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More Healthy Foods & Antioxidants

The Okinawan Diet: Health Implications of a Low-Calorie, Nutrient-Dense, Antioxidant-Rich Dietary Pattern Low in Glycemic Load (1) Free full text

This 2009 review provides helpful information on the healthy eating habits of the people of Okinawa. The authors suggest, "Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products."


The antioxidant nutrients and disease prevention-what do we know and what do we need to find out? (2) Free full text

Although this summary report from a symposium of nutritionists was written more than 20 years ago, the author provides some good information of what was known then about antioxidants and disease prevention. "The symposium started with several lectures that outlined and explained the mechanistic background necessary to understand free radical reactions, and especially those reactions that are important in free radical biology. These lectures stressed the widespread nature of radical-mediated oxidative processes in normal biochemistry as well as in pathology and also the role of antioxidant nutrients in protecting biological systems against oxidative stress."

Functional Foods as Modifiers of Cardiovascular Disease (3) Free full text

This 2009 review emphasizes the following: "Since oxidative stress plays a prominent role in immune system activation, regular ingestion of ample amounts of fruits and vegetables (8+ servings/d) rich in antioxidant compounds, the polyphenols, carotenoids, and vitamin C (e.g., citrus, tomatoes, berries, carrots, and greens), lowers inflammatory mediators and risk for chronic disease. Whole grains, legumes, and nuts have also been demonstrated in clinical trials to effectively reduce inflammatory mediators and risk for CVD. Hence, as proclaimed in antiquity, 'let food be thy medicine and medicine be thy food."


Walnut consumption is associated with lower risk of type 2 diabetes in women  (4) Free full text

This 2013 study was undertaken by the Harvard School of Public Health. The researchers investigated "the association between walnut intake and incident type 2 diabetes in 2 large cohort studies: the Nurses' Health Study (NHS) and NHS II. We prospectively followed 58,063 women aged 52-77 y in NHS (1998-2008) and 79,893 women aged 35-52 y in NHS II (1999-2009) without diabetes, cardiovascular disease, or cancer at baseline." "Consumption of walnuts and other nuts was assessed every 4 y using validated food frequency questionnaires. Self-reported type 2 diabetes was confirmed by a validated supplemental questionnaire. We documented a total of 5,930 incident type 2 diabetes cases during 10 y of follow-up. In the multivariable-adjusted Cox proportional hazards model without body mass index (BMI), walnut consumption was associated with a lower risk of type 2 diabetes, and the HRs (95% CIs) for participants consuming 1-3 servings/mo (1 serving = 28 g), 1 serving/wk, and ≥2 servings/wk of walnuts were 0.93 (0.88-0.99), 0.81 (0.70-0.94), and 0.67 (0.54-0.82) compared with women who never/rarely consumed walnuts (P-trend < 0.001). Further adjustment for updated BMI slightly attenuated the association and the HRs (95% CIs) were 0.96 (0.90-1.02), 0.87 (0.75-1.01), and 0.76 (0.62-0.94), respectively (P-trend = 0.002). The consumption of total nuts (P-trend < 0.001) and other tree nuts (P-trend = 0.03) was also inversely associated with risk of type 2 diabetes, and the associations were largely explained by BMI." The researchers concluded, "Our results suggest that higher walnut consumption is associated with a significantly lower risk of type 2 diabetes in women."


 Association of Nut Consumption with Total and Cause-Specific Mortality (5) Free full text

Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function (5) Free full text

This 2006 study was conducted by investigators from Spain who noted, "Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal." "We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals." "In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal." The researchers concluded, "Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells."


More About Nuts:

Health Benefits of Nut Consumption (6) Free full text

This 2010 review stated, "Interventional studies consistently show that nut intake has a cholesterol-lowering effect, even in the context of healthy diets, and there is emerging evidence of beneficial effects on oxidative stress, inflammation, and vascular reactivity. Blood pressure, visceral adiposity and the metabolic syndrome also appear to be positively influenced by nut consumption. Thus it is clear that nuts have a beneficial impact on many cardiovascular risk factors. Contrary to expectations, epidemiologic studies and clinical trials suggest that regular nut consumption is unlikely to contribute to obesity and may even help in weight loss. Safety concerns are limited to the infrequent occurrence of nut allergy in children. In conclusion, nuts are nutrient rich foods with wide-ranging cardiovascular and metabolic benefits, which can be readily incorporated into healthy diets."

Health benefits of nuts: potential role of antioxidants (7)

This 2006 review was written by Norwegian researchers. The abstract states, "A diet rich in fruits, vegetables and minimally refined cereals is associated with lower risk for chronic degenerative diseases. Since oxidative stress is common in chronic degenerative disease, it has been assumed that dietary antioxidants may explain this protective effect. Every dietary plant contains numerous types of antioxidants with different properties. Many of these antioxidants cooperate in oxidative stress reduction in plants, and we hypothesize that many different antioxidants may also be needed for the proper protection of animal cells. To test this hypothesis, it is useful to identify dietary plants with high total antioxidant content. Several nuts are among the dietary plants with the highest content of total antioxidants. Of the tree nuts, walnuts, pecans and chestnuts have the highest contents of antioxidants. Walnuts contain more than 20 mmol antioxidants per 100 g, mostly in the walnut pellicles. Peanuts (a legume) also contribute significantly to dietary intake of antioxidants. These data are in accordance with our present extended analysis of an earlier report on nut intake and death attributed to various diseases in the Iowa Women's Health Study. We observed that the hazard ratio for total death rates showed a U-shaped association with nut/peanut butter consumption. Hazard ratio was 0.89 (CI = 0.81-0.97) and 0.81 (CI = 0.75-0.88) for nut/peanut butter intake once per week and 1-4 times per week, respectively. Death attributed to cardiovascular and coronary heart diseases showed strong and consistent reductions with increasing nut/peanut butter consumption. Further studies are needed to clarify whether antioxidants contribute to this apparent beneficial health effect of nuts." [Health-e-Iron note: the thin pellicle layer that surround the meat of a nut contains tannins. One of the health-protective benefits of tannins is that they block excess dietary absorption of iron]

Nuts Improve Diet Quality Compared to Other Energy-Dense Snacks While Maintaining Body Weight (8) Free full text

This study reported in 2011 reports these novel results of a body composition study: "Previous studies have reported that regular nut consumption reduces cardiovascular disease (CVD) risk and does not promote weight gain despite the fact that nuts are energy-dense. However, no studies have investigated the body composition of those regularly consuming nuts compared to similar intakes of other snacks of equal energy density. This parallel study (n = 118) examined the effects of providing daily portions (~1100 kJ/d) of hazelnuts, chocolate, or potato crisps compared to a control group receiving no snacks for twelve weeks. Effects on body weight and composition, blood lipids and lipoproteins, resting metabolic rate (RMR), appetite indices, and dietary quality were compared. At week 12, there was no significant difference in any of the outcome measurements between the groups except for dietary quality, which improved significantly in the nut group. The researchers reported, "Nuts can be incorporated into the diet without adversely affecting body weight and can improve diet quality."


