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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

Vegetables, fruit, and antioxidant-related nutrients and risk of non-Hodgkin's lymphoma: a National Cancer Institute Surveillance, Epidemiology, and End Results population-based case-control study.

Linda E Kelemen, James R Cerhan, Unhee Lim, Scott Davis, Wendy Cozen, Maryjean Schenk, Joanne Colt, Patricia Hartge, and Mary H. Ward

Background: Factors related to DNA damage and altered immunologic responses, such as reactive oxygen species production, are associated with the risk of non-Hodgkin's lymphoma (NHL).

Objective: The aim was to evaluate NHL risk with intakes of vegetables, fruit, and nutrients involved in antioxidant activities.

Design: Incident case subjects aged 20-74 y were identified between 1998 and 2000 from a National Cancer Institutesponsored study by using four Surveillance, Epidemiology, and End Results registries. Control subjects, who were selected by random dialing (<65 y) and from Medicare files (65 y), were matched to cases by age, center, race, and sex. Of 1,321 case and 1,057 control subjects who enrolled, dietary data were collected on a subset (466 cases and 391 controls). Carotenoid intakes were estimated by using updated values from the US Department of Agriculture nutrient databases. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs.

Results: NHL risk was inversely associated with higher number of weekly servings of all vegetables (multivariable OR for highest compared with lowest quartile: 0.58; 95% CI: 0.35, 0.95; P for trend = 0.04), green leafy vegetables (OR: 0.59; 95% CI: 0.36, 0.96; P for trend = 0.01), and cruciferous vegetables (OR: 0.62; 95% CI: 0.39, 1.00; P for trend = 0.05) and with higher daily intakes of lutein and zeaxanthin (OR: 0.54; 95% CI: 0.32, 0.91; P for trend = 0.06) and zinc (OR: 0.58; 95% CI: 0.36, 0.91; P for trend = 0.02). An effect modification by exercise and NHL subtype was observed with some food groups and nutrients.

Conclusion: Higher intakes of vegetables, lutein and zeaxanthin, and zinc are associated with a lower NHL risk.

Source: American Journal of Clinical Nutrition 2006;83(6):1401-1410.


Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer.

Arshi Malik, Farrukh Afaq, Sami Sarfaraz, Vaqar M. Adhami, Deeba N. Syed, and Hasan Mukhtar

Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and anti-inflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 µg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-XL and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rv1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans.

Source: Proceedings of the National Academy of Sciences 2006;102(41):14813-14818.


An endogenous peptide signal in Arabidopsis activates components of the innate immune response.

Alisa Huffaker, Gregory Pearce, and Clarence A. Ryan

Innate immunity is initiated in animals and plants through the recognition of a variety of pathogen-associated molecules that in animals are called pathogen-associated molecular patterns and in plants are called elicitors. Some plant pathogen-derived elicitors have been identified as peptides, but peptide elicitors derived from the plant itself that activate defensive genes against pathogens have not been previously identified. Here, we report the isolation and characterization of a 23-aa peptide from Arabidopsis, called AtPep1, which activates transcription of the defensive gene defensin (PDF1.2) and activates the synthesis of H2O2, both being components of the innate immune response. The peptide is derived from a 92-aa precursor encoded within a small gene that is inducible by wounding, methyl jasmonate, and ethylene. Constitutive expression of the AtPep1 precursor gene PROPEP1 in transgenic Arabidopsis plants causes a constitutive transcription of PDF1.2. When grown in soil, the transgenic plants exhibited an increased root development compared with WT plants and an enhanced resistance toward the root pathogen Pythium irregulare. Six paralogs of PROPEP1 are present in Arabidopsis, and orthologs have been identified in species of several agriculturally important plant families, where they are of interest for their possible use in crop improvement.

Source: Proceedings of the National Academy of Sciences June 2006;103(26):10098-10103.


Cognitive behavioral therapy vs. Zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial.

Borge Sivertsen, PsyD; Siri Omvik, PsyD; Stale Pallesen, PhD; et al.

Background: Insomnia, a common condition in older adults, is associated with numerous adverse medical, social and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking. The study examined short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia.

Methods and Results: A randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 years; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a Norwegian university-based outpatient clinic for adults and elderly patients. Patients were given one of three therapies: CBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation), sleep medication (7.5 mg zopiclone each night), or placebo medication (n = 12). The trial lasted for six weeks, with two active treatments followed up at six months. Ambulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all three assessment points. CBT resulted in improved short- and long-term outcomes compared with zopiclone on three out of four outcome measures. For most outcomes, zopiclone did not differ from the placebo. Participants receiving CBT improved their sleep efficiency from 81.4 percent at pretreatment to 90.1 percent at the six-month follow-up. The zopiclone group compared with a decrease from 82.3 percent to 81.9 percent. Participants in the CBT group spent much more time in slow-wave sleep (stages three and four) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all three groups. At the six-month review, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone.

Conclusion: These results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults.

Source: Journal of the American Medical Association, June 28, 2006;295(24).


Eugenol and isoeugenol, characteristic aromatic constituents of spices, are biosynthesized via reduction of a coniferyl alcohol ester.

Takao Koeduka, Eyal Fridman, David R. Gang, Daniel G. Vassão, et al.

Phenylpropenes such as chavicol, t-anol, eugenol, and isoeugenol are produced by plants as defense compounds against animals and microorganisms and as floral attractants of pollinators. Moreover, humans have used phenylpropenes since antiquity for food preservation and flavoring and as medicinal agents. Previous research suggested that the phenylpropenes are synthesized in plants from substituted phenylpropenols, although the identity of the enzymes and the nature of the reaction mechanism involved in this transformation have remained obscure. We show here that glandular trichomes of sweet basil (Ocimum basilicum), which synthesize and accumulate phenylpropenes, possess an enzyme that can use coniferyl acetate and NADPH to form eugenol. Petunia (Petunia hybrida cv. Mitchell) flowers, which emit large amounts of isoeugenol, possess an enzyme homologous to the basil eugenol-forming enzyme that also uses coniferyl acetate and NADPH as substrates but catalyzes the formation of isoeugenol. The basil and petunia phenylpropene-forming enzymes belong to a structural family of NADPH-dependent reductases that also includes pinoresinollariciresinol reductase, isoflavone reductase, and phenylcoumaran benzylic ether reductase.

Source: Proceedings of the National Academy of Sciences 2006;103(26):10128-10133.


Serum ionized magnesium levels in relation to metabolic syndrome in type 2 diabetic patients.

Francesco Corica, MD, Andrea Corsonello, MD, Riccardo Ientile, ChD, Domenico Cucinotta, MD, Antonino Di Benedetto, MD, Francesco Perticone, MD, Ligia J. Dominguez, MD and Mario Barbagallo, MD

Objective: To evaluate circulating serum ionized magnesium (i-Mg) concentrations in patients with type 2 diabetes mellitus, and to investigate its relationship with the components of the metabolic syndrome.

Design/Setting: Cross-sectional study; outpatients' service for diabetic patients at the University Hospital of Messina, Italy.

Subjects: 290 patients with type 2 diabetes mellitus.

Measures of Outcome: Serum i-Mg was measured by ion selective electrode. Age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, HbA1c, HDL cholesterol, triglycerides, and urinary albumin excretion rate (UAER) were considered in the analyses. Patients with hypomagnesemia, defined as serum i-Mg <0.46 mmol/l, were compared with those having normal serum i-Mg levels, and variables proven to be associated with low i-Mg levels in the univariate analysis were entered in a multivariable logistic regression model to obtain a deconfounded estimate of the association between metabolic parameters and hypomagnesemia.

Results: In univariate analysis, serum i-Mg levels were significantly reduced in patients with low HDL cholesterol, high triglycerides values, high waist circumference, high blood pressure, microalbuminuria and clinical proteinuria. Hypomagnesemia was highly prevalent in our study population (N = 143, 49.3%). After adjusting for potential confounders, plasma triglycerides (OR = 4.71; 95% CI = 2.56-8.67), waist circumference (OR = 2.21; 95% CI = 1.21-4.04), microalbuminuria (OR = 2.43; 95% CI = 1.16-5.08) and clinical proteinuria (OR = 2.04; 95% CI = 1.02-5.68) were independently associated with hypomagnesemia.

Conclusions: Hypomagnesemia is highly prevalent in diabetic outpatients. High plasma triglycerides, waist circumference and albuminuria are independent correlates of hypomagnesemia.

Source: Journal of the American College of Nutrition 2006;25(3):210-215.



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Date Last Modified - Friday, 17-Oct-2008 12:10:24 PDT