_4.15.23%20(LARGE%20bold%20.png/:/rs=h:200,cg:true,m/qt=q:95)
_4.15.23%20(LARGE%20bold%20.png/:/rs=h:104,cg:true,m/qt=q:95)
antioxidants & Prooxidants
What are antioxidants? How do they work in the body? Could too much of a good thing be bad?
What are antioxidants? How do they work in the body? Could too much of a good thing be bad? According to Taber's Cyclopedic Medical Dictionary an antioxidant is "An agent that prevents or inhibits oxidation. Antioxidants are substances that may protect cells from the damaging effects of oxygen radicals, highly reactive chemicals that play a part in atherosclerosis and some forms of cancer." Antioxidants reduce prooxidants by either donating an electron, or hydrogen atom. Examples of exogenous antioxidants (ingested from foods and supplements) include vitamin's A, C and E, alpha lipoic acid (thioctic acid) and various polyphenols, such as epigallocatechin-3-gallate (EGCG) from green tea, curcuminoids from turmeric, gingerols from ginger root, quercetin from apples and onions, and resveratrol from red wine, red grapes, and peanuts, among others. Examples of endogenous antioxidants (synthesized inside our body) include glutathione (GSH), superoxide dismutases (SODs), catalase, and also alpha lipoic acid.
What are prooxidants? Prooxidants, or reactive oxygen species (ROSs), are oxygen-containing molecules. Examples of exogenous prooxidants include reactive metals, such as iron and copper, xenobiotics (any foreign substances, especially artificial colors/flavors and various environmental toxins), and yes, even polyphenols. Examples of endogenous prooxidants include superoxide, hydrogen peroxide, hydroxyl radical, singlet oxygen, and lipid hydroperoxide, among others. Although oxidative stress is an normal part of physiological and biochemical reactions necessary for life excessive oxidative stress (e.g. physical, chemical, or emotion stress) can overwhelm our antioxidant system leading to various metabolic diseases.
Now, while polyphenols, such as EGCG and curcuminoids, are able to directly reduce various prooxidants on a one-to-one basis, and can also be recycled and reused, this effect is minimal compared to their prooxidant effect, which activates our far more potent endogenous antioxidant system (Keap1/Nrf2/ARE - Antioxidant Response Element) (see top right image).
So, what amount of polyphenols should we consume to help support our endogenous antioxidant system? Should we be consuming supraphysiologic amounts with the thinking, if a little is good, more is better? Let's take a look at green tea polyphenols. The major ones include catechins, epicatechin (EC), EC 3-gallate (ECG), epigallocatechin (EGC) and (EGCG). You can see in the second image to the right the antioxidant effect of EGCG against lipid peroxidation (oxidative stress) at various doses. EGCG at up to 50 micromoles (uM) (22.93 mg) results in increased GSH synthesis and reduced ROSs, malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), but above this level GSH begins to decline and at doses somewhere north of 200 uM (91.71 mg) ROSs begin to increase, which is clearly seen at 400 uM (183.42 mg). This effect is called hormesis, "a little bit of a bad thing is good (see images three & four)." But, as the research shows, if a little is good, more is not better. Overwhelming our powerful, but limited endogenous antioxidant system can cause the exact cellular damage we're trying to prevent. Now the above study was done by "incubating cells outside the human body with EGCG at various concentrations." Oral intake and gastrointestinal (GI) digestion would result in a much lower absorption rate, about 20% reaching circulation.
So, how much green tea would you have to consume to potentially cause such a negative reaction? According to the United States Department of Agriculture (USDA) Flavonoid Database one cup of brewed green tea (240 ml) contains approximately 160 - 190 mg of EGCG (range 2 - 203 mg, 100 samples). Assuming 20% absorption into circulation, per cup of green tea, or let's say 175 mg EGCG per cup x 20% = 35 mg absorbed. With toxicity seen at 183 mg absorption, or possibly as low as 137 mg (300 uM), drinking approximately 4-5 cups of green tea could theoretically begin to show hepatic (liver) adverse effects (AEs), such as a rise in the liver transaminases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and in gamma glutamyltransferase (GGT), alkaline phosphatase (AP), and bilirubin, all indicators of oxidative stress.
Comparing the incubated cells study with human studies, hepatic AEs began to occur at 800 EGCG. Again, using the 20% absorption assumption, an 800 mg dose of EGCG would result in 160 mg being absorbed. Divide this by 35 mg per cup of green tea = 4.57 cups. Summarizing from these studies, we could assume that something under 4-5 cups of green tea would be the maximum consumed to gain the antioxidant benefits without risking the adverse effects.
