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Abstracts

Life Extension Magazine January 2010
Abstracts

Phytonutrients

Fruit and vegetable consumption and risk factors for cardiovascular disease.

The international guidelines issued by the World Health Organization recommend reduction in dietary saturated fat and cholesterol intakes as means to prevent hypercholesterolemia and cardiovascular disease (CVD); however, only limited data are available on the benefits of fruit and vegetable consumption on CVD risk factors in a community-based population. The aim of this study was to examine whether, and to what extent, intake of fruits and vegetables is inversely associated with CVD risk factors in adults. In this population-based cross-sectional study, a representative sample of 840 Tehranian adults (male and female) aged 18 to 74 years was randomly selected in 1998. Multivariate logistic regression adjusted for lifestyle and nutritional confounders was used in 2 models. After adjusting for confounders, dietary fruit and vegetable were found to be significantly and inversely associated with CVD risk factors. Adjusted odds ratio for high low-density lipoprotein concentrations were 1.00, 0.88, 0.81, and 0.75 (P for trend < .01) in the first model, which was adjusted for age, sex, keys score, body mass index, energy intake, smoking status, dietary cholesterol, and history of diabetes mellitus and coronary artery disease, a trend which was not appreciably altered by additional adjustment for education, physical activity, and saturated, polyunsaturated, and total fat intakes. This association was observed across categories of smoking status, physical activity, and tertiles of the Keys score. Exclusion of subjects with prevalent diabetes mellitus or coronary artery disease did not alter these results significantly. Consumption of fruits and vegetables is associated with lower concentrations of total and low-density lipoprotein cholesterol and with the risk of CVD per se in a dose-response manner.

Metabolism. 2009 Apr;58(4):460-8

Supplementation of conventional therapy with the novel grain Salba (Salvia hispanica L.) improves major and emerging cardiovascular risk factors in type 2 diabetes: results of a randomized controlled trial.

OBJECTIVE: To determine whether addition of Salba (Salvia hispanica L.), a novel whole grain that is rich in fiber, alpha-linolenic acid (ALA), and minerals to conventional treatment is associated with improvement in major and emerging cardiovascular risk factors in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using a single-blind cross-over design, subjects were randomly assigned to receive either 37 +/- 4 g/day of Salba or wheat bran for 12 weeks while maintaining their conventional diabetes therapies. Twenty well-controlled subjects with type 2 diabetes (11 men and 9 women, aged 64 +/- 8 years, BMI 28 +/- 4 kg/m2, and A1C 6.8 +/- 0.9%) completed the study. This study was set in the outpatient clinic of the Risk Factor Modification Center, St. Michael’s Hospital, Toronto, Canada. RESULTS: Compared with the control treatment, Salba reduced systolic blood pressure (SBP) by 6.3 +/- 4 mmHg (P < 0.001), high-sensitivity C-reactive protein (hs-CRP) (mg/l) by 40 +/- 1.6% (P = 0.04), and vonWillebrand factor (vWF) by 21 +/- 0.3% (P = 0.03), with significant decreases in A1C and fibrinogen in relation to the Salba baseline but not with the control treatment. There were no changes in safety parameters including liver, kidney and hemostatic function, or body weight. Both plasma ALA and eicosapentaenoic polyunsaturated fatty acid levels were increased twofold (P < 0.05) while consuming Salba. CONCLUSIONS: Long-term supplementation with Salba attenuated a major cardiovascular risk factor (SBP) and emerging factors (hs-CRP and vWF) safely beyond conventional therapy, while maintaining good glycemic and lipid control in people with well-controlled type 2 diabetes.

Diabetes Care. 2007 Nov;30(11):2804-10

Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat.

