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Vitamin C, the water soluble antioxidant

  Vitamin C the water-soluble antioxidant http://healthfully.org/rc/id20.html  9/3/20


                                                               Ascorbic  acid                    dehydroascorbic acid

Ascorbic acid (vitamin C), and its non-acidic ascorbate forms has two essential functions:  as a vitamin, essential biological co- factor[1] in 8 essential processes.  For health consequences it is an enzyme in the production of collagen[2]; and as a scavenger for reactive chemicals--especially reactive oxygen.  It is a very effective water-soluble antioxidant, one that is used as a food preservative.  “Vitamin C is a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions…. these reactions are especially important in wound-healing and in preventing bleeding from capillaries.  However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity, underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymatic reactions that are stereospecific…. Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can be found only at low pH, but in neutral solutions above pH 5 is predominantly found in the ionized form, ascorbate.[3]  All [forms] have vitamin C activity, therefore, and are used synonymously with vitamin C, unless otherwise specified.  The biological role of ascorbate is to act as a reducing agent, donating electrons to various enzymatic and a few non-enzymatic reactions. The one- and two-electron oxidized forms of vitamin C, semi-dehydroascorbic acid and dehydroascorbic acid, respectively, can be reduced in the body by glutathione and NADPH-dependent enzymatic mechanisms.  Glutathione in cells and extracellular fluids helps maintain ascorbate in a reduced state” 2017 Wiki.  Glutathione antioxidant functions are essential for life. 

“The vast majority of animals and plants are able to synthesize vitamin C, through a sequence of enzyme-driven steps, which convert monosaccharides [sugars] to vitamin C.  In plants, this is accomplished through the conversion of mannose or galactose to ascorbic acid.  In some animals, glucose needed to produce ascorbate in the liver (in mammals and perching birds) is extracted from glycogen [in cells as needed]…  In reptiles and birds the biosynthesis is carried out in the kidneys.  Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.  This discrepancy constitutes much of the basis of the controversy on current recommended dietary allowances. It is countered by arguments that humans are very good at conserving dietary vitamin C, and are able to maintain blood levels of vitamin C comparable with other simians, on a far smaller dietary intake.  Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues that maintain vitamin C concentrations far higher than in blood. Biological tissues that accumulate over 100 times the level in blood plasma of vitamin C are the adrenal glands, pituitary, thymus, corpus luteum, and retina.[40] Those with 10 to 50 times the concentration present in blood plasma include the brain, spleen, lung, testicle, lymph nodes, liver, thyroid, small intestinal mucosa, leukocytes, pancreas, kidney, and salivary glands[4]  Wiki.  Evolution has a purpose for apes and guinea pigs not producing ascorbate, but why?  On the western diet, there might be a need to vitamin C supplement besides use as an antioxidant.  Diabetics are abnormally low.  Testing should be done for concentration in leukocytes rather than blood level, since blood level is the amount which the kidney sets.  Taking a supplement every 2 hours can quadruple the blood level, but its health benefits need further research.  High concentrations give protection from oxidative damage to those tissues listed; and it “protects phagocytic cells involved in the defense against pathogens” at.  Most studies are flawed:  they measure the serum level which reflects current intake; best is tissue levels which  “requires specialized laboratories which few are equipped or trained to carry out” Wiki  The absorption of vitamin C is tightly controlled (see cancer below) so that a meg dose (above a gram) is mostly wasted.  Only bats, primates, and guinea pigs don’t make ascorbate, thus studies of diabetic rats must be viewed cautiously, since diabetic humans have low ascorbate but not rats.  Ascorbate is a coenzyme in the production of glutathione, an essential antioxidant.  Protection from oxidation and infection is the logic behind the use of high-dose supplementation, preferable divided into frequent, small does.  Absorption is highly controlled based on serum ascorbate.   It is healthful for those who are above their thin-body weight, an indicator of insulin resistance, metabolic dysfunction caused by mitochondrial dysfunction; thus over 90% of seniors in the US would benefit.  

In addition to its roles as an antioxidant (note above), ascorbate functions as an electron donor for 8 different enzymes.  It is essential for the production of the ubiquitous collagen, the production of carnitine, the neurotransmitters including the catecholamines norepinephrine and epinephrine, serotonin, the regulation of histamines, absorption of iron in the non-heme form found in plants.  As an antioxidant it rejuvenates vitamin E.  Both vitamins are found in LDL, which they protect from oxidative damage.  Ascorbate also clears excess metal through the process of chelation, and this includes iron, copper.  Ascorbate also reduces the rate of polyunsaturated oxidation by reducing Fe(III) to the inactive form of Fe(II)—at 1989.  Ascorbate supplement is prudent in large amounts because of its function as an antioxidant.  There is strong evidence from many sources for the value of antioxidants, and also on ascorbate’s function as am antioxidant.   I must cherry pick the results because of pharma’s tobacco science that by design produces negative results--see for typical examples.   Journals rely upon pharma; thus, their articles are subject to  a sham review--link.

[1] A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's activity as a catalyst, a substance that increases the rate of a chemical reaction—also called a coenzyme Wikipedia, cofactor

[2] Collagen is the main structural protein in extracellular space in the various connective tissues in animal bodies.  It is the main component t in connective tissues forms the matrix for calcification in the formation of bones, and makes up 25 to 35% of body’s  protein.   As coenzyme vitamin C is essential to the production of collagen of which there are 29 types--Wiki.   It is a coenzyme in at least 8 different pathway producing proteins and other essential compounds.  

[3]  “Ascorbate that completely protects plasma lipids against detectable peroxidative damage [includes LDL] at, also.

[4] Because of transport to those tissues listed, blood measurements of glutathione level will not significantly rise with oral administration.  A second cause is that “hydrolysis of glutathione by intestinal and hepatic gama glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione” at.

Antioxidant:  Vitamin C readily scavenges reactive oxygen and nitrogen species and may thereby prevent oxidative damage to important biological macromolecules such as DNA, lipids [LDL, HDL & other and proteins]. We found compelling evidence for antioxidant protection of lipids by vitamin C in biological fluids, animals, and humans . . .Although the data on protein oxidation in humans are sparse and inconclusive, the available data in animals consistently show an antioxidant role of vitamin C.  Vitamin C also reduces redox active transition metal ions in the active sites of specific biosynthetic enzymes” short, full, 1999.  In this paper, we show that it is indeed ascorbate that completely protects plasma lipids against detectable peroxidative damage induced by aqueous peroxyl radicals and that ascorbate is the only plasma antioxidant that can do so. Plasma devoid of ascorbate, but no other endogenous antioxidant, is extremely vulnerable to oxidant stress and susceptible to peroxidative damage to lipids … ascorbate is a physiological antioxidant of major importance for protection against diseases & degenerative processes caused by oxidant stress” at.  This protect “of phagystic cells [those that ingest and destroy  foreign particles, bacteria and cell debris] involved in the defense against pathogen invasion… “ at 86.  This protective function explains why leucocytes and certain other tissues accumulate up to 100 times the blood level of vitamin C (page 1 above).  The oxidative damage along with glycation causes the age related diseases that afflict seniors.  Ascorbic acid is protective against hydrogen peroxide a causal factor for Parkinson’s and Alzheimer’s diseases (a 78% reduction after 3 years).  Note other protective agents include CoQ10, vitamin E testosterone and estradiol which work synergistically.  Ascorbic acid also reduces glycation of protein, 1 gram supplement reduced serum glycation by 47%, at 1997.

Asthma:  From our review, we found a number of studies that support the use of vitamin C in asthma and allergy. Significant results include positive effects on pulmonary function tests, broncho-provocation challenges  with  methacholine  or histamine or allergens,  improvement in white blood cell function and motility, and a decrease  in    respiratory infectionsat, 1994; “protection from through antioxidant effect” at, and 36% lower level ascorbate  at.  

Cancer:  “Epidemiologic evidence of a protective effect of vitamin C for non-hormone-dependent cancers is strong. Of the 46 such studies in which a dietary vitamin C index was calculated, 33 found statistically significant protection, with high intake conferring approximately a twofold protective effect compared with low intake. Of 29 additional studies that assessed fruit intake, 21 found significant protection.  For cancers of the esophagus, larynx, oral cavity, and pancreas, evidence for a protective effect of vitamin C or some component in fruit is strong and consistent. For cancers of the stomach, rectum, breast, and cervix there is also strong evidence. Several recent lung cancer studies found significant protective effects of vitamin C or of foods that are better sources of vitamin C than of beta-carotene” AJCN, 1991.  Linus Pauling holds that vitamin C functions through immune functions; thus the use cytotoxic drugs that damage the immune system (standard chemotherapies) entail minimal benefit from high-does vitamin C.  In 1974 Cameron and Campbell preformed a matching study using patients in a hospital in Scotland which doesn’t use chemotherapy on terminal patient thus not damaging their immune systems; palliative care was the norm.  One hundred patients were treated with a daily dose of 10 g of vitamin C with varying dose patterns in an effort to discover what was the most effective.  About half of them received for the first several weeks the mega dose intravenously.  Intravenous turned out to be the most effective, since the serum level is tightly controlled.  Later Pauling and Cameron compared their treated patient group with 1000 untreated patients matched for key factors.  The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days)” at 1976.  However pharma responded with 2 trial done for them at the Mayo clinic which by design failed to show benefit (it didn’t use intravenous ascorbate—2017 review which also contains the current science as to why Pauling and Cameron got such dazzling results. This article with highlights is also pasted at healthfully.  The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer” at NAS, 1976; and for their discussion of the mechanism of prevention of metastatic cancer at ARGIS.[1] “Our results also suggest that ascorbic acid is a potent anticancer agent for prostate cancer cells” The Prostate 1998.  Resistance to development of cancer:  The factors involved in host resistance are briefly reviewed, and the relationship between these factors and ascorbic acid metabolism is presented in detail. It is shown that many factors involved in host resistance to neoplasia are significantly dependent upon the availability of ascorbate” at 1979.  Here, we show that a Warburg effect triggered by activation of the hypoxia-inducible factor (HIF) pathway greatly enhances Vc-induced toxicity in multiple cancer cell lines…. Through affect upon the cancer metabolism… for the preferential effect of Vc on cancer cells” at 2014. Pharma following it pattern did shortly thereafter 2 studies through the Mayo clinic which failed to show benefit, they didn’t include the intravenous 10 gram then gram infusion—see 2017.   An experiment using IV infusion of vitamin C for treating cancer in rats had positive results, at 2015, and.  A ketogenic diet and fasting would improve efficacy of mega vitamin C—see (Otto) Warburg effect 2011 and Thomas Seyfried’s work. 

Cardiovascular Disease, Stroke All Causes of Mortality:  “A meta-analysis of 44 clinical trials has shown a significant positive effect of vitamin C on endothelial functions [prevents endothelial dysfunction thus cardiovascular disease] when taken at doses greater than 500 mg per day. The researchers noted that the effect of vitamin C supplementation appeared to be dependent on health status, with stronger effects in those at higher cardiovascular disease risk” Wiki. The same conclusion was drawn in a trial on 17 volunteers, publish AHA.  By inhibiting the oxidative modification of LDL, ascorbate prevented the uptake and degradation of oxidatively modified LDL by the scavenger-receptor mechanism of cultured human monocyte derived macrophages” a step leading to atherosclerosis at 1990.[2]  This role explains why LDL carries two antioxidants, CoQ10 and Vitamin C. “Vitamin C was shown to protect neutrophils from reactive oxygen species during phagocytosis, to prevent endogenous oxidative damage to lymphocytes … to lipids, proteins and DNA, which has been implicated as a major contributing factor in the development of chronic diseases such as cardiovascular disease, cancer, and cataract… in the maintenance of endothelial function, mainly by preventing or reversing endothelial dysfunctions leading to the development of CVD” at.  The overall consequence of these antioxidant activities is the beneficial control of lipid peroxidation of cellular membranes including those surrounding as well as within intracellular organelles. Intracellular free radical attack on non-lipid nuclear material may also be diminished, at 1986.  For 730 elderly who completed a dietary record of 7 days in 1973-4, “Mortality from stroke… the highest third of distribution of vitamin C intake had a relative risk of 0.5 compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors” at.  “Based on serum AA  those with normal to high had a lower cardiovascular disease by 25% and all causes of mortality of 29%” at; “Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile” at.[3]  The heart muscles has the 2nd highest rate of metabolism, and as a consequence their mitochondria leak reactive chemical at a proportionally higher rate; this explains why of all organs their myocytes (muscles cells) have the 2nd highest level of vitamin C.     

Diabetes:  a large body of research on low tissue vitamin C in diabetes mellitus and its effects upon the production of collage.  Vitamin C is a cofactor responsible for the cross linking of the strands of collagen which form its helix structure; that structure is compromised depending on the degree of diminished amounts of Vitamin C.  Defective collagen the researchers finds is significantly causals for the comorbidities associated with diabetes, and stands counter to pharma’s claim of high serum glucose—see articles pasted.  Since diabetes is an extreme form of insulin resistance (hyperinsulinemia) for which excess fat (lipid droplets) in the pancreas cause inflammation leading to under production of insulin.   Vitamin is a cofactor in at least 8 other essential process, one of which involves the restoration of glutathione to its active form.  These two are of particular interest among researchers.  In independent of pharma studies, a mega dose (gram or more) daily lowers risks of the many pathogenic consequences of diabetes—as too a ketogenic (low insulin) diet.  Before drugs in the 1960s, type-2 diabetes was managed with a very low carbohydrate diet, one in which glucose was not secreted in the urine.  The older standard test, using strips, for diabetes—and should be today.

Dementia, Alzheimer’s disease, Parkinson’s, neuro-degenerative rate is reduce with use of the combination of the fat soluble vitamin E and the water soluble vitamin C by 66%

Gout (an inflammatory arthritis caused by high level of uric acid in the blood which from crystals in joints and tendons, most often involving the big toe.  Affects about 2% of the Western population.)  Supplementation with 500 mg/day of vitamin C for 2 months reduces serum uric acid, suggesting that vitamin C might be beneficial in the prevention and management of gout and other urate-related diseases” at 2005. The urea crystal has been shown to damage the kidneys and thereby through water retention raise blood pressure. 

Immune Enhancing Function: a number of studies support its promotion of immune function.  “The high cellular concentration of vitamin C and its rapid decline in plasma and leukocytes during stress and infection suggests a role in the process of immune response” at.  For the common cold, the results have been a modest benefit, not enough to justify its usage for this purpose.  But for other infections which result in oxidative stress, ascorbate is beneficial, at. 

Mitochondrial protection:  At the heart of the health disaster for those populations on the western diet, is mitochondrial dysfunction caused by the import from the cytosol of proteins and polyunsaturated fats which have been glycated mainly by fructose.  In the mitochondria these glycated molecules undergo further reaction causing oxidative damage to mtDNA, membranes, and proteins for which in excess it causes mitochondrial dysfunction, and this results in reduced production of ATP.  We found that the oxidized form of vitamin C, dehydroascorbic acid (DHA), enters mitochondria via facilitative glucose transporter 1 (Glut1) and accumulates mitochondrially as ascorbic acid (mtAA)” at Oct. 2005.  By reducing this damage ascorbate reduces the rate of all the age-related conditions, also called conditions associated with the western diet.  I take 2-grams a day of calcium ascorbate powder added to my drinking water—gradual absorption is best.. 

Rheumatoid arthritis (RH) and Osteoarthritis:  “The rapid depletion of ascorbic acid at sites of inflammation, as in the inflamed rheumatoid joint, may therefore facilitate proteolytic damage” in an article on the protection of inflamed rheumatoid joints,1987.  Our studies indicate that in some cases the intake required to maintain adequate vitamin C levels in the plasma are much above the average requirement for normal individuals” at 1936, similar 2010.  Its dual role is in the collagen that forms the matrix for bones and as a protective antioxidant.  Our western diet with polyunsaturated fats that undergo rancidity, and the reactive high sugars compounded by insulin resistance are also causal. 

Benefits of Ascorbate high dose supplement:  A variety of evidence supports that “immuno-stimulant, anti-inflammatory, and anti-carcinogenic effects are well documented in the existing biomedical literature”, at 1984.  Ascorbate’s main health benefit is  as a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions. . . .Wiki 2017.  For those with health issues on the western high sugar diet who are thus insulin resistance high dose of ascorbate is likely beneficial, for those on a low sugar diet, life long, the net benefits of high dose are minuscule or none existent. 

RECOMMENDATIONs:   Based upon this review of the literature, a general knowledge of cell biology, pathology, & the natural high levels of vitamin C found in various tissues for protection from oxidative damage, its low cost, and the lack of side effects; for all these reasons, I recommend 500 mg per day starting in the 2nd decade and being increased to 1 g in the 5th, and 2 grams in the 7th in the ascorbate form because it one change the PH of the blood. To acidic  I use sodium ascorbate.[4]  I mix a portion of the powder into tea or juices.  Another choice which I also once used is the pleasant-tasting chewable sodium ascorbate 500 mg which is sweetened with sorbitol; available from Costco.  Because it is used as an antioxidant--not vitamin function--the addition of bioflavonoids is not beneficial to the consumer.  The record of research on bioflavonoids is polluted with marketing studies to show benefit.  Those studies by pharma and government are designed to show that vitamin C offers no benefits—a strong sign that it is healthful.  Business is a corrupt master of science.   Cheaper is better because, price matters to most people.   Over the internet I purchased 5 kg of sodium ascorbate and I now take 2 gm daily, and give samples to friends.  I also take the chewable gram sodium ascorbate sweetened with sorbitol when desiring something sweet.   

[1] Pharma in damage control mode has funded studies using patients who had received chemotherapy prior to concluded that vitamin C “is not effective against advanced malignant diseases…,” at 1985, and there are a number of other articles.  But Pauling used those who immune system had not been compromised by chemotherapy, because Vitamin C enhances immune functions. 

[2] Actually it is the polyunsaturated triglycerides carried by the LDL that are because of oxidation pathogenic, at. 

[3] This is weak evidence for the benefit of vitamin C, because it doesn’t control for the beneficial effect of modify the diet so that fruits are eaten instead of the standard deserts, and that of the eating fruits are more likely to have an assortment of diet and lifestyle differences that are healthful.  Fruits as an alternative to other sweets has a lower effect upon insulin, and hyperinsulinemia (such as in type 2 diabetes) is associated with significantly higher death rate, for diabetes it is 2 fold. 

[4] I once recommended calcium ascorbate but after watching Dr. Jason Fung lecture on the lack of benefit of calcium, and modest harm caused by calcium supplements, I switched to sodium.  The sodium warning is lacking science.  Primitive oriental societies on a traditional diet have intakes of calcium in the range of 300 mg, yet osteoporosis is unknown—Dr. Jason Fung, 2013. A second reason is that there are in the sodium ascorbate co-transporters (SVCTs) and Hexose transporter (GLUTs) thus the absorption of and transport into cells is favored for the sodium form of ascorbate.  Pharma has corrupted the science on hypertension.  

Irwin Stone recommends 70 mg/kg, or for 70 kg 4.9 grams daily divided into several smaller doses. The Riordan Clinic gives intravenous mega doses

Vitamin C megadosage is a term describing the consumption or injection of vitamin C (ascorbate) in doses comparable to the amounts produced by the livers of most other mammals. Such dosages correspond to amounts well beyond the current Recommended Dietary Allowance of 90 mg/day, and often well beyond the Tolerable upper intake level of 2000 mg/day.[1]  [Obviously false since many clinics give up to about 10 grams a day and Pauling and Cameron used ~10 grams to treat terminal colon cancer.]  Oral dosages are usually divided and consumed in portions over the day. Injections of hundreds of grams per day are advocated by some physicians for the treatment of certain conditions, poisonings, or recovery from trauma. People who practice vitamin C mega-dosage may consume many vitamin C pills throughout each day or dissolve pure vitamin C crystals in water or juice and drink it throughout the day.

Historic advocates of vitamin C mega-dosage include Linus Pauling, who won the Nobel Prize in Chemistry in 1954. Pauling argued that, due to a non-functional form of L-gulonolactone oxidase, an enzyme required to make vitamin C that is functional in most other mammalian relatives, humans have developed a number of adaptations to cope with the relative deficiency. These adaptations, he argued, ultimately shortened lifespan but could be reversed or mitigated by supplementing humans with the hypothetical amount of vitamin C that would have been produced in the body if the enzyme were working.

About 70-90% of vitamin C is adsorbed by the body when taken orally at normal levels (30–180 mg daily). Adsorption is only about 50% for daily doses of 1 g. Oral administration, even of mega doses, cannot raise blood concentration above 0.22 mM.[17]

Humans and other species that do not synthesize vitamin C carry a mutated and ineffective form of the enzyme L-gulonolactone oxidase, the fourth and last step in the ascorbate-producing machinery. In the anthropoids lineage, this mutation likely occurred 40 to 25 million years ago. The three surviving enzymes continue to produce the precursors to vitamin C, but the process is incomplete and the body then disassembles them.  His book How to Live Longer and Feel Better was a bestseller and advocated taking more than 10 grams per day orally, thus approaching the amounts released by the liver directly into the circulation in other mammals: an adult goat, a typical example of a vitamin-C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in normal health and much more when stressed.[19]  Stone[23] and Pauling[24] believed that the optimum daily requirement of vitamin C is around 2,300 milligrams for a human requiring 2,500 kcal a day.

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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment.