Abstract-Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7Ϯ7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. O bservational studies suggest dietary flavonoids decrease the risk of death from coronary heart disease, 1 cancer, 1 and stroke. 2 Flavonoid-rich foods include fruits and vegetables as well as tea, red wine, and chocolate. 3 The high flavonoid content, particularly in flavanols (ie, catechins) and their procyanidin oligomers, of these foods may contribute to some of their putative cardiovascular benefits. 4,5 The antioxidant protection afforded by flavonoids in the vascular endothelium may reduce the risk for atherosclerosis, including their action of inhibiting the oxidative conversion of NO to peroxynitrite. 6 Accordingly, cocoa flavonoids decreased oxidant-induced peroxynitrite production in vitro 7 and increased NO synthase (NOS) expression and NO-dependent vasorelaxation in rabbit aortic rings. 8 In healthy adults, drinking flavanol-rich cocoa increased NO-dependent vasorelaxation in finger arteries, 9 and eating flavanol-rich dark chocolate (DC) improved flow-mediated dilation (FMD) in brachial arteries in association with an increase in plasma epicatechin. 10 Impaired NO-dependent vasorelaxation also contributes to a dysregulation of blood pressure (BP) 11 and a decrement of insulin-mediated glucose uptake. 12 In contrast, increased endothelial NOS expression and NO bioavailability ameliorate endothelial dysfunction, and thereby have the potential to decrease BP, increase insulin sensitivity, and slow down atherogenetic processes. In this regard, the anthocyanin cyanidin-3-glucoside was able to increase NOS expression and NO bioavailability in vascular endothelial cells. 13 We recently demonstrated decrements in BP and increments in insulin sensitivity in healthy volunteers after 15 days of DC intake. 14 Thus, we studied patients with essential hypertension (EH) to evaluate the effects of flavanol-rich DC on 24-hour ambulatory BP monitoring (ABPM), endotheliumdependent vasorelaxation via FMD of the brachial artery, insulin sensitivity via oral glucose tolerance tests (OGTTs), and 2 serum biomarkers of vascular inflammation: highsensitive C-reactive protein (hsCRP) and intercellular adhesion molecule-1 (ICAM-1).

Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC ameliorated insulin sensitivity and beta-cell function, decreased BP, and increased FMD in IGT hypertensive patients. These findings suggest flavanol-rich, low-energy cocoa food products may have a positive impact on CVD risk factors.

Tea is an important dietary source of flavanols and flavonols. In vitro and animal studies provide strong evidence that tea polyphenols may possess the bioactivity to affect the pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. However, the results from epidemiological and clinical studies of the relationship between tea and health are mixed. International correlations do not support this relationship although several, better controlled case-referent and cohort studies suggest an association with a moderate reduction in the risk of chronic disease. Conflicting results between human studies may arise, in part, from confounding by socioeconomic and lifestyle factors as well as by inadequate methodology to define tea preparation and intake. Clinical trials employing putative intermediary indicators of disease, particularly biomarkers of oxidative stress status, suggest tea polyphenols could play a role in the pathogenesis of cancer and heart disease.

Chamomile (Matricaria recutita L., Chamomilla recutita L., Matricaria chamomilla) is one of the most popular single ingredient herbal teas, or tisanes. Chamomile tea, brewed from dried flower heads, has been used traditionally for medicinal purposes. Evidence-based information regarding the bioactivity of this herb is presented. The main constituents of the flowers include several phenolic compounds, primarily the flavonoids apigenin, quercetin, patuletin, luteolin and their glucosides. The principal components of the essential oil extracted from the flowers are the terpenoids alpha-bisabolol and its oxides and azulenes, including chamazulene. Chamomile has moderate antioxidant and antimicrobial activities, and significant antiplatelet activity in vitro. Animal model studies indicate potent antiinflammatory action, some antimutagenic and cholesterol-lowering activities, as well as antispasmotic and anxiolytic effects. However, human studies are limited, and clinical trials examining the purported sedative properties of chamomile tea are absent. Adverse reactions to chamomile, consumed as a tisane or applied topically, have been reported among those with allergies to other plants in the daisy family, i.e. Asteraceae or Compositae.

Peppermint (Mentha piperita L.) is one of the most widely consumed single ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant leaves, and the essential oil of peppermint are used in traditional medicines. Evidence-based research regarding the bioactivity of this herb is reviewed. The phenolic constituents of the leaves include rosmarinic acid and several flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile components of the essential oil are menthol and menthone. In vitro, peppermint has significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential. Human studies on the GI, respiratory tract and analgesic effects of peppermint oil and its constituents have been reported. Several clinical trials examining the effects of peppermint oil on irritable bowel syndrome (IBS) symptoms have been conducted. However, human studies of peppermint leaf are limited and clinical trials of peppermint tea are absent. Adverse reactions to peppermint tea have not been reported, although caution has been urged for peppermint oil therapy in patients with GI reflux, hiatal hernia or kidney stones.

Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.

Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related side effects. Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. However, other data suggest that antioxidants can protect normal tissues from chemotherapy- or radiation-induced damage without decreasing tumor control. We review some of the data regarding the putative benefits and potential risks of antioxidant supplementation concurrent with cytotoxic therapy. On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.

The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl-alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha-tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products.