Chemoprevention by chlorophyll (Chl) was investigated in a rat multi-organ carcinogenesis model. Twenty-one male F344 rats in three gavage groups (N = 7 rats each) received five daily doses of 250 microg/kg [(3)H]-aflatoxin B(1) ([(3)H]-AFB(1)) alone, or with 250 mg/kg chlorophyllin (CHL), or an equimolar amount (300 mg/kg) of Chl. CHL and Chl reduced hepatic DNA adduction by 42% (P = 0.031) and 55% (P = 0.008), respectively, AFB(1)-albumin adducts by 65% (P < 0.001) and 71% (P < 0.001), respectively, and the major AFB-N(7)-guanine urinary adduct by 90% (P = 0.0047) and 92% (P = 0.0029), respectively. To explore mechanisms, fluorescence quenching experiments established formation of a non-covalent complex in vitro between AFB(1) and Chl (K(d) = 1.22 +/- 0.05 microM, stoichiometry = 1Chl:1AFB(1)) as well as CHL (K(d) = 3.05 +/- 0.04 microM; stoichiometry = 1CHL:1AFB(1)). The feces of CHL and Chl co-gavaged rats contained 137% (P = 0.0003) and 412% (P = 0.0048) more AFB(1) equivalents, respectively, than control feces, indicating CHL and Chl inhibited AFB(1) uptake. However, CHL or Chl treatment in vivo did not induce hepatic quinone reductase (NAD(P)H:quinone oxidoreductase) or glutathione S-transferase (GST) above control levels. These results are consistent with a mechanism involving complex-mediated reduction of carcinogen uptake, and do not support a role for phase II enzyme induction in vivo under these conditions. In a second study, 30 rats in three experimental groups were dosed as in study 1, but for 10 days. At 18 weeks, CHL and Chl had reduced the volume percent of liver occupied by GST placental form-positive foci by 74% (P < 0.001) and 77% (P < 0.001), respectively compared with control livers. CHL and Chl reduced the mean number of aberrant crypt foci per colon by 63% (P = 0.0026) and 75% (P = 0.0004), respectively. These results show Chl and CHL provide potent chemoprotection against early biochemical and late pathophysiological biomarkers of AFB(1) carcinogenesis in the rat liver and colon.

Carcinogenesis. 2007 Jun;28(6):1294-302

The effects of spirulina on allergic rhinitis.

The prevalence of allergic rhinitis is increasing globally due to various causes. It affects the quality life of a large group of people in all around the world. Allergic rhinitis still remains inadequately controlled with present medical means. The need of continuous medical therapy makes individuals anxious about the side effects of the drugs. So there is a need for an alternative strategy. Effects of spirulina, tinospora cordifolia and butterbur were investigated recently on allergic rhinitis in just very few investigations. Spirulina represents a blue-green alga that is produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. This double blind, placebo controlled study, evaluated the effectiveness and tolerability of spirulina for treating patients with allergic rhinitis. Spirulina consumption significantly improved the symptoms and physical findings compared with placebo (P < 0.001***) including nasal discharge, sneezing, nasal congestion and itching. Spirulina is clinically effective on allergic rhinitis when compared with placebo. Further studies should be performed in order to clarify the mechanism of this effect.

Eur Arch Otorhinolaryngol. 2008 Oct;265(10):1219-23

Wholegrain foods made from a novel high-amylose barley variety (Himalaya 292) improve indices of bowel health in human subjects.

Himalaya 292 (Hordeum vulgare var. Himalaya 292) is a novel hull-less barley variety lacking activity of a key enzyme of starch synthesis giving a grain containing less total starch, more amylose and higher total dietary fibre. Animal trials have shown that Himalaya 292 contains more resistant starch and has greater positive impact on biomarkers of large-bowel health than comparable wholegrain cereal products. The present study compared the effects of foods made from wholegrain Himalaya 292 with those made from wholegrain wheat on faecal biomarkers of bowel health in human subjects. Seventeen male and female volunteers aged 31-66 years consumed similar quantities of Himalaya 292, whole-wheat or refined cereal foods daily for 4 weeks in a randomised cross-over design. Total dietary fibre intakes from weighed food records were 45, 32, and 21 g/d for the Himalaya 292, whole-wheat and refined cereal periods, respectively. Compared with the refined cereal foods, consumption of Himalaya 292 foods resulted in 33% higher faecal weight, a lowering of faecal pH from 7.24 to 6.98, a 42% higher faecal concentration and a 91% higher excretion of butyrate, a 57% higher faecal total SCFA excretion and a 33% lower faecal p-cresol concentration. pH and butyrate concentration and excretion were also significantly different compared with wholemeal wheat. It is concluded that consumption of a diet that included foods made from Himalaya 292 supplied more fibre and improved indices of bowel health compared with refined cereal foods and, for some indices, similar wholemeal wheat foods at equivalent levels of intake.

