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Unraveling the AntiOxidantControversy

Oxygen? "I rarely use it myself, sir. It promotes rust." Robby the Robot, Forbidden Planet (1956)

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Review of fundamentals: types of bonds

“RedOx”• The term redox comes from the two concepts of reduction and oxidation. It can be explained in simple terms:– Oxidation describes the loss of electrons / hydrogen or gain of oxygen / increase in oxidation state by a molecule, atom or ion

– Reduction describes the gain of electrons / hydrogen or a loss of oxygen / decrease in oxidation state by a molecule, atom or ion

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What’s a “free radical”?

Moses Gomberg, the founder of radical 

chemistry (1866‐1947)

•In chemistry, radicals (often referred to as free radicals) are atoms, molecules, or ions with unpaired electrons on an otherwise open shell configuration.

•These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions.

•Radicals play an important role in combustion, atmospheric chemistry, polymerization, plasma chemistry, biochemistry, and many other chemical processes, including human physiology.

•For example, superoxide and nitric oxide regulate many biological processes, such as controlling vascular tone.

•The first organic free radical identified was triphenylmethyl radical, by Moses Gomberg in 1900 at the University of Michigan.

Formation of Free Radicals•The formation of radicals may involve breaking of covalent bonds homolytically, a process that requires significant amounts of energy.

•The bond energy between two covalently bonded atoms is affected by the structure of the molecule as a whole, not just the identity of the two atoms, and radicals requiring more energy to form are less stable than those requiring less energy.

•Homolytic bond cleavage most often happens between two atoms of similar electronegativity. In organic chemistry this is often the O-O bond in peroxide species or O-N bonds. However, propagation is a very exothermic reaction.

•Radicals may also be formed by single electron oxidation or reduction of an atom or molecule. An example is the production of superoxide by the electron transport chain. (We MAKE them!!)

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The electron transport chain in the mitochondrion is the site of oxidative phosphorylation in eukaryotes. The NADH and succinate generated in the citric acid cycle is oxidized, providing energy to power ATP synthase.

Figure 1. Powering up lifespan.The electron transport chain of mitochondria is the major source of free radicals in the cell. Because of electron leak, free radicals react with oxygen (O2) to generate superoxide radicals (O2 ). The major sites of generation includes the iron‐sulfur clusters of complex I, coenzyme Q associated with complex III, and components of the tricarboxylic acid cycle, including alpha‐ketoglutarate dehydrogenase. Superoxide radicals are dismutated by manganese superoxide dismutase in the mitochondrial matrix to generate O2 and hydrogen peroxide (H2O2). H2O2 is then converted to H2O by either catalase or glutathione peroxidase (GPx) which uses glutathione (GSH). Aging is associated with increased mitochondrial production of H2O2, leading to oxidative damage and mitochondrial DNA mutations. Schriner et al. find that they can substantially extend lifespan in mice and reduce age‐associated disease by overexpressing catalase in mitochondria in mice.

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The LIVER produces large quantities of free radicals in the very process of detox!!! 

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Buettner & Schafer 11Ascorbate Chemistry Society For Free Radical Biology and Medicine

The Pecking Order

Buettner GR. (1993) The pecking order of free radicals and antioxidants: Lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys. 300:535-543. [PDF]

Note that the donor antioxidants are found in the middle of the “pecking order”.

Free radicals in biology•Free radicals play an important role in a number of biological processes, some of which are necessary for life, such as the intracellular killing of bacteria by neutrophil granulocytes. Free radicals have also been implicated in certain cell signalling processes. This is dubbed redox signaling.

•The two most important oxygen-centered free radicals are superoxide and hydroxyl radical. They are derived from molecular oxygen under reducing conditions. However, because of their reactivity, these same free radicals can participate in unwanted side reactions resulting in cell damage.

•Many forms of cancer are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy.

•Some of the symptoms of aging such as atherosclerosis are also attributed to free-radical induced oxidation of many of the chemicals making up the body.

•In addition free radicals contribute to alcohol-induced liver damage, perhaps more than alcohol itself. Radicals in cigarette smoke have been implicated in inactivation of alpha 1-antitrypsin in the lung. This process promotes the development of emphysema.

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Free radicals in biology (continued)•Free radicals may also be involved in Parkinson's disease, senile and drug-induced deafness, schizophrenia, and Alzheimer's.

•The classic free-radical syndrome, the iron-storage disease hemochromatosis, is typically associated with a constellation of free-radical-related symptoms including movement disorder, psychosis, skin pigmentary melanin abnormalities, deafness, arthritis, and diabetes mellitus.

•The free radical theory of aging proposes that free radicals underlie the aging process itself, whereas the process of mitohormesis suggests that repeated exposure to free radicals may extend life span.

•Because free radicals are necessary for life, the body has a number of mechanisms to minimize free radical induced damage and to repair damage which does occur, such as the enzymes superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase.

•In addition, antioxidants play a key role in these defense mechanisms. These are often the three vitamins, vitamin A, vitamin C and vitamin E and polyphenol antioxidants.

•Further, there is good evidence bilirubin and uric acid can act as antioxidants to help neutralize certain free radicals. Bilirubin comes from the breakdown of red blood cells' contents, while uric acid is a breakdown product of purines. Too much bilirubin, though, can lead to jaundice, which could eventually damage the central nervous system, while too much uric acid causes gout .

References• Oakley, R.T. Prog. Inorg. Chem. 1998, 36, 299• Banister, A.J., et al. Adv. Hetero. Chem. 1995, 62, 137• Griller, D.; Ingold, K. U. Acc. Chem. Res. 1976, 9, 13.• Lomnicki S, Truong H, Vejerano E, Dellinger B. Copper oxide-based

model of persistent free radical formation on combustion-derived particulate matter Environ Sci Technol. 2008 Jul 1;42(13):4982-8

• Pacher P, Beckman JS, Liaudet L (2007). "Nitric oxide and peroxynitritein health and disease". Physiol. Rev. 87 (1): 315–424. doi:10.1152/physrev.00029.2006. PMID 17237348.

• An overview of the role of free radicals in biology and of the use of electron spin resonance in their detection may be found in a recent book: *Rhodes C.J.: Toxicology of the Human Environment - the critical role of free radicals, Taylor and Francis, London (2000).

• G. Herzberg (1971), "The spectra and structures of simple free radicals" ISBN 048665821X

• 28th International Symposium on Free Radicals[1]

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Harman’s Theory of aging: fraud or fact?1956 2009

The Oxidant Defense System

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Glutathione: a partner with C and E!

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Synthesized from the amino acids L‐cysteine, L‐glutamic acid and glycine.

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Supplementation of Glutathione

Raising GSH levels through direct supplementation of glutathione is difficult. Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione."

Calcitriol, the active metabolite of vitamin D synthesized in the kidney, increases glutathione levels in the brain and appears to be a catalyst for glutathione production.

In addition, plasma and liver GSH concentrations can be raised by administration of certain supplements that serve as GSH precursors. N-acetylcysteine, commonly referred to as NAC, is the most bioavailable precursor of glutathione. Other supplements, including S-adenosylmethionine (SAMe) and whey protein have also been shown to increase glutathione content within the cell.

NAC is available both as a drug and as a generic supplement. Alpha lipoic acid has also been shown to restore intracellular glutathione. Melatonin has been shown to stimulate a related enzyme, glutathione peroxidase, and silymarin, an extract of the seeds of the milk thistle plant (Silybum marianum), has also demonstrated an ability to replenish glutathione levels in lab rats.

Buettner & Schafer 20Ascorbate Chemistry Society For Free Radical Biology and Medicine

C and E as Co-antioxidantsAs seen in the thermodynamic pecking orderabove, the tocopherol radical, TO•, is moreoxidizing then Asc•-. It is thought that ascorbatecontributes to the recycling of TO• back to TOH.

TO• + AscH- → TOH + Asc•-

This mechanism is clearly important in protectingLDL from unwanted oxidations, because LDL lacksenzymes that could recycle TO•. But its importancein cells and tissues is still being debated.

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Buettner & Schafer 21Ascorbate Chemistry Society For Free Radical Biology and Medicine

C and E as Co-Antioxidants (1)

Buettner GR. (1993) Arch Biochem Biophys.300:535-543. [PDF]

This cartoon represents one leaflet of the lipid bilayer of a membrane.

Once oxygen reacts with the lipid chain, the change in dipole moment will cause the peroxyl radical to “float” to the interface.

Vitamin E

Lipid

Buettner & Schafer 22Ascorbate Chemistry Society For Free Radical Biology and Medicine

C and E as Co-Antioxidants (2)

Buettner GR. (1993) Arch Biochem Biophys.300:535-543. [PDF]

Lipid

Vitamin E

Vitamin E removes theperoxyl radical; ascorbatecan recycle E; enzymes thenremove the damaged fattyacid and insert a new one,repairing the lipid.

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Glutathione: a major protector!

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Glutathione: a major protector!

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•Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production.

•Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.

•Inborn deficiency of GSH metabolism result in hemolysis and neurological defects.

•Also can cause cataract and brain damage. The brain’s main antioxidant is glutathione- it’s importance cannot be overstated.

•Oxidative stress and glutathione are important factors in brain injury, neurodegenerative disease, schizophrenia, Down syndrome and other pathologies.

•Little evidence that supplementation works!! We must eat the foods that allow the body to MAKE it!!!

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But what about the “controversy”:…..some preliminary information

NEPHROTOXICITY - -Acetylcysteine - ………Acetylcysteine is used as a mucolytic, a hepatoprotectant, and an antioxidant. The antioxidant activity is a probable reason for benefit in the prevention of radiocontrast-induced nephrotoxicity. -Acetylcysteine is a variant of the amino acid L-cysteine, and is converted by the body into metabolites that can stimulate the synthesis of the antioxidant glutathione. …………..“Evidence-Based Practice for the Use of -acetylcysteine,” Marthaler MT, Keresztes PA, Dimensions of Critical Care Nursing, November/December 2004;23(6):270-273. 42473

ANTIOXIDANT ‐ Coenzyme Q10, Grapeseed Extract, Lipoic Acid, Multimineral, Multivitamin, ‐Acetylcysteine, Oxidative Stress, Selenium, Vitamin C, Vitamin E ‐ Over 100 million Americans consume dietary supplements, and many of these do so without medical input. Eighty healthcare professionals in good health who were between 35 and 52 years of age were evaluated in this study. In the first group, 21 females and 8 males received a multivitamin mineral supplement, twice daily, which included 2,000 mg of calcium ascorbate, 600 IU of vitamin E as d‐alpha‐tocopheryl succinate, 5,000 IU of beta‐carotene, 40 mg of grapeseed extract, 30 mg of coenzyme Q10 and 30 mg of alpha‐lipoic acid. In addition, this group also received 1,000 mg of ‐acetylcysteine for 6 weeks. The second group of 22 females and 8 males received the same nutritional supplements without ‐acetylcysteine. Total antioxidant function was evaluated by the Spectrox ™, which involves the incubation of peripheral mononuclear cells in media with optimal concentrations of each growth factor. Following stimulation of the cells with phytohemagglutinin, increasing levels of cumenehydroperoxide were added as a source of oxidative stress. Vitamin C as total ascorbate was measured photometrically by the method of Lee et al (ClinChim, 1977;43:154‐157). Vitamin E was measured in the serum by high pressure liquid chromatography (Steghens JP, et al, Chromatography, 1997;694:71‐81). ……………….

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Although there were increases in antioxidant function in both groups, when the pre‐supplementation antioxidant level was less than 40%, larger increases in antioxidant function were noted in those not receiving ‐acetylcysteine at 120% vs. 45%, respectively. In those individuals with pre‐supplementation antioxidant function levels >75% in the non‐‐acetylcysteine group, which was the second group, the antioxidant function decreased by 24% following supplementation. In the first group, which included ‐acetylcysteine, only 1 patient had a pre‐supplementation antioxidant function >75%. Following supplementation, this subject showed a 36% decrease in function. This study provided preliminary data showing a prooxidant effect of antioxidant vitamin supplementation on antioxidant function. In the total population of subjects tested, 42.8% of the individuals showed a reduction in antioxidant function after supplementation. This negative change in antioxidant function was not restricted to those individuals with higher pre‐supplementation antioxidant function levels. In all, 45.8% (11 of 24) of all the negative changes in antioxidant function occurred in those individuals with pre‐supplementation antioxidant levels of <50%. These changes were unrelated to the presence or absence of ‐acetylcysteine. ………………

Supplementation with ‐acetylcysteine appeared to have a protective, or sparing, effect on the prooxidant potential of antioxidant supplementation when pre‐supplementation antioxidant levels were >80%. Overall, 57.2% of the individuals improved their antioxidant function by supplementing with the antioxidant formulations. In these individuals, the presence or absence of ‐acetylcysteine with the antioxidant supplementation had little effect on the final post‐supplementation antioxidant status. When the pre‐supplementation antioxidant function was high (>80%), ‐acetylcysteine appeared to act as a buffer to the prooxidant effect of the antioxidant formulation. Vitamin E levels were increased in individuals receiving ‐acetylcysteine and in those not receiving ‐acetylcysteine. However, ‐acetylcysteine promoted higher circulating vitamin E levels. In those individuals who had a reduction in antioxidant function after supplementation and received ‐acetylcysteine, serum vitamin C levels decreased. These data suggest that supplementation regimens need to be individualized due to genetic and environmental influences. “Health Personnel Antioxidant Study (HPAS): Effects of Antioxidant Supplementation on Functional Antioxidant Capacity,” Baum SJ, Kramer N, Crawford JF, JANA, Winter 2004;7(1):25‐31. 

What do we learn from this???

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COGNITION ‐ Antioxidant, Beta‐carotene, Copper, Vitamin C, Vitamin E, Zinc ‐ In a study of 2,166 elderly subjects (mean age 75 years, age range 61‐87 years) who were participants in the Age‐Related Eye Disease Study, subjects were randomly assigned to receive either daily antioxidants (vitamin C at 500 mg, vitamin E at 400 IU and beta‐carotene at 15 mg), zinc (as zinc oxide) at 80 mg and copper (as cupric oxide) at 2 mg, the antioxidants plus zinc and copper, or placebo. There were 566 subjects in the antioxidant group, 528 in the antioxidant plus zinc group, 538 in the zinc only group and 534 in the placebo group. After administering a variety of cognitive tests to the 2,166 elderly individuals after a median of 6.9 years with treatment, there were no differences on any of the 6 cognitive tests, which indicates no support of the beneficial or harmful effects of antioxidants or zinc and copper on cognitive function in older adults. “Impact of Antioxidants, Zinc, and Copper on Cognition in the Elderly ‐ A Randomized, Controlled Trial,” Age‐Related Eye Disease Study Group, Neurology, November 2004;63(1 of 2):1705‐1707.

…Why not???

FRIEDREICH ATAXIA - Antioxidant, Coenzyme Q10, Vitamin E - In a study of 77 subjects who were confirmed clinically and genetically to have Friedreichataxia (age range 10-57.7 years), subjects were given two 525-IU tablets of vitamin E, 2 times daily, and two 100-mg capsules of coenzyme Q10, 2 times daily. There was significant improvement in cardiac and skeletal muscle bioenergetics maintained throughout the 47 months of therapy. Echocardiographic data showed significant increases in fractional shortening at the 35- and 47-month time points. Comparison with cross-sectional data from 77 patients with Friedreich ataxia showed that changes in total International Cooperative Ataxia Rating Scale and kinetic scores over the time period were better than predicted for 7 patients, but the posture and gait and hand dexterity scores progressed as predicted. The therapy of coenzyme Q10 and vitamin E sustained improvement in mitochondrial energy synthesis that was associated with a slowing of the progression of certain clinical features and a significant improvement in cardiac function in this group of Friedreich ataxia patients. Serum vitamin E levels increased 2.2- to 6-fold and coenzyme Q10 levels increased 2.3- to 7.4-fold in all patients. “Antioxidant Treatment of Patients With Friedreich Ataxia: Four-Year Follow-up,” Hart PE, Lodi R, et al, Arch Neurol, April 2005;62:621-626.

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OBESITY - Insulin Resistance, Vitamin E - This letter to the editor comments that supplemental vitamin E reduces the risk of myocardial infarction, including sudden death in hemodialysis patients. Vitamin E has a number of effects that are independent of its antioxidant actions. The mechanism underlying the improvement in insulin sensitivity with vitamin E supplementation remains to be determined. Vitamin E can act as a prooxidant under specific conditions in vitro. There is little direct evidence that it occurs in vivo. It is hypothesized that coantioxidants, such as ascorbate, regenerate the tocopherol radical and prevent tocopherol-mediated peroxidation in vivo. The author comments on the statement by Vale S, Diabetes Care, 2005;28:230, that high doses of vitamin E may have an acute toxic effect and may increase the risk of coronary death. This assumption is based on a higher number of early deaths in the vitamin E group compared with the placebo group in the Cambridge Heart Antioxidant Study. ………..The author notes prior studies supplementing with vitamin E in individuals at higher risk for cardiovascular events for similar or longer duration and with comparable doses, and there were no reported adverse effects. The author states that taken together, the available data did not suggest that overweight subjects who were assigned to vitamin E were at an increased risk of coronary death. “Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects,” Manning PJ, Sutherland WHF, Walker RJ, Diabetes Care, January 2005;28(1).

ENDOTHELIAL FUNCTION, CARDIOVASCULAR DISEASE - Red Wine, Green Olive Oil, Mediterranean Diet, Antioxidants Reference: "Postprandial improvement of endothelial function by red wine and olive oil antioxidants: a synergistic effect of components of the Mediterranean diet," Zampelas A, KaratziK, et al, J Am Coll Nutr, 2008; 27(4): 448-53.

Summary: In a study involving 15 healthy subjects, combined consumption of antioxidant-rich red wine and green olive oil was found to improve flow mediated dilation postprandially, which remained improved 1 and 2 hours after the meal, as compared to fasting levels. The study was carried out over 4 days, during which time subjects consumed one standard meal each day which contained 50 g of olive oil and 250 ml of wine. Two different types of olive oil were used (green olive oil rich in antioxidants and refined olive oil poor in antioxidants), and two different types of wine were used (red wine rich in antioxidants, white wine poor in antioxidants). Results found improvement in postprandial FMD with both the red wine and the green olive oil. The authors conclude, "These findings provide an additional favorable effect of components of the Mediterranean diet and of their antioxidant substances on endothelial function, at the postprandial state."

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"Dietary antioxidant intake and risk of an aneurysmal rupture subarachnoid hemorrhage in Japan," Okamoto K, Horisawa R, Eur J Clin Nutr, 2007; 61(9): 1140-2.

Summary: In a case-control study involving 201 patients with subarachnoid hemorrhage (SAH), and 201 gender- and age-matched controls, results indicate that dietary antioxidant intake may be inversely related with risk of SAH. Dietary antioxidant intake scores were calculated from diet information obtained using a self-administered food frequency questionnaire. After adjusting for potential confounders, an inverse association was observed between dietary antioxidant intake score and risk of SAH. The highest score was associated with a 46% reduced risk of SAH, compared with the lowest score. Thus, the authors of this study conclude, "These findings suggest that the development of SAH may be reduced by the frequent intake of various antioxidants in the diet. Prospective studies are needed to confirm the relationship of dietary antioxidants to SAH risk in Japanese men and women."

Topic: Antioxidant Intake May Reduce DNA Damage Reference: “Dietary antioxidants and beneficial effect on oxidativelydamaged DNA,” Moller P, Loft S, Free Radical Biology and Medicine, 2006; 41(3): 388‐415. 

Summary: In an article reviewing studies related to the role of antioxidant intake on DNA damage, it was concluded that antioxidant intake does indeed reduce DNA damage in white blood cells and urine. 139 cross‐sectional and intervention studies were identified, out of which 85 met the eligibility criteria set by the reviewers. Of the 27 cross‐sectional studies, 10 found a negative correlation between antioxidant intake and oxidativelydamaged DNA. While mixed results were found in the 62 intervention studies, a significant number of the studies reported reduced levels of oxidatively damaged DNA in white blood cells and urine. This review also found that antioxidant intake through consumption of antioxidant‐rich foods was more effective at lowering urinary excretion of oxidativelydamaged DNA than supplementation with single antioxidants. These results suggest that consumption of antioxidants may be associated with reduced levels of DNA damage. Additional studies are warranted. 

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Oxidative stress and Alzheimer’s Disease!

Amyloid beta (Aβ or Abeta) is a peptide of 39–43 amino acids that appear to be the main constituent of amyloid plaques in the brains of Alzheimer's disease patients

Topic: Curcumin May Have a Role in Diabetes Prevention Reference: "Curcumin prevents streptozotocin‐induced islet damage by scavenging free radicals: a prophylactic and protective role," Meghana K, Sanjeev G, Ramesh B, Eur J Pharmacol, 2007; 577(1‐3): 183‐91. 

Summary: In an in vitro study designed to examine the effect of curcumin ‐ an active agent found in the popular curry spice, turmeric ‐ on the development of diabetes mellitus, curcumin was found to protect pancreatic islet cells from streptozotocin‐induced damage. Isolated pancreatic islet cells from C57/BL6J mice were incubated with curcumin for 24 hours, after which they were exposed to streptozotocin for 8 hours. Metabolic status of these cells was compared to that of islet cells untreated with curcumin. Results found that compared to untreated islets, islet cells pre‐treated with curcumin were found to have significantly higher islet viability and secreted insulin. Furthermore, curcumin was found to retard the generation of islet reactive oxygen species, inhibit Poly ADP‐ribose polymerase‐1 activation, and prevent the reduction in cellular free radical scavenging enzymes. The authors conclude, "We show here for the first time, that prophylactic use of curcumin may effectively rescue islets from damage without affecting the normal function of these cellular structures." 

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Topic: Auricular Acupressure May Benefit Patients with High‐risk Diabetes Mellitus Reference: "Effect of auricular pellet acupressure on antioxidative systems in high‐risk diabetes mellitus," Liu CF, Yu LF, et al, J Altern Complement Med, 2008; 14(3): 303‐7. 

Summary: In a study involving 69 patients with high‐risk diabetes mellitus, applying pressure to specific points on the ear (auricular acupressure) with pellets was found to increase the concentration of antioxidant enzymes in blood, as compared to subjects who did not receive auricular acupressure treatment (controls). Subjects in the intervention group received auricular pellet acupressure over a period of 20 days. Subjects received the auricular pellet acupressure 3 times per day, for 5 consecutive days on one ear, followed by a 2 day rest period, after which the treatment was given on the other ear. Acupressure was performed twice on both ears. Results found significantly higher levels of superoxide dismutase (SOD) and catalase concentrations in subjects who received the treatment, as compared to those in the control group. These results suggest that diabetic patients, particularly those with 'high‐risk diabetes mellitus,' may benefit from auricular acupressure, through its beneficial effects on levels of antioxidative enzymes, thereby reducing "free radicals and lipid peroxides, both of which are easily formed in the diabetic state," and which, "…play an important role in the development of diabetic complications." Additional research into the use of this safe and effective therapy is warranted. 

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Caffeine and amyloid formation!

Beta‐amyloid results when two enzymes, BACE and PS1, cut a larger protein in the cell membrane of brain cells called APP. Newly formed molecules of beta‐amyloid then aggregate into plaques. Caffeine reduces the level of both BACE and PS1 enzymes, resulting in less beta‐amyloid in the brain. (Recommended dose: 500 mg per day!)

http://www.dagorret.net/2009/06/26/caffeine‐reduces‐the‐risk‐of‐alzheimer‐s‐disease/Do web search: caffeine, alzheimer’s

Prostate Ca: anti/pro‐oxidant balance issue??

•Ceruloplasmin (Cp) is officially known as ferroxidase or iron(II):oxygen oxidoreductase. It is the major copper‐carrying protein in the blood, and in addition plays a role in iron metabolism. 

•Ceruloplasmin exhibits a copper‐dependent oxidase activity, which is associated with possible oxidation of Fe2+ (ferrous iron) into Fe3+ (ferric iron), therefore assisting in its transport in the plasma in association with transferrin, which can only carry iron in the ferric state. 

1/17/2012

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So what do we do?

172 Beecher G (01 Oct 2003). "Overview of dietary flavonoids: nomenclature, occurrence and intake". J Nutr 133 (10): 3248S–3254S. PMID 14519822. http://jn.nutrition.org/cgi/content/full/133/10/3248S.

200 "Antioxidants and Cancer Prevention: Fact Sheet". National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/antioxidantsprevention. Retrieved on 2007-02-27.

201 Ortega RM (2006). "Importance of functional foods in the Mediterranean diet". Public Health Nutr 9 (8A): 1136–40. doi:10.1017/S1368980007668530. PMID 17378953.

202 Goodrow EF, Wilson TA, Houde SC, et al. (October 2006). "Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations". J. Nutr. 136 (10): 2519–24. PMID 16988120.

For those who will not eat….Grape Seed Extract Combo: 2Herbal OPC Combo: 2-4Hawthorn extract: 2-3Vitamin A-C-P product: 3-6Vitamin E product: 3-6

Remember: our goal is to FEED the oxidant defense system that is naturally active, NOT do “anti-oxidant” therapy!!!!!!!