A Review of the Health Benefits of Cherries.

Increased oxidative stress contributes to development and progression of several human chronic inflammatory diseases. Cherries are a rich source of polyphenols and vitamin C which have anti-oxidant and anti-inflammatory properties. Our aim is to summarize results from human studies regarding health benefits of both sweet and tart cherries, including products made from them (juice, powder, concentrate, capsules); all referred to as cherries here. We found 29 (tart 20, sweet 7, unspecified 2) published human studies which examined health benefits of consuming cherries. Most of these studies were less than 2 weeks of duration (range 5 h to 3 months) and served the equivalent of 45 to 270 cherries/day (anthocyanins 55-720 mg/day) in single or split doses. Two-thirds of these studies were randomized and placebo controlled. Consumption of cherries decreased markers for oxidative stress in 8/10 studies; inflammation in 11/16; exercise-induced muscle soreness and loss of strength in 8/9; blood pressure in 5/7; arthritis in 5/5, and improved sleep in 4/4. Cherries also decreased hemoglobin A1C (HbA1C), Very-low-density lipoprotein (VLDL) and triglycerides/high-density lipoprotein (TG/HDL) in diabetic women, and VLDL and TG/HDL in obese participants. These results suggest that consumption of sweet or tart cherries can promote health by preventing or decreasing oxidative stress and inflammation.

Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults.

Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits decreased cell proliferation and inflammation in animal studies. We hypothesized that limonin glucoside (LG) supplementation in vivo will decrease the ex vivo proliferation of T cells and the production of inflammatory cytokines by monocytes and T cells. In a double-blind, randomized, cross-over study, 10 overweight/obese human subjects were served purified LG or placebo drinks for 56 days each to determine the effects of LG on immune cell functions. The percentage of CD14+CD36+ cells in whole blood was analyzed by flow cytometry. Peripheral blood mononuclear cells were isolated and activated with CD3 plus CD28 antibodies (T-lymphocyte activation) or lipopolysaccharide (monocyte activation). Interferon γ, tumor necrosis factor α, interleukin (IL) 2, IL-4, and IL-10 were measured in supernatants from activated T cells. Supernatants from activated monocytes were analyzed for the production of tumor necrosis factor α, IL-1ß, and IL-6. Peripheral blood mononuclear cells were prestained with PKH dye and activated with CD3 plus CD28 antibodies to determine the proliferative responses of CD4+ and CD8+ T lymphocytes by flow cytometry. No differences were observed for CD14+CD36+ monocyte populations, T-cell proliferation, or the production of T cell and monocyte cytokines between the 2 treatments. Thus, LG supplementation in vivo did not affect ex vivo functions of T cells and monocytes, whereas it decreased several circulating markers of hepatic inflammation as we previously reported.

Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice.

Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.

Arachidonate 5-lipoxygenase gene variants affect response to fish oil supplementation by healthy African Americans.

Arachidonate 5-lipoxygenase (ALOX5) gene variants that are common in people of African ancestry are associated with a differential cardiovascular disease (CVD) risk that may be ameliorated by intake of (n-3) PUFA, such as EPA or DHA. We conducted a double-masked, placebo (PL)-controlled trial of fish oil (FO) supplements to determine if changes in erythrocyte (n-3) PUFA composition, heart rate, blood pressure, and plasma lipid and lipoprotein concentrations are modified by genotype. Participants received 5 g/d FO (2 g EPA, 1 g DHA) or 5 g/d corn/soy oil (PL). A total of 116 healthy adults of African ancestry with selected genotypes (genotypes = "dd," "d5," and "55" with "d" representing the deletion of 1 or 2 Sp1 binding sites in the ALOX5 promoter and "5" indicating the common allele with 5 sites) were enrolled and 98 completed the study. FO caused significant increases (relative to PL) in erythrocyte EPA, DHA, and total (n-3) PUFA and a decrease in the (n-6) PUFA:(n-3) PUFA ratio in the low-CVD risk "d5" and "55" genotypes but not in the high-risk "dd" genotype. Similarly, HDL particle concentration decreased with FO relative to PL in the "d5" and "55" but not "dd" genotypes. The plasma TG concentration decreased significantly with FO relative to PL in the "d5" but not "dd" and "55" genotypes. No changes were seen in LDL particle or cholesterol concentrations, heart rate, or blood pressure. These findings indicate that the efficacy of FO supplements vary by ALOX5 genotype.

Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice.

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men.

BACKGROUND: Short-term high copper intake does not appear to affect indexes of copper status or functions related to copper status, but the effects of long-term high copper intake are unknown. OBJECTIVE: A study was conducted in men to determine the effect of long-term high copper intake on indexes of copper status, oxidant damage, and immune function. DESIGN: Nine men were confined to a metabolic research unit (MRU) for 18 d and were fed a 3-d rotating menu providing an average of 1.6 mg Cu/d. The men continued the study under free-living conditions for 129 d and supplemented their usual diets with 7 mg Cu/d. The men then returned to the MRU for 18 d of the same diet as during the first period, except that copper intake was 7.8 mg/d. Plasma copper, ceruloplasmin activity, ceruloplasmin protein, plasma malondialdehyde, benzylamine oxidase activity, erythrocyte superoxide dismutase, hair copper, urinary copper, and urinary thiobarbituric acid-reactive substances were measured during each MRU period. RESULTS: Ceruloplasmin activity, benzylamine oxidase, and superoxide dismutase were significantly higher at the end of the second MRU period than at the end of the first. Urinary copper excretion, hair copper concentrations, and urinary thiobarbituric acid-reactive substances were significantly higher during the second MRU period than during the first. Polymorphonuclear cell count, the percentage of white blood cells, lymphocyte count, and interleukin 2R were affected by copper supplementation. Antibody titer for the Beijing strain of influenza virus was significantly lower in supplemented subjects after immunization than in unsupplemented control subjects. CONCLUSIONS: Under highly controlled conditions, long-term high copper intake results in increases in some indexes of copper status, alters an index of oxidant stress, and affects several indexes of immune function. The physiologic implications of these changes are unknown.

Consumption of cherries lowers plasma urate in healthy women.

To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.

Immune functions are maintained in healthy men with low zinc intake.

Although immunity is impaired during severe zinc deficiency, there is limited information about the effects of mild zinc depletion on immune response in humans. We evaluated the effects of a zinc-restricted diet (4.6 mg/d) on several indices of immunity in 8 healthy men. The subjects consumed zinc supplements with 9.1 mg/d during the 5-wk baseline (BL) and 5-wk repletion (RP) periods, and placebos during the 10-wk zinc-restriction (ZR) period. Leukocyte numbers and functions were studied at the end of each metabolic period. After ZR, there were reductions in the proliferation of peripheral blood mononuclear cells (PBMNC) stimulated with phytohemagglutinin (PHA, 1.2, 2.5, 5.0, 10.0 [corrected] and 20.0 mg/L; P < 0.01) and in the in vitro secretion of interleukin-2 receptor (IL-2R) (PHA, 2.5 mg/L; P = 0.058). These variables remained reduced (P < 0.05) even after 5 wk of zinc repletion. The amount of zinc consumed did not alter the numbers of circulating neutrophils, monocytes and lymphocytes, the in vitro PBMNC secretion of interferon-gamma and tumor necrosis factor-alpha or neutrophil superoxide production. The results suggest that changes in lymphocyte proliferation and IL-2R expression may be early markers of mild zinc deficiency.