Vitamin C
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| Natta projection of structural formula for L-ascorbic acid | |
| Ball-and-stick model of L-ascorbic acid | |
| Clinical data | |
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| Pronunciation | /əˈskɔːrbɪk/, /əˈskɔːrbeɪt, -bɪt/ |
| Trade names | Ascor, Cecon, Cevalin, others |
| Other names | l-ascorbic acid, ascorbic acid, ascorbate |
| AHFS/Drugs.com | Monograph [archive] |
| MedlinePlus | a682583 [archive] |
| [[Regulation of therapeutic goods |Template:Engvar data]] | |
| Routes of administration | By mouth, intramuscular (IM), intravenous (IV), subcutaneous |
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| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | Rapid, diminishes as dose increases[4] |
| Protein binding | Negligible |
| Elimination half-life | Varies according to plasma concentration |
| Excretion | Kidney |
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| NIAID ChemDB | |
| PDB ligand | |
| E number | {{#property:P628}} |
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| ECHA InfoCard | {{#property:P2566}} [archive]Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value). |
| Chemical and physical data | |
| Formula | C6H8O6 |
| Molar mass | 176.124 g·mol−1 |
| 3D model (JSmol) | |
| Density | 1.694 g/cm3 |
| Melting point | 190 to 192 °C (374 to 378 °F) |
| Boiling point | 552.7 °C (1,026.9 °F) [5] |
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Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription dietary supplement. As a therapy, it is used to prevent and treat scurvy, a disease caused by vitamin C deficiency.
Vitamin C is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for immune system function.[6] It also functions as an antioxidant. Vitamin C may be taken by mouth or by intramuscular, subcutaneous or intravenous injection. Various health claims exist on the basis that moderate vitamin C deficiency increases disease risk, such as for the common cold, cancer or COVID-19. There are also claims of benefits from vitamin C supplementation in excess of the recommended dietary intake for people who are not considered vitamin C deficient. Vitamin C is generally well-tolerated. Large doses may cause gastrointestinal discomfort, headache, trouble sleeping, and flushing of the skin. The United States Institute of Medicine recommends against consuming large amounts.[7]: 155–165
Most animals are able to synthesize their own vitamin C. However, apes (including humans) and monkeys (but not all primates), most bats, most fish, some rodents, and certain other animals must acquire it from dietary sources because a gene for a synthesis enzyme has mutations that render it dysfunctional.
Vitamin C was discovered in 1912, isolated in 1928, and in 1933, was the first vitamin to be chemically produced. Partly for its discovery, Albert Szent-Györgyi was awarded the 1937 Nobel Prize in Physiology or Medicine.
Chemistry
The name "vitamin C" always refers to the l-enantiomer of ascorbic acid and its oxidized form, dehydroascorbate (DHA). Therefore, unless written otherwise, "ascorbate" and "ascorbic acid" refer in the nutritional literature to l-ascorbate and l-ascorbic acid respectively. 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 solutions above pH 5 is predominantly found in the ionized form, ascorbate.[8]
Numerous analytical methods have been developed for ascorbic acid detection. For example, vitamin C content of a food sample such as fruit juice can be calculated by measuring the volume of the sample required to decolorize a solution of dichlorophenolindophenol (DCPIP) and then calibrating the results by comparison with a known concentration of vitamin C.[9][10]
Deficiency
Plasma vitamin C is the most widely applied test for vitamin C status.[8] Adequate levels are defined as near 50 μmol/L. Hypovitaminosis of vitamin C is defined as less than 23 μmol/L, and deficiency as less than 11.4 μmol/L.[11] For people 20 years of age or above, data from the US 2017-18 National Health and Nutrition Examination Survey showed mean serum concentrations of 53.4 μmol/L. The percent of people reported as deficient was 5.9%.[12] Globally, vitamin C deficiency is common in low and middle-income countries, and not uncommon in high income countries. In the latter, prevalence is higher in males than in females.[13]
Plasma levels are considered saturated at about 65 μmol/L, achieved by intakes of 100 to 200 mg/day, which are well above the recommended intakes. Even higher oral intake does not further raise plasma nor tissue concentrations because absorption efficiency decreases and any excess that is absorbed is excreted in urine.[8]
Diagnostic testing
Vitamin C content in plasma is used to determine vitamin status. For research purposes, concentrations can be assessed in leukocytes and tissues, which are normally maintained at an order of magnitude higher than in plasma via an energy-dependent transport system, depleted slower than plasma concentrations during dietary deficiency and restored faster during dietary repletion,[7]: 103–109 but these analysis are difficult to measure, and hence not part of standard diagnostic testing.[8][14]
Diet
Recommended consumption
Recommendations for vitamin C intake by adults have been set by various national agencies:
- 40 mg/day: India National Institute of Nutrition, Hyderabad[15]
- 45 mg/day or 300 mg/week: the World Health Organization[16]
- 80 mg/day: the European Commission Council on nutrition labeling[17]
- 90 mg/day (males) and 75 mg/day (females): Health Canada 2007[18]
- 90 mg/day (males) and 75 mg/day (females): United States National Academy of Sciences[7]: 134–152
- 100 mg/day: Japan National Institute of Health and Nutrition[19]
- 110 mg/day (males) and 95 mg/day (females): European Food Safety Authority[20]
| US vitamin C recommendations (mg per day)[7]: 134–152 | |
|---|---|
| RDA (children ages 1–3 years) | 15 |
| RDA (children ages 4–8 years) | 25 |
| RDA (children ages 9–13 years) | 45 |
| RDA (girls ages 14–18 years) | 65 |
| RDA (boys ages 14–18 years) | 75 |
| RDA (adult female) | 75 |
| RDA (adult male) | 90 |
| RDA (pregnancy) | 85 |
| RDA (lactation) | 120 |
| UL (adult female) | 2,000 |
| UL (adult male) | 2,000 |
In 2000, the chapter on Vitamin C in the North American Dietary Reference Intake was updated to give the Recommended Dietary Allowance (RDA) as 90 milligrams per day for adult men, 75 mg/day for adult women, and setting a Tolerable upper intake level (UL) for adults of 2,000 mg/day.[7]: 134–152 The table (right) shows RDAs for the United States and Canada for children, and for pregnant and lactating women,[7]: 134–152 as well as the ULs for adults.
For the European Union, the EFSA set higher recommendations for adults, and also for children: 20 mg/day for ages 1–3, 30 mg/day for ages 4–6, 45 mg/day for ages 7–10, 70 mg/day for ages 11–14, 100 mg/day for males ages 15–17, 90 mg/day for females ages 15–17. For pregnancy 100 mg/day; for lactation 155 mg/day.[20]
Cigarette smokers and people exposed to secondhand smoke have lower serum vitamin C levels than nonsmokers.[11] The thinking is that inhalation of smoke causes oxidative damage, depleting this antioxidant vitamin.[7]: 152–153 The US Institute of Medicine estimated that smokers need 35 mg more vitamin C per day than nonsmokers, but did not formally establish a higher RDA for smokers.[7]: 152–153 An inverse relationship between vitamin C intake and lung cancer was observed, although the conculsion was that more research is needed to confirm this observation.[21]
The US National Center for Health Statistics conducts biannual National Health and Nutrition Examination Survey (NHANES) to assess the health and nutritional status of adults and children in the United States. Some results are reported as What We Eat In America. The 2013–2014 survey reported that for adults ages 20 years and older, men consumed on average 83.3 mg/d and women 75.1 mg/d. This means that half the women and more than half the men are not consuming the RDA for vitamin C.[22] The same survey stated that about 30% of adults reported they consumed a vitamin C dietary supplement or a multi-vitamin/mineral supplement that included vitamin C, and that for these people total consumption was between 300 and 400 mg/d.[23]
Tolerable upper intake level
In 2000, the Institute of Medicine of the US National Academy of Sciences set a Tolerable upper intake level (UL) for adults of 2,000 mg/day. The amount was chosen because human trials had reported diarrhea and other gastrointestinal disturbances at intakes of greater than 3,000 mg/day. This was the Lowest-Observed-Adverse-Effect Level (LOAEL), meaning that other adverse effects were observed at even higher intakes. ULs are progressively lower for younger and younger children.[7]: 155–165 In 2006, the European Food Safety Authority (EFSA) also pointed out the disturbances at that dose level, but reached the conclusion that there was not sufficient evidence to set a UL for vitamin C,[24] as did the Japan National Institute of Health and Nutrition in 2010.[19]
Food labeling
For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin C labeling purposes, 100% of the Daily Value was 60 mg, but as of May 27, 2016, it was revised to 90 mg to bring it into agreement with the RDA.[25][26] A table of the old and new adult daily values is provided at Reference Daily Intake.
European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For vitamin C, 100% RI was set at 80 mg in 2011.[27]
Sources
Although also present in other plant-derived foods, the richest natural sources of vitamin C are fruits and vegetables.[4][6] Vitamin C is the most widely taken dietary supplement.[6]
Plant sources
The following table is approximate and shows the relative abundance in different raw plant sources.[4][6][28] The amount is given in milligrams per 100 grams of the edible portion of the fruit or vegetable:
| Raw plant source[29] | Amount (mg / 100g) |
|---|---|
| Kakadu plum | 1000–5300[30] |
| Camu camu | 2800[31] |
| Acerola | 1677[32] |
| Indian gooseberry | 445[33][34] |
| Rose hip | 426 |
| Common sea-buckthorn | 400[35] |
| Guava | 228 |
| Blackcurrant | 200 |
| Yellow bell pepper/capsicum | 183 |
| Red bell pepper/capsicum | 128 |
| Kale | 120 |
| Broccoli | 90 |
| Kiwifruit | 90 |
| Raw plant source[29] | Amount (mg / 100g) |
|---|---|
| Green bell pepper/capsicum | 80 |
| Brussels sprouts | 80 |
| Loganberry, redcurrant | 80 |
| Cloudberry, elderberry | 60 |
| Strawberry | 60 |
| Papaya | 60 |
| Orange, lemon | 53 |
| Cauliflower | 48 |
| Pineapple | 48 |
| Cantaloupe | 40 |
| Passion fruit, raspberry | 30 |
| Grapefruit, lime | 30 |
| Cabbage, spinach | 30 |
| Raw plant source[29] | Amount (mg / 100g) |
|---|---|
| Mango | 28 |
| Blackberry, cassava | 21 |
| Potato | 20 |
| Honeydew melon | 20 |
| Tomato | 14 |
| Cranberry | 13 |
| Blueberry, grape | 10 |
| Apricot, plum, watermelon | 10 |
| Avocado | 8.8 |
| Onion | 7.4 |
| Cherry, peach | 7 |
| Apple | 6 |
| Carrot, asparagus | 6 |
Animal sources
Compared to plant sources, animal-sourced foods do not provide so great an amount of vitamin C, and what there is, is largely destroyed by the heat used when it is cooked. For example, raw chicken liver contains 17.9 mg/100 g, but fried, the content is reduced to 2.7 mg/100 g. Vitamin C is present in human breast milk at 5.0 mg/100 g. Cow's milk contains 1.0 mg/100 g, but the heat of pasteurization destroys it.[36]
Food preparation
Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature at which they are stored.[37] Cooking can reduce the vitamin C content of vegetables by around 60%, possibly due to increased enzymatic destruction.[38] Longer cooking times may add to this effect.[39] Another cause of vitamin C loss from food is leaching, which transfers vitamin C to the cooking water, which is decanted and not consumed.[40]
Supplements
Vitamin C dietary supplements are available as tablets, capsules, drink mix packets, in multi-vitamin/mineral formulations, in antioxidant formulations, and as crystalline powder.[41] Vitamin C is also added to some fruit juices and juice drinks. Tablet and capsule content ranges from 25 mg to 1500 mg per serving. The most commonly used supplement compounds are ascorbic acid, sodium ascorbate and calcium ascorbate.[41] Vitamin C molecules can also be bound to the fatty acid palmitate, creating ascorbyl palmitate, or else incorporated into liposomes.[42]
Food fortification
Countries fortify foods with nutrients to address known deficiencies.[43] While many countries mandate or have voluntary programs to fortify wheat flour, maize (corn) flour or rice with vitamins,[44] none include vitamin C in those programs.[44] As described in Vitamin C Fortification of Food Aid Commodities (1997), the United States provides rations to international food relief programs, later under the asupices of the Food for Peace Act and the Bureau for Humanitarian Assistance.[45] Vitamin C is added to corn-soy blend and wheat-soy blend products at 40 mg/100 grams. (along with minerals and other vitamins). Supplemental rations of these highly fortified, blended foods are provided to refugees and displaced persons in camps and to beneficiaries of development feeding programs that are targeted largely toward mothers and children.[40] The report adds: "The stability of vitamin C (L-ascorbic acid) is of concern because this is one of the most labile vitamins in foods. Its main loss during processing and storage is from oxidation, which is accelerated by light, oxygen, heat, increased pH, high moisture content (water activity), and the presence of copper or ferrous salts. To reduce oxidation, the vitamin C used in commodity fortification is coated with ethyl cellulose (2.5 percent). Oxidative losses also occur during food processing and preparation, and additional vitamin C may be lost if it dissolves into cooking liquid and is then discarded."[40]
Food preservation additive
Ascorbic acid and some of its salts and esters are common additives added to various foods, such as canned fruits, mostly to slow oxidation and enzymatic browning.[46] It may be used as a flour treatment agent used in breadmaking.[47] As food additives, they are assigned E numbers, with safety assessment and approval the responsibility of the European Food Safety Authority.[48] The relevant E numbers are:
- E300 ascorbic acid (approved for use as a food additive in the UK,[49] US[50] Canada,[51] Australia and New Zealand[52])
- E301 sodium ascorbate (approved for use as a food additive in the UK,[49] US,[53] Canada,[51] Australia and New Zealand[52])
- E302 calcium ascorbate (approved for use as a food additive in the UK,[49] US[50] Canada,[51] Australia and New Zealand[52])
- E303 potassium ascorbate (approved in Australia and New Zealand,[52] but not in the UK, US or Canada)
- E304 fatty acid esters of ascorbic acid such as ascorbyl palmitate (approved for use as a food additive in the UK,[49] US,[50] Canada,[51] Australia and New Zealand[52])
The stereoisomers of Vitamin C have a similar effect in food despite their lack of efficacy in humans. They include erythorbic acid and its sodium salt (E315, E316).[49]
Pharmacology
Pharmacodynamics is the study of how the drug – in this instance vitamin C – affects the organism, whereas pharmacokinetics is the study of how an organism affects the drug.
Pharmacodynamics
Pharmacodynamics includes enzymes for which vitamin C is a cofactor, with function potentially compromised in a deficiency state, and any enzyme cofactor or other physiological function affected by administration of vitamin C, orally or injected, in excess of normal requirements. At normal physiological concentrations, vitamin C serves as an enzyme substrate or cofactor and an electron donor antioxidant. The enzymatic functions include the synthesis of collagen, carnitine, and neurotransmitters; the synthesis and catabolism of tyrosine; and the metabolism of microsomes. In nonenzymatic functions it acts as a reducing agent, donating electrons to oxidized molecules and preventing oxidation in order to keep iron and copper atoms in their reduced states.[8] At non-physiological concentrations achieved by intravenous dosing, vitamin C may function as a pro-oxidant, with therapeutic toxicity against cancer cells.[54][55]
Vitamin C functions as a cofactor for the following enzymes:[8]
- Three groups of enzymes (prolyl-3-hydroxylases, prolyl-4-hydroxylases, and lysyl hydroxylases) that are required for the hydroxylation of proline and lysine in the synthesis of collagen. These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule via prolyl hydroxylase and lysyl hydroxylase, both requiring vitamin C as a cofactor. The role of vitamin C as a cofactor is to oxidize prolyl hydroxylase and lysyl hydroxylase from Fe2+ to Fe3+ and to reduce it from Fe3+ to Fe2+. Hydroxylation allows the collagen molecule to assume its triple helix structure, and thus vitamin C is essential to the development and maintenance of scar tissue, blood vessels, and cartilage.
- Two enzymes (ε-N-trimethyl-L-lysine hydroxylase and γ-butyrobetaine hydroxylase) are necessary for synthesis of carnitine. Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation.
- Hypoxia-inducible factor-proline dioxygenase enzymes (isoforms: EGLN1, EGLN2, and EGLN3) allows cells to respond physiologically to low concentrations of oxygen.
- Dopamine beta-hydroxylase participates in the biosynthesis of norepinephrine from dopamine.
- Peptidylglycine alpha-amidating monooxygenase amidates peptide hormones by removing the glyoxylate residue from their c-terminal glycine residues. This increases peptide hormone stability and activity.
As an antioxidant, ascorbate scavenges reactive oxygen and nitrogen compounds, thus neutralizing the potential tissue damage of these free radical compounds. Dehydroascorbate, the oxidized form, is then recycled back to ascorbate by endogenous antioxidants such as glutathione.[7]: 98–99 In the eye, ascorbate is thought to protect against photolytically generated free-radical damage; higher plasma ascorbate is associated with lower risk of cateracts.[56] Ascorbate may also provide antioxidant protection indirectly by regenerating other biological antioxidants such as α-tocopherol back to an active state.[7]: 98–99 In addition, ascorbate also functions as a non-enzymatic reducing agent for mixed-function oxidases in the microsomal drug-metabolizing system that inactivates a wide variety of substrates such as drugs and environmental carcinogens.[7]: 98–99
Pharmacokinetics
Ascorbic acid is absorbed in the body by both simple diffusion and active transport.[57] Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day. However, at doses above 1,000 mg/day, absorption falls to less than 50% as the active transport system becomes saturated.[4] Active transport is managed by Sodium-Ascorbate Co-Transporter proteins (SVCTs) and Hexose Transporter proteins (GLUTs). SVCT1 and SVCT2 import ascorbate across plasma membranes.[58] The Hexose Transporter proteins GLUT1, GLUT3 and GLUT4 transfer only the oxydized dehydroascorbic acid (DHA) form of vitamin C.[59][60] The amount of DHA found in plasma and tissues under normal conditions is low, as cells rapidly reduce DHA to ascorbate.[61]
SVCTs are the predominant system for vitamin C transport within the body.[58] In both vitamin C synthesizers (example: rat) and non-synthesizers (example: human) cells maintain ascorbic acid concentrations much higher than the approximately 50 micromoles/liter (µmol/L) found in plasma. For example, the ascorbic acid content of pituitary and adrenal glands can exceed 2,000 µmol/L, and muscle is at 200–300 µmol/L.[62] The known coenzymatic functions of ascorbic acid do not require such high concentrations, so there may be other, as yet unknown functions. A consequence of all this high concentration organ content is that plasma vitamin C is not a good indicator of whole-body status, and people may vary in the amount of time needed to show symptoms of deficiency when consuming a diet very low in vitamin C.[62]
Excretion (via urine) is as ascorbic acid and metabolites. The fraction that is excreted as unmetabolized ascorbic acid increases as intake increases. In addition, ascorbic acid converts (reversibly) to DHA and from that compound non-reversibly to 2,3-diketogulonate and then oxalate. These three metabolites are also excreted via urine. During times of low dietary intake, vitamin C is reabsorbed by the kidneys rather than excreted. This salvage process delays onset of deficiency. Humans are better than guinea pigs at converting DHA back to ascorbate, and thus take much longer to become vitamin C deficient.[8][60]
Synthesis
Most animals and plants are able to synthesize vitamin C through a sequence of enzyme-driven steps, which convert monosaccharides to vitamin C. Yeasts do not make l-ascorbic acid but rather its stereoisomer, erythorbic acid.[63] In plants, synthesis is accomplished through the conversion of mannose or galactose to ascorbic acid.[64][65] In animals, the starting material is glucose. In some species that synthesize ascorbate in the liver (including mammals and perching birds), the glucose is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process.[66] In humans and in animals that cannot synthesize vitamin C, the enzyme l-gulonolactone oxidase (GULO), which catalyzes the last step in the biosynthesis, is highly mutated and non-functional.[67][68][69][70]
Animal synthesis
There is some information on serum vitamin C concentrations maintained in animal species that are able to synthesize vitamin C. One study of several breeds of dogs reported an average of 35.9 μmol/L.[71] A report on goats, sheep and cattle reported ranges of 100–110, 265–270 and 160–350 μmol/L, respectively.[72]
The biosynthesis of ascorbic acid in vertebrates starts with the formation of UDP-glucuronic acid. UDP-glucuronic acid is formed when UDP-glucose undergoes two oxidations catalyzed by the enzyme UDP-glucose 6-dehydrogenase. UDP-glucose 6-dehydrogenase uses the co-factor NAD+ as the electron acceptor. The transferase UDP-glucuronate pyrophosphorylase removes a UMP and glucuronokinase, with the cofactor ADP, removes the final phosphate leading to d-glucuronic acid. The aldehyde group of this compound is reduced to a primary alcohol using the enzyme glucuronate reductase and the cofactor NADPH, yielding l-gulonic acid. This is followed by lactone formation—utilizing the hydrolase gluconolactonase—between the carbonyl on C1 and hydroxyl group on C4. l-Gulonolactone then reacts with oxygen, catalyzed by the enzyme L-gulonolactone oxidase (which is nonfunctional in humans and other Haplorrhini primates; see Unitary pseudogenes) and the cofactor FAD+. This reaction produces 2-oxogulonolactone (2-keto-gulonolactone), which spontaneously undergoes enolization to form ascorbic acid.[65][73][60] Reptiles and older orders of birds make ascorbic acid in their kidneys. Recent orders of birds and most mammals make ascorbic acid in their liver.[65]
Non-synthesizers
Some mammals have lost the ability to synthesize vitamin C, including simians and tarsiers, which together make up one of two major primate suborders, Haplorhini. This group includes humans. The other more primitive primates (Strepsirrhini) have the ability to make vitamin C. Synthesis does not occur in some species in the rodent family Caviidae, which includes guinea pigs and capybaras, but does occur in other rodents, including rats and mice.[74]
Synthesis does not occur in most bat species,[75] but there are at least two species, frugivorous bat Rousettus leschenaultii and insectivorous bat Hipposideros armiger, that retain (or regained) their ability of vitamin C production.[76][77] A number of species of passerine birds also do not synthesize, but not all of them, and those that do not are not clearly related; it has been proposed that the ability was lost separately a number of times in birds.[78] In particular, the ability to synthesize vitamin C is presumed to have been lost and then later re-acquired in at least two cases.[79] The ability to synthesize vitamin C has also been lost in about 96% of extant fish[80] (the teleosts).[79]
On a milligram consumed per kilogram of body weight basis, simian non-synthesizer species consume the vitamin in amounts 10 to 20 times higher than what is recommended by governments for humans.[81] This discrepancy constituted some of the basis of the controversy on human recommended dietary allowances being set too low.[82] However, simian consumption does not indicate simian requirements. Merck's veterinary manual states that daily intake of vitamin C at 3–6 mg/kg prevents scurvy in non-human primates.[83] By way of comparison, across several countries, the recommended dietary intake for adult humans is in the range of 1–2 mg/kg.
Evolution of animal synthesis
Ascorbic acid is a common enzymatic cofactor in mammals used in the synthesis of collagen, as well as a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS). Given that ascorbate has these important functions, it is surprising that the ability to synthesize this molecule has not always been conserved. In fact, anthropoid primates, Cavia porcellus (guinea pigs), teleost fishes, most bats, and some passerine birds have all independently lost the ability to internally synthesize vitamin C in either the kidney or the liver.[84][79] In all of the cases where genomic analysis was done on an ascorbic acid auxotroph, the origin of the change was found to be a result of loss-of-function mutations in the gene that encodes L-gulono-γ-lactone oxidase, the enzyme that catalyzes the last step of the ascorbic acid pathway outlined above.[85] One explanation for the repeated loss of the ability to synthesize vitamin C is that it was the result of genetic drift; assuming that the diet was rich in vitamin C, natural selection would not act to preserve it.[86][87]
In the case of the simians, it is thought that the loss of the ability to make vitamin C may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred soon after the appearance of the first primates, yet sometime after the split of early primates into the two major suborders Haplorrhini (which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the Strepsirrhini ("wet-nosed" primates), which retained the ability to make vitamin C.[88] According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 million years ago.[89] Approximately three to five million years later (58 million years ago), only a short time afterward from an evolutionary perspective, the infraorder Tarsiiformes, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines.[90][91] Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 million years ago).[88]
It has also been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down uric acid, also a characteristic of primates. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.[92]
Plant synthesis
There are many different biosynthesis pathways to ascorbic acid in plants. Most proceed through products of glycolysis and other metabolic pathways. For example, one pathway utilizes plant cell wall polymers.[67] The principal plant ascorbic acid biosynthesis pathway seems to be via l-galactose. The enzyme l-galactose dehydrogenase catalyzes the overall oxidation to the lactone and isomerization of the lactone to the C4-hydroxyl group, resulting in l-galactono-1,4-lactone.[73] l-Galactono-1,4-lactone then reacts with the mitochondrial flavoenzyme l-galactonolactone dehydrogenase[93] to produce ascorbic acid.[73] l-Ascorbic acid has a negative feedback on l-galactose dehydrogenase in spinach.[94] Ascorbic acid efflux by embryos of dicot plants is a well-established mechanism of iron reduction and a step obligatory for iron uptake.[lower-alpha 1]
All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, synthesis of plant hormones, as an antioxidant and regenerator of other antioxidants.[96] Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or mannose (all simple sugars) and proceeds to l-galactose, l-galactonolactone and ascorbic acid.[96][97] This biosynthesis is regulated following a diurnal rhythm.[97] Enzyme expression peaks in the morning to supporting biosynthesis for when mid-day sunlight intensity demands high ascorbic acid concentrations.[97][98] Minor pathways may be specific to certain parts of plants; these can be either identical to the vertebrate pathway (including the GLO enzyme), or start with inositol and get to ascorbic acid via l-galactonic acid to l-galactonolactone.[96]
Industrial synthesis
Vitamin C can be produced from glucose by two main routes. The no longer utilized Reichstein process, developed in the 1930s, used a single fermentation followed by a purely chemical route. The modern two-step fermentation process, originally developed in China in the 1960s, uses additional fermentation to replace part of the later chemical stages. The Reichstein process and the modern two-step fermentation processes both use glucose as the starting material, convert that to sorbitol, and then to sorbose using fermentation.[99] The two-step fermentation process then converts sorbose to 2-keto-l-gulonic acid (KGA) through another fermentation step, avoiding an extra intermediate. Both processes yield approximately 60% vitamin C from the glucose starting point.[100] Researchers are exploring means for one-step fermentation.[101][102]
China produces about 70% of the global vitamin C market. The rest is split among European Union, India and North America. The global market is expected to exceed 141 thousand metric tons in 2024.[103] Cost per metric ton (1000 kg) in US dollars was $2,220 in Shanghai, $2,850 in Hamburg and $3,490 in the US.[104]
Medical uses
Vitamin C has a definitive role in treating scurvy, which is a disease caused by vitamin C deficiency. Beyond that, a role for vitamin C as prevention or treatment for various diseases is disputed, with reviews often reporting conflicting results. No effect of vitamin C supplementation reported for overall mortality.[105] It is on the World Health Organization's List of Essential Medicines and on the World Health Organization's Model Forumulary.[106] In 2021, it was the 255th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[107]
Scurvy
Scurvy is a disease resulting from a deficiency of vitamin C. Without this vitamin, collagen made by the body is too unstable to perform its function and several other enzymes in the body do not operate correctly. Early symptoms are malaise and lethargy, progressing to shortness of breath, bone pain and susceptibility to bruising. As the disease progressed, it is characterized by spots on and bleeding under the skin and bleeding gums. The skin lesions are most abundant on the thighs and legs. A person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there is fever, old wounds may become open and suppurating, loss of teeth, convulsions and, eventually, death. Until quite late in the disease the damage is reversible, as healthy collagen replaces the defective collagen with vitamin C repletion.[6][41][108]
Notable human dietary studies of experimentally induced scurvy were conducted on conscientious objectors during World War II in Britain and on Iowa state prisoners in the late 1960s to the 1980s. Men in the prison study developed the first signs of scurvy about four weeks after starting the vitamin C-free diet, whereas in the earlier British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed. Men in both studies had blood levels of ascorbic acid too low to be accurately measured by the time they developed signs of scurvy. These studies both reported that all obvious symptoms of scurvy could be completely reversed by supplementation of only 10 mg a day.[109][110] Treatment of scurvy can be with vitamin C-containing foods or dietary supplements or injection.[41][7]: 101
Sepsis
People in sepsis may have micronutrient deficiencies, including low levels of vitamin C.[111] An intake of 3.0 g/day, which requires intravenous administration, appears to be needed to maintain normal plasma concentrations in people with sepsis or severe burn injury.[112][113] Sepsis mortality is reduced with administration of intravenous vitamin C.[114][115]
Common cold
Research on vitamin C in the common cold has been divided into effects on prevention, duration, and severity. Oral intakes of more than 200 mg/day taken on a regular basis was not effective in prevention of the common cold. Restricting analysis to trials that used at least 1000 mg/day also saw no prevention benefit. However, taking a vitamin C supplement on a regular basis did reduce the average duration of the illness by 8% in adults and 14% in children, and also reduced the severity of colds.[116] Vitamin C taken on a regular basis reduced the duration of severe symptoms but had no effect on the duration of mild symptoms.[117] Therapeutic use, meaning that the vitamin was not started unless people started to feel the beginnings of a cold, had no effect on the duration or severity of the illness.[116]
Vitamin C distributes readily in high concentrations into immune cells, promotes natural killer cell activities, promotes lymphocyte proliferation, and is depleted quickly during infections, effects suggesting a prominent role in immune system function.[118] The European Food Safety Authority concluded there is a cause and effect relationship between the dietary intake of vitamin C and functioning of a normal immune system in adults and in children under three years of age.[119][120]
COVID-19
During March through July 2020, vitamin C was the subject of more US FDA warning letters than any other ingredient for claims for prevention and/or treatment of COVID-19.[121] In April 2021, the US National Institutes of Health (NIH) COVID-19 Treatment Guidelines stated that "there are insufficient data to recommend either for or against the use of vitamin C for the prevention or treatment of COVID-19."[122] In an update posted December 2022, the NIH position was unchanged:
- There is insufficient evidence for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of vitamin C for the treatment of COVID-19 in nonhospitalized patients.
