Antioxidative stress

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Antioxidative stress is an overabundance of bioavailable antioxidant compounds that interfere with the immune system's ability to neutralize pathogenic threats. The fundamental opposite is oxidative stress, which can lead to such disease states as coronary heart disease or cancer. [1]

Contents

Antioxidant compounds reduce reactive oxygen species (ROS), which reduces emitted free-radicals. When ROS function is impaired, there is more susceptibility to atopic disorders or diseases due to impairment of the attack-kill-present-respond behavior of the Th-1 immune response chain. Over-consumption of antioxidants could thus lead to antioxidative stress, where antioxidants might weaken or block the adaptive stress responses and cause dangerous health conditions and cause harm. [2]

Health effects

The concept of antioxidative stress may best be described by excessive or detrimental nutritional consumption of a diet rich in antioxidants, [3] unbalancing the immune systems' pathogenic response processes. Serious health conditions can result if these processes are chronically unbalanced, ranging from acute to chronic. Immunological stress by over-supplementation of antioxidants facilitates adverse health effects specifically including allergies, asthma, and physiological alterations (especially of the skin).

Many foods contain antioxidant content, while numerous dietary supplements are exceptionally rich in antioxidants. [4] Products marketed with health benefits routinely tout antioxidant content as a beneficial product aspect without consideration of overall dietary oxidative balances. [5] This is generally due to the biological effects of antioxidants being misunderstood in popular culture, focusing only on their beneficial qualities to reduce ROS to prevent excessive free-radicals which may otherwise lead to well-known disease conditions.

Correlation with medical conditions

Many antioxidative compounds are also antinutrients, such as phenolic compounds, found in plant foods belonging to the families of phenolic acids, flavonoids, isoflavonoids, and tocopherols, among others. Phenolic compounds found in foods generally contribute to their astringency and may also reduce the availability of certain minerals such as zinc. [6] Zinc deficiency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, and eye and skin lesions. [7]

High-dose supplements of antioxidants may be linked to health risks in some cases, including higher mortality rates. For example, high doses of beta-carotene and vitamin E was found to increase the risk of lung cancer and overall mortality in smokers. [2] High doses of vitamin E may increase risks of prostate cancer and one type of stroke. Antioxidant supplements may also interact with some medicines.

Role of free-radicals

The primary factor in antioxidants causing or promoting the aforementioned health issues, is the attenuation or inactivation of reactive oxygen species (ROS), which immune system responders use to kill or destroy pathogens, mainly bacteria and fungi. ROS produce free-radicals as a by-product of the oxygen burst used to kill pathogens. Excess free-radicals that are not effectively scavenged and collected result in oxidative stress that can also be harmful. [8]

Free-radicals are not the enemy that popular culture has made them out to be, as they aid in proper biochemical signaling that make them necessary in a healthy immune system. Several complex biological free-radical collection systems already exist for the purpose of scavenging, which normally, do not require augmentation by supplementation of antioxidants to function nominally. [9]

Role in disease

Antioxidants attenuate the Th-1 immune response, responsible for eliminating bacterial and fungal threats, while the Th-2 immune response compensates for a weak Th-1 response by increasing its own responders, which may be not only ineffective, but overall destructive to healthy surrounding tissues, thus harmful. The net result: over-supplementation of antioxidants are a direct, underlying cause of allergenic diseases and skin alterations, spurring signs (objective indications) and symptoms (subjective states) of localized and disseminated medical conditions.

Because of the low-level biochemical nature of these immunological systems and their processes, the consequences of antioxidative stress can result in overlying symptoms, leading or contributing to chronic, co-morbid, localized, and/or disseminated disease states, that are clinically challenging to successfully treat.

A diet rich in anti-oxidants could allow for skin alterations such as acute acne or chronic non-infectious lesions, especially when the Th-1 immune process is persistently compromised by an overload of dietary antioxidant sources, like daily ingesting of vitamin C supplements, for example. Allergenic reactions by invading atopic pathogens, well beyond the scope of microbiota, can become initial factors triggering chronic atopic disease.

