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Critical Research

Critical Research is a regular feature in Naturopathy Digest. Each month, we provide abstracts from studies published in the top peer-reviewed journals; each abstract includes the complete citation and an online link to the journal. Whenever possible, this link directs you to a page where you can order the full text of the study, if desired.

This Month's Featured Abstract

Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels.

Williams CM, El Mohsenb MA, Vauzourbet D, et al.

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaKMII and CaCMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to increases in the activation state of Akt, mTOR, and the levels of Arc.Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway.

Source: Free Radic Biol Med. 2008 [E-pub ahead of print].

Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: A randomized, double blind placebo controlled trial

Bundy R, Walker AF, Middleton RW, et al.s

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0mmol/l, with 75 suitable volunteers randomized onto the trial. Volunteers consumed 1280mg of a standardized ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favorable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.

Source: Phytomedicine. 2008 Sep;15(9):668-75.

Outdoor activity reduces the prevalence of myopia in children

Rose KA, Morgan IG, Ip J, et al.

Objective: To assess the relationship of near, midworking distance, and outdoor activities with prevalence of myopia in school-aged children.

Design: Cross-sectional study of 2 age samples from 51 Sydney schools, selected using a random cluster design.

Participants: One thousand seven hundred sixty-five 6-year-olds (year 1) and 2367 12-year-olds (year 7) participated in the Sydney Myopia Study from 2003 to 2005.

Methods: Children had a comprehensive eye examination, including cycloplegic refraction. Parents and children completed detailed questionnaires on activity.

Main Outcome Measures: Myopia prevalence and mean spherical equivalent (SE) in relation to patterns of near, midworking distance, and outdoor activities. Myopia was defined as SE refraction < or = -0.5 diopters (D).

Results: Higher levels of outdoor activity (sport and leisure activities) were associated with more hyperopic refractions and lower myopia prevalence in the 12-year-old students. Students who combined high levels of near work with low levels of outdoor activity had the least hyperopic mean refraction (+0.27 D; 95% confidence interval [CI], 0.02-0.52), whereas students who combined low levels of near work with high levels of outdoor activity had the most hyperopic mean refraction (+0.56 D; 95% CI, 0.38-0.75). Significant protective associations with increased outdoor activity were seen for the lowest (P = 0.04) and middle (P = 0.02) tertiles of near-work activity. The lowest odds ratios for myopia, after adjusting for confounders, were found in groups reporting the highest levels of outdoor activity. There were no associations between indoor sport and myopia. No consistent associations between refraction and measures of activity were seen in the 6-year-old sample.

Conclusions: Higher levels of total time spent outdoors, rather than sport per se, were associated with less myopia and a more hyperopic mean refraction, after adjusting for near work, parental myopia, and ethnicity.

Source: Ophthalmology. 2008 Aug;115(8):1279-85.

Adherence to Mediterranean diet and health status: meta-analysis

Sofi F, Cesari F, Abbate R, et al.

Objective: To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention setting. DESIGN: Meta-analysis of prospective cohort studies.

Data Sources: English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008. Studies reviewed Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574 299 subjects followed for a time ranging from three to 18 years were included.

Results: The cumulative analysis among eight cohorts (514 816 subjects and 33 576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson’s disease and Alzheimer’s disease (0.87, 0.80 to 0.96).

Conclusions: Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson’s disease and Alzheimer’s disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.

Source: BMJ. 2008 Sep 11;337:a1344.

Sleep quality and elevated blood pressure in adolescents

Javaheri S, Storfer-Isser A, Rosen CL, Redline S

Background: We assessed whether insufficient sleep is associated with prehypertension in healthy adolescents.

MethodsandResults: We undertook a cross-sectional analysis of 238 adolescents, all without sleep apnea or severe comorbidities. Participants underwent multiple-day wrist actigraphy at home to provide objective estimates of sleep patterns. In a clinical research facility, overnight polysomnography, anthropometry, and 9 blood pressure measurements over 2 days were made. Exposures were actigraphy-defined low weekday sleep efficiency, an objective measure of sleep quality (low sleep efficiency < or =85%), and short sleep duration (< or =6.5 hours). The main outcome was prehypertension (> or =90th percentile for age, sex, and height), with systolic and diastolic blood pressures as continuous measures as secondary outcomes. Prehypertension, low sleep efficiency, and short sleep duration occurred in 14%, 26%, and 11% of the sample, respectively. In unadjusted analyses, the odds of prehypertension increased 4.5-fold (95% CI, 2.1 to 9.7) in adolescents with low sleep efficiency and 2.8-fold (95% CI, 1.1 to 7.3) in those with short sleep. In analyses adjusted for sex, body mass index percentile, and socioeconomic status, the odds of prehypertension increased 3.5-fold (95% CI, 1.5. 8.0) for low sleep efficiency and 2.5-fold (95% CI, 0.9 to 6.9) for short sleep. Adjusted analyses showed that adolescents with low sleep efficiency had on average a 4.0+/-1.2-mm Hg higher systolic blood pressure than other children (P<0.01).

Conclusions: Poor sleep quality is associated with prehypertension in healthy adolescents. Associations are not explained by socioeconomic status, obesity, sleep apnea, or known comorbidities, suggesting that inadequate sleep quality is associated with elevated blood pressure.

Source: Circulation. 2008 Sep 2;118(10):1034-40.

25-hydroxyvitamin D levels and the risk of mortality in the general population

Melamed ML, Michos ED, Post W, Astor B

Background: In patients undergoing dialysis, therapy with calcitriol or paricalcitol or other vitamin D agents is associated with reduced mortality. Observational data suggests that low 25-hydroxyvitamin D levels (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown.

Methods: We tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the Third National Health and Nutrition Examination Survey (NHANES III) linked mortality files. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000.

Results: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL [to convert to nanomoles per liter, multiply by 2.496]), while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models (adjusted for baseline demographics, season, and traditional and novel CVD risk factors), compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The adjusted models of CVD and cancer mortality revealed a higher risk, which was not statistically significant.

Conclusion: The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Source: Arch Intern Med. 2008 Aug 11;168(15):1629-37.

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