Br J Nutr. 2008 May;99(5):1032-40

Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer patients: a pilot study.

Myelotoxicity induced by chemotherapy may become life-threatening. Neutropenia may be prevented by granulocyte colony-stimulating factors (GCSF), and epoetin may prevent anemia, but both cause substantial side effects and increased costs. According to non-established data, wheat grass juice (WGJ) may prevent myelotoxicity when applied with chemotherapy. In this prospective matched control study, 60 patients with breast carcinoma on chemotherapy were enrolled and assigned to an intervention or control arm. Those in the intervention arm (A) were given 60 cc of WGJ orally daily during the first three cycles of chemotherapy, while those in the control arm (B) received only regular supportive therapy. Premature termination of treatment, dose reduction, and starting GCSF or epoetin were considered as “censoring events.” Response rate to chemotherapy was calculated in patients with evaluable disease. Analysis of the results showed that five censoring events occurred in Arm A and 15 in Arm B (P = 0.01). Of the 15 events in Arm B, 11 were related to hematological events. No reduction in response rate was observed in patients who could be assessed for response. Side effects related to WGJ were minimal, including worsening of nausea in six patients, causing cessation of WGJ intake. In conclusion, it was found that WGJ taken during FAC chemotherapy may reduce myelotoxicity, dose reductions, and need for GCSF support, without diminishing efficacy of chemotherapy. These preliminary results need confirmation in a phase III study.

Nutr Cancer. 2007;58(1):43-8

Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection.

The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). Supplementation increased survival, decreased the severity of infection, and shortened recovery time following intranasal infection with flu, as determined by the recovery of body weight and epithelial integrity in the lungs. AHCC increased NK activity in lungs at d 1 (P < 0.05) and d 4 (P < 0.01) and in the spleen at d 2 postinfection (P < 0.01). Supplementation increased the percentage (P < 0.05) and number (P < 0.01) of NK1.1+ cells in the lung and reduced the infiltration of lymphocytes and macrophages compared with controls (P < 0.01). These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. Bolstering innate immunity with dietary bioactives may be one avenue for improving the immune response to primary flu infection.

J Nutr. 2006 Nov;136(11):2868-73

Cordysinocan, a polysaccharide isolated from cultured Cordyceps, activates immune responses in cultured T-lymphocytes and macrophages: signaling cascade and induction of cytokines.

Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumor, anti-oxidation and stimulating the immune response; however, the identity of active component(s) is not determined. A strain of Cordyceps sinensis, namely UST 2000, has been isolated. By using activity-guided purification, a novel polysaccharide of molecular weight approximately 82 kDa was isolated from the conditioned medium of cultured Cordyceps. The isolated exo-polysaccharide, namely cordysinocan, contains glucose, mannose, galactose in a ratio of 2.4:2:1. In cultured T-lymphocytes, application of cordysinocan induced the cell proliferation and the secretion of interleukin-2, interleukin-6 and interleukin-8. In addition, the phosphorylation of extracellular signal-regulated kinases (ERK) was induced transiently by the treatment of cordysinocan. Moreover, application of cordysinocan in cultured macrophages increased the phagocytosis activity and the enzymatic activity of acid phosphatase. These results therefore verify the important role of Cordyceps polysaccharide in triggering such immune responses.