So, does this mean you should never drink more than 4-5 cups of green tea per day. Not necessarily. The human study was using a single dose of green tea containing 800 mg of EGCG. Drinking 4-5 cups over a 12 hour period will likely allow your liver to better metabolize and excrete the catechins. Other factors to consider are the quality of green tea (higher quality = higher EGCG); drinking during a fasting (greater absorption) vs. fed state, an individual's genetic / physiological makeup; taking EGCG supplements (some contain as high as 500 - 1,000 mg EGCG), and combining EGCG supplements with other polyphenols (e.g. curcumin, gingerol, quercetin, etc.).
Although exogenous antioxidant's prooxidant reaction can stimulate our endogenous antioxidant system, we still need to be consuming the raw materials to be able to synthesize these antioxidants. So, which nutrients are necessary for building up our endogenous antioxidant system? In a nutshell. GSH requires the amino acids, cysteine, glutamic acid and glycine, as well as the cofactor, selenium (for GSH peroxidase); the various SOD antioxidants require, zinc, copper, iron, and manganese; and catalase requires manganese and iron.
(Taber's Cyclopedic Medical Dictionary, 21st Edition, 2009)
(Antioxidant Status, Diet, Nutrition, and Health, Edited by Andreas M. Papas, 1999)
Now, lets take a quick look at curcumin, one of the primary and most studied polyphenol antioxidants in turmeric. Turmeric contains approximately 3% curcumin, and at this it is not well-absorbed. However, when supplementing, "Human studies have shown that curcumin at doses ranging from 0.9 to 3.6 g day per day for 1–4 months originates some adverse effects including nausea and diarrhea and causes an increase in serum alkaline phosphatase and lactate dehydrogenase." Some curcumin supplements contain as much as 1,000 mg (95% standardized curcuminoids) and often use black pepper, or nanoparticles to improve absorption by as much as 600x. Why did God limit turmeric's curcumin absorption to only 3%? Do we really want to absorb it at 600x this level?
Whole foods are always best, but everything in moderation. Supplements have there place, but pay attention to the quality and concentration of active compounds in the supplements you purchase. As the research shows, too much of a good thing can be bad.
http://www.aginganddisease.org/EN/10.14336/AD.2018.0513
https://chrismasterjohnphd.substack.com/p/8-beneficial-toxins-phytochemicals
https://chrismasterjohnphd.com/?s=ama
https://academic.oup.com/view-large/163875524
https://academic.oup.com/jn/article/132/6/1282/4687979
https://www.sciencedirect.com/science/article/pii/S0273230018300928
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5239
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.24967
https://pubmed.ncbi.nlm.nih.gov/17044766/
antioxidants & Prooxidants
What are antioxidants? How do they work in the body? Could too much of a good thing be bad?
What are antioxidants? How do they work in the body? Could too much of a good thing be bad? According to Taber's Cyclopedic Medical Dictionary an antioxidant is "An agent that prevents or inhibits oxidation. Antioxidants are substances that may protect cells from the damaging effects of oxygen radicals, highly reactive chemicals that play a part in atherosclerosis and some forms of cancer." Antioxidants reduce prooxidants by either donating an electron, or hydrogen atom. Examples of exogenous antioxidants (ingested from foods and supplements) include vitamin's A, C and E, alpha lipoic acid (thioctic acid) and various polyphenols, such as epigallocatechin-3-gallate (EGCG) from green tea, curcuminoids from turmeric, gingerols from ginger root, quercetin from apples and onions, and resveratrol from red wine, red grapes, and peanuts, among others. Examples of endogenous antioxidants (synthesized inside our body) include glutathione (GSH), superoxide dismutases (SODs), catalase, and also alpha lipoic acid.
What are prooxidants? Prooxidants, or reactive oxygen species (ROSs), are oxygen-containing molecules. Examples of exogenous prooxidants include reactive metals, such as iron and copper, xenobiotics (any foreign substances, especially artificial colors/flavors and various environmental toxins), and yes, even polyphenols. Examples of endogenous prooxidants include superoxide, hydrogen peroxide, hydroxyl radical, singlet oxygen, and lipid hydroperoxide, among others. Although oxidative stress is an normal part of physiological and biochemical reactions necessary for life excessive oxidative stress (e.g. physical, chemical, or emotion stress) can overwhelm our antioxidant system leading to various metabolic diseases.
Now, while polyphenols, such as EGCG and curcuminoids, are able to directly reduce various prooxidants on a one-to-one basis, and can also be recycled and reused, this effect is minimal compared to their prooxidant effect, which activates our far more potent endogenous antioxidant system (Keap1/Nrf2/ARE - Antioxidant Response Element) (see top right image).
So, what amount of polyphenols should we consume to help support our endogenous antioxidant system? Should we be consuming supraphysiologic amounts with the thinking, if a little is good, more is better? Let's take a look at green tea polyphenols. The major ones include catechins, epicatechin (EC), EC 3-gallate (ECG), epigallocatechin (EGC) and (EGCG). You can see in the second image to the right the antioxidant effect of EGCG against lipid peroxidation (oxidative stress) at various doses. EGCG at up to 50 micromoles (uM) ( 91.71 mg) results in increased GSH synthesis and reduced ROSs, malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), but above this level GSH begins to decline and at doses somewhere north of 200 uM (91.71 mg) ROSs begin to increase, which is clearly seen at 400 uM (183.42 mg). This effect is called hormesis, "a little bit of a bad thing is good (see images three & four)." But, as the research shows, if a little is good, more is not better. Overwhelming our powerful, but limited endogenous antioxidant system can cause the exact cellular damage we're trying to prevent. Now the above study was done by "incubating cells outside the human body with EGCG at various concentrations." Oral intake and gastrointestinal (GI) digestion would result in a much lower absorption rate, about 20% reaching circulation.
So, how much green tea would you have to consume to potentially cause such a negative reaction? According to the United States Department of Agriculture (USDA) Flavonoid Database one cup of brewed green tea (240 ml) contains approximately 160 - 190 mg of EGCG (range 2 - 203 mg, 100 samples). Assuming 20% absorption into circulation, per cup of green tea, or let's say 175 mg EGCG per cup x 20% = 35 mg absorbed. With toxicity seen at 183 mg absorption, or possibly as low as 137 mg (300 uM), drinking approximately 4-5 cups of green tea could theoretically begin to show hepatic (liver) adverse effects (AEs), such as a rise in the liver transaminases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and in gamma glutamyltransferase (GGT), alkaline phosphatase (AP), and bilirubin, all indicators of oxidative stress.
Comparing the incubated cells study with human studies, hepatic AEs began to occur at 800 EGCG. Again, using the 20% absorption assumption, an 800 mg dose of EGCG would result in 160 mg being absorbed. Divide this by 35 mg per cup of green tea = 4.57 cups. Summarizing from these studies, we could assume that something under 4-5 cups of green tea would be the maximum consumed to gain the antioxidant benefits without risking the adverse effects.
So, does this mean you should never drink more than 4-5 cups of green tea per day. Not necessarily. The human study was using a single dose of green tea containing 800 mg of EGCG. Drinking 4-5 cups over a 12 hour period will likely allow your liver to better metabolize and excrete the catechins. Other factors to consider are the quality of green tea (higher quality = higher EGCG); drinking during a fasting (greater absorption) vs. fed state, an individual's genetic / physiological makeup; taking EGCG supplements (some contain as high as 500 - 1,000 mg EGCG), and combining EGCG supplements with other polyphenols (e.g. curcumin, gingerol, quercetin, etc.).
Although exogenous antioxidant's prooxidant reaction can stimulate our endogenous antioxidant system, we still need to be consuming the raw materials to be able to synthesize these antioxidants. So, which nutrients are necessary for building up our endogenous antioxidant system? In a nutshell. GSH requires the amino acids, cysteine, glutamic acid and glycine, as well as the cofactor, selenium (for GSH peroxidase); the various SOD antioxidants require, zinc, copper, iron, and manganese; and catalase requires manganese and iron.
(Taber's Cyclopedic Medical Dictionary, 21st Edition, 2009)
(Antioxidant Status, Diet, Nutrition, and Health, Edited by Andreas M. Papas, 1999)
Now, lets take a quick look at curcumin, one of the primary and most studied polyphenol antioxidants in turmeric. Turmeric contains approximately 3% curcumin, and at this it is not well-absorbed. However, when supplementing, "Human studies have shown that curcumin at doses ranging from 0.9 to 3.6 g day per day for 1–4 months originates some adverse effects including nausea and diarrhea and causes an increase in serum alkaline phosphatase and lactate dehydrogenase." Some curcumin supplements contain as much as 1,000 mg (95% standardized curcuminoids) and often use black pepper, or nanoparticles to improve absorption by as much as 600x. Why did God limit turmeric's curcumin absorption to only 3%? Do we really want to absorb it at 600x this level?
Whole foods are always best, but everything in moderation. Supplements have there place, but pay attention to the quality and concentration of active compounds in the supplements you purchase. As the research shows, too much of a good thing can be bad.
http://www.aginganddisease.org/EN/10.14336/AD.2018.0513
https://chrismasterjohnphd.substack.com/p/8-beneficial-toxins-phytochemicals
https://chrismasterjohnphd.com/?s=ama
https://academic.oup.com/view-large/163875524
https://academic.oup.com/jn/article/132/6/1282/4687979
https://www.sciencedirect.com/science/article/pii/S0273230018300928
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5239
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.24967
https://pubmed.ncbi.nlm.nih.gov/17044766/