Chronic and acute effects of walnuts on antioxidant capacity and nutritional status in humans: a randomized, cross-over pilot study  (9) Free full text

This 2010 reported study analyzed "the dose-response effects of walnut intake on biomarkers of antioxidant activity, oxidative stress, and nutrient status. Subjects were randomized to receive either 21 or 42 g raw walnuts/d during each 6 wk intervention phase with a 6 wk washout between phases. Subjects were instructed to consume their usual diet, but refrain from eating any other tree nuts, seeds, peanuts, or ellagitannin-rich foods during the entire study, and other polyphenol-rich foods for 2 d prior to each study visit." "Compared to baseline levels, red blood cell (RBC) linoleic acid and plasma pyridoxal phosphate (PLP) were significantly higher after 6 wk with 42 g/d walnuts (P < 0.05 for both). Overall, changes in plasma total thiols, and other antioxidant biomarkers, were not significant with either walnut dose. However, when compared to fasting levels, plasma total thiols were elevated within 1 h of walnut consumption with both doses during the baseline and end visits for each intervention phase (P < 0.05 for all)." [Health-e-Iron note: The study participant were described as generally healthy; this could have had an effect on the outcome]


A Walnut Diet Improves Endothelial Function in Hypercholesterolemic Subjects:  A Randomized Crossover Trial (10) Free full text

In this 2004 study the researchers set out "To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced ~32% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks." "The walnut diet significantly reduced total cholesterol ... and LDL cholesterol ... Cholesterol reductions correlated with increases of both dietary alpha-linolenic acid and LDL gamma-tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterolto-HDL ratios... The researchers concluded, "Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering."


The Role of Tree Nuts and Peanuts in the Prevention of Coronary Heart Disease: Multiple Potential Mechanisms (11) Free full text

This is a comprehensive analysis published in 2007 that covers some of the relevant nut studies done prior to that date. Its full abstract follows: "Epidemiologic and clinical trial evidence has demonstrated consistent benefits of nut and peanut consumption on coronary heart disease (CHD) risk and associated risk factors. The epidemiologic studies have reported various endpoints, including fatal CHD, total CHD death, total CHD, and nonfatal myocardial infarct. A pooled analysis of 4 U.S. epidemiologic studies showed that subjects in the highest intake group for nut consumption had an ~35% reduced risk of CHD incidence. The reduction in total CHD death was due primarily to a decrease in sudden cardiac death. Clinical studies have evaluated the effects of many different nuts and peanuts on lipids, lipoproteins, and various CHD risk factors, including oxidation, inflammation, and vascular reactivity. Evidence from these studies consistently shows a beneficial effect on these CHD risk factors. The LDL cholesterol-lowering response of nut and peanut studies is greater than expected on the basis of blood cholesterol-lowering equations that are derived from changes in the fatty acid profile of the diet. Thus, in addition to a favorable fatty acid profile, nuts and peanuts contain other bioactive compounds that explain their multiple cardiovascular benefits. Other macronutrients include plant protein and fiber; micronutrients including potassium, calcium, magnesium, and tocopherols; and phytochemicals such as phytosterols, phenolic compounds, resveratrol, and arginine. Nuts and peanuts are food sources that are a composite of numerous cardioprotective nutrients and if routinely incorporated in a healthy diet, population risk of CHD would therefore be expected to decrease markedly."


Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men (12)

This 2009 reported study was aimed "to evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects." "20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA)." "The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.)." The researchers concluded, "Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts."


Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: a randomized controlled trial (13) Free full text

In this study reported in 2011 from Brazil 17 obese female adolescents ~ 15 years of age, BMI ~ 36 "were randomized 1:1 in two groups with the diet supplemented either with Brazil nuts [BNG, n = 08, 15-25 g/day (equivalent to 3 to 5 units/day)] or placebo [PG (lactose), n = 09, one capsule/day] and followed for 16 weeks. Anthropometry, metabolic-lipid profiles, oxidative stress and morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak (RBCVmax) and time (TRBCVmax) to reach it during post-occlusive reactive hyperemia, after 1 min arterial occlusion] microvascular variables were assessed by nailfold videocapillaroscopy at baseline (T0) and after intervention (T1)." "T0 characteristics were similar between groups. At T1, BNG (intra-group variation) had increased selenium levels (p = 0.02), RBCV (p = 0.03) and RBCVmax (p = 0.03) and reduced total (TC) (p = 0.02) and LDL-cholesterol (p = 0.02). Compared to PG, Brazil nuts intake reduced TC (total cholesterol) (p = 0.003), triglycerides (p = 0.05) and LDL-ox (p = 0.02) and increased RBCV (p = 0.03)." The researchers concluded, "Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances."


Peanut consumption and reduced risk of colorectal cancer in women: A prospective study in Taiwan (14) Free full text

This 2006 reported study was undertaken in Japan. The aim of the study was to "examine whether peanut consumption is associated with a reduced risk of colorectal cancer in a prospective cohort with a 10-year follow-up." "In 1990-1992, residents (12,026 men and 11,917 women aged 30 to 65 years) in 7 townships, Taiwan, were interviewed and recruited into a cancer-screening cohort and annually followed up. Colorectal cancer cases in this cohort were identified from cancer registry and death certificates. Incidence rates of this disease by the end of 2001 were calculated by gender for the primary study variable and covariates. The dietary intake was assessed by means of weekly food frequency measures, including frequently consumed food groups and folk dishes including sweet potato, bean products, peanut products, pickled foodstuffs, nitrated or smoked foodstuffs." "During the study period, 107 new colorectal cancer cases (68 men and 39 women) were confirmed. The multivariate Cox's proportional hazard model showed that the relative risk (RR) of peanut consumption was 0.73 [95% confidence interval (CI) = 0.44-1.21] for men and 0.42 (95% CI = 0.21-0.84) for women. However, frequent intake of pickled foodstuffs was harmful for women (RR = 2.15, 95% CI = 0.99-4.65). The risk of colorectal cancer was also elevated among cigarette smokers but not significant (P<0.05)." The researchers concluded, "This study suggests that frequent intake of peanut and its products may reduce colorectal cancer risk in women, demonstrating the anti-proliferating effect of peanut intake." [Health-e-Iron note: peanut consumption demonstrated a protective trend in males, but the results did not reach statistical significance]


Nut and peanut butter consumption and risk of type 2 diabetes in women (15) Free full text

This research study was published in 2002. It was a "prospective cohort study of 83,818 women from 11 states in the Nurses' Health Study. The women were aged 34 to 59 years, had no history of diabetes, cardiovascular disease, or cancer, completed a validated dietary questionnaire at baseline in 1980, and were followed up for 16 years." "We documented 3,206 new cases of type 2 diabetes. Nut consumption was inversely associated with risk of type 2 diabetes after adjustment for age, body mass index (BMI), family history of diabetes, physical activity, smoking, alcohol use, and total energy intake. The multivariate relative risks (RRs) across categories of nut consumption (never/almost never, or =5 times/week) for a 28-g (1 oz) serving size were 1.0, 0.92 (95% confidence interval [CI], 0.85-1.00), 0.84 (0.95% CI, 0.76-0.93), and 0.73 (95% CI, 0.60-0.89) (P for trend <.001). Further adjustment for intakes of dietary fats, cereal fiber, and other dietary factors did not appreciably change the results. The inverse association persisted within strata defined by levels of BMI, smoking, alcohol use, and other diabetes risk factors. Consumption of peanut butter was also inversely associated with type 2 diabetes. The multivariate RR was 0.79 (95% CI, 0.68-0.91; P for trend <.001) in women consuming peanut butter 5 times or more a week (equivalent to > or =140 g [5 oz] of peanuts/week) compared with those who never/almost never ate peanut butter." The researchers concluded, "Our findings suggest potential benefits of higher nut and peanut butter consumption in lowering risk of type 2 diabetes in women. To avoid increasing caloric intake, regular nut consumption can be recommended as a replacement for consumption of refined grain products or red or processed meats."