When relating to atopic skin conditions caused by chronic antioxidative stress, symptoms similar to Chronic granulomatous disease (CGD) may appear, a disease where phagocytes have an impaired ability to destroy pathogens due to a genetic inability to effectively kill pathogens by ROS, versus supplementation induced inability caused by antioxidative stress. [10]

Dietary balance

Nearly all living creatures consume antioxidants in some quantity. Inadequate consumption of dietary antioxidants can be detrimental. For example, a deficiency of vitamin C is a primary cause of scurvy. Vitamin C can be ingested by eating certain fruits. A dietary balance of oxidants and antioxidants are critical in maintaining optimal health.

There have been studies on antioxidant capacities of various supplements and compounds. [11] However, there has not been a dietary system devised to quantify what levels of oxidants or antioxidants are "healthy". Unfortunately, in laboratory testing, there is no single gold standard assay to determine clinically-accepted antioxidant capacity due to numerous available assay methods, though there are several accepted popular assays that can be merged into a final result to produce a representative antioxidative value. [12] Resulting values are subjective because assay methods comprising a final value can vary drastically between individual assay results. [13]

Additionally, such a value does not highlight prevalence in types of antioxidants compounds over others (like lycopene versus ascorbic acid), meaning that while a resulting content value between two substances may be similar, though the potential overlying resulting effect can differ, making clinical assessments of resulting symptoms highly unreliable as to the underlying condition. However, a Norwegian scientific study created a table of 3139 products [14] over a period of eight years, with normalized values based on a modified assay, giving a more comprehensive picture when comparing a variety of food antioxidant capacities. [4]

While it is not known what constitutes healthy oxidative levels, it is known that regular exercise essentially tightens this balance, by both emitting more ROS, while reducing the capacity of leukocytes for oxidant release. [15] Available antioxidant research has noted the significant challenge in determining what qualifies as oxidative and antioxidative stress, citing a wide range of variables to consider, such as a person's physiology, status, environment, and other factors. [16]

Precipitating nutritional factors

Numerous nutritional substances, compounds, and foods have some degree of antioxidant capacity. High-capacity antioxidants include, but not limited to, vitamins C and E, resveratrol and flavonoids (e.g. wine), Sangre de grado (Croton lechleri) aka Dragons Blood, green and black teas, cloves, cinnamon, most commonly used spices and herbs, mints, several berry and nut species, coffee and chocolates.

Normal intake of antioxidants, traditionally considered staples of healthy food, may exert beneficial properties towards some disease states such as neurological disorders, inflammatory conditions, and depression. However, chronic unbalanced ingestion or high quantity supplementation could result in serious ailments due to the suppression of ROS. Allergies, asthma, bacterial and fungal infections of the skin (alterations) are known conditions that stem from antioxidant stress. [3]

Components of antioxidants

There are many types of antioxidant compounds. Examples are, but not limited to, Carotenoids (Beta-carotene, Lycopene), Lutein, Manganese, Magnesium, Selenium, Vitamin A (retinol), Vitamin C (ascorbic acid, ascorbates), and Vitamin E (α‐Tocopherol, tocotrienols), and many more. These compounds can be found as ingredients in various products, or as components of ingredients, or as broader categorical classifications of components. Determining the compound makeup of a product or ingredient allows for general identification of antioxidant compounds, and thus, the potential antioxidant content a product exhibits.

Research

Because overall research and reporting on antioxidative stress is sparse, a fundamental knowledge gap exists in this medically-significant field. Long-term effects of chronic antioxidant stress are not well-researched. Safe levels of antioxidant consumption have yet to be established in human diets. The lack of overall awareness of the subject has invoked comparatively few clinical or field studies, sparse data and statistics, and may suggest a valuable field of nutritional research has been categorically dismissed or overlooked.

Assays for oxidative stress and antioxidant reserves are offered by at least one diagnostic company. Diagnosing antioxidative stress is currently extremely rare due to factors such as widespread unfamiliarity, lacking proper understanding in the clinical environment, and trivial modern medical training on the subject. Speculatively, when considering the general abundance of oxidative stress-related conditions (e.g. cancer), a comparable statistical population of antioxidative stress-related conditions (e.g. allergies) is hypothetically viable, based upon available documented research regarding the known resulting pathology of antioxidative stress.

See also

Related Research Articles

Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol, or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitamin E, can cause nerve problems. Vitamin E is a fat-soluble antioxidant which may help protect cell membranes from reactive oxygen species. Worldwide, government organizations recommend adults consume in the range of 3 to 15 mg per day. As of 2016, consumption was below recommendations according to a worldwide summary of more than one hundred studies that reported a median dietary intake of 6.2 mg per day for alpha-tocopherol. Foods rich in vitamin E include seeds and nuts, seed oils, peanut butter, and vitamin E-fortified foods, such as margarine.

<span class="mw-page-title-main">Flavonoid</span> Class of plant and fungus secondary metabolites

Flavonoids are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.

<span class="mw-page-title-main">Polyphenol</span> Class of chemical compounds

Polyphenols are a large family of naturally occurring phenols. They are abundant in plants and structurally diverse. Polyphenols include phenolic acids, flavonoids, tannic acid, and ellagitannin, some of which have been used historically as dyes and for tanning garments.

<span class="mw-page-title-main">Reactive oxygen species</span> Highly reactive molecules formed from diatomic oxygen (O₂)

In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.

<span class="mw-page-title-main">Cat food</span> Food for consumption by cats

Cat food is food specifically formulated and designed for consumption by cats. As obligate carnivores, cats have specific requirements for their dietary nutrients, namely nutrients found only in meat or synthesised, such as taurine and Vitamin A. Certain nutrients, including many vitamins and amino acids, are degraded by the temperatures, pressures and chemical treatments used during manufacture, and hence must be added after manufacture to avoid nutritional deficiency. Cat food is typically sold as dry kibble, or as wet food in cans and pouches.

Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives. It occurs when free radicals, specifically reactive oxygen species (ROS), interact with lipids within cell membranes, typically polyunsaturated fatty acids (PUFAs) as they have carbon–carbon double bonds. This reaction leads to the formation of lipid radicals, collectively referred to as lipid peroxides or lipid oxidation products (LOPs), which in turn react with other oxidizing agents, leading to a chain reaction that results in oxidative stress and cell damage.

Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.

NADPH oxidase is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2.

<span class="mw-page-title-main">Oxidative stress</span> Free radical toxicity

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O−
2, OH and H2O2. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.

Oxygen radical absorbance capacity (ORAC) was a method of measuring antioxidant capacities in biological samples in vitro. Because no physiological proof in vivo existed in support of the free-radical theory or that ORAC provided information relevant to biological antioxidant potential, it was withdrawn in 2012.

<span class="mw-page-title-main">Myricetin</span> Chemical compound

Myricetin is a member of the flavonoid class of polyphenolic compounds, with antioxidant properties. Common dietary sources include vegetables, fruits, nuts, berries, tea, and red wine.

<span class="mw-page-title-main">Antioxidant effect of polyphenols and natural phenols</span>

A polyphenol antioxidant is a hypothetized type of antioxidant, in which each instance would contain a polyphenolic substructure; such instances which have been studied in vitro. Numbering over 4,000 distinct chemical structures, such polyphenols may have antioxidant activity {{{1}}} in vitro (although they are unlikely to be antioxidants in vivo). Hypothetically, they may affect cell-to-cell signaling, receptor sensitivity, inflammatory enzyme activity or gene regulation, although high-quality clinical research has not confirmed any of these possible effects in humans as of 2020.

<span class="mw-page-title-main">Folin–Ciocalteu reagent</span> Chemical mixture

The Folin–Ciocâlteu reagent (FCR) or Folin's phenol reagent or Folin–Denis reagent, is a mixture of phosphomolybdate and phosphotungstate used for the colorimetric in vitro assay of phenolic and polyphenolic antioxidants, also called the gallic acid equivalence method (GAE). It is named after Otto Folin, Vintilă Ciocâlteu, and Willey Glover Denis. The Folin-Denis reagent is prepared by mixing sodium tungstate and phosphomolybdic acid in phosphoric acid. The Folin–Ciocalteu reagent is just a modification of the Folin-Denis reagent. The modification consisted of the addition of lithium sulfate and bromine to the phosphotungstic-phosphomolybdic reagent.

Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example, an overdose of the analgesic paracetamol (acetaminophen) can fatally damage the liver, partly through its production of reactive oxygen species.

<span class="mw-page-title-main">Selenium in biology</span> Use of Selenium by organisms

Selenium is an essential micronutrient for animals, though it is toxic in large doses. In plants, it sometimes occurs in toxic amounts as forage, e.g. locoweed. Selenium is a component of the amino acids selenocysteine and selenomethionine. In humans, selenium is a trace element nutrient that functions as cofactor for glutathione peroxidases and certain forms of thioredoxin reductase. Selenium-containing proteins are produced from inorganic selenium via the intermediacy of selenophosphate (PSeO33−).

Reductive stress (RS) is defined as an abnormal accumulation of reducing equivalents despite being in the presence of intact oxidation and reduction systems. A redox reaction involves the transfer of electrons from reducing agents (reductants) to oxidizing agents (oxidants) and redox couples are accountable for the majority of the cellular electron flow. RS is a state where there are more reducing equivalents compared to reductive oxygen species (ROS) in the form of known biological redox couples such as GSH/GSSG, NADP+/NADPH, and NAD+/NADH. Reductive stress is the counterpart to oxidative stress, where electron acceptors are expected to be mostly reduced. Reductive stress is likely derived from intrinsic signals that allow for the cellular defense against pro-oxidative conditions. There is a feedback regulation balance between reductive and oxidative stress where chronic RS induce oxidative species (OS), resulting in an increase in production of RS, again.

<span class="mw-page-title-main">Senior dog diet</span>

Senior dog food diets are pet foods that are catered toward the senior or mature pet population. The senior dog population consists of dogs that are over the age of seven for most dog breeds, though in general large and giant breed dogs tend to reach this life stage earlier when compared to smaller breed dogs. Senior dog foods contain nutrients and characteristics that are used to improve the health of the aging dog. Aging in dogs causes many changes to occur physiologically that will require a change in nutrient composition of their diet.

Nutritional immunology is a field of immunology that focuses on studying the influence of nutrition on the immune system and its protective functions. Indeed, every organism will under nutrient-poor conditions "fight" for the precious micronutrients and conceal them from invading pathogens. As such, bacteria, fungi, plants secrete for example iron chelators (siderophores) to acquire iron from their surrounding

References

  1. ↑ Valko, M.; Rhodes, C. J.; Moncol, J.; Izakovic, M.; Mazur, M. (2006-03-10). "Free radicals, metals and antioxidants in oxidative stress-induced cancer". Chemico-Biological Interactions. 160 (1): 1–40. doi:10.1016/j.cbi.2005.12.009. ISSN   0009-2797. PMID   16430879.
  2. 1 2 Poljsak, B.; Milisav, I. (Feb 17, 2012). "The Neglected Significance of "Antioxidative Stress"". Oxidative Medicine and Cellular Longevity. 2012: 480895. doi: 10.1155/2012/480895 . PMC   3357598 . PMID   22655114.
  3. 1 2 Katharina Schroecksnadel, Bentham Science Publisher; Fischer, Bentham Science Publisher Birgit; Schennach, Bentham Science Publisher Harald; Weiss, Bentham Science Publisher Guenter; Fuchs, Bentham Science Publisher Dietmar (2007-09-01). "Antioxidants Suppress Th1-Type Immune Response In Vitro". Drug Metabolism Letters. 1 (3): 166–171. doi:10.2174/187231207781369816. ISSN   1874-0758. PMID   19356038.
  4. 1 2 Carlsen, Monica H; Halvorsen, Bente L; Holte, Kari; Bøhn, Siv K; Dragland, Steinar; Sampson, Laura; Willey, Carol; Senoo, Haruki; Umezono, Yuko (2010-01-22). "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide". Nutrition Journal. 9: 3. doi: 10.1186/1475-2891-9-3 . ISSN   1475-2891. PMC   2841576 . PMID   20096093.
  5. ↑ Sifferlin, Alexandra (Aug 6, 2013). "The Truth About Antioxidants". Time. Time Inc.
  6. ↑ Shahidi, Fereidoon (1997). "Beneficial Health Effects and Drawbacks of Antinutrients and Phytochemicals in Foods". Antinutrients and Phytochemicals in Food. ACS Symposium Series. Vol. 662. pp. 1–9. doi:10.1021/bk-1997-0662.ch001. ISBN   978-0-8412-3498-7.
  7. ↑ "Office of Dietary Supplements – Zinc". ods.od.nih.gov. Retrieved 2016-05-11.
  8. ↑ Percival, Mark (January 1996). "Antioxidants" (PDF).
  9. ↑ Pham-Huy, Lien Ai; He, Hua; Pham-Huy, Chuong (2008-06-01). "Free Radicals, Antioxidants in Disease and Health". International Journal of Biomedical Science. 4 (2): 89–96. ISSN   1550-9702. PMC   3614697 . PMID   23675073.
  10. ↑ Kim, J.h.; Campbell, B.c.; Mahoney, N.; Chan, K.l.; May, G.s. (2006-07-01). "Targeting antioxidative signal transduction and stress response system: control of pathogenic Aspergillus with phenolics that inhibit mitochondrial function". Journal of Applied Microbiology. 101 (1): 181–189. doi: 10.1111/j.1365-2672.2006.02882.x . ISSN   1365-2672. PMID   16834605.
  11. ↑ Wojcikowski, Ken; Stevenson, Lesley; Leach, David; Wohlmuth, Hans; Gobe, Glenda (2007-01-01). "Antioxidant Capacity of 55 Medicinal Herbs Traditionally Used to Treat The Urinary System: A Comparison Using A Sequential Three-Solvent Extraction Process". Journal of Alternative and Complementary Medicine . 13 (1): 103–110. doi:10.1089/acm.2006.6122. ISSN   1075-5535. PMID   17309384.
  12. ↑ Huang, Dejian; Ou, Boxin; Prior, Ronald L. (2005-03-01). "The Chemistry behind Antioxidant Capacity Assays". Journal of Agricultural and Food Chemistry. 53 (6): 1841–1856. doi:10.1021/jf030723c. ISSN   0021-8561. PMID   15769103.
  13. ↑ Wojcikowski, Ken; Stevenson, Lesley; Leach, David; Wohlmuth, Hans; Gobe, Glenda (2007-02-01). "Antioxidant capacity of 55 medicinal herbs traditionally used to treat the urinary system: a comparison using a sequential three-solvent extraction process". Journal of Alternative and Complementary Medicine. 13 (1): 103–109. doi:10.1089/acm.2006.6122. ISSN   1075-5535. PMID   17309384.
  14. ↑ Carlsen, MH; Halvorsen, BL; Holte, K; Bøhn, SK; Dragland, S; Sampson, L; Willey, C; Senoo, H; Umezono, Y; Sanada, C; Barikmo, I; Berhe, N; Willett, WC; Phillips, KM; Jacobs, DR; Blomhoff, R (Jan 22, 2010). "Additional file 1: The Antioxidant Food Table". Nutr J. 9: 3. doi: 10.1186/1475-2891-9-3 . PMC   2841576 . PMID   20096093.
  15. ↑ Niess, A. M.; Dickhuth, H. H.; Northoff, H.; Fehrenbach, E. (1999-01-01). "Free radicals and oxidative stress in exercise—immunological aspects". Exercise Immunology Review. 5: 22–56. ISSN   1077-5552. PMID   10519061.
  16. ↑ Moreno-Macias, Hortensia; Romieu, Isabelle (May 2014). "Effects of antioxidant supplements and nutrients on patients with asthma and allergies". Journal of Allergy and Clinical Immunology. 133 (5): 1237–1244. doi:10.1016/j.jaci.2014.03.020. PMID   24766873.
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