I came across this article in a paper by Moskaug et al. Polyphenols and glutathione synthesis regulation. The American Journal of Clinical Nutrition, Volume 81, Issue 1, January 2005, Pages 277S–283S, https://doi.org/10.1093/ajcn/81.1.277S. I am compelled to share because of the vital role polyphenols play in the synthesis and upregulation of glutathione-a notable antioxidant.
The hallmark of oxidative stress is the increased production of reactive oxygen species (ROS), in amounts that exceed cellular antioxidant defenses. The consequence of oxidative stress may be oxidative damage of lipids, proteins, and DNA, with subsequent disease development and ageing. ROS production can result from exogenous factors such as radiation and drug exposure or endogenous factors such as increased mitochondrial respiration and oxidative enzymes in infections and inflammation. A mechanism for the protective effects of fruits and vegetables with respect to disease is that bioactive compounds in these food items reduce oxidative stress. Fruits and vegetables contain several thousand structurally diverse phytochemicals, of which a large fraction are polyphenols.
Polyphenols have antioxidant properties (i.e., reductants) and can react directly with reactive chemical species, forming products with much lower reactivity. Alternatively, compounds in a plant-based diet can increase the capacity of endogenous antioxidant defences and modulate the cellular redox state. Changes in the cellular redox state, conveying physiologic stimuli through regulation of signalling pathways, can have wide-ranging consequences for cellular growth and differentiation. Polyphenols modulate protein kinase activities, serve as ligands for transcription factors, and modulate protease activities. Thus, dietary polyphenols as antioxidants, can protect against oxidative damage by directly neutralizing reactive oxidants.
The most important endogenous antioxidant defense systems are composed of the thiol-containing tripeptide glutathione and small thiol-containing proteins such as thioredoxin, glutaredoxin, and peroxiredoxin. Of these, glutathione is found in most cells and is the major contributor to the redox state of the cell. Glutathione exists in cells in both a reduced form (GSH) and an oxidized form (GSSG); it may also be covalently bound to proteins through a process called glutathionylation. The ratio of GSH to GSSG is determined by the overall redox state of the cell. Glutathione is synthesized enzymatically by gamma-glutamylcysteine synthetase (GGCS) and glutathione synthetase, with the former (GGCS) being the rate-limiting enzyme. A key task for cellular glutathione is to scavenge free radicals and peroxides produced during normal cellular respiration, which would otherwise oxidize proteins, lipids, and nucleic acids. Also, detoxification of xenobiotics requires sufficient glutathione synthesis for conjugation and excretion of GSH-conjugated metabolites. Therefore, polyphenol-stimulated glutathione synthesis is considered beneficial in the cellular handling of toxic substance
Oxidative stress is a general term intimately linked to the production of reactive oxygen, nitrogen, or iron species and the overall redox state of the cell. Oxidative stress can be assessed by measuring GSH and GSSG, and it is frequently expressed as the ratio between the two. Indeed, the ratio is considered a clinical marker in diseases in which oxidative stress is particularly important. GSH is oxidized to GSSG in an age-dependent manner- reflecting accumulating oxidative stress. A decreased ratio between GSH and GSSG is also associated with the progression of tumours and decreased total glutathione concentrations are found among patients with chronic diseases of the body, including genitourinary, gastrointestinal, cardiovascular, and musculoskeletal diseases. Oxidative stress in general and GSH concentrations are also associated with neurodegenerative disorders and viral infections. In Parkinson’s disease, ROS concentrations are increased in parts of the substantia nigra, and glutathione concentrations are decreased. Polyphenol-mediated regulation of glutathione alters cellular processes. Glutathione is important in many diseases, and regulation of intracellular glutathione concentrations is one mechanism by which diet influences disease development.
Polyphenols are found in plant‐based foods and beverages, notably apples, berries, citrus fruit, plums, broccoli, cocoa, tea and coffee and many others. A diet high in polyphenol‐rich fruit, vegetables, cocoa, and beverages protects against developing cardiovascular disease and type 2 diabetes. Common polyphenols in the diet are flavanols (cocoa, tea, apples, broad beans), flavanones (hesperidin in citrus fruit), hydroxycinnamates (coffee, many fruits), flavonols (quercetin in onions, apples, and tea) and anthocyanins (berries). Polyphenols therefore play a key role against the development of chronic diseases (Williamson G. The role of polyphenols in modern nutrition. British Nutrition Foundation. Nutrition Bulletin, 42, 226–235. 2017).
Table: Flavan-3-ol Content and AntioxidantCapacity of Various Foods and Beverages
Antioxidant activity is reported as oxygen radical absorbance capacity (ORAC) and expressed as mmol Trolox equivalents. Data are provided on a per-weight and per-kcal basis to facilitate comparison among foods (Katz et al. Cocoa and Chocolate in Human Health and Disease. ANTIOXIDANTS & REDOX SIGNALINGVolume 15, Number 10, 2011).
Cocoa has more phenolics and higher antioxidant capacity than green tea, black tea or red wine. On a per-serving basis, cocoa has higher flavonoid content and antioxidant capacity than red wine (2 times), green tea (2-3 times), and black tea (4-5 times). Consume more polyphenol-rich cocoa for improved health and well-being.
DR. EDWARD O. AMPORFUL
CHIEF PHARMACIST
COCOA CLINIC.