Frequent nut consumption and decreased risk of cholecystectomy in women (16) Free full text

In this 2004 study from the Harvard medical School and Brigham and Women's Hospital the researchers first noted, "Gallstone disease is a major source of morbidity in the developed countries. Nuts are rich in several compounds that may protect against gallstone disease." "We prospectively studied nut (peanuts, other nuts, and peanut butter) consumption in relation to the risk of cholecystectomy in a cohort of 80,718 women from the Nurses' Health Study who were 30-55 y old in 1980 and had no history of gallstone disease." "During 1,393,256 person-years of follow-up from 1980 to 2000, we documented 7,831 cholecystectomies. After adjustment for age and other known or suspected risk factors, women who consumed > or =5 units of nuts (1 unit = 1 oz or 28.6 g nuts)/wk (frequent consumption) had a significantly lower risk of cholecystectomy (relative risk: 0.75; 95% CI: 0.66, 0.85; P for trend < 0.0001) than did women who never ate nuts or who ate <1 unit/mo (rare consumption)." "In analyses examining consumption of peanuts and other nuts separately, both were associated with a lower risk of cholecystectomy." The researchers concluded, "In women, frequent nut consumption is associated with a reduced risk of cholecystectomy."


A prospective cohort study of nut consumption and the risk of gallstone disease in men (17) Free full text

In another 2004 study from Harvard, similar to the one described directly-above, the researchers objective was "to examine the relation between nut consumption and gallstone disease in the Health Professionals Follow-up Study. The consumption of nuts was assessed starting in 1986 as part of a 131-item semiquantitative food frequency questionnaire. The main outcome measure was newly diagnosed symptomatic gallstones. During 457,305 person-years of follow-up, 1,833 participants reported gallstone disease. After adjustment for age and other known or suspected risk factors, men consuming 5 or more units of nuts per week (frequent consumption) had a significantly lower risk of gallstone disease (relative risk = 0.70, 95% confidence interval: 0.60, 0.86; ptrend < 0.001) than did men who never ate or who ate less than 1 unit per month (rare consumption) (1 unit = 1 ounce (0.028 kg) of nuts). The researchers concluded, "Our findings suggest that frequent nut consumption is associated with a reduced risk of gallstone disease in men."


Nuts and health outcomes: new epidemiologic evidence (18) Free full text

The author of this 2009 article reviews "recent epidemiologic evidence on nut intake and health outcomes. It focuses on studies in which nut consumption is directly assessed or when nuts are included in a dietary score or pattern. Epidemiologic studies have been remarkably consistent in showing an association between nut consumption and a reduced risk of coronary heart disease (CHD). Some evidence has emerged recently to suggest health-protective benefits of nuts other than CHD. Frequent nut intake probably reduces risk of diabetes mellitus among women, but its effects on men are unknown. Evidence on the anticarcinogenic effects of nuts is somewhat limited because studies in the past 2 decades have examined only 3 tumor sites, and the benefits appear to be manifested only in women. However, the protective benefits of frequent nut consumption on gallstone diseases are observed in both sexes. Long-term nut consumption is linked with lower body weight and lower risk of obesity and weight gain. A dietary pattern or score that includes nuts is consistently related with beneficial health outcomes, and this provides an indirect evidence of the salutary benefits of nut consumption. More longitudinal studies are needed to clarify the possible effects of nuts on diseases other than CHD."


Nuts and berries for heart health (19)

This is the full abstract of this 2010 review article from Spain: "Nuts are nutrient-dense foods with complex matrices rich in unsaturated fatty acids and other bioactive compounds, such as L-arginine, fiber, minerals, tocopherols, phytosterols, and polyphenols. By virtue of their unique composition, nuts are likely to beneficially impact heart health. Epidemiologic studies have associated nut consumption with a reduced incidence of coronary heart disease in both genders and diabetes in women. Limited evidence also suggests beneficial effects on hypertension and inflammation. Interventional studies consistently show that nut intake has a cholesterol-lowering effect and there is emerging evidence of beneficial effects on oxidative stress, inflammation, and vascular reactivity. Blood pressure, visceral adiposity, and glycemic control also appear to be positively influenced by frequent nut consumption without evidence of undue weight gain. Berries are another plant food rich in bioactive phytochemicals, particularly flavonoids, for which there is increasing evidence of benefits on cardiometabolic risk that are linked to their potent antioxidant power."

Nuts and novel biomarkers of cardiovascular disease (20) Free full text

This is a 2009 review from the author of the directly-above paper. The full text contains a description of of the science behind what the author suggests contribute to the cardioprotective value of nut consumption. The author further suggests that, "Although more studies are warranted, the emerging picture is that nut consumption beneficially influences cardiovascular risk beyond cholesterol lowering."


Pecans acutely increase plasma postprandial antioxidant capacity and catechins and decrease LDL oxidation in humans (21) Free full text

This was a 2011 reported study undertaken in California. "We examined postprandial changes in plasma oxygen radical absorbance capacity (ORAC) and in concentrations of tocopherols, catechins, oxidized LDL, and malondialdehyde (MDA) in response to pecan test meals. Sixteen healthy men and women (23-44 y, BMI 22.7 ± 3.4) were randomly assigned to 3 sequences of test meals composed of whole pecans, blended pecans, or an isocaloric meal of equivalent macronutrient composition but formulated of refined ingredients in a crossover design with a 1-wk washout period between treatments. Blood was sampled at baseline and at intervals up to 24 h postingestion." "Post whole pecan consumption, oxidized LDL decreased 30, 33, and 26% at 2, 3, and 8 h, respectively (P < 0.05), and epigallocatechin-3-gallate concentrations at 1 h (mean ± SEM; 95.1 ± 30.6 nmol/L) and 2 h (116.3 ± 80.5 nmol/L) were higher than at baseline (0 h) and after the control test meal at 1 h (P < 0.05). The postprandial molar ratio of MDA: triglycerides decreased by 37, 36, and 40% at 3, 5, and 8 h, respectively (P < 0.05), only when whole and blended pecan data were pooled." The researchers concluded, "These results show that bioactive constituent of pecans are absorbable and contribute to postprandial antioxidant defenses."

Pistachio Intake Increases High Density Lipoprotein Levels and Inhibits Low-Density Liproprotein Oxidation in Rats (22) Free full text

In this 2007 study of laboratory rats the investigators "sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group." "However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. The researchers concluded, "the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation."


Pistachio Nut Consumption and Serum Lipid Levels (23) Free full text

This was a 2007 reported study undertaken as a "randomized crossover trial. setting: Outpatient dietary counseling and blood analysis. subjects: 15 subjects with moderate hypercholesterolemia. intervention: Fours weeks of dietary modification with 15% caloric intake from pistachio nuts. Measures of Outcome: Endpoints were serum lipid levels of total cholesterol, HDL-C, LDL-C, VLDL-C, triglycerides and apolipoproteins A-1 and B-100. BMI, blood pressure, and nutrient intake (total energy, fat, protein, and fiber) were also measured at baseline, during, and after dietary intervention." "On the pistachio nut diet, statistically significant increases were seen for percent energy from polyunsaturated fat (mean difference, 6.5%; 95% CI, 4.2% to 8.9%; p<.0001) and fiber intake (mean difference, 15 g; 95% CI, 8.4 g to 22 g; p = 0.0003). On the pistachio diet, statistically significant reductions were seen in TC/HDL-C .., LDL-C/HDL-C .., ... and a statistically significant increase was seen in HDL-C... No statistically significant differences were seen for total cholesterol, triglycerides, LDL-C, VLDL-C, apolipoprotein A-1 or apolipoprotein B-100. No changes were observed in BMI or blood pressure." The researchers concluded, "A diet consisting of 15% of calories as pistachio nuts (about 2-3 ounces per day) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease."


Effects of pistachios on body weight in Chinese subjects with metabolic syndrome (24) Free full text

This 2012 study was undertaken in China "to investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome." "Ninety subjects with metabolic syndrome ... (without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks." "Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (1.13 +/- 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (0.77 +/-2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (0.15 +/- 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (0.38 +/- 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups." The researchers concluded, "Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome."


