Achim Bub

Critical review: vegetables and fruit in the prevention of chronic diseases

BackgroundVegetables and fruit provide a significant part of human nutrition, as they are important sources of nutrients, dietary fibre, and phytochemicals. However, it is uncertain whether the risk of certain chronic diseases can be reduced by increased consumption of vegetables or fruit by the general public, and what strength of evidence has to be allocated to such an association.MethodsTherefore, a comprehensive analysis of the studies available in the literature and the respective study results has been performed and evaluated regarding obesity, type 2 diabetes mellitus, hypertension, coronary heart disease (CHD), stroke, cancer, chronic inflammatory bowel disease (IBD), rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD), asthma, osteoporosis, eye diseases, and dementia. For judgement, the strength of evidence for a risk association, the level of evidence, and the number of studies were considered, the quality of the studies and their estimated relevance based on study design and size.ResultsFor hypertension, CHD, and stroke, there is convincing evidence that increasing the consumption of vegetables and fruit reduces the risk of disease. There is probable evidence that the risk of cancer in general is inversely associated with the consumption of vegetables and fruit. In addition, there is possible evidence that an increased consumption of vegetables and fruit may prevent body weight gain. As overweight is the most important risk factor for type 2 diabetes mellitus, an increased consumption of vegetables and fruit therefore might indirectly reduces the incidence of type 2 diabetes mellitus. Independent of overweight, there is probable evidence that there is no influence of increased consumption on the risk of type 2 diabetes mellitus. There is possible evidence that increasing the consumption of vegetables and fruit lowers the risk of certain eye diseases, dementia and the risk of osteoporosis. Likewise, current data on asthma, COPD, and RA indicate that an increase in vegetable and fruit consumption may contribute to the prevention of these diseases. For IBD, glaucoma, and diabetic retinopathy, there was insufficient evidence regarding an association with the consumption of vegetables and fruit.ConclusionsThis critical review on the associations between the intake of vegetables and fruit and the risk of several chronic diseases shows that a high daily intake of these foods promotes health. Therefore, from a scientific point of view, national campaigns to increase vegetable and fruit consumption are justified. The promotion of vegetable and fruit consumption by nutrition and health policies is a preferable strategy to decrease the burden of several chronic diseases in Western societies.

Fruit juice consumption modulates antioxidative status, immune status and DNA damage

Polyphenolic compounds exert a variety of physiological effects in vitro including antioxidative, immunomodulatory and antigenotoxic effects. In a randomized crossover study in healthy men on a low-polyphenol diet, we determined the effects of 2 polyphenol-rich juices (330 ml/d) supplemented for 2 weeks on bioavailability of polyphenols, markers of antioxidative and immune status, and reduction of DNA damage. Juices provided 236 mg (A) and 226 mg (B) polyphenols with cyanidin glycosides (A) and epigallocatechin gallate (B) as major polyphenolic ingredients. There was no accumulation of plasma polyphenols after two weeks of juice supplementation. In contrast, plasma malondialdehyde decreased with time during juice interventions. Moreover, juice consumption also increased lymphocyte proliferative responsiveness, with no difference between the two juices. Interleukin-2 secretion by activated lymphocytes and the lytic activity of natural killer cells were significantly increased by both juices. Juice intervention had no effect on single DNA strand breaks, but significantly reduced oxidative DNA damage in lymphocytes. A time-delay was observed between the intake of fruit juice and the reduction of oxidative DNA damage and the increase in interleukin-2 secretion. We conclude that consumption of either juice enhanced antioxidant status, reduced oxidative DNA damage and stimulated immune cell functions. However, fruit juice consumption for 2 weeks did not result in elevated plasma polyphenols in subjects after overnight fasting. Further studies should focus on the time-delay between juice intake and changes in measured physiological functions, as well as on active polyphenolic metabolites mediating the observed effects.

