance walked during the 6MWT increased (from 525 +/- 20 to 580 +/- 20 m; P = 0.002), and the ventilatory threshold during the incremental test was delayed by 1.2 min (P = 0.01). Central factors such as resting stroke volume, systolic pulmonary arterial pressure, cardiac systolodiastolic functions, and heart-rate reserve were not modified, but LAS significantly increased the NO:endothelin ratio (from 2.49 +/- 0.38 to 3.31 +/- 0.39; P = 0.03).

Conclusion: Oral LAS may be a useful adjuvant therapeutic to improve quality of life and exercise tolerance in HTx recipients.

Doutreleau S, et al. L-Arginine supplementation improves exercise capacity after a heart transplant. Am J Clin Nutr. 2010 May;91(5):1261-7. Epub 2010 Mar 3.

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19. Corticosteroids May Contribute to Vitamin D Deficiency in Asthmatic Children

Background: There is little knowledge about clinical variables associated with vitamin D (VitD) insufficiency in asthmatic children.

Objective: We sought to investigate disease variables associated with VitD insufficiency in patients with childhood asthma and interaction of VitD with corticosteroid-mediated anti-inflammatory responses.

Methods: We analyzed 25-hydroxyvitamin D serum levels in 100 asthmatic children to investigate relationships between 25-hydroxyvitamin D levels and patients' characteristics. We determined VitD's effects on dexamethasone (DEX) induction of mitogen-activated protein kinase phosphatase 1 and IL-10 in PBMCs.

Results: The median 25-hydroxyvitamin D serum level was 31 ng/mL. Forty-seven percent of subjects had VitD levels in the insufficient range (<30 ng/mL), whereas 17% were VitD deficient (<20 ng/mL). Log10 IgE (P = .01, ρ = −0.25) and the number of positive aeroallergen skin prick test responses (P = .02, ρ = −0.23) showed a significant inverse correlation with VitD levels, whereas FEV1 percent predicted (P = .004, ρ = 0.34) and FEV1/forced vital capacity ratio (P = .01, ρ = 0.30) showed a significant positive correlation with VitD levels.

The use of inhaled steroids (P = .0475), use of oral steroids (P = .02), and total steroid dose (P = .001) all showed significant inverse correlations with VitD levels. The amount of mitogen-activated protein kinase phosphatase 1 and IL10 mRNA induced by VitD plus DEX was significantly greater than that induced by DEX alone (P < .01). In an experimental model of steroid resistance in which DEX alone did not inhibit T-cell proliferation, addition of VitD to DEX resulted in significant dose-dependent suppression of cell proliferation.

Conclusions: Corticosteroid use and worsening airflow limitation are associated with lower VitD serum levels in asthmatic patients. VitD enhances glucocorticoid action in PBMCs from asthmatic patients and enhances the immunosuppressive function of DEX in vitro.

Searing DA, et al.Decreased serum vitamin D levels in children with asthma are associated with increased corticosteroid use. The Journal of Allergy and Clinical Immunology 2010;125(5):995-1000.

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