- There is insufficient evidence for the Panel to recommend either for or against the use of vitamin C for the treatment of COVID-19 in hospitalized patients.[123]
For people hospitalized with severe COVID-19 there are reports of a significant reduction in the risk of all-cause, in-hospital mortality with the administration of vitamin C relative to no vitamin C. There were no significant differences in ventilation incidence, hospitalization duration or length of intensive care unit stay between the two groups. The majority of the trials incorporated into these meta-analyses used intravenous administration of the vitamin.[124][125][126] Acute kidney injury was lower in people treated with vitamin C treatment. There were no differences in the frequency of other adverse events due to the vitamin.[126] The conclusion was that further large-scale studies are needed to affirm its mortality benefits before issuing updated guidelines and recommendations.[124][125][126]
Cancer
There is no evidence that vitamin C supplementation reduces the risk of lung cancer in healthy people or those at high risk due to smoking or asbestos exposure.[127] It has no effect on the risk of prostate cancer,[128] and there is no good evidence vitamic C supplementation affects the risk of colorectal cancer[129] or breast cancer.[130]
There is research investigating whether high dose intravenous vitamin C administration as a co-treatment will suppress cancer stem cells, which are responsible for tumor recurrence, metastasis and chemoresistance.[131][132]
Cardiovascular disease
There is no evidence that vitamin C supplementation decreases the risk cardiovascular disease,[133] although there may be an association between higher circulating vitamin C levels or dietary vitamin C and a lower risk of stroke.[134] There is a positive effect of vitamin C on endothelial dysfunction when taken at doses greater than 500 mg per day. (The endothelium is a layer of cells that line the interior surface of blood vessels.)[135]
Blood pressure
Serum vitamin C was reported to be 15.13 μmol/L lower in people with hypertension compared to normotensives. The vitamin was inversely associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP).[136] Oral supplementation of the vitamin resulted in a very modest but statistically significant decrease in SBP in people with hypertension.[137][138] The proposed explanation is that vitamin C increases intracellular concentrations of tetrahydrobiopterin, an endothelial nitric oxide synthase cofactor that promotes the production of nitric oxide, which is a potent vasodilator. Vitamin C supplementation might also reverse the nitric oxide synthase inhibitor NG-monomethyl-L-arginine 1, and there is also evidence cited that vitamin C directly enhances the biological activity of nitric oxide, a vasodilator.[137]
Type 2 diabetes
There are contradictory reviews. From one, vitamin C supplementation cannot be recommended for management of type 2 diabetes.[139] However, another reported that supplementation with high doses of vitamin C can decrease blood glucose, insulin and hemoglobin A1c.[140]
Iron deficiency
One of the causes of iron-deficiency anemia is reduced absorption of iron. Iron absorption can be enhanced through ingestion of vitamin C alongside iron-containing food or supplements. Vitamin C helps to keep iron in the reduced ferrous state, which is more soluble and more easily absorbed.[141]
Topical application to prevent signs of skin aging
Human skin contains vitamin C, which supports collagen synthesis, decreases collagen degradation, and assists in antioxidant protection against UV-induced photo-aging, including photocarcinogenesis. This knowledge is often used as a rationale for the marketing of vitamin C as a topical "serum" ingredient to prevent or treat facial skin aging, melasma (dark pigmented spots) and wrinkles. The purported mechanism is that it functions as an antioxidant, neutralizing free radicals from sunlight exposure, air pollutants or normal metabolic processes.[142] The efficacy of topical treatment, as opposed to oral intake is poorly understood.[143][144] The clinical trial literature is characterized as insufficient to support health claims, one reason being put forward was that "All the studies used vitamin C in combination with other ingredients or therapeutic mechanisms, thereby complicating any specific conclusions regarding the efficacy of vitamin C."[145] More research is needed.[146]
Cognitive impairment and Alzheimer's disease
Lower plasma vitamin C concentrations were reported in people with cognitive impairment and Alzheimer's disease compared to people with normal cognition.[147][148][149]
Eye health
Higher dietary intake of vitamin C was associated with lower risk of age-related cataracts.[150][151] Vitamin C supplementation did not prevent age-related macular degeneration.[152]
Periodontal disease
Low intake and low serum concentration were associated with greater progression of periodontal disease.[153][154]
Adverse effects
Oral intake as dietary supplements in excess of requirements are poorly absorbed,[4] and excesses in the blood rapidly excreted in the urine, so it exhibits low acute toxicity.[6] More than two to three grams, consumed orally, may cause nausea, abdominal cramps and diarrhea. These effects are attributed to the osmotic effect of unabsorbed vitamin C passing through the intestine.[7]: 156 In theory, high vitamin C intake may cause excessive absorption of iron. A summary of reviews of supplementation in healthy subjects did not report this problem, but left as untested the possibility that individuals with hereditary hemochromatosis might be adversely affected.[7]: 158
There is a longstanding belief among the mainstream medical community that vitamin C increases risk of kidney stones.[155] "Reports of kidney stone formation associated with excess ascorbic acid intake are limited to individuals with renal disease".[7]: 156–157 A review states that "data from epidemiological studies do not support an association between excess ascorbic acid intake and kidney stone formation in apparently healthy individuals",[156] although one large, multi-year trial did report a nearly two-fold increase in kidney stones in men who regularly consumed a vitamin C supplement.[157]
There is extensive research on the purported benefits of intravenous vitamin C for treatment of sepsis,[112] severe COVID-19[124][125] and cancer.[158] Reviews list trials with doses as high as 24 grams per day.[124] Concerns about possible adverse effects are that intravenous high-dose vitamin C leads to a supraphysiological level of vitamin C followed by oxidative degradation to dehydroascorbic acid and hence to oxalate, increasing the risk of oxalate kidney stones and oxalate nephropathy. The risk may be higher in people with renal impairment, as kidneys efficiently excrete excess vitamin C. Second, treatment with high dose vitamin C should be avoided in patients with glucose-6-phosphate dehydrogenase deficiency as it can lead to acute hemolysis. Third, treatment might interfere with the accuracy of glucometer measurement of blood glucose levels, as both vitamin C and glucose have similar molecular structure, which could lead to false high blood glucose readings. Despite all these concerns, meta-analyses of patients in intensive care for sepsis, septic shock, COVID-19 and other acute conditions reported no increase in new-onset kidney stones, acute kidney injury or requirement for renal replacement therapy for patients receiving short-term, high-dose, intravenous vitamin C treatment. This suggests that intravenous vitamin C is safe under these short-term applications.[159][160][161]
History
Scurvy was known to Hippocrates, described in book two of his Prorrheticorum and in his Liber de internis affectionibus, and cited by James Lind.[162] Symptoms of scurvy were also described by Pliny the Elder: (i) Pliny. "49". Naturalis historiae. Vol. 3.; and (ii) Strabo, in Geographicorum, book 16, cited in the 1881 International Encyclopedia of Surgery.[163]
Scurvy at sea
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In the 1497 expedition of Vasco da Gama, the curative effects of citrus fruit were known.[164] In the 1500s, Portuguese sailors put in to the island of Saint Helena to avail themselves of planted vegetable gardens and wild-growing fruit trees.[165] Authorities occasionally recommended plant food to prevent scurvy during long sea voyages. John Woodall, the first surgeon to the British East India Company, recommended the preventive and curative use of lemon juice in his 1617 book, The Surgeon's Mate.[166] In 1734, the Dutch writer Johann Bachstrom gave the firm opinion, "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens."[167][168] Scurvy had long been a principal killer of sailors during the long sea voyages.[169] According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230;...all mainly to scurvy."[170]
The first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the Royal Navy, James Lind. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on cider, vinegar, sulfuric acid or seawater, along with their normal rations, in one of the world's first controlled experiments.[171] The results showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy.[172]
Fresh fruit was expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles).[39] It was 1796 before the British navy adopted lemon juice as standard issue at sea. In 1845, ships in the West Indies were provided with lime juice instead, and in 1860 lime juice was used throughout the Royal Navy, giving rise to the American use of the nickname "limey" for the British.[171] Captain James Cook had previously demonstrated the advantages of carrying "Sour krout" on board, by taking his crew on a 1772-75 Pacific Ocean voyage without losing any of his men to scurvy.[173] For his report on his methods the British Royal Society awarded him the Copley Medal in 1776.[174]
The name antiscorbutic was used in the eighteenth and nineteenth centuries for foods known to prevent scurvy. These foods included lemons, limes, oranges, sauerkraut, cabbage, malt, and portable soup.[175] In 1928, the Canadian Arctic anthropologist Vilhjalmur Stefansson showed that the Inuit avoided scurvy on a diet of largely raw meat. Later studies on traditional food diets of the Yukon First Nations, Dene, Inuit, and Métis of Northern Canada showed that their daily intake of vitamin C averaged between 52 and 62 mg/day.[176]
Discovery
Vitamin C was discovered in 1912, isolated in 1928 and synthesized in 1933, making it the first vitamin to be synthesized.[177] Shortly thereafter Tadeus Reichstein succeeded in synthesizing the vitamin in bulk by what is now called the Reichstein process.[178] This made possible the inexpensive mass-production of vitamin C. In 1934, Hoffmann–La Roche bought the Reichstein process patent, trademarked synthetic vitamin C under the brand name Redoxon, and began to market it as a dietary supplement.[179][180]
In 1907, a laboratory animal model which would help to identify the antiscorbutic factor was discovered by the Norwegian physicians Axel Holst and Theodor Frølich, who when studying shipboard beriberi, fed guinea pigs their test diet of grains and flour and were surprised when scurvy resulted instead of beriberi. Unknown at that time, this species did not make its own vitamin C (being a caviomorph), whereas mice and rats do.[181] In 1912, the Polish biochemist Casimir Funk developed the concept of vitamins. One of these was thought to be the anti-scorbutic factor. In 1928, this was referred to as "water-soluble C", although its chemical structure had not been determined.[182]
From 1928 to 1932, Albert Szent-Györgyi and Joseph L. Svirbely's Hungarian team, and Charles Glen King's American team, identified the anti-scorbutic factor. Szent-Györgyi isolated hexuronic acid from animal adrenal glands, and suspected it to be the antiscorbutic factor.[184] In late 1931, Szent-Györgyi gave Svirbely the last of his adrenal-derived hexuronic acid with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it. This led to a bitter dispute over priority.[184] In 1933, Walter Norman Haworth chemically identified the vitamin as l-hexuronic acid, proving this by synthesis in 1933.[185][186][187][188] Haworth and Szent-Györgyi proposed that L-hexuronic acid be named a-scorbic acid, and chemically l-ascorbic acid, in honor of its activity against scurvy.[188][177] The term's etymology is from Latin, "a-" meaning away, or off from, while -scorbic is from Medieval Latin scorbuticus (pertaining to scurvy), cognate with Old Norse skyrbjugr, French scorbut, Dutch scheurbuik and Low German scharbock.[189] Partly for this discovery, Szent-Györgyi was awarded the 1937 Nobel Prize in Medicine,[183] and Haworth shared that year's Nobel Prize in Chemistry.[190]
In 1957, J. J. Burns showed that some mammals are susceptible to scurvy as their liver does not produce the enzyme l-gulonolactone oxidase, the last of the chain of four enzymes that synthesize vitamin C.[191][192] American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the idea that humans possess a mutated form of the l-gulonolactone oxidase coding gene.[193] Stone introduced Linus Pauling to the theory that humans needed to consume vitamin C in quantities far higher than what was considered a recommended daily intake in order to optimize health.[194]
In 2008, researchers discovered that in humans and other primates the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized l-dehydroascorbic acid (DHA) back into ascorbic acid for reuse by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.[195]
History of large dose therapies
Vitamin C megadosage is a term describing the consumption or injection of vitamin C in doses comparable to or higher than the amounts produced by the livers of mammals which are able to synthesize vitamin C. An argument for this, although not the actual term, was described in 1970 in an article by Linus Pauling. Briefly, his position was that for optimal health, humans should be consuming at least 2,300 mg/day to compensate for the inability to synthesize vitamin C. The recommendation also fell into the consumption range for gorillas – a non-synthesizing near-relative to humans.[82] A second argument for high intake is that serum ascorbic acid concentrations increase as intake increases until it plateaus at about 190 to 200 micromoles per liter (µmol/L) once consumption exceeds 1,250 milligrams.[196] As noted, government recommendations are a range of 40 to 110 mg/day and normal plasma is approximately 50 µmol/L, so 'normal' is about 25% of what can be achieved when oral consumption is in the proposed megadose range.
Pauling popularized the concept of high dose vitamin C as prevention and treatment of the common cold in 1970. A few years later he proposed that vitamin C would prevent cardiovascular disease, and that 10 grams/day, initially administered intravenously and thereafter orally, would cure late-stage cancer.[197] Mega-dosing with ascorbic acid has other champions, among them chemist Irwin Stone[194] and the controversial Matthias Rath and Patrick Holford, who both have been accused of making unsubstantiated treatment claims for treating cancer and HIV infection.[198][199] The idea that large amounts of intravenous ascorbic acid can be used to treat late-stage cancer or ameliorate the toxicity of chemotherapy is – some forty years after Pauling's seminal paper – still considered unproven and still in need of high quality research.[200][201][158]
Dosage
An optimal daily dosage is 100-400 mg. Spread it out in two or more doses.
Optimal dosage for most people is 100-140 mg/d. Higher dosage of 250 mg/d for prevention of colds.[202]
Maximum dosage should be 400 mg/d.[203]
Sources include fruits and vegetables.
Vitamin C and viral infections
Used prophylactically, dosage is 200 mg to 500 mg per day. Higher dosages of 1000 or even 3000 to 5000 mg per day are not needed while healthy. The upper limit for vitamin C is 2,000 mg.
The I MASK protocol recommends 500 to 1000 mg twice daily.[204]
At first sign of illness use: Powdered Vitamin C ascorbates: Take 2000 mg every 2 hours until “bowel tolerance.”
To treat acute illness, much higher dosage is needed, upward of 6 grams of liposomal Vitamin C.[205]
Vitamin C megadosage
Vitamin C megadosage is a term describing the consumption or injection of vitamin C (ascorbic acid) in doses well beyond the current United States Recommended Dietary Allowance of 90 milligrams per day, and often well beyond the tolerable upper intake level of 2,000 milligrams per day.[7] There is no scientific evidence that vitamin C megadosage helps to cure or prevent cancer, the common cold, or some other medical conditions.[206][200]
Historical advocates of vitamin C megadosage include Linus Pauling, who won the Nobel Prize in Chemistry in 1954. Pauling argued that because humans lack a functional form of L-gulonolactone oxidase, an enzyme required to make vitamin C that is functional in most other mammals, plants, insects, and other life forms, 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.
Vitamin C megadoses are claimed by alternative medicine advocates including Matthias Rath and Patrick Holford to have preventive and curative effects on diseases such as cancer and AIDS,[207][208] but the available scientific evidence does not support these claims.[200] Some trials show some effect in combination with other therapies, but this does not imply vitamin C megadoses in themselves have any therapeutic effect.[209]
Background
Vitamin C is an essential nutrient used in the production of collagen and other biomolecules, and for the prevention of scurvy.[210] It is also an antioxidant, which has led to its endorsement by some researchers as a complementary therapy for improving quality of life.[211] Certain animal species, including the haplorhine primates (which include humans),[82][212] members of the Caviidae family of rodents (including guinea pigs and capybaras),[213] most species of bats,[214] many passerine birds,[78] and about 96% of fish (the teleosts),[78] cannot synthesize vitamin C internally and must therefore rely on external sources, typically obtained from food.
For humans, the World Health Organization recommends a daily intake of 45 mg/day of vitamin C for healthy adults, and 25–30 mg/day in infants.[215]
Since its discovery, vitamin C has been considered almost a panacea by some,[216] although this led to suspicions of it being overhyped by others.[217] Vitamin C has long been promoted in alternative medicine as a treatment for the common cold, cancer, polio, and various other illnesses. The evidence for these claims is mixed. Since the 1930s, when it first became available in pure form, some physicians have experimented with higher-than-recommended vitamin C consumption or injection.[218] Orthomolecular-based megadose recommendations for vitamin C are based mainly on theoretical speculation and observational studies, such as those published by Fred R. Klenner from the 1940s through the 1970s. There is a strong advocacy movement for very high doses of vitamin C, yet there is an absence of large-scale, formal trials in the 10 to 200+ grams per day range.
The single repeatable side effect of oral megadose vitamin C is a mild laxative effect if the practitioner attempts to consume too much too quickly. In the United States and Canada, a tolerable upper intake level (UL) was set at 2,000 mg/day, citing this mild laxative effect as the reason for establishing the UL.[7] However, the European Food Safety Authority (EFSA) reviewed the safety question in 2006 and reached the conclusion that there was not sufficient evidence to set a UL for vitamin C.[219] The Japan National Institute of Health and Nutrition reviewed the same question in 2010 and also reached the conclusion that there was not sufficient evidence to set a UL.[220]
About 70–90% of vitamin C is absorbed by the body when taken orally at normal levels (30–180 mg daily). Only about 50% is absorbed from daily doses of 1 gram (1,000 mg). Even oral administration of megadoses of 3g every four hours cannot raise blood concentration above 220 micromol/L.[221]
Relative deficiency hypothesis
Humans and other species that cannot synthesize their own 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.[citation needed] The three surviving enzymes continue to produce the precursors to vitamin C, but the absence of the fourth enzyme means the process is never completed, and the body ultimately disassembles the precursors.
In the 1960s, the Nobel-Prize-winning chemist Linus Pauling, after contact with Irwin Stone,[222] began actively promoting vitamin C as a means to greatly improve human health and resistance to disease. 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.[citation needed]
Matthias Rath is a controversial German physician who worked with and published two articles discussing the possible relationship between lipoprotein and vitamin C with Pauling.[223][224] He is an active proponent and publicist for high-dose vitamin C. Pauling's and Rath's extended theory states that deaths from scurvy in humans during the Pleistocene, when vitamin C was scarce, selected for individuals who could repair arteries with a layer of cholesterol provided by lipoprotein(a), a lipoprotein found in vitamin C-deficient species.[225]
Stone[226] and Pauling[82] believed that the optimum daily requirement of vitamin C is around 2,300 milligrams for a human requiring 2,500 kcal per day. For comparison, the FDA's recommended daily allowance of vitamin C is only 90 milligrams.[7]
Adverse effects
Although sometimes considered free of toxicity, there are in fact known side effects from vitamin C intake, and it has been suggested that intravenous injections should require "a medical environment and trained professionals."[227]
For example, a genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD) can cause affected people to develop hemolytic anemia after using intravenous vitamin C treatment.[228] The G6PD deficiency test is a common laboratory test.
Because oxalic acid is produced during metabolism of vitamin C, hyperoxaluria can be caused by intravenous administration of ascorbic acid.[227] Vitamin C administration may also acidify the urine and could promote the precipitation of kidney stones or drugs in the urine.[227]
Although vitamin C can be well tolerated at doses well above what government organizations recommend, adverse effects can occur at doses above 3 grams per day. The common "threshold" side effect of megadoses is diarrhea. Other possible adverse effects include increased oxalate excretion and kidney stones, increased uric acid excretion, systemic conditioning ("rebound scurvy"), preoxidant effects, iron overload, reduced absorption of vitamin B12 and copper, increased oxygen demand, and acid erosion of the teeth when chewing vitamin C tablets.[7] In addition, one case has been noted of a woman who received a kidney transplant followed by high-dose vitamin C and died soon afterwards as a result of calcium oxalate deposits that destroyed her new kidney. Her doctors concluded that high-dose vitamin C therapy should be avoided in patients with kidney failure.[229]
Overdose
As discussed previously, vitamin C generally exhibits low toxicity. The LD50 (the dose that will kill 50% of a population) is generally accepted to be 11,900 milligrams (11.9 grams) per kilogram in rat populations.[230] The American Association of Poison Control Centers has reported zero deaths from vitamin C toxicity[when?].[231]
Interactions
Pharmaceuticals designed to reduce stomach acid, such as the proton-pump inhibitors (PPIs), are among the most widely sold drugs in the world. One PPI, omeprazole (Prilosec), has been found to lower the bioavailability of vitamin C by 12% after 28 days of treatment, independent of dietary intake. The probable mechanism of vitamin C reduction, intragastric pH elevated into alkalinity, would apply to all other PPI drugs, though not necessarily to doses of PPIs low enough to keep the stomach slightly acidic.[232] In another study, 40 mg/day of omeprazole lowered the fasting gastric vitamin C levels from 3.8 to 0.7 µg/mL.[233] Aspirin may also inhibit the absorption of vitamin C.[234][235]
Regulation
There are regulations in most countries that limit the claims regarding treatment of disease that can be placed on food and dietary supplement product labels. For example, claims of therapeutic effect with respect to the treatment of any medical condition or disease are prohibited by the United States Food and Drug Administration even if the substance in question has gone through well conducted clinical trials with positive outcomes. Claims are limited to "structure and function" phrasing (like "helps maintain a healthy immune system") and the following notice is mandatory on food and dietary supplement product labels that make these types of health claims: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.[236]
Research
Cancer
The use of vitamin C in high doses as a treatment for cancer was promoted by Linus Pauling, based on a 1976 study published with Ewan Cameron which reported intravenous vitamin C significantly increased lifespans of patients with advanced cancer.[237][206] This trial was criticized by the National Cancer Institute for being designed poorly, and three subsequent trials conducted at the Mayo Clinic could not replicate the results.[206][238]
Preliminary clinical trials in humans have shown that it is unlikely to be a "miracle pill" for cancer and more research is necessary before any definitive conclusions about efficacy can be reached.[227] A 2010 review of 33 years of research on vitamin C to treat cancer stated "we have to conclude that we still do not know whether Vitamin C has any clinically significant antitumor activity. Nor do we know which histological types of cancers, if any, are susceptible to this agent. Finally, we don't know what the recommended dose of Vitamin C is, if there is indeed such a dose, that can produce an anti-tumor response."[238]
The American Cancer Society has stated, "Although high doses of vitamin C have been suggested as a cancer treatment, the available evidence from clinical trials has not shown any benefit."[206]
Burns
One clinical trial used high intravenous doses of vitamin C (66 mg/kg/hour for 24 hours, for a total dose of around 110 grams) after severe burn injury,[239] but despite being described as promising, it has not been replicated by independent institutions and thus is not a widely accepted treatment.[240] Based on that study, the American Burn Association (ABA) considers high-dose ascorbic acid an option to be considered for adjuvant therapy in addition to the more accepted standard treatments.[241]
Cardiac effects
Atrial fibrillation (AF) is a common cardiac rhythm disturbance associated with oxidative stress. Four meta-analyses have concluded that there is strong evidence that consuming 1–2 g/day of vitamin C before and after cardiac operations can decrease the risk of post-operative AF.[242][243][244][245] However, five randomized studies did not find any such benefit in the United States, so that the benefit was restricted to less wealthy countries.[245][246]
Exercise-induced bronchoconstriction
Exercise-induced bronchoconstriction (EIB) indicates acute narrowing of the airways as a result of vigorous exercise. EIB seems to be caused by the loss of water caused by increased ventilation, which may lead to the release of mediators such as histamine, prostaglandins, and leukotrienes, all of which cause bronchoconstriction. Vitamin C participates in the metabolism of these mediators and might thereby influence EIB.[247] A meta-analysis showed that 0.5 to 2 g/day of vitamin C before exercise decreased EIB by half.[248]
Endothelial function
A meta-analysis showed a significant positive effect of vitamin C on endothelial function. Benefit was found of vitamin C in doses ranging from 0.5 to 4 g/day, whereas lower doses from 0.09 to 0.5 g/day were not effective. No effect on endothelial function was seen in healthy volunteers or healthy smokers.[249]
Common cold
A frequently cited meta-analysis calculated that various doses of vitamin C (daily doses under 0.2 grams were excluded) do not prevent the common cold in the general community, although 0.25 to 1 g/day of vitamin C halved the incidence of colds in people under heavy short-term physical stress.[250] Another meta-analysis calculated that, in children, 1–2 g/day vitamin C shortened the duration of colds by 18%, and in adults 1–4 g/day vitamin C shortened the duration of colds by 8%.[250] There is evidence of linear dose-dependency in the effect of vitamin C on common cold duration up to 6–8 g/day.[251]Template:Technical inline As noted above, there is an absence of large-scale, formal trials in the 10 to 200+ grams per day range, so no information is available for these higher dosages. Additionally, the cited studies of larger daily doses of vitamin C do not take into account the fast excretion rate of vitamin C at gram-level doses, which makes it necessary to give the total daily amount in smaller, more frequent doses to maintain higher plasma levels.[252] As of 2014, at least 16 studies had found that vitamin C supplements did not prevent the common cold and had minimal effect at best in shortening cold lengths.[200]
Intravenous ascorbic acid
| Vitamin C | |
|---|---|
| File:Infuuszakjes.jpg Intravenous bag and drip chamber on a pole, used to administer ascorbic acid solution through peripheral IV line | |
| Other names | Vitamin C, Ascorbate, L-ascorbic acid |
| Specialty | {{#statements:P1995}} |
| ICD-10-PCS | Z51.81 [archive] |
| ICD-9-CM | 267 [archive] |
| This article is part of a series on |
| Alternative medicine |
|---|
| File:Outline-body-aura.svg |
Intravenous Ascorbic Acid (also known as vitamin C or L-ascorbic acid), is a process that delivers soluble ascorbic acid directly into the bloodstream. It is not approved for use to treat any medical condition.[253]
The use of intravenous ascorbic acid as a proposed cancer treatment or co-treatment has been a controversial topic since the emergence of misleading data in the 1970s.[254]
Contraindications
High doses of ascorbic acid administered by intravenous infusion have been shown to increase the absorption of iron.[255] In individuals with hemochromatosis (a genetic disorder where the body takes up and stores too much iron), intravenous ascorbic acid is contraindicated as high dosages of ascorbic acid may result in iron overloading and therefore, lead to life-threatening complications such as heart disease, diabetes, or tissue damage.[256]
High dosages of ascorbic acid (such as those used in intravenous therapy) have been reported to cause some intestinal discomfort, diarrhoea, as well as increased gas and urination.[257]
Alternative medicine and unproven applications
Sepsis
The "Marik protocol", or "HAT" protocol, as devised by Paul E. Marik, proposed a combination of intravenous vitamin C, hydrocortisone, and thiamine as a treatment for preventing sepsis for people in intensive care. Marik's own initial research, published in 2017,[258] showed a dramatic evidence of benefit, leading to the protocol becoming popular among intensive care physicians,[259] especially after the protocol received attention on social media and National Public Radio, drawing criticism of science by press conference from the wider medical community.[260][261] Subsequent independent research failed to replicate Marik's positive results, indicating the possibility that they had been compromised by bias.[261][262] A systematic review of trials in 2021 found that the claimed benefits of the protocol could not be confirmed.[263]
Pharmacology
Mechanism of action
Ascorbic acid operates as an anti-oxidant and essential enzyme cofactor in the human body. In in vitro studies, the primary mechanism of high dosage intravenous ascorbic acid can be related to ascorbic acid's pro-oxidant activity, whereby hydrogen peroxide is formed.[264][265][266] In the extracellular fluid of cells, ascorbic acid dissociates into an ascorbate radical upon the reduction of transition metal ions, such as ferric or cupric cations.[264] These transition metal ions will then reduce dissolved oxygen into a superoxide radical – this will then react with hydrogen to form hydrogen peroxide.[265]
Furthermore, according to Fenton chemistry, these transition metal ions can be further oxidised by hydrogen peroxide to generate a highly reactive hydroxyl radical.[267] The formation of hydrogen peroxide and hydroxyl radicals is believed to induce cytotoxicity and apoptosis of cancer cells.[267] Although many in vitro studies have studied hydrogen peroxide generation by ascorbic acid, the pharmacological mechanism of intravenous ascorbic acid in vivo is still unclear.[267]
History
Pioneering research
Although the pharmacology of ascorbic acid had been studied since its discovery in the 1930s,[268] the method of administration and its medicinal potential to human patients was not investigated until the 1940s.[269] In 1949, American physician, Frederick Klenner, published his scientific report, “The Treatment of Poliomyelitis and Other Virus Diseases with ascorbic acid”,[270] which detailed the use of intravenous ascorbic acid to treat polio in children.[269] Klenner's research pioneered future studies investigating the medicinal role of intravenous ascorbic acid. Klenner's work was recognised by Linus Pauling in the foreword to the Clinical Guide: "Dr. Fred Klenner's early research reports provide much information on the use of high-dose ascorbic acid for the prevention and cure of many diseases, and these reports are still important."[271]
Linus Pauling
Nobel Prize winner and biochemist, Linus Pauling, was pivotal in the re-emergence of intravenous ascorbic acid research. Over the course of the 1970s, Pauling would begin a long-term collaboration with fellow physician, Ewan Cameron, on the medical potential of intravenous ascorbate acid as cancer therapy in terminally ill patients. In 1976, Pauling and Cameron co-authored a study whereby a group of 100 terminal cancer patients underwent supplementary ascorbic acid therapy (10g/day by intravenous infusion and oral thereafter) and the control group of 1,000 patients did not.[272] Their findings reported that the survival rate of the terminal cancer patients increased by four-fold, compared to the control group, stating that: "the treatment of ascorbate in amounts of 10g/day or more is of real value in extending the life of patients with advanced cancer."[272]
Subsequent studies by Pauling and Cameron hypothesised that ascorbic acid's role in enhanced collagen production would lead to the encapsulation of tumours and thus, protect normal tissue from metastasis.[273] Following these findings, Pauling became a strong advocate for vitamin megadosing and continued to investigate the medicinal potential of intravenous ascorbic acid across a range of illnesses, including: HIV transmission, the common cold, atherosclerosis, and angina pectoris.[274][275][276]
Medical controversy
The efficacy of intravenous ascorbic acid therapy came under scrutiny of the medical and science community, following the numerous high-profile studies authored by Linus Pauling in the 1970s.[266] The experimental design of Pauling and Cameron's 1976 publication, "Supplemental ascorbate in the supportive treatment of cancer",[272] had garnered considerable criticism as it was neither randomised nor placebo controlled. To test the validity of Pauling and Cameron's findings, the Mayo Clinic conducted three independent experiments in 1979, 1983 and 1985, whereby terminal cancer patients were given doses of oral ascorbic acid under randomised, double bind and placebo-controlled conditions.[277][278][279] All studies concluded that high doses of oral ascorbic acid were not effective against cancer.
The use of intravenous ascorbic acid in the treatment of cancer has been a contentious issue. There is no evidence to indicate that intravenous ascorbic acid therapy can cure cancer.[280][279] According to the U.S. Food and Drug Administration (FDA), high-dose vitamin C (such as intravenous ascorbic acid therapy) has not been approved as a treatment for cancer or any other medical condition.[253]
There many been multiple studies devoted to investigating the medicinal properties of ascorbic acid. The use of high-dosage intravenous ascorbic acid as a cancer treatment was first promoted by Linus Pauling and Ewan Cameron in the 1970s;[272][273] however, these findings were not reproduced using oral administration by subsequent Mayo Clinic studies in the 1980s.[277][278][279] In 2010, an academic review which detailed 33 years of ascorbic acid and cancer research stated: "we still do not know whether Vitamin C has any clinically significant anti-tumor activity. Nor do we know which histological types of cancers, if any, are susceptible to this agent. Finally, we don't know what the recommended dose of Vitamin C is, if there is indeed such a dose, that can produce an anti-tumor response".[281]
Research
The turn of the 21st century saw a renewed interest in the medical potential of intravenous ascorbic acid therapy. In the early 2010s, in vitro preclinical and clinical trials were undertaken to investigate the pharmacological mechanism of action of intravenous ascorbic acid therapy.[282][283] These findings demonstrated ascorbic acid's pro-oxidant capabilities to produce hydrogen peroxide and thus, proposed a possible pharmacological mechanism of action against cancer cells. Nonetheless, ascorbic acid's potential as an anti-tumour therapy is still dubious, as other pro-oxidant substances (such as menadione[284][285]) have been unsuccessful in the treatment of cancer patients.[286]
Notes
- ↑ Dicot plants transport only ferrous iron (Fe2+), but if the iron circulates as ferric complexes (Fe3+), it has to undergo a reduction before it can be actively transported. Plant embryos efflux high amounts of ascorbate that chemically reduce iron(III) from ferric complexes.[95]
References
- ↑ "Ascorbic acid injection 500mg/5ml" [archive]. (emc). 15 July 2015. Archived [archive] from the original on 14 October 2020. Retrieved October 12, 2020.
- ↑ "Ascorbic acid 100mg tablets" [archive]. (emc). 29 October 2018. Archived from the original [archive] on September 21, 2020. Retrieved October 12, 2020.
- ↑ "Ascor- ascorbic acid injection" [archive]. DailyMed. October 2, 2020. Archived [archive] from the original on 29 October 2020. Retrieved October 12, 2020.
- ↑ 4.0 4.1 4.2 4.3 4.4 "Vitamin C: Fact sheet for health professionals" [archive]. Office of Dietary Supplements, US National Institutes of Health. March 26, 2021. Archived [archive] from the original on July 30, 2017. Retrieved 25 February 2024.
- ↑ "Vitamin C" [archive]. Chem Spider. Royal Society of Chemistry. Archived [archive] from the original on July 24, 2020. Retrieved July 25, 2020.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 "Vitamin C" [archive]. Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. July 1, 2018. Archived [archive] from the original on July 12, 2019. Retrieved June 19, 2019.
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 Institute of Medicine (US) Panel on Dietary Antioxidants Related Compounds (2000). "Vitamin C" [archive]. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: The National Academies Press. pp. 95–185. doi:10.17226/9810 [archive]. ISBN 978-0-309-06935-9. PMID 25077263 [archive]. Archived [archive] from the original on September 2, 2017. Retrieved September 1, 2017. Cite error: Invalid
<ref>tag; name "DRItext" defined multiple times with different content - ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Marriott MP, Birt DF, Stallings VA, Yates AA, eds. (2020). "Vitamin C". Present Knowledge in Nutrition, Eleventh Edition. London, United Kingdom: Academic Press (Elsevier). pp. 155–70. ISBN 978-0-323-66162-1.
- ↑ "Testing foods for vitamin C (ascorbic acid)" [archive] (PDF). British Nutrition Foundation. 2004. Archived [archive] (PDF) from the original on November 23, 2015.
- ↑ "Measuring the vitamin C content of foods and fruit juices" [archive]. Nuffield Foundation. November 24, 2011. Archived [archive] from the original on July 21, 2015.
- ↑ 11.0 11.1 Schleicher RL, Carroll MD, Ford ES, Lacher DA (November 2009). "Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES)" [archive]. The American Journal of Clinical Nutrition. 90 (5): 1252–63. doi:10.3945/ajcn.2008.27016 [archive]. PMID 19675106 [archive].
- ↑ Narayanan S, Kumar SS, Manguvo A, Friedman E (June 2021). "Current estimates of serum vitamin C and vitamin C deficiency in the United States" [archive]. Curr Dev Nutr. 7 (5): 1067. doi:10.1093/cdn/nzab053_060 [archive]. PMC 8180804 [archive].
- ↑ Rowe S, Carr AC (July 2020). "Global vitamin C status and prevalence of deficiency: A cause for concern?" [archive]. Nutrients. 12 (7): 2008. doi:10.3390/nu12072008 [archive]. PMC 7400810 [archive]. PMID 32640674 [archive].
- ↑ Emadi-Konjin P, Verjee Z, Levin AV, Adeli K (May 2005). "Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC)". Clinical Biochemistry. 38 (5): 450–6. doi:10.1016/j.clinbiochem.2005.01.018 [archive]. PMID 15820776 [archive].
- ↑ "Dietary guidelines for Indians" [archive] (PDF). National Institute of Nutrition, India. 2011. p. 90. Archived from the original [archive] (PDF) on December 22, 2018. Retrieved February 10, 2019.
- ↑ World Health Organization (2005). "Chapter 7: Vitamin C". Vitamin and mineral requirements in human nutrition (2nd ed.). Geneva: World Health Organization. hdl:10665/42716 [archive]. ISBN 978-92-4-154612-6.
- ↑ "Commission Directive 2008/100/EC of 28 October 2008 amending Council Directive 90/496/EEC on nutrition labeling for foodstuffs as regards recommended daily allowances, energy conversion factors and definitions" [archive]. The Commission of the European Communities. October 29, 2008. Archived [archive] from the original on October 2, 2016.
- ↑ "Vitamin C" [archive]. Natural Health Product Monograph. Health Canada. Archived from the original [archive] on April 3, 2013.
- ↑ 19.0 19.1 "Overview of dietary reference intakes for Japanese" [archive] (PDF). Ministry of Health, Labor and Welfare (Japan). 2015. p. 29. Archived [archive] (PDF) from the original on October 21, 2022. Retrieved August 19, 2021.
- ↑ 20.0 20.1 "Scientific Opinion on Dietary Reference Values for vitamin C" [archive]. EFSA Journal. 11 (11). November 2013. doi:10.2903/j.efsa.2013.3418 [archive]. Archived [archive] from the original on October 26, 2020. Retrieved 1 March 2024.
- ↑ Luo J, Shen L, Zheng D (2014). "Association between vitamin C intake and lung cancer: a dose-response meta-analysis" [archive]. Scientific Reports. 4: 6161. Bibcode:2014NatSR...4E6161L [archive]. doi:10.1038/srep06161 [archive]. PMC 5381428 [archive]. PMID 25145261 [archive].
- ↑ "TABLE 1: Nutrient intakes from food and beverages" [archive] (PDF). National Health and Nutrition Examination Survey: What We Eat in America, DHHS-USDA Dietary Survey Integration. Centers for Disease Control and Prevention, U.S. Department of Health & Human Services. Archived from the original [archive] (PDF) on February 24, 2017.
- ↑ "TABLE 37: Nutrient intakes from dietary supplements" [archive] (PDF). National Health and Nutrition Examination Survey: What We Eat in America, DHHS-USDA Dietary Survey Integration. Centers for Disease Control and Prevention, U.S. Department of Health & Human Services. Archived from the original [archive] (PDF) on October 6, 2017.
- ↑ "Tolerable upper intake levels for vitamins and minerals" [archive] (PDF). European Food Safety Authority. 2006. Archived [archive] (PDF) from the original on March 16, 2016.
- ↑ "Federal Register May 27, 2016 food labeling: Revision of the nutrition and supplement facts labels. FR page 33982" [archive] (PDF). Archived [archive] (PDF) from the original on August 8, 2016.
- ↑ "Daily Value Reference of the Dietary Supplement Label Database (DSLD)" [archive]. Dietary Supplement Label Database (DSLD). Archived from the original [archive] on April 7, 2020. Retrieved May 16, 2020.
- ↑ REGULATION (EU) No 1169/2011 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL [archive] Archived [archive] July 26, 2017, at the Wayback Machine. Official Journal of the European Union. page 304/61. (2009).
- ↑ "NDL/FNIC food composition database home page" [archive]. USDA Nutrient Data Laboratory, the Food and Nutrition Information Center and Information Systems Division of the National Agricultural Library. Archived [archive] from the original on January 15, 2023. Retrieved 30 November 2014.
- ↑ 29.0 29.1 29.2 "USDA national nutrient database for standard reference legacy: vitamin C" [archive] (PDF). U.S. Department of Agriculture, Agricultural Research Service. 2018. Archived [archive] (PDF) from the original on November 18, 2021. Retrieved September 27, 2020.
- ↑ Brand JC, Rae C, McDonnell J, Lee A, Cherikoff V, Truswell AS (1987). "The nutritional composition of Australian aboriginal bushfoods. I". Food Technology in Australia. 35 (6): 293–6.
- ↑ Justi KC, Visentainer JV, Evelázio de Souza N, Matsushita M (December 2000). "Nutritional composition and vitamin C stability in stored camu-camu (Myrciaria dubia) pulp". Archivos Latinoamericanos de Nutricion. 50 (4): 405–8. PMID 11464674 [archive].
- ↑ Vendramini AL, Trugo LC (2000). "Chemical composition of acerola fruit (Malpighia punicifolia L.) at three stages of maturity". Food Chemistry. 71 (2): 195–8. doi:10.1016/S0308-8146(00)00152-7 [archive].
- ↑ Begum RM (2008). A textbook of foods, nutrition & dietetics [archive]. Sterling Publishers Pvt. Ltd. p. 72. ISBN 978-81-207-3714-3.
- ↑ Sinha N, Sidhu J, Barta J, Wu J, Cano MP (2012). Handbook of fruits and fruit processing [archive]. John Wiley & Sons. ISBN 978-1-118-35263-2.
- ↑ Gutzeit D, Baleanu G, Winterhalter P, Jerz G (2008). "Vitamin C content in sea buckthorn berries (Hippophaë rhamnoides L. ssp . rhamnoides) and related products: A kinetic study on storage stability and the determination of processing effects". J Food Sci. 73 (9): C615–C20. doi:10.1111/j.1750-3841.2008.00957.x [archive]. PMID 19021790 [archive].
- ↑ Clark S (8 January 2007). "Comparing milk: human, cow, goat & commercial infant formula" [archive]. Washington State University. Archived from the original [archive] on January 29, 2007. Retrieved February 28, 2007.
- ↑ Roig MG, Rivera ZS, Kennedy JF (May 1995). "A model study on rate of degradation of L-ascorbic acid during processing using home-produced juice concentrates". International Journal of Food Sciences and Nutrition. 46 (2): 107–15. doi:10.3109/09637489509012538 [archive]. PMID 7621082 [archive].
- ↑ Allen MA, Burgess SG (1950). "The losses of ascorbic acid during the large-scale cooking of green vegetables by different methods" [archive]. The British Journal of Nutrition. 4 (2–3): 95–100. doi:10.1079/BJN19500024 [archive]. PMID 14801407 [archive].
- ↑ 39.0 39.1 "Safety (MSDS) data for ascorbic acid" [archive]. Oxford University. October 9, 2005. Archived [archive] from the original on February 9, 2007. Retrieved February 21, 2007.
- ↑ 40.0 40.1 40.2 "Introduction" [archive]. Vitamin C fortification of food aid commodities: final report. National Academies Press (US). 1997. Archived [archive] from the original on January 21, 2024. Retrieved January 3, 2024.
- ↑ 41.0 41.1 41.2 41.3 "Ascorbic acid (Monograph)" [archive]. The American Society of Health-System Pharmacists. Archived [archive] from the original on December 30, 2016. Retrieved December 8, 2016.
- ↑ Davis JL, Paris HL, Beals JW, Binns SE, Giordano GR, Scalzo RL, Schweder MM, Blair E, Bell C (2016). "Liposomal-encapsulated ascorbic acid: influence on vitamin C bioavailability and capacity to protect against ischemia-reperfusion injury" [archive]. Nutrition and Metabolic Insights. 9: 25–30. doi:10.4137/NMI.S39764 [archive]. PMC 4915787 [archive]. PMID 27375360 [archive].
- ↑ "Why fortify?" [archive]. Food Fortification Initiative. December 2023. Archived [archive] from the original on March 8, 2023. Retrieved January 3, 2024.
- ↑ 44.0 44.1 "Map: Count of nutrients in fortification standards" [archive]. Global Fortification Data Exchange. Archived [archive] from the original on April 11, 2019. Retrieved January 3, 2024.
- ↑ "USAID's Bureau for Humanitarian Assistance website" [archive]. November 21, 2023.
- ↑ Washburn C, Jensen C (2017). "Pretreatments to prevent darkening of fruits prior to canning or dehydrating" [archive]. Utah State University. Archived [archive] from the original on December 15, 2020. Retrieved January 26, 2020.
- ↑ "Ingredients" [archive]. The Federation of Bakers. Archived [archive] from the original on February 26, 2021. Retrieved April 3, 2021.
- ↑ "Frequently asked questions | why food additives" [archive]. Food Additives and Ingredients Association UK & Ireland- Making life taste better. Archived [archive] from the original on June 1, 2019. Retrieved October 27, 2010.
- ↑ 49.0 49.1 49.2 49.3 49.4 UK Food Standards Agency: "Approved additives and their E numbers" [archive]. Archived [archive] from the original on October 7, 2010. Retrieved October 27, 2011.
- ↑ 50.0 50.1 50.2 US Food and Drug Administration:"Listing of food additives status part I" [archive]. Food and Drug Administration. Archived from the original [archive] on January 17, 2012. Retrieved October 27, 2011.
- ↑ 51.0 51.1 51.2 51.3 Health Canada "List of permitted preservatives (lists of permitted food additives) - Government of Canada" [archive]. Government of Canada. November 27, 2006. Archived [archive] from the original on October 27, 2022. Retrieved October 27, 2022.
- ↑ 52.0 52.1 52.2 52.3 52.4 Australia New Zealand Food Standards Code"Standard 1.2.4 – labeling of ingredients" [archive]. September 8, 2011. Archived [archive] from the original on September 2, 2013. Retrieved October 27, 2011.
- ↑ "Listing of food additives status part II" [archive]. US Food and Drug Administration. Archived [archive] from the original on November 8, 2011. Retrieved October 27, 2011.
- ↑ Böttger F, Vallés-Martí A, Cahn L, Jimenez CR (October 2021). "High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer" [archive]. J Exp Clin Cancer Res. 40 (1): 343. doi:10.1186/s13046-021-02134-y [archive]. PMC 8557029 [archive]. PMID 34717701 [archive].
- ↑ Park S, Ahn S, Shin Y, Yang Y, Yeom CH (2018). "Vitamin C in cancer: a metabolomics perspective" [archive]. Front Physiol. 9: 762. doi:10.3389/fphys.2018.00762 [archive]. PMC 6018397 [archive]. PMID 29971019 [archive].
- ↑ Sideri O, Tsaousis KT, Li HJ, Viskadouraki M, Tsinopoulos IT (2019). "The potential role of nutrition on lens pathology: a systematic review and meta-analysis". Surv Ophthalmol. 64 (5): 668–78. doi:10.1016/j.survophthal.2019.03.003 [archive]. PMID 30878580 [archive]. S2CID 81981938 [archive].
- ↑ Lykkesfeldt J, Tveden-Nyborg P (October 2019). "The pharmacokinetics of vitamin C" [archive]. Nutrients. 11 (10): 2412. doi:10.3390/nu11102412 [archive]. PMC 6835439 [archive]. PMID 31601028 [archive].
- ↑ 58.0 58.1 Savini I, Rossi A, Pierro C, Avigliano L, Catani MV (April 2008). "SVCT1 and SVCT2: key proteins for vitamin C uptake". Amino Acids. 34 (3): 347–55. doi:10.1007/s00726-007-0555-7 [archive]. PMID 17541511 [archive]. S2CID 312905 [archive].
- ↑ Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M (July 1997). "Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid" [archive]. The Journal of Biological Chemistry. 272 (30): 18982–9. doi:10.1074/jbc.272.30.18982 [archive]. PMID 9228080 [archive].
- ↑ 60.0 60.1 60.2 Linster CL, Van Schaftingen E (January 2007). "Vitamin C. Biosynthesis, recycling and degradation in mammals" [archive]. The FEBS Journal. 274 (1): 1–22. doi:10.1111/j.1742-4658.2006.05607.x [archive]. PMID 17222174 [archive]. S2CID 21345196 [archive].
- ↑ May JM, Qu ZC, Neel DR, Li X (May 2003). "Recycling of vitamin C from its oxidized forms by human endothelial cells". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1640 (2–3): 153–61. doi:10.1016/S0167-4889(03)00043-0 [archive]. PMID 12729925 [archive].
- ↑ 62.0 62.1 Padayatty SJ, Levine M (September 2016). "Vitamin C: the known and the unknown and Goldilocks" [archive]. Oral Diseases. 22 (6): 463–93. doi:10.1111/odi.12446 [archive]. PMC 4959991 [archive]. PMID 26808119 [archive].
- ↑ Branduardi P, Fossati T, Sauer M, Pagani R, Mattanovich D, Porro D (October 2007). "Biosynthesis of vitamin C by yeast leads to increased stress resistance" [archive]. PLOS ONE. 2 (10): e1092. Bibcode:2007PLoSO...2.1092B [archive]. doi:10.1371/journal.pone.0001092 [archive]. PMC 2034532 [archive]. PMID 17971855 [archive].
- ↑ Wheeler GL, Jones MA, Smirnoff N (May 1998). "The biosynthetic pathway of vitamin C in higher plants". Nature. 393 (6683): 365–9. Bibcode:1998Natur.393..365W [archive]. doi:10.1038/30728 [archive]. PMID 9620799 [archive]. S2CID 4421568 [archive].
- ↑ 65.0 65.1 65.2 Stone I (1972). "The natural history of ascorbic acid in the evolution of the mammals and primates and is significance for present-day man evolution of mammals and primates" [archive] (PDF). Journal of Orthomolecular Psychiatry. 1 (2): 82–9. Archived [archive] (PDF) from the original on October 2, 2023. Retrieved December 31, 2023.
- ↑ Bánhegyi G, Mándl J (2001). "The hepatic glycogenoreticular system". Pathology & Oncology Research. 7 (2): 107–10. CiteSeerX 10.1.1.602.5659 [archive]. doi:10.1007/BF03032575 [archive]. PMID 11458272 [archive]. S2CID 20139913 [archive].
- ↑ 67.0 67.1 Valpuesta V, Botella MA (2004). "Biosynthesis of L-ascorbic acid in plants: new pathways for an old antioxidant" [archive] (PDF). Trends in Plant Science. 9 (12): 573–7. doi:10.1016/j.tplants.2004.10.002 [archive]. PMID 15564123 [archive]. Archived [archive] (PDF) from the original on December 25, 2020. Retrieved October 8, 2018.
- ↑ Nishikimi M, Yagi K (December 1991). "Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis" [archive]. The Amer J Clin Nutr. 54 (6 Suppl): 1203S–8S. doi:10.1093/ajcn/54.6.1203s [archive]. PMID 1962571 [archive].
- ↑ Nishikimi M, Kawai T, Yagi K (October 1992). "Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species" [archive]. The Journal of Biological Chemistry. 267 (30): 21967–72. doi:10.1016/S0021-9258(19)36707-9 [archive]. PMID 1400507 [archive].
- ↑ Ohta Y, Nishikimi M (October 1999). "Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis". Biochimica et Biophysica Acta (BBA) - General Subjects. 1472 (1–2): 408–11. doi:10.1016/S0304-4165(99)00123-3 [archive]. PMID 10572964 [archive].
- ↑ Wang S, Berge GE, Sund RB (August 2001). "Plasma ascorbic acid concentrations in healthy dogs". Res. Vet. Sci. 71 (1): 33–5. doi:10.1053/rvsc.2001.0481 [archive]. PMID 11666145 [archive].
- ↑ Ranjan R, Ranjan A, Dhaliwal GS, Patra RC (2012). "l-Ascorbic acid (vitamin C) supplementation to optimize health and reproduction in cattle". Vet Q. 32 (3–4): 145–50. doi:10.1080/01652176.2012.734640 [archive]. PMID 23078207 [archive]. S2CID 1674389 [archive].
- ↑ 73.0 73.1 73.2 Dewick PM (2009). Medicinal natural products: a biosynthetic approach (3rd ed.). John Wiley and Sons. p. 493. ISBN 978-0-470-74167-2.
- ↑ Miller RE, Fowler ME (2014). Fowler's zoo and wild animal medicine, volume 8 [archive]. Elsevier Health Sciences. p. 389. ISBN 978-1-4557-7399-2. Archived [archive] from the original on December 7, 2016. Retrieved 2 June 2016.
- ↑ Jenness R, Birney E, Ayaz K (1980). "Variation of l-gulonolactone oxidase activity in placental mammals". Comparative Biochemistry and Physiology B. 67 (2): 195–204. doi:10.1016/0305-0491(80)90131-5 [archive].
- ↑ Cui J, Pan YH, Zhang Y, Jones G, Zhang S (February 2011). "Progressive pseudogenization: vitamin C synthesis and its loss in bats" [archive]. Molecular Biology and Evolution. 28 (2): 1025–31. doi:10.1093/molbev/msq286 [archive]. PMID 21037206 [archive].
- ↑ Cui J, Yuan X, Wang L, Jones G, Zhang S (Nov 2011). "Recent loss of vitamin C biosynthesis ability in bats" [archive]. PLOS ONE. 6 (11): e27114. Bibcode:2011PLoSO...627114C [archive]. doi:10.1371/journal.pone.0027114 [archive]. PMC 3206078 [archive]. PMID 22069493 [archive].
- ↑ 78.0 78.1 78.2 Martinez del Rio C (July 1997). "Can passerines synthesize vitamin C?" [archive]. The Auk. 114 (3): 513–6. doi:10.2307/4089257 [archive]. JSTOR 4089257 [archive]. Cite error: Invalid
<ref>tag; name "Martinez del Rio_1997" defined multiple times with different content - ↑ 79.0 79.1 79.2 Drouin G, Godin JR, Pagé B (August 2011). "The genetics of vitamin C loss in vertebrates" [archive]. Current Genomics. 12 (5): 371–8. doi:10.2174/138920211796429736 [archive]. PMC 3145266 [archive]. PMID 22294879 [archive].
- ↑ Berra TM (2008). Freshwater fish distribution [archive]. University of Chicago Press. p. 55. ISBN 978-0-226-04443-9.
- ↑ Milton K (June 1999). "Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?" [archive] (PDF). Nutrition. 15 (6): 488–98. CiteSeerX 10.1.1.564.1533 [archive]. doi:10.1016/S0899-9007(99)00078-7 [archive]. PMID 10378206 [archive]. Archived [archive] (PDF) from the original on August 10, 2017.
- ↑ 82.0 82.1 82.2 82.3 Pauling L (December 1970). "Evolution and the need for ascorbic acid" [archive]. Proceedings of the National Academy of Sciences of the United States of America. 67 (4): 1643–8. Bibcode:1970PNAS...67.1643P [archive]. doi:10.1073/pnas.67.4.1643 [archive]. PMC 283405 [archive]. PMID 5275366 [archive]. Cite error: Invalid
<ref>tag; name "pmid5275366" defined multiple times with different content - ↑ Parrott, Terri (October 2022). "Nutritional diseases of nonhuman primates" [archive]. Merck Veterinary Manual. Archived [archive] from the original on December 24, 2023. Retrieved 24 December 2023.
- ↑ Lachapelle MY, Drouin G (February 2011). "Inactivation dates of the human and guinea pig vitamin C genes". Genetica. 139 (2): 199–207. doi:10.1007/s10709-010-9537-x [archive]. PMID 21140195 [archive]. S2CID 7747147 [archive].
- ↑ Yang H (June 2013). "Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis". Biochemical Genetics. 51 (5–6): 413–25. doi:10.1007/s10528-013-9574-0 [archive]. PMID 23404229 [archive]. S2CID 14393449 [archive].
- ↑ Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M (2010). "Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates" [archive]. Genome Biology. 11 (3): R26. doi:10.1186/gb-2010-11-3-r26 [archive]. PMC 2864566 [archive]. PMID 20210993 [archive].
- ↑ Koshizaka T, Nishikimi M, Ozawa T, Yagi K (February 1988). "Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis" [archive]. The Journal of Biological Chemistry. 263 (4): 1619–21. doi:10.1016/S0021-9258(19)77923-X [archive]. PMID 3338984 [archive].
- ↑ 88.0 88.1 Pollock JI, Mullin RJ (1987). "Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius". American Journal of Physical Anthropology. 73 (1): 65–70. doi:10.1002/ajpa.1330730106 [archive]. PMID 3113259 [archive].
- ↑ Poux C, Douzery EJ (2004). "Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP". American Journal of Physical Anthropology. 124 (1): 01–16. doi:10.1002/ajpa.10322 [archive]. PMID 15085543 [archive].
- ↑ Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G, Groves CP (June 1998). "Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence". Molecular Phylogenetics and Evolution. 9 (3): 585–98. doi:10.1006/mpev.1998.0495 [archive]. PMID 9668008 [archive]. S2CID 23525774 [archive].
- ↑ Porter CA, Page SL, Czelusniak J, Schneider H, Schneider MP, Sampaio I, Goodman M (April 1997). "Phylogeny and evolution of selected primates as determined by sequences of the ε-globin locus and 5′ flanking regions". Int J Primatology. 18 (2): 261–95. doi:10.1023/A:1026328804319 [archive]. hdl:2027.42/44561 [archive]. S2CID 1851788 [archive].
- ↑ Proctor P (1970). "Similar functions of uric acid and ascorbate in man?" [archive]. Nature. 228 (5274): 868. Bibcode:1970Natur.228..868P [archive]. doi:10.1038/228868a0 [archive]. PMID 5477017 [archive]. S2CID 4146946 [archive].
- ↑ Leferink NG, van den Berg WA, van Berkel WJ (February 2008). "l-Galactono-gamma-lactone dehydrogenase from Arabidopsis thaliana, a flavoprotein involved in vitamin C biosynthesis" [archive]. The FEBS Journal. 275 (4): 713–26. doi:10.1111/j.1742-4658.2007.06233.x [archive]. PMID 18190525 [archive]. S2CID 25096297 [archive].
- ↑ Mieda T, Yabuta Y, Rapolu M, Motoki T, Takeda T, Yoshimura K, Ishikawa T, Shigeoka S (September 2004). "Feedback inhibition of spinach L-galactose dehydrogenase by L-ascorbate" [archive]. Plant & Cell Physiology. 45 (9): 1271–9. doi:10.1093/pcp/pch152 [archive]. PMID 15509850 [archive].
- ↑ Grillet L, Ouerdane L