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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.

Dietary patterns and breast cancer risk in the Shanghai Breast Cancer Study.

X Cui, Q Dai, M Tseng, et al.

The association of breast cancer with dietary patterns such as a western diet has not been studied in Asian women. We examined this among Shanghai Breast Cancer Study participants. Cases were of ages 25 to 64 years, diagnosed 08/1996-03/1998, and identified through a rapid case ascertainment system supplemented by the Shanghai Cancer Registry. Controls, selected from the general population of urban Shanghai, were frequency matched to cases by 5-year age group. Participants provided information on diet, lifestyle, and reproductive factors. In principal component analysis among 1,556 controls, two patterns emerged: a "vegetable-soy" pattern (tofu, cauliflower, beans, bean sprouts, green leafy vegetables) and a "meat-sweet" pattern (shrimp, chicken, beef, pork, candy, desserts). In adjusted unconditional logistic regression analyses including 1,446 cases and 1,549 controls with complete covariate data, risk was not associated with the vegetable-soy pattern. It was associated with the meat-sweet pattern (4th versus 1st quartile: odds ratio, 1.3; 95% confidence interval, 1.0-1.7; P(trend) = 0.03), but only in postmenopausal women, specifically among those with estrogen receptor-positive tumors (4th versus 1st quartile: odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P(trend) = 0.03). Our findings indicate that a western diet increases breast cancer risk in postmenopausal Chinese women. They also suggest the value of quantifying aggregate risk for common combinations of foods.

Source: Cancer Epidemiol Biomarkers Prev, July 2007;16(7):1443-8.


Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin.

Milan Fiala, Philip T. Liu, Araceli Espinosa-Jeffrey, et al.

We have tested a hypothesis that the natural product curcuminoids, which has epidemiologic and experimental rationale for use in AD, may improve the innate immune system and increase amyloid-{beta} (A{beta}) clearance from the brain of patients with sporadic Alzheimer's disease (AD). Macrophages of a majority of AD patients do not transport A{beta} into endosomes and lysosomes, and AD monocytes do not efficiently clear A{beta} from the sections of AD brain, although they phagocytize bacteria. In contrast, macrophages of normal subjects transport A{beta} to endosomes and lysosomes, and monocytes of these subjects clear A{beta} in AD brain sections. Upon A{beta} stimulation, mononuclear cells of normal subjects up-regulate the transcription of {beta}-1,4-mannosyl-glycoprotein 4-{beta}-N-acetylglucosaminyltransferase (MGAT3) (P < 0.001) and other genes, including Toll like receptors (TLRs), whereas mononuclear cells of AD patients generally down-regulate these genes. Defective phagocytosis of A{beta} may be related to down-regulation of MGAT3, as suggested by inhibition of phagocytosis by using MGAT3 siRNA and correlation analysis. Transcription of TLR3, TLR4, TLR5, TLR7, TLR8, TLR9, and TLR10 upon A{beta} stimulation is severely depressed in mononuclear cells of AD patients in comparison to those of control subjects. In mononuclear cells of some AD patients, the curcuminoid compound bisdemethoxycurcumin may enhance defective phagocytosis of A{beta}, the transcription of MGAT3 and TLRs, and the translation of TLR2–4. Thus, bisdemethoxycurcumin may correct immune defects of AD patients and provide a previously uncharacterized approach to AD immunotherapy.

Source: Proc Natl Acad Sci USA, July 24, 2007 [Epub ahead of print].


Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community.

Ravi Dhingra, Lisa Sullivan, Paul F. Jacques, et al.

Background: Consumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals.

Methods and Results: We related the incidence of metabolic syndrome and its components to soft drink consumption in participants in the Framingham Heart Study (6039 person-observations, 3470 in women; mean age 52.9 years) who were free of baseline metabolic syndrome. Metabolic syndrome was defined as the presence of >/=3 of the following: waist circumference >/=35 inches (women) or >/=40 inches (men); fasting blood glucose >/=100 mg/dL; serum triglycerides >/=150 mg/dL; blood pressure >/=135/85 mm Hg; and high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women). Multivariable models included adjustments for age, sex, physical activity, smoking, dietary intake of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Cross-sectionally, individuals consuming >/=1 soft drink per day had a higher prevalence of metabolic syndrome (odds ratio [OR], 1.48; 95% CI, 1.30 to 1.69) than those consuming <1 drink per day. On follow-up (mean of 4 years), new-onset metabolic syndrome developed in 765 (18.7%) of 4095 participants consuming <1 drink per day and in 474 (22.6%) of 2059 persons consuming >/=1 soft drink per day. Consumption of >/=1 soft drink per day was associated with increased odds of developing metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74), obesity (OR, 1.31; 95% CI, 1.02 to 1.68), increased waist circumference (OR, 1.30; 95% CI, 1.09 to 1.56), impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48), higher blood pressure (OR, 1.18; 95% CI, 0.96 to 1.44), hypertriglyceridemia (OR, 1.25; 95% CI, 1.04 to 1.51), and low high-density lipoprotein cholesterol (OR, 1.32; 95% CI 1.06 to 1.64).