J Ethnopharmacol. 2009 Jul 6;124(1):61-8

Clinical application of Cordyceps sinensis on immunosuppressive therapy in renal transplantation.

OBJECTIVE: We sought to explore the adjunctive effects of Cordyceps sinensis (CS) in clinical renal transplantation. MATERIALS AND METHODS: Patients (n = 202) were divided randomly by lottery into a treatment (n = 93) and a control group (n = 109). Patients in the treatment group were treated with CS 1.0 g 3 times a day in addition to the immunosuppressive regimen given to the control group. We compared patient and graft survivals, incidence, time and severity of acute rejection episodes, chronic allograft nephropathy (CAN), hepatotoxicity and nephrotoxicity, biochemistry parameters including indicators of liver and kidney functions, fats, proteinuria, dosages, and whole blood concentrations of cyclosporine (CsA). RESULTS: Patient and graft survival rates, serum creatinine (SCr), and blood urea nitrogen (BUN) were not significantly different between the 2 groups (P > .05). Serum uric acid (UA) and 24-hour urinary total protein (24-hour UTP) were

significantly lower in the treatment group than in the control group (P < .05). The incidences (11.83% vs 15.60%) and times to acute renal allograft rejection (23.48 +/- 7.22 vs 22.27 +/- 8.03 days posttransplantation) were not significantly different between the treated and control groups (P > .05). Patients receiving thymoglobulin antirejection therapy (3 cases) were fewer in the heated versus control group (13 cases; P = .014). The incidences of hepatotoxicity and nephrotoxicity in the treated group were 12.90% and 19.35%, significantly lower than 24.77% and 33.94% in the control group, respectively (P < .05). At 2 to 6 months posttransplantation, the CsA dosages in the treated group were significantly lower than those in the control group (P < .05). The whole blood trough CsA concentrations in the treated group were significantly lower than those in the control group at 3 to 6 months posttransplantation (P < .05). The decreasing trends of the 2 aforementioned parameters in the treatment group were approximately linear among treated subjects compared with approximately quadratic in the control group (P < .05). The incidence of CAN in the treated group was 7.53%, which was significantly lower than 18.35% in the control group (P = .024). The 24-hour UTP level in CAN patients within the treated group was significantly lower than the control group after transplantation (P = .045). The differences in total bilirubin, SCr, serum UA, and total cholesterol levels among otherwise normal patients in the treated group were significantly lower than those among the control group (P < .05). CONCLUSIONS: The use of CS may allow decreased dosages and concentrations of CsA causing fewer side effects without an increased risk of acute rejection. In addition, CS with reduced dose CsA may decrease proteinuria and retard CAN progression.

Transplant Proc. 2009 Jun;41(5):1565-9

Induction of apoptosis and inhibition of telomerase activity in human lung carcinoma cells by the water extract of Cordyceps militaris.

Cordyceps militaris is well known as a traditional medicinal mushroom and is a potentially interesting candidate for use in cancer treatment. In this study, the potential of the water extract of C. militaris (WECM) to induce apoptosis in human lung carcinoma A549 cells and its effects on telomerase activity were investigated. The growth inhibition and apoptosis induction by WECM treatment in A549 cells was associated with the induction of Fas, catalytic activation of caspase-8, and Bid cleavage. Activation of caspases, downregulation of anti-apoptotic Bcl-2 expression, and upregulation of pro-apoptotic Bax protein were also observed in WECM-treated cells. However, the cytotoxic effects and apoptotic characteristics induced by WECM were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that caspase-3 plays in the process. In addition, WECM exerted a dose-dependent inhibition of telomerase activity via downregulation of human telomerase reverse transcriptase (hTERT), c-myc and Sp1 expression. Taken together, the data from this study indicate that WECM induces the apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic caspase pathways. It was also conclude that apoptotic events due to WECM were mediated with diminished telomerase activity through the inhibition of hTERT transcriptional activity.

Food Chem Toxicol. 2009 Jul;47(7):1667-75