Almond consumption reduces oxidative DNA damage and lipid peroxidation in male smokers  (25) Free full text

This 2007-reported study was undertaken in China. The researchers noted. "Smoking increases the risk of several chronic diseases associated with elevated oxidative stress status. Almonds are a good source of antioxidant nutrients and may diminish smoking-related biomarkers of oxidative stress. We investigated whether almond consumption decreases biomarkers of oxidative stress in young male smokers. We conducted a randomized, crossover clinical trial with 60 healthy male soldiers (18-25 y) who were habitual smokers (5-20 cigarettes/d) and supplemented their diet with 84 g almonds or 120 g pork (to control for calories) daily for 4 wk with a 4-wk washout period between treatment periods. In addition, 30 healthy nonsmoking men were provided the same daily serving of pork as reference comparison. Blood and urine were collected and assessed for biomarkers of oxidative stress. Baseline values of urinary 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) and peripheral lymphocyte DNA strand breaks were significantly higher by 185, 64, and 97% in smokers than nonsmokers, whereas activities of plasma superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase were significantly lower by 15, 10, and 9%, respectively. After the almond intervention, serum alpha-tocopherol, SOD, and GPX increased significantly in smokers by 10, 35, and 16%, respectively and 8-OHdG, MDA, and DNA strand breaks decreased significantly by 28, 34, and 23%. In smokers, after almond supplementation, the concentration of 8-OHdG remained significantly greater than in nonsmokers by 98%. The researchers concluded, "These results suggest almond intake can enhance antioxidant defenses and diminish biomarkers of oxidative stress in smokers."


Berries, Grains and Fiber:

Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study (26) Free full text

This 2007 study undertaken in the U.S. first noted, "Whether the intake of dietary fiber can protect against colorectal cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been inconsistent." "The analytic cohort consisted of 291,988 men and 197,623 women aged 50-71 y. Diet was assessed with a self-administered food-frequency questionnaire at baseline in 1995-1996; 2974 incident colorectal cancer cases were identified during 5 y of follow-up..." "Total dietary fiber intake was not associated with colorectal cancer. The multivariate RR for the highest compared with the lowest intake quintile (RR(Q5-Q1)) was 0.99 (95% CI: 0.85, 1.15; P for trend = 0.96). In analyses of fiber from different food sources, only fiber from grains was associated with a lower risk of colorectal cancer (multivariate RR(Q5-Q1): 0.86; 95% CI: 0.76, 0.98; P for trend = 0.01). Whole-grain intake was inversely associated with colorectal cancer risk: the multivariate RR(Q5-Q1) was 0.79 (95% CI: 0.70, 0.89) for the whole cohort (P for trend < 0.001). The association with whole grain was stronger for rectal than for colon cancer." The researchers concluded, "In this large prospective cohort study, total dietary fiber intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk."

Berries: emerging impact on cardiovascular health (27) Free full text

 This 2010 report was published by the Department of Nutrition at Oklahoma State University. The authors provide a comprehensive review of the literature covering more than 20 berry studies. We recommend opening the full text article and viewing Tables 1 and 2 located following the bibliography in this paper. The abstract of this paper follows: "Berries are a good source of polyphenols, especially anthocyanins, micronutrients, and fiber. In epidemiological and clinical studies, these constituents have been associated with improved cardiovascular risk profiles. Human intervention studies using chokeberries, cranberries, blueberries, and strawberries (either fresh, or as juice, or freeze-dried), or purified anthocyanin extracts have demonstrated significant improvements in LDL oxidation, lipid peroxidation, total plasma antioxidant capacity, dyslipidemia, and glucose metabolism. Benefits were seen in healthy subjects and in those with existing metabolic risk factors. Underlying mechanisms for these beneficial effects are believed to include upregulation of endothelial nitric oxide synthase, decreased activities of carbohydrate digestive enzymes, decreased oxidative stress, and inhibition of inflammatory gene expression and foam cell formation. Though limited, these data support the recommendation of berries as an essential fruit group in a heart-healthy diet."


Tart Cherry Juice Decreases Oxidative Stress in Healthy Older Men and Women (28) Free full text

This research reported in 2009 noted, "Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease." "This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 +/- 4 y (61-75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F(2)-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F(2)-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes." "These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids."


Strawberry Modulates LDL Oxidation and Postprandial Lipemia in Response to High-Fat Meal in Overweight Hyperlipidemic Men and Women (29) Free full text

This 2010 research was published by the University of California at Davis. The researchers noted, "Elevated levels of lipids, such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), are widely recognized as risk factors for cardiovascular disease (CVD). Oxidized LDL (OxLDL) is an emerging risk factor considered relevant in oxidative stress and endothelial dysfunction, which is implicated in the progression of CVD. Consumption of a diet rich in polyphenols may be cardioprotective through its impact on oxidative stress and protecting LDL from oxidation." The researchers tested 24 men and women in a crossover trial. The subject consumed either an active strawberry beverage or placebo. All subjects were tested with a high-fat challenge meal a total of three times, twice before randomization and once again at the crossover point. Both TC and LDL were significantly reduced after the high fat meal in subjects who were randomized to the strawberry beverage. The researchers concluded, "The present results support a role for strawberry in mitigating fed-state oxidative stressors that may contribute to atherogenesis."


Plasma Antioxidant Capacity Changes Following a Meal as a Measure of the Ability of a Food to Alter In Vivo Antioxidant Status (30) Free full text

In this research reported in 2007 from the Arkansas Children’s Nutrition Center the investigators set out to determine 1) if consumption of a meal of different fruits or berries increases plasma hydrophilic (H-) or lipophilic (L-) antioxidant capacity (AOC) measured as Oxygen Radical Absorbance Capacity (ORACFL); 2) if including macronutrients in the meal alters postprandial changes in AOC; and 3) if preliminary recommendations can be developed for antioxidant intake" The results of this study are detailed in the full text. The researchers concluded, "We have demonstrated that consumption of certain berries and fruits such as blueberries, mixed grape and kiwifruit, was associated with increased plasma AOC in the postprandial state and consumption of an energy source of macronutrients containing no antioxidants was associated with a decline in plasma AOC. However, without further long term clinical studies, one cannot necessarily translate increased plasma AOC into a potential decreased risk of chronic degenerative disease. Preliminary estimates of antioxidant needs based upon energy intake were developed. Consumption of high antioxidant foods with each meal is recommended in order to prevent periods of postprandial oxidative stress."


Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress (31) Free full text

The purpose of this 2012 German study was "to examine the association of red meat and whole-grain bread consumption with plasma levels of biomarkers related to glucose metabolism, oxidative stress, inflammation and obesity." They studied a sub-cohort of 2,198 men and women for an investi9gfation of biological predictors of diabetes and cardiovascular diseases. "After multivariable adjustment, higher consumption of whole-grain bread was significantly (P trend <0.05) associated with lower levels of GGT, ALT and hs-CRP, whereas higher consumption of red meat was significantly associated with higher levels of GGT and hs-CRP when adjusted for potential confounding factors related to lifestyle and diet. Further adjustment for body mass index and waist circumference attenuated the association between red meat and hs-CRP (P=0.19)." The researchers concluded, "The results of this study suggest that high consumption of whole-grain bread is related to lower levels of GGT, ALT and hs-CRP, whereas high consumption of red meat is associated with higher circulating levels of GGT and hs-CRP." [Health-e-Iron note: Table 2 in the full paper provides a good presentation of the relative effects of high versus low red meat intake and high versus low whole-grain bread intake. High whole-grain bread intake and low red meat intake both correlate strongly with low GGT measures. Interestingly, adiponectin, a proven predictor of type 2 diabetes is not related to either red meat or whole-grain bread intake. In the paper described directly below, however, adiponectin and GGT are both strongly associated with type 2 diabetes-- see also paper #33 below on this topic]  

Diet and risk of chronic diseases: results from the first 8 years of follow-up in the EPIC-Potsdam study (32)

This is a 2013, interim follow-up report on a large epidemiologic study ongoing in Germany. "We used data from 23 531 participants of the EPIC-Potsdam study to analyse the associations between 45 single food groups and risk of major chronic diseases, namely, cardiovascular diseases (CVD), type 2 diabetes and cancer using multivariable-adjusted Cox regression." "Higher intakes of whole-grain bread, raw vegetables, coffee and cakes and cookies were found to be significantly associated with a lower risk of chronic diseases. Conversely, higher intakes of low-fat dairy, butter, red meat and sauce were associated with higher risks of chronic diseases." The investigators concluded, "overall, a healthy diet was characterized by a high consumption of whole-grain bread, raw vegetables and a low consumption of red meat and possibly butter, which is generally in line with previous findings. The paradoxical findings concerning the potential health benefit of coffee as well as cakes and cookies are interesting and should be investigated further."


Estimation of the contribution of biomarkers of different metabolic pathways to risk of type 2 diabetes (33) Free full text

This 2010 study was focused on blood biomarkers predictive of type 2 diabetes. In a case-control study of "613 participants with incident diabetes and 1,965 participants without diabetes" circulating blood markers were analyzed.' "Summarized risk of each biomarker was estimated by an index based on quintiles of gamma-glutamyltransferase (GGT), HDL-cholesterol, hs-CRP, and adiponectin. Cox proportional hazard regression was used to estimate relative risks adjusted for age, sex, body mass index, waist-circumference, education, sport activity, cycling, occupational activity, smoking, alcohol intake, and consumptions of red meat, coffee and whole grain bread." "Adiponectin explained a total of 32.1% (CI = 16.8, 49.1%) of the risk related to index. For the other biomarkers the corresponding proportions were 23.5% (CI = 10.1, 37.8%) by HDL-cholesterol, 21.5% (CI = 11.5, 32.8%) by GGT, and 15.5% (CI = 4.44, 27.3%) by hs-CRP. The results support the hypothesis that the different biological pathways reflected by GGT, HDL-cholesterol, hs-CRP and adiponectin independent from each other contribute to the risk of type 2 diabetes. Of these pathways the highest contribution was observed for adiponectin which contributed one-third to the risk and that equal proportion was contributed by GGT and HDL-cholesterol, although the contribution of inflammation was lower." The researchers did note that, "Caution is needed when interpreting the results of the analyses on proportion of the association explained." [Health-e-Iron note: we concur with the authors suggestion of caution. Their finding relative to adiponectin might be specific to type 2 diabetes only, whereas elevated GGT has been shown to be a risk factor for numerous diseases. See also study # 33 below which relates to GGT and diabetes and hypertension]

Comparison of the antioxidant activities of nine different fruits in human plasma (34)

In this 2005 study reported from Korea the researchers noted, "Oxidative stress in humans is associated with damage to DNA, proteins, and biological membranes. Oxidative stress, which often arises as a result of an imbalance in the human antioxidant status, has been implicated in aging and a number of human diseases such as cancer, atherosclerosis, and rheumatoid arthritis." "This study was performed to test the hypothesis that the consumption of fruit juices may improve antioxidant status in human plasma. Ten healthy men 25-26 years old were recruited for the study. After overnight fasting, study subjects were fed 150 mL of fruit juice, and blood was collected at 0, 30, 60, 90, and 120 minutes after consumption. After a 1-day wash-out period, subjects were fed with the next sample of fruit juice until all nine juices (pear, apple, orange, grape, peach, plum, kiwi, melon, and watermelon) had been evaluated. All juices were prepared from pure fruits ground in a home-style mixer." "Except for pear juice, eight kinds of juices exhibited potent antioxidant effects in human plasma. Within 30 minutes after consumption, orange, melon, grape, peach, plum, apple, and kiwi juices already effectively suppressed reactive oxygen species generation. This radical scavenging effect of fruit juices was maintained for up to 90 minutes post-consumption, but the relative DCF fluorescence had rebounded to near the initial levels at 2 hours post-consumption in most samples tested. Interestingly, however, grape juice continuously exerted persistent antioxidant activity until 2 hours after supplementation." The investigators suggested that "the consumption of fruits or fruit juices may reduce damage from oxidative stress, and that this effect may be a consequence of the antioxidant activity of fruits in scavenging the reactive oxygen species generated in human plasma."


Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study  (35) Free full text

This 2002-reported study was published by investigators from the Tulane University School of Public Health. "The objective was to examine the relation between fruit and vegetable intake and the risk of cardiovascular disease." "We studied 9,608 adults aged 25-74 y participating in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study and free of cardiovascular disease at the time of their baseline examination between 1971 and 1975. Fruit and vegetable intake at baseline was measured with a food-frequency questionnaire. The incidence of and mortality from cardiovascular disease were obtained from medical records and death certificates." "Over an average of 19 y, 888 strokes (218 fatal), 1786 ischemic heart disease events (639 fatal), 1145 cardiovascular disease deaths, and 2530 all-cause deaths were documented. Consuming fruit and vegetables > or = 3 times/d compared with <1 time/d was associated with a 27% lower stroke incidence [relative risk (RR): 0.73; 95% CI: 0.57, 0.95; P for trend = 0.01), a 42% lower stroke mortality (0.58; 0.33, 1.02; P for trend = 0.05), a 24% lower ischemic heart disease mortality (0.76; 0.56, 1.03; P for trend = 0.07), a 27% lower cardiovascular disease mortality (0.73; 0.58, 0.92; P for trend = 0.008), and a 15% lower all-cause mortality (0.85; 0.72, 1.00; P for trend = 0.02) after adjustment for established cardiovascular disease risk factors." The investigators concluded, "We showed an inverse association of fruit and vegetable intake with the risk of cardiovascular disease and all-cause mortality in the general US population."


Combined Fruit and Vegetable Intake Is Correlated with Improved Inflammatory and Oxidant Status from a Cross-Sectional Study in a Community Setting (36) Free full text

Reported in 2012, the study investigators stated objective "was to determine if an increase in combined self-reported fruit and vegetable (F&V) intake in a community setting was associated with improved multiple markers of inflammatory and oxidant status." The investigators enrolled 1,023 subjects who were studied over a 12 week period. The study utilized a number of oxidative status markers as well as blood inflammatory biomarkers as detailed in the full paper. The relationship of these markers across categories of fruit and vegetable intake were examined. The analysis was controlled for other important lifestyle and dietary factors. The investigators reported that inflammatory markers were significantly lower and markers of antioxidant capacity were significantly higher across categories of increased fruit and vegetable intake. The investigators concluded, "In a community study, several markers of both inflammation and oxidant status were associated in a putatively salutary direction by higher intake of combined F&V (fruit and vegetables), supporting current guidelines suggesting increased F&V consumption for the prevention of chronic diseases." [Health-e-Iron note: although this study did not includes direct measures of GGT and iron status, the biomarkers that were selected and results and effect correlate with direct markers of GGT and iron as demonstrated in other papers on this web site.. For example, see study #1 on our GGT & Healthy Foods page for effect and the research reported directly below both inflammatory and oxidative stress biomarkers and effect]

Gamma glutamyltransferase is a predictor of incident diabetes and hypertension: the CARDIA Study (37) Free full text