Conclusions: In middle-aged adults, soft drink consumption is associated with a higher prevalence and incidence of multiple metabolic risk factors.

Source: Circulation, July 23, 2007 [Epub ahead of print].


Reduction in neural-tube defects after folic acid fortification in Canada.

P De Wals, F Tairou, MI Van Allen, et al.

Background: In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented.

Methods: The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented.

Results: A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively).

Conclusions: Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high.

Source: N Engl J Med, July 12, 2007;357(2):135-42.


Effects of high-intensity interval walking training on physical fitness and blood pressure in middle-aged and older people.

K Nemoto, H Gen-no, S Masuki, et al.

Objective: To examine whether high-intensity interval walking training increased thigh muscle strength and peak aerobic capacity and reduced blood pressure more than moderate-intensity continuous walking training.

Participants and Methods: From May 18, 2004, to October 15, 2004 (5-month study period), 60 men and 186 women with a mean +/- SD age of 63 +/- 6 years were randomly divided into 3 groups: no walking training, moderate-intensity continuous walking training, and high-intensity interval walking training. Participants in the moderate-intensity continuous walking training group were instructed to walk at approximately 50% of their peak aerobic capacity for walking, using a pedometer to verify that they took 8000 steps or more per day for 4 or more days per week. Those in the high-intensity interval walking training group, who were monitored by accelerometry, were instructed to repeat 5 or more sets of 3-minute low-intensity walking at 40% of peak aerobic capacity for walking followed by a 3-minute high-intensity walking above 70% of peak aerobic capacity for walking per day for 4 or more days per week. Isometric knee extension and flexion forces, peak aerobic capacity for cycling, and peak aerobic capacity for walking were all measured both before and after training.

Results: The targets were met by 9 of 25 men and 37 of 59 women in the no walking training group, by 8 of 16 men and 43 of 59 women in the moderate-intensity continuous walking training group, and by 11 of 19 men and 31 of 68 women in the high-intensity interval walking training group. In the high-intensity interval walking training group, isometric knee extension increased by 13%, isometric knee flexion by 17%, peak aerobic capacity for cycling by 8%, and peak aerobic capacity for walking by 9% (all, P<.001), all of which were significantly greater than the increases observed in the moderate-intensity continuous walking training group (all, P<.01). Moreover, the reduction in resting systolic blood pressure was higher for the high-intensity interval walking training group (P=.01).

Conclusion: High-intensity interval walking may protect against age-associated increases in blood pressure and decreases in thigh muscle strength and peak aerobic capacity.

Source: Mayo Clin Proc, July 2007;82(7):803-11.


Sugars and satiety: does the type of sweetener make a difference?

P Monsivais, MM Perrigue, A Drewnowski

Background: Widespread use of high-fructose corn syrup (HFCS) in beverages has been linked to rising obesity rates. One hypothesis is that HFCS in beverages has little satiating power.

Objective: The objective of the study was to compare the relative effect of commercial beverages containing sucrose or HFCS on hunger, satiety, and energy intakes at the next meal with the use of a within-subject design.

Design: Thirty-seven volunteers (19 men, 18 women) aged 20-29 y consumed isocaloric cola beverages (215 kcal) sweetened with sucrose, HFCS 42, or HFCS 55. HFCS 42 contains 42% fructose, and HFCS 55 contains 55% fructose. Diet cola (2 kcal), 1%-fat milk (215 kcal), and no beverage were the control conditions. The 5 beverages were consumed at 1010 (2 h after a standard breakfast). Participants rated hunger, thirst, and satiety at baseline and at 20-min intervals after ingestion. A tray lunch (1708 kcal) was served at 1230, and energy intakes were measured. The free sugars content of sucrose-sweetened cola was assayed at the time of the study.

Results: We found no differences between sucrose- and HFCS-sweetened colas in perceived sweetness, hunger and satiety profiles, or energy intakes at lunch. The 4 caloric beverages tended to partially suppress energy intakes at lunch, whereas the no-beverage and diet beverage conditions did not; the effect was significant (P < 0.05) only for 1%-fat milk. Energy intakes in the diet cola and the no-beverage conditions did not differ significantly.

Conclusion: There was no evidence that commercial cola beverages sweetened with either sucrose or HFCS have significantly different effects on hunger, satiety, or short-term energy intakes.

Source: Am J Clin Nutr, July 2007;86(1):116-23.


Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents.

FL Weng, J Shults, MB Leonard, et al.

Background: Serum 25-hydroxyvitamin D [25(OH)D] concentrations serve as a biomarker for vitamin D stores. Prior studies have not examined the risk factors for low vitamin D concentrations in a multiethnic sample of US youth across a broad age range.

Objective: The objective was to determine the prevalence of and factors associated with low concentrations of 25(OH)D in children and adolescents. DESIGN: Serum 25(OH)D concentrations were measured in 382 healthy children aged 6-21 y living in the northeastern United States. Dietary and supplemental vitamin D intake was assessed by interview. Fat and lean mass were assessed by dual-energy X-ray absorptiometry. Multivariable ordinal logistic regression was used to determine factors associated with decreased concentrations of 25(OH)D.

Results: The median concentration of 25(OH)D was 28 ng/mL (interquartile range: 19-35 ng/mL), and 55% of subjects had 25(OH)D concentrations <30 ng/mL. 25(OH)D concentrations were inversely correlated with parathyroid hormone concentrations (Spearman's r = -0.31, P < 0.001) but were not significantly correlated with 1,25-dihydroxyvitamin D concentrations. In the multivariable model, older age (P < 0.001), black race [odds ratio (OR): 14.2; 95% CI: 8.53, 23.5], wintertime study visit (OR: 3.55; 95% CI: 2.29, 5.50), and total daily vitamin D intake <200 IU (OR: 1.58; 95% CI: 1.02, 2.46) were associated with low vitamin D concentrations. Fat and lean mass were not independently associated with vitamin D status in this healthy-weight sample.

Conclusion: Low serum 25(OH)D concentrations are prevalent in otherwise healthy children and adolescents in the northeastern United States and are related to low vitamin D intake, race, and season.

Source: Am J Clin Nutr, July 2007;86(1):150-8.


Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis.

KM Connor, JP Sangiovanni, C Lofqvist, et al.

Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.

Source: Nat Med, July 2007;13(7):868-73.


Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins.

T Islam, WJ Gauderman, W Cozen, TM Mack

Objective: To address the role of childhood sun exposure on the risk of multiple sclerosis (MS) after controlling for genetic susceptibility, we investigated the association between sun exposure and MS comparing disease-discordant monozygotic (MZ) twins.

Method: Twins with MS were sought by yearly newspaper advertisements throughout North America from 1980 to 1992. Diagnosis was verified by updated medical documentation through 2005. This analysis was restricted to 79 disease- and exposure-discordant monozygotic twin pairs who had ranked themselves before 1993 in relation to each of nine childhood sun exposure activities. A sun exposure index (SI) was defined as the sum of those exposures for which one twin ranked higher than his or her co-twin. The SI difference within each twin pair was calculated by subtracting the SI value of the affected twin from the SI value of the unaffected twin (range -9 to +9). The results were then analyzed using conditional logistic models.

Result: Each of the nine sun exposure-related activities during childhood seemed to convey a strong protection against MS within MZ twin pairs. Depending on the activity, the odds ratio (OR) ranged from 0.25 to 0.57. For example, the risk of subsequent MS was substantially lower (OR 0.40, 95% CI 0.19 to 0.83) for the twin who spent more time suntanning in comparison with the co-twin. For each unit increase in SI, the relative risk of MS decreased by 25%.

Conclusion: Early sun avoidance seems to precede the diagnosis of multiple sclerosis (MS). This protective effect is independent of genetic susceptibility to MS.

Source: Neurology, July 24, 2007;69(4):381-8.


Prospective study of fruit and vegetable intake and risk of prostate cancer.

VA Kirsh, U Peters, ST Mayne, et al.

Background: Several epidemiologic studies have reported associations between fruit and vegetable intake and reduced risk of prostate cancer, but the findings are inconsistent and data on clinically relevant advanced prostate cancer are limited.

Methods: We evaluated the association between prostate cancer risk and intake of fruits and vegetables in 1338 patients with prostate cancer among 29361 men (average follow-up = 4.2 years) in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Participants completed both a general risk factor and a 137-item food-frequency questionnaire at baseline. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.

Results: Vegetable and fruit consumption was not related to prostate cancer risk overall; however, risk of extraprostatic prostate cancer (stage III or IV tumors) decreased with increasing vegetable intake (RR = 0.41, 95% CI = 0.22 to 0.74, for high versus low intake; P(trend) = .01). This association was mainly explained by intake of cruciferous vegetables (RR = 0.60, 95% CI = 0.36 to 0.98, for high versus low intake; P(trend) = .02), in particular, broccoli (RR = 0.55, 95% CI = 0.34 to 0.89, for >1 serving per week versus <1 serving per month; P(trend) = .02) and cauliflower (RR = 0.48, 95% CI = 0.25 to 0.89 for >1 serving per week versus <1 serving per month; P(trend) = .03). We found some evidence that risk of aggressive prostate cancer decreased with increasing spinach consumption, but the findings were not consistently statistically significant when restricted to extraprostatic disease.

Conclusion: High intake of cruciferous vegetables, including broccoli and cauliflower, may be associated with reduced risk of aggressive prostate cancer, particularly extraprostatic disease.

Source: J Natl Cancer Inst, July 24; 2007 [Epub ahead of print].



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