Modulation of human T-lymphocyte functions by the consumption of carotenoid-rich vegetables

A human intervention study was conducted to determine the effect of the consumption of carotenoid-rich vegetables on the immune system. Subjects, (twenty-three men), who were non-smokers, were not restricted in their daily diet, except that they had to abstain from fruit and vegetables high in carotenoids throughout the whole study period. The study was divided into four periods, each lasting 2 weeks: weeks 1-2: low-carotenoid period; throughout weeks 3-8: daily consumption of 330 ml tomato juice (40 mg lycopene/d, 1.5 mg beta-carotene/d) (weeks 3-4), 330 ml carrot juice (21.6 mg beta-carotene/d, 15.7 mg alpha-carotene/d, 0.5 mg lutein/d) (weeks 5-6), 10 g dried spinach powder (11.3 mg lutein/d, 3.1 mg beta-carotene/d) (weeks 7-8). Blood was collected weekly from subjects after a 12 h fast. T-lymphocyte functions were assessed by measuring proliferation and secretion of immunoreactive cytokines. The consumption of a low-carotenoid diet resulted in a significantly reduced proliferation of peripheral blood mononuclear cells (PBMC) cultured with concanavalin A. After 2 weeks of tomato juice consumption and until the end of the intervention period lymphocyte proliferation was not significantly changed compared with proliferation at the end of the depletion period. Secretion of cytokines by T-helper-1-like lymphocytes (interleukin (IL)-2) and by T-helper-2-like lymphocytes (IL-4) was influenced by the dietary intervention. IL-2 and IL-4 secretion values were significantly suppressed after the low-carotenoid diet (P < 0.001 and P < 0.05 respectively compared with baseline). Tomato juice consumption significantly enhanced IL-2 (P < 0.001) and IL-4 secretion (P < 0.05) compared with the end of depletion period. After carrot juice and spinach powder consumption the cytokine secretion capacity of PBMC was not significantly different from that at the end of the depletion period. In conclusion, the results of the present study indicate that a low-carotenoid diet reduces T-lymphocyte functions and addition of tomato juice restores these functions. This modulation could not be explained by changes in the plasma carotenoid concentrations. The active constituents in tomato juice as well as the biological significance of this immunomodulation remain to be determined.

Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk.

OBJECTIVE In recent years high sensitive C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were recognized as risk factors for cardiovascular disease (CVD). The aim of the present study was to investigate the relationship between these vascular and systemic markers of low-grade inflammation and traditional risk factors, the metabolic syndrome (MetS) or insulin resistance (IR). METHODS AND RESULTS In 137 adults (41-78 years) with at least 2 risk factors for atherosclerosis the following parameters were determined: hsCRP, sVCAM-1, sICAM-1, PAI-1, fibrinogen, waist circumference (WC), blood pressure, Body Mass Index (BMI), fasting serum glucose (FSG), insulin, triglycerides (TG), total cholesterol (TC), LDL, and HDL. The presence or absence of MetS according to the AHA/NHLBI Scientific Statement criteria was assessed. IR was defined using the homeostasis model (HOMA-IR). Subjects with MetS had significantly higher values of hsCRP, sICAM-1, sVCAM-1, PAI-1, fibrinogen (each P<0.05) and lower HDL-levels (P<0.05) compared with subjects without MetS. Similar results were found using HOMA-IR-quartiles. Subjects in the bottom quartile (HOMA-IR<or=1.32) had significantly lower levels of hsCRP, sVCAM-1, sICAM-1, and PAI-1 (each P<0.05) than subjects in the top quartile (HOMA-IR>or=5.03). HDL was significantly higher (P<0.05) in subjects in the lowest quartile versus those in the highest quartile. Incidentally we found no significant differences in total and LDL cholesterol among MetS, HOMA, and traditional CVD risk factor groups, respectively. CONCLUSION Systemic and vascular markers of inflammation showed significant associations with IR and the MetS and may be incorporated into traditional CVD risk prediction models. Such models should be established and validated in forthcoming large scale prospective studies on CVD risk.

Supplementation of a Low-Carotenoid Diet with Tomato or Carrot Juice Modulates Immune Functions in Healthy Men

Background: β-Carotene has been shown to enhance immune functions in humans. Whether vegetables rich in carotenoids, such as β-carotene or lycopene, modulate immune functions in healthy humans is presently not known. The objective of this study was to investigate the effects of a low-carotenoid diet supplemented with either tomato (providing high amounts of lycopene) or carrot juice (providing high amounts of α- and β-carotene) on immune functions in healthy men. Method: In a blinded, randomized, cross-over study, male subjects on a low-carotenoid diet consumed 330 ml/day of either tomato juice (37.0 mg/day lycopene) or carrot juice (27.1 mg/day β-carotene and 13.1 mg/day α-carotene) for 2 weeks with a 2-week depletion period after juice intervention. Immune status was assessed by measuring lytic activity of natural killer (NK) cells, secretion of cytokines (IL-2, IL-4, TNFα), and proliferation by activated peripheral blood mononuclear cells. Results: Juice consumption resulted in relatively fast responses in plasma carotenoid concentrations (p < 0.0002) which were not accompanied by concomitant changes in immune functions. For IL-2, NK cell cytotoxicity, and lymphocyte proliferation, maximum responses were observed during depletion periods. The highest production rate was measured only for TNFα at the end of the first intervention period. Juice intervention did not modulate the secretion of IL-4. Conclusions: Increased plasma carotenoid concentrations after vegetable juice consumption are accompanied by a time-delayed modulation of immune functions in healthy men consuming a low-carotenoid diet.

Bioavailability and Nutritional Effects of Carotenoids from Organically and Conventionally Produced Carrots in Healthy Men

It has been hypothesised that organically grown vegetables are healthier than conventionally produced ones due to a higher content of phytochemicals. However, few data from controlled human studies exist. The aim of the present study was to compare the carotenoid content and antioxidant capacity of organically and conventionally produced carrots under defined conditions. Furthermore, a human intervention study was conducted to compare bioavailability, plasma antioxidant capacity, endogenous DNA strand breaks and immune parameters in healthy men ingesting carrots from different agricultural systems. Thirty-six volunteers consumed either organically or conventionally produced blanched carrots (200 g/d; 2 weeks) or no carrots in a double-blind, randomised intervention study. No statistically significant differences were observed in the total carotenoid contents (121 (sd 7) microg/g organic v. 116 (sd 13) microg/g conventional) and the antioxidant capacities (0.43 (sd 0.08) mumol Trolox equivalents/g organic v. 0.32 (sd 0.07) mumol Trolox equivalents/g conventional) of the carrots administered to the volunteers. Intake of organically or conventionally produced carrots significantly increased (P < 0.001) plasma alpha- and beta-carotene concentrations in both intervention groups without differences in plasma carotenoid concentrations. Consumption of carrots did not lead to significant changes in the plasma antioxidant status, endogenous DNA strand breaks and parameters of the immune system in all groups. Therefore, these results indicate that the agricultural system has neither an effect on the carotenoid content, the antioxidant capacity of carrots, nor on the bioavailability of carotenoids and on antioxidant, antigenotoxic and immunological effects as assessed in a human intervention study.

A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners.

Abstract This study investigated whether a 21.1 km (half-marathon) or a 42.195 km (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km and 41.195 km, respectively, were assessed 10 days before and immediately after the finish. There was no increase in the levels of endogenous DNA strand breaks immediately after half-marathon or marathon races. A statistically significant increase in the levels of oxidative DNA damage in lymphocytes was found using endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was significantly decreased after both races. The levels of plasma antioxidants such as α-tocopherol, β-carotene and lycopene were close to, or higher than, those considered optimal for reducing the risk of cardiovascular diseases and there were no significant changes after the races in antioxidant capacity of LDL (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and percentage of granulocytes and monocytes able to generate oxidative burst were significantly increased after both races, but the lytic activity of NK cells was significantly increased at the end of the half-marathon; no effect was observed in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the antioxidant capacity to protect lymphocytes against DNA strand breaks and increased the formation of reactive species by phagocytes in well-nourished hobby runners indicating moderate oxidative damage during such high-intensity exercise.

CLA Does Not Impair Endothelial Function and Decreases Body Weight as Compared with Safflower Oil in Overweight and Obese Male Subjects

Objective: Conjugated linoleic acid (CLA) showed a wide range of beneficial biological effects with relevance for cardiovascular health in animal models and humans. Most human studies used olive oil as a reference. This study assessed the effect of CLA as compared with safflower oil on endothelial function and markers of cardiovascular risk in overweight and obese men. Heated safflower oil and olive oil were given for additional descriptive control. Methods: Eighty-five overweight men (aged 45–68 years, body mass index 25–35 kg/m2) were randomized to receive 4.5 g/d of the CLA isomeric mixture, safflower oil, heated safflower oil, or olive oil in a 4-week double-blind study. Endothelial function was assessed by peripheral arterial tonometry (PAT) index determination in the fasting and postprandial state (i.e., 4 hours after consumption of a fat- and sucrose-rich meal). Results: CLA as compared with safflower oil consumption did not impair fasting or postprandial PAT index but decreased body weight. CLA as compared with safflower oil did not change total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol; triglycerides; insulin sensitivity indices; C-reactive protein; soluble adhesion molecules; oxidized LDL; lipoprotein a (Lp[a]); paraoxonase; or platelet-activating factor acetylhydrolase (PAF-AH) activity, but significantly reduced arylesterase activity and increased concentrations of the F2-isoprostane 8-iso-prostaglandin F (PGF)2α. Conclusion: CLA did not impair endothelial function. Other parameters associated with metabolic syndrome and oxidative stress were not changed or were slightly improved. Results suggest that CLA does not increase cardiovascular risk. Increased F2-isoprostane concentrations in this context may not indicate increased oxidative stress.

Paraoxonase 1 Q192R (PON1-192) polymorphism is associated with reduced lipid peroxidation in healthy young men on a low-carotenoid diet supplemented with tomato juice

The HDL-bound enzyme paraoxonase (PON) protects LDL from oxidation and may therefore attenuate the development of atherosclerosis. We examined the effect of tomato and carrot juice consumption on PON1 activity and lipid peroxidation in healthy young volunteers with different PON1-192 genotypes (Q/R substitution at position 192). In this randomized cross-over study twenty-two healthy, non-smoking men on a low-carotenoid diet received 330 ml/d tomato juice (37.0 mg lycopene, 1.6 mg beta-carotene) or carrot juice (27.1 mg beta-carotene, 13.1 mg alpha-carotene) for 2 weeks. Intervention periods were preceded by 2-week low-carotenoid intake. We determined the PON1-192 genotype by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) and measured ex vivo LDL oxidation (lag time), plasma malondialdehyde and PON1 activity at the beginning and end of each intervention period. At baseline, lag time was higher (P<0.05) in QQ (111 (sd 9) min) than in QR/RR subjects (101 (sd 8) min). Neither tomato nor carrot juice consumption had significant effects on PON1 activity. However, tomato juice consumption reduced (P<0.05) plasma malondialdehyde in QR/RR (Delta: -0.073 (sd 0.11) micromol/l) as compared to QQ subjects (Delta:+0.047 (sd 0.13) micromol/l). Carrot juice had no significant effect on malondialdehyde irrespective of the PON1-192 genotype. Male volunteers with the QR/RR genotype showed an increased lipid peroxidation at baseline. Although tomato and carrot juice fail to affect PON1 activity, tomato juice intake reduced lipid peroxidation in healthy volunteers carrying the R-allele of the PON1-192 genotype and could thus contribute to CVD risk reduction in these individuals.

Generation of Se‐fortified broccoli as functional food: impact of Se fertilization on S metabolism

Selenium (Se)-fortified broccoli (Brassica oleracea var. italica) has been proposed as a functional food for cancer prevention, based on its high glucosinolate (GSL) content and capacity for Se accumulation. However, as selenate and sulphate share the initial assimilation route, Se fertilization could interfere with sulphur metabolism and plant growth. Consequently, GSL accumulation could be compromised. To evaluate these potentially adverse effects of Se fertilization, we performed a comprehensive study on sand-grown young broccoli plants (weekly selenate applications of 0.8 µmol plant(-1) via the root) and field-grown adult broccoli plants during head formation (single foliar selenate application: 25.3 or 253 µmol plant(-1) ). The results show that under these conditions, Se application does not affect plant growth, contents of cysteine, glutathione, total GSL, glucoraphanin (major aliphatic GSL) or the expression of BoMYB28 (encoding a functionally confirmed master regulator for aliphatic GSL biosynthesis). Conversely, due to the changed expression of sulphate transporters (BoSULTR1;1, 1;2, 2;1, and 2;2), sulphate and total S contents increased in the shoot of young plants while decreasing in the root. We conclude that broccoli can be fertilized with Se without reduction in GSL content, even with Se accumulation exceeding the level recommended for human consumption.