This 2003 reported study of participant from the CARDIA study included (after exclusions) a total of 4,844 black and white men and women ages 18-30 years.  In the full paper the researchers noted, "The positive association between baseline GGT and incident diabetes and/or hypertension was observed among all race and sex subgroups, although power was reduced in the subgroup analyses and the subgroup relationship did not always reach statistical significance. For example, compared with individuals with GGT below the median in each race-sex group, after adjusting for study center, race, sex, age, alcohol consumption, BMI, smoking, and physical activity, RRs for diabetes among individuals with year 0 GGT at or above the 75th percentile were 2.5 (95% CI, 1.1–5.7) in black men, 1.8 (95% CI, 1.0 –3.3) in black women, 1.6 (95% CI, 0.6 –3.7) in white men, and 8.8 (95% CI, 1.1–72.7) in white women. Similarly, RRs for hypertension among individuals with GGT at or above the 75th percentile were 1.6 (95% CI, 1.1–2.2) in black men, 1.5 (95% CI, 1.1–2.1) in black women, 1.6 (95% CI, 1.0 –2.5) in white men, and 1.4 (95% CI, 0.7–2.5) in white women. For the combined cohort, "After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0–8.1), and 5.5 (2.7–11.1) for 15-year incident diabetes and 1.0, 1.2, 1.7 (1.2–2.2), 2.3 (1.7–3.2), and 2.3 (1.7–3.2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor." The researchers concluded, "Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension." [Health-e-Iron note: the authors of this 2003 study noted "At present, studies on GGT are at an early stage." In their discussion however, the authors hypothesized that iron overload and oxidative stress and the impairment of intracellular glutathione function provided a possible mechanism underlying the associations they discovered. Studies reported during the last decade have proved this 2003 hypothesis to be correct]

Chocolate and Cocoa:

Chocolate Intake and Incidence of Heart Failure: A Population-Based Prospective Study of Middle-Aged and Elderly Women (38) Free full text

The researchers in this 2010 study "conducted a prospective cohort study of 31,823 women aged 48 to 83 years without baseline diabetes or a history of HF (heart failure) or myocardial infarction who were participants in the Swedish Mammography Cohort. In addition to answering health and lifestyle questions, participants completed a food-frequency questionnaire. Women were followed from January 1, 1998, through December 31, 2006, for HF hospitalization or death through the Swedish inpatient and cause-of-death registers. Over 9 years of follow-up, 419 women were hospitalized for incident HF (n=379) or died of HF (n=40). Compared with no regular chocolate intake, the multivariable-adjusted rate ratio of HF was 0.74 (95% CI, 0.58 to 0.95) for women consuming 1 to 3 servings of chocolate per month, 0.68 (95% CI, 0.50 to 0.93) for those consuming 1 to 2 servings per week, 1.09 (95% CI, 0.74 to 1.62) for those consuming 3 to 6 servings per week, and 1.23 (95% CI, 0.73 to 2.08) for those consuming ≥1 servings per day (P=0.0005 for quadratic trend)." The researchers concluded, "In this population, moderate habitual chocolate intake was associated with a lower rate of HF hospitalization or death, but the protective association was not observed with intake of ≥1 servings per day."


Letter by Marcadenti and Oliveira de Abreu Silva regarding article, "Chocolate intake and incidence of heart failure: a population-based, prospective study of middle-aged and elderly women" (39) Free full text

The full text of this letter to the Editor was published in regard to the study reported immediately above. The authors here suggested that several confounding issues including study structure, dietary changes that could have occurred since baseline questionnaires were completed and several other factors could have contributed to the above-described findings.  


Chocolate and prevention of cardiovascular disease: a systematic review (40) Free full text

In this 2006 published study from the Harvard University School of Public Health the authors note that "Consumption of chocolate has been often hypothesized to reduce the risk ofcardiovascular disease (CVD) due to chocolate's high levels of stearic acid and antioxidant flavonoids." The authors reviewed the literature and noted "a total of 136 publications were selected based on relevance, and quality of design and methods. An updated meta-analysis of flavonoid intake and CHD mortality was also conducted." The authors reported that "...the large body of prospective studies of  flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality. Our updated meta-analysis indicates that intake of flavonoids may lower risk of CHD mortality, RR = 0.81 (95% CI: 0.71–0.92) comparing highest and lowest tertiles." The author's concluded, "Multiple lines of evidence from laboratory experiments and randomized trials suggest stearic acid may be neutral, while flavonoids are likely protective against CHD mortality."


The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model (41) Free full text

This is a 2012 reported study. It was reported as "Best case scenario analysis using a Markov model."  The investigators studied  "2,013 people with hypertension who met the criteria for metabolic syndrome, with no history of cardiovascular disease and not receiving antihypertensive therapy." The results of this investigation indicated "daily consumption of dark chocolate (polyphenol content equivalent to 100 g of dark chocolate) can reduce cardiovascular events by 85 (95% confidence interval 60 to 105) per 10,000 population treated over 10 years. $A40 (£25; €31; $42) could be cost effectively spent per person per year on prevention strategies using dark chocolate. These results assume 100% compliance and represent a best case scenario." The investigators concluded, "The blood pressure and cholesterol lowering effects of dark chocolate consumption are beneficial in the prevention of cardiovascular events in a population with metabolic syndrome. Daily dark chocolate consumption could be an effective cardiovascular preventive strategy in this population."


Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis (42) Free full text

The objective of this 2011 study was to "evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders." "Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported." "From 4,576 references seven studies met the inclusion criteria (including 114,009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels." The researchers concluded, "Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption."


Clinical benefit and preservation of flavonols in dark chocolate manufacturing (43)

The entirety of the abstract from this 2008 review follows: "The consumption of high-cacao-content chocolate has been associated with positive health benefits ascribed to flavanol antioxidants derived from the ground, fermented cocoa seeds of Theobroma cacao. However, flavanols  impart a bitter, astringent flavor to foodstuffs, frequently masked in chocolates and confections by aggressive processing and adulteration with other flavors. Recent reports have implied that not all varieties of dark chocolate are created equally, and significant caveats exist regarding its potential health benefits. It is perhaps not surprising that extensive processing, dilution, and the addition of flavor modifiers may improve the palatability of chocolate, but could have negative nutritional and clinical benefits. This article examines the chemical composition of chocolate and the clinical data associated with the consumption of flavonoid-rich cocoa. We review the steps in chocolate manufacturing that directly affect the antioxidant levels in chocolate products, and the caveats associated with claims of health benefits from the consumption of dark chocolate."


Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials (44) Free full text

The objective of this 2010 study was "aimed to identify and quantify the effect of cocoa on total cholesterol, LDL cholesterol, and HDL cholesterol."  "Eight trials (involving 215 participants) were included and evaluated. Because there was only one relatively longer-term study, we focused on the short-term data to evaluate the effects of cocoa on plasma lipid. Cocoa consumption significantly lowered LDL cholesterol by 5.87 mg/dL (95% CI: -11.13, -0.61; P < 0.05) and marginally lowered total cholesterol by 5.82 mg/dL (95% CI: -12.39, 0.76; P = 0.08). However, no significant change was seen in LDL cholesterol in high-quality studies (3 studies included; -4.98 mg/dL; 95% CI: -13.18, 3.21; P = 0.23). Subgroup analyses suggested a cholesterol-lowering effect only in those subjects who consumed a low dose of cocoa and with cardiovascular disease risks. There was no evidence of a dose-effect relation, of any effect in healthy subjects, or of any change in HDL cholesterol." The researchers concluded, "Short-term cocoa consumption significantly reduced blood cholesterol, but the changes were dependent on the dose of cocoa consumption and the healthy status of participants. There was no dose response and no effect in healthy participants. Future high-quality studies are needed to determine the efficiency of moderate cocoa consumption on lipid profile in long-term intervention and in subjects with other cardiometabolic risk factors."


Cocoa, hazelnuts, sterols and soluble fiber cream reduces lipids and inflammation biomarkers in hypertensive patients: a randomized controlled trial (45) Free full text

In this 2012 reported study the investigators "compared the effects of 4 cocoa cream products on some of these (cardiovascular disease - CVD) biomarkers." The investigators describe four different test groups assigned to four products, each of which contained cocoa cream, three contained hazelnuts of which two had different separate ingredients. One product contained a soluble fiber and was considered a patented "LMN product."  With relatively minor differences, each product reduced LDL cholesterol, several other CVD biomarkers and both systolic and diastolic blood pressure. The researchers noted in their conclusion, "The creams (particularly the LMN) have anti-inflammatory and antioxidant effects in addition to lowering LDL-c, Apo B and ApoB/ApoA ratio. Thus, the soluble fiber effects amplified with sterols (as contained in the cocoa creams) provide new dietary therapeutic perspectives."


Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis (46)

The investigators in this 2011 reported study noted, "Cocoa products, which are rich sources of flavonoids, have been shown to reduce blood pressure and the risk of cardiovascular disease. Dark chocolate contains saturated fat and is a source of dietary calories; consequently, it is important to determine whether consumption of dark chocolate adversely affects the blood lipid profile." "In all, 10 clinical trials consisting of 320 participants were included in the analysis. Treatment duration ranged from 2 to 12 weeks. Intervention with dark chocolate/cocoa products significantly reduced serum low-density lipoprotein (LDL) and total cholesterol (TC) levels (differences in means (95% CI) were -5.90 mg/dl (-10.47, -1.32 mg/dl) and -6.23 mg/dl (-11.60, -0.85 mg/dl), respectively). No statistically significant effects were observed for high-density lipoprotein (HDL) (difference in means (95% CI): -0.76 mg/dl (-3.02 to 1.51 mg/dl)) and triglyceride (TG) (-5.06 mg/dl (-13.45 to 3.32 mg/dl))." The researchers noted, " these data are consistent with beneficial effects of dark chocolate/cocoa products on total and LDL cholesterol and no major effects on HDL and TG in short-term intervention trials."


Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans (47)

The researchers in this 2004 study stated, "Cocoa powder is rich in polyphenols and, thus, may contribute to the reduction of lipid peroxidation. Our aim was to study the effects of long-term ingestion of chocolate, with differing amounts of polyphenols, on serum lipids and lipid peroxidation ex vivo and in vivo." "We conducted a 3 week clinical supplementation trial of 45 nonsmoking, healthy volunteers. Participants consumed 75 g daily of either white chocolate (white chocolate, WC group), dark chocolate (dark chocolate, DC group), or dark chocolate enriched with cocoa polyphenols (high-polyphenol chocolate, HPC group). In the DC and HPC groups, an increase in serum HDL cholesterol was observed (11.4% and 13.7%, respectively), whereas in the WC group there was a small decrease (-2.9%, p < 0.001). The concentration of serum LDL diene conjugates, a marker of lipid peroxidation in vivo, decreased 11.9% in all three study groups." "No changes were seen in the total antioxidant capacity of plasma, in the oxidation susceptibility of serum lipids or VLDL + LDL, or in the concentration of plasma F2-isoprostanes or hydroxy fatty acids." The researchers concluded, "Cocoa polyphenols may increase the concentration of HDL cholesterol, whereas chocolate fatty acids may modify the fatty acid composition of LDL and make it more resistant to oxidative damage."


Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans (48) Free full text

In this 2001 study the researchers "evaluated the effects of a diet high in cocoa powder and dark chocolate (CP-DC diet) on LDL oxidative susceptibility, serum total antioxidant capacity, and urinary prostaglandin concentrations." "We conducted a randomized, 2-period, crossover study in 23 healthy subjects fed 2 diets: an average American diet (AAD) controlled for fiber, caffeine, and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate (CP-DC diet), providing approximately 466 mg procyanidins/d." "LDL oxidation lag time was approximately 8% greater (P = 0.01) after the CP-DC diet than after the AAD. Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4% greater (P = 0.04) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time (r = 0.32, P = 0.03). HDL cholesterol was 4% greater after the CP-DC diet (P = 0.02) than after the AAD; however, LDL-HDL ratios were not significantly different. Twenty-four-hour urinary excretion of thromboxane B(2) and 6-keto-prostaglandin F(1)(alpha) and the ratio of the 2 compounds were not significantly different between the 2 diets." The researchers concluded, "Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility, increasing serum total antioxidant capacity and HDL-cholesterol concentrations, and not adversely affecting prostaglandins."


Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults (49) Free full text 

The objective of this 2004 study was "To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects." "The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz)." "High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p < or = 0.001) but not in the low-flavonoid group (17.5 +/- 9 nmol/L, p = 0.99)." The researchers concluded, "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."


Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults (50)

The purpose of this 2009 reported study was "To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation..." "The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men" "Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress." "Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of flow velocity reserve (CFVR) after 2 weeks of intake (p<0.01)..." The researchers concluded, "Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects."


Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives (51) Free full text

The researchers in this 2005 reported crossover study of 20 patients with essential hypertension (EH) were randomized to receive either dark chocolate (DC) or white chocolate (WC), following a 7-day chocolate-free period. After a second "7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD (flow-mediated dialation), OGTT (oral glucose tolerance tests), serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment." "Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI (quantitative insulin sensitivity check index), ISI (insulin sensitivity index) , and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives." The researchers stated "these results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH."


Cocoa and cardiovascular health (52) Free full text

This 2009 review "review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption."


Cocoa and chocolate flavanoids: implications for cardiovascular health (53)

This is a 2003 review suggested that "Cocoa and chocolate contribute to trace mineral intake, which is necessary for optimum functioning of all biologic systems and for vascular tone. Thus, multiple components in chocolate, particularly flavonoids, can contribute to the complex interplay of nutrition and health. Applications of this knowledge include recommendations by health professionals to encourage individuals to consume a wide range of phytochemical-rich foods, which can include dark chocolate in moderate amounts."


Cocoa and chocolate in human health and disease (54)

Researchers in this 2011 reported review from Yale University Prevention Research Center noted and suggested the following, "Cocoa contains more phenolic antioxidants than most foods. Flavonoids, including catechin, epicatechin, and procyanidins predominate in antioxidant activity. The tricyclic structure of the flavonoids determines antioxidant effects that scavenge reactive oxygen species, chelate Fe2+ and Cu+, inhibit enzymes, and upregulate antioxidant defenses. The epicatechin content of cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated through anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-κB. Antioxidant effects of cocoa may directly influence insulin resistance and, in turn, reduce risk for diabetes. Further, cocoa consumption may stimulate changes in redox-sensitive signaling pathways involved in gene expression and the immune response. Cocoa can protect nerves from injury and inflammation, protect the skin from oxidative damage from UV radiation in topical preparations, and have beneficial effects on satiety, cognitive function, and mood. As cocoa is predominantly consumed as energy-dense chocolate, potential detrimental effects of overconsumption exist, including increased risk of weight gain. Overall, research to date suggests that the benefits of moderate cocoa or dark chocolate consumption likely outweigh the risks."


Chocolate, gut microbiota, and human health (55) Free full text

This short commentary published in 2013 is a commentary on a 2012 article by Tremaroli and Backhed entitled, "Functional interactions between the gut microbiota and host metabolism." The full text of the article referenced by this commentary can be accessed by clicking this  "Free full text" link.


Consumption of high-polyphenol dark chocolate improves endothelial function in individuals with stage 1 hypertension and excess body weight (56) Free full text

The researchers of this 2012-reported study noted, "Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m(2). All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols) for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical). Results. Twenty participants (10 men) completed the study. Comparison of pre-post intervention revealed that (1) there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2) the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P = 0.01. They researchers concluded, "In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function."



Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: a comparative study with vitamin C  (57) Free full text

This 2004 published study "investigated the effects of short-term supplementation with cactus pear fruit compared with vitamin C alone on total-body oxidative status in healthy humans. "Cactus pear (Opuntia ficus-indica) fruit contains vitamin C and characteristic betalain pigments, the radical-scavenging properties and antioxidant activities of which have been shown in vitro." "In a randomized, crossover, double-treatment study, 18 healthy volunteers received either 250 g fresh fruit pulp or 75 mg vitamin C twice daily for 2 wk, with a 6-wk washout period between the treatments. Before (baseline) and after each treatment, 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) and malondialdehyde in plasma, the ratio of reduced to oxidized glutathione (GSH:GSSG) in erythrocytes, and lipid hydroperoxides in LDL were measured as biomarkers of oxidative stress; plasma Trolox-equivalent antioxidant activity (TEAC) and vitamins A, E, and C were evaluated as indexes of antioxidant status." "Both treatments caused comparable increases compared with baseline in plasma concentrations of vitamin E and vitamin C (P < 0.05); vitamin A and TEAC did not change significantly. After supplementation with cactus pear fruit, 8-epi-PGF(2)alpha and malondialdehyde decreased by approximately 30% and 75%, respectively; GSH:GSSG shifted toward a higher value (P < 0.05); and LDL hydroperoxides were reduced by almost one-half. Supplementation with vitamin C did not significantly affect any marker of oxidative stress." The investigators concluded, "Consumption of cactus pear fruit positively affects the body's redox balance, decreases oxidative damage to lipids, and improves antioxidant status in healthy humans. Supplementation with vitamin C at a comparable dosage enhances overall antioxidant defense but does not significantly affect body oxidative stress. Components of cactus pear fruit other than antioxidant vitamins may play a role in the observed effects."


Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats (58)

This was a 2012-reported study from Mexico. "Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats." 


Dietary flavonoid intakes and risk of type 2 diabetes in US men and women (59) Free full text

this 2012 paper was produced by the Harvard School of Public Health. The authors noted, "Data from mechanistic studies support a beneficial effect of specific flavonoids on insulin sensitivity. However, few studies have evaluated the relation between intakes of different flavonoid subclasses and type 2 diabetes." "The objective was to evaluate whether dietary intakes of major flavonoid subclasses (ie, flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) are associated with the risk of type 2 diabetes in US adults." "We followed up a total of 70,359 women in the Nurses' Health Study (NHS; 1984-2008), 89,201 women in the NHS II (1991-2007), and 41,334 men in the Health Professionals Follow-Up Study (1986-2006) who were free of diabetes, cardiovascular disease, and cancer at baseline." "During 3,645,585 person-years of follow-up, we documented 12,611 incident cases of type 2 diabetes. Higher intakes of anthocyanins were significantly associated with a lower risk of type 2 diabetes (pooled HR for the 3 cohorts from a comparison of extreme quintiles: 0.85; 95% CI: 0.80, 0.91; P-trend < 0.001) after multivariate adjustment for age, BMI, and lifestyle and dietary factors. Consumption of anthocyanin-rich foods, particularly blueberries (pooled HR: 0.77 from a comparison of ≥2 servings/wk with <1 serving/mo; 95% CI: 0.68, 0.87; P-trend < 0.001) and apples/pears (pooled HR: 0.77 from a comparison of ≥5 servings/wk with <1 serving/mo; 95% CI: 0.65, 0.83; P-trend < 0.001), was also associated with a lower risk of type 2 diabetes. No significant associations were found for total flavonoid intake or other flavonoid subclasses. The researchers concluded, "A higher consumption of anthocyanins and anthocyanin-rich fruit was associated with a lower risk of type 2 diabetes."


The antioxidant effect of fermented papaya preparation involves iron chelation (60)

This is a 2012-reported study from Israel. "Iron-overload is a major clinical problem in various diseases. Under this condition, serum iron which surpasses the binding capacity of transferrin is present as non-transferrin bound iron and cellular unbound Labile Iron Pool (LIP) is increased. LIP participates in the generation of free radicals, including reactive oxygen species (ROS). Increased ROS, with concomitant decrease in anti-oxidants, results in oxidative stress and toxicity to the liver, heart and other tissues, causing serious morbidity and eventually mortality. Therapeutic iron chelation reduces the LIP and thereby ameliorates oxidative stress-mediated toxicity. Many food-derived antioxidants have the capacities to scavenge ROS and chelate iron. We have reported that fermented papaya preparation (FPP) has ROS scavenging effect on blood cells in vitro or in vivo (in thalassemic patients and experimental animals). We now investigated FPP's iron chelating effect - its ability to prevent (and revert) LIP accumulation. Liver- and heart-derived cells, and RBCs were exposed to non-transferrin bound iron in the form of ferrous ammonium sulfate and the effect of FPP on their LIP content and ROS generation was measured by flow-cytometry. The results indicate that FPP reduces LIP and ROS, and suggests that its antioxidant mechanism is related, at least in part, to iron chelation."


Iron chelation in the biological activity of curcumin (61) Free full text

This is a 2006 study from Wake forest University Health Sciences. "Curcumin is among the more successful chemopreventive compounds investigated in recent years, and is currently in human trials to prevent cancer. The mechanism of action of curcumin is complex and likely multifactorial. We have made the unexpected observation that curcumin strikingly modulates proteins of iron metabolism in cells and in tissues, suggesting that curcumin has properties of an iron chelator. Curcumin increased mRNA levels of ferritin and GSTalpha in cultured liver cells. Unexpectedly, however, although levels of GSTalpha protein increased in parallel with mRNA levels in response to curcumin, levels of ferritin protein declined. Since iron chelators repress ferritin translation, we considered that curcumin may act as an iron chelator. To test this hypothesis, we measured the effect of curcumin on transferrin receptor 1, a protein stabilized under conditions of iron limitation, as well as the ability of curcumin to activate iron regulatory proteins (IRPs). Both transferrin receptor 1 and activated IRP, indicators of iron depletion, increased in response to curcumin. Consistent with the hypothesis that curcumin acts as an iron chelator, mice that were fed diets supplemented with curcumin exhibited a decline in levels of ferritin protein in the liver. These results suggest that iron chelation may be an additional mode of action of curcumin."


Endothelial aging associated with oxidative stress can be modulated by a healthy mediterranean diet  (62) Free full text

The authors of this 2013 review noted, "Aging is a condition which favors the development of atherosclerosis, which has been associated with a breakdown in repair processes that occurs in response to cell damage. The dysregulation of the biological systems associated with aging are produced partly through damage which accumulates over time. One major source of this injury is oxidative stress, which can impair biological structures and the mechanisms by which they are repaired. These mechanisms are based on the pathogenesis of endothelial dysfunction, which in turn is associated with cardiovascular disease, carcinogenesis and aging." ... "In addition, aging, inflammation and oxidative stress are endogenous factors that cause telomere shortening, which is dependent on oxidative cell damage. Moreover, telomere length correlates with lifestyle and the consumption of a healthy diet. Thus, diseases associated with aging and age may be caused by the long-term effects of oxidative damage, which are modified by genetic and environmental factors. Considering that diet is a very important source of antioxidants, in this review we will analyze the relationship between oxidative stress, aging, and the mechanisms which may be involved in a higher survival rate and a lower incidence of the diseases associated with aging in populations which follow a healthy diet."


[Health-e-Iron note: Reminder, when GGT is elevated, glutathione and most other antioxidants are insufficient!]

"Understanding Antioxidants" (2:31)

"Antioxidants vs. free radicals" (3:10)

Dr. Mercola on "Is iron helping or slowly killing you?"

Dr. Mercola on iron as "anti-antioxidant?" (8:44)

To learn more about the antioxidant protection afforded by various fruits, you can read more on this site:



[Health-e-Iron note: Reminder, when GGT is elevated, glutathione and most other antioxidants are insufficient!]

"Understanding Antioxidants" (2:31)

"Antioxidants vs. free radicals" (3:10)

Dr. Mercola on "Is iron helping or slowly killing you?"

Dr. Mercola on iron as "anti-antioxidant?" (8:44)

To learn more about the antioxidant protection afforded by various fruits, you can read more on this site: