ABSTRACT
A series of dietary ingredients and metabolites are able to induce an adaptive stress response either by generation of reactive oxygen species (ROS) and/or
via
activation of the Nrf2/Keap1 ...stress response network. Most of the molecules belong to activated Michael acceptors, electrophiles capable to S-alkylate redox sensitive cysteine thiols. This review summarizes recent advances in the (re)search of these compounds and classifies them into distinct groups. More than 60 molecules are described that induce the Nrf2 network, most of them found in our daily diet. Although known as typical antioxidants, a closer look reveals that these molecules induce an initial mitochondrial or cytosolic ROS formation and thereby trigger an adaptive stress response and hormesis, respectively. This, however, leads to higher levels of intracellular glutathione and increased expression levels of antioxidant enzymes such as glutathione peroxidase, thioredoxin reductase, and superoxide dismutase. According to this principle, the author suggests the term
hormetics
to describe these indirect antioxidants.
Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species ...(ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisomeproliferator-activated receptor gamma (PPARγ), and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants (P< 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.
Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose ...availability decreases
Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be dispensable for this phenotype, whereas disruption of
aak-2, a homolog of AMP-dependent kinase (AMPK), abolishes extension of life span due to impaired glycolysis. Reduced glucose availability promotes formation of reactive oxygen species (ROS), induces catalase activity, and increases oxidative stress resistance and survival rates, altogether providing direct evidence for a hitherto hypothetical concept named mitochondrial hormesis or “mitohormesis.” Accordingly, treatment of nematodes with different antioxidants and vitamins prevents extension of life span. In summary, these data indicate that glucose restriction promotes mitochondrial metabolism, causing increased ROS formation and cumulating in hormetic extension of life span, questioning current treatments of type 2 diabetes as well as the widespread use of antioxidant supplements.
Complementary and alternative medicine (CAM) supplements are widely used by cancer patients. Dietary supplements, vitamins and minerals, herbal remedies, and antioxidants are especially popular. In a ...systematic literature review, 37 studies, each including more than 1000 participants, on CAM, dietary supplement, and vitamin use among cancer patients were identified. Accordingly, cancer patients use antioxidants such as vitamin C (from 2.6% (United Kingdom) to 41.6% (United States)) and vitamin E (from 2.9% (China) to 48% (United States)). Dietary supplements and vitamins are taken for different reasons, but often during conventional cancer treatment involving chemotherapy or radiotherapy and in a self-decided manner without seeking medical advice from healthcare professionals. Drug–drug interactions with dietary supplements or vitamins involving multiple signaling pathways are well described. Since most of the anticancer drugs generate reactive oxygen species (ROS), an adaptive stress response of healthy and malignant cells, mainly driven by the Nrf-2-Keap I network, can be observed. On the one hand, healthy cells should be protected from ROS-overproducing chemotherapy and radiotherapy; on the other hand, ROS production in cancer cells is a “desirable side effect” during anticancer drug treatment. We here describe the paradoxical use of antioxidants and supplements during cancer therapy, possible interactions with anticancer drugs, and the involvement of the Nrf-2 transcription factor.
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•Food policies foster policy network developments and interactions.•Policy network analysis identifies powerful actors in the health food sector.•Information from political groups ...considered more important than from interest groups.•Food industry interests are overrepresented compared to consumer interests.
This paper focuses on policy networks and implications surrounding the complex legal requirements on functional foods in the European Union (EU). Using social network analysis, we empirically identify relevant network actors, both private and public, and quantitatively analyse network structures in terms of reputation, information exchange, and communication. Although private network actors outnumber public network actors, their importance is incontrovertible higher. The study identifies the European Commissions’ Directorate-General for Health and Food Safety (DG SANTE), FoodDrinkEurope, and the European Consumer Organisation (BEUC) as the three most powerful network actors; among Council members, Great Britain vested an outstanding position before Brexit. Overall, the findings paint a precise picture of the functional food policy domain network in the EU by linking formal legislative decision-making and informal interest intermediation in policy formulation. Thus, our research shows the importance of information for network actors’ strategic positive positioning.
Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human vitamin E metabolites, that ...long-chain ω-carboxylates are potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13'-COOH) can be synthesized from α-tocopherol in a human liver-on-chip, and is detected in human and mouse plasma at concentrations (8-49 nM) that inhibit 5-lipoxygenase in human leukocytes. α-T-13'-COOH accumulates in immune cells and inflamed murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together, our data suggest that the immune regulatory and anti-inflammatory functions of α-tocopherol depend on its endogenous metabolite α-T-13'-COOH, potentially through inhibiting 5-lipoxygenase in immune cells.
Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan. In contrast with recent observations, here we find that overexpression of sir-2.1, the ortholog of ...mammalian SirT1, does extend Caenorhabditis elegans lifespan. Sirtuins mandatorily convert NAD(+) into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, even in the absence of sir-2.1. We identify a previously unknown C. elegans nicotinamide-N-methyltransferase, encoded by a gene now named anmt-1, to generate MNA from NAM. Disruption and overexpression of anmt-1 have opposing effects on lifespan independent of sirtuins, with loss of anmt-1 fully inhibiting sir-2.1-mediated lifespan extension. MNA serves as a substrate for a newly identified aldehyde oxidase, GAD-3, to generate hydrogen peroxide, which acts as a mitohormetic reactive oxygen species signal to promote C. elegans longevity. Taken together, sirtuin-mediated lifespan extension depends on methylation of NAM, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation.
Beverages are an integral part of human nutrition, yet little is known about their contribution to daily intakes of minerals and trace elements in German consumers. Using inductively coupled ...plasma-mass spectrometry, we determined the concentration of five minerals and six trace elements in beverage samples (
= 990, assigned to different beverage groups) collected throughout Germany. For a calculation of their relative contribution to the mineral supply, available beverage consumption data was combined with our quantitative analysis to calculate the average contribution of beverage groups to meet the respective dietary reference values currently used in Germany, Austria and Switzerland (D-A-CH region). Based on their presence in beverages and their consumption, the top three minerals are phosphorous, calcium and magnesium, and they, therefore, may reasonably contribute to the reference values. Among the trace elements, beverages mostly contributed to the manganese supply, whereas at the same time, concentrations of iron, cobalt and copper were low across all tested groups. Our study provides an overview of the assumed mineral and trace element intake via beverages in Germany and may, thus, serve as a foundation for a mineral and trace element database of beverages that needs to be expanded in the future.
The European Union (EU) has one of the strictest pesticide policies. As one component of the regulatory framework, Regulation (EC) No 396/2005 sets harmonised maximum residue levels for pesticide ...residues in food and feed in the European Union to ensure high levels of consumer protection. Under certain circumstances, a notification in the Rapid Alert System for Food and Feed (RASFF) is released for pesticide residues exceeding a specific or a default maximum limit. Despite being a major food hazard in the European Union, no detailed analysis of notifications on pesticide residues over a longer period is available to date. Thus, an analysis of notifications on pesticide residues in food submitted in the RASFF between 2002 and 2020 was conducted. A total of 5211 notifications, including 15.8% alert notifications, 36.5% information notifications and 47.8% border rejections, were analysed with a focus on concerned products, causative pesticides and involved countries of origin. The notifications often concerned vegetables (53.8%) and fruits, tree nuts (24.2%) and reported a total of 7413 residues involving 251 pesticides in products mainly originating from third countries (82.4%), with multiple residues in 22.0% of notifications. Overall, the notifications on pesticide residues in food appear to be linked to the regulatory framework and selected risk management measures. While import controls and border rejections appear to be an effective means of protecting European consumers from non-compliant and potentially harmful products from third countries, the problem of unauthorised pesticide residues in products from EU/EFTA countries and of products not available at the time of publication in the RASFF might require further measures for food safety in the European single market.
•An analysis of RASFF notifications on pesticide residues in food was conducted.•5211 notifications on pesticide residues were released from 2002 to 2020.•The notifications often concerned vegetables (53.8%) or fruits/tree nuts (24.2%).•7413 residues of 251 pesticides were reported, often as multiple residues.•Products from third countries were involved in 82.4% of notifications.
Natural chromanols and chromenols comprise a family of molecules with enormous structural diversity and biological activities of pharmacological interest. A recently published systematic review ...described more than 230 structures that are derived from a chromanol ortpd chromenol core. For many of these compounds structure-activity relationships have been described with mostly anti-inflammatory as well as anti-carcinogenic activities. To extend the knowledge on the biological activity and the therapeutic potential of these promising class of natural compounds, we here present a report on selected chromanols and chromenols based on the availability of data on signaling pathways involved in inflammation, apoptosis, cell proliferation, and carcinogenesis. The chromanol and chromenol derivatives seem to bind or to interfere with several molecular targets and pathways, including 5-lipoxygenase, nuclear receptors, and the nuclear-factor "kappa-light-chain-enhancer" of activated B-cells (NFκB) pathway. Interestingly, available data suggest that the chromanols and chromenols are promiscuitively acting molecules that inhibit enzyme activities, bind to cellular receptors, and modulate mitochondrial function as well as gene expression. It is also noteworthy that the molecular modes of actions by which the chromanols and chromenols exert their effects strongly depend on the concentrations of the compounds. Thereby, low- and high-affinity molecular targets can be classified. This review summarizes the available knowledge on the biological activity of selected chromanols and chromenols which may represent interesting lead structures for the development of therapeutic anti-inflammatory and chemopreventive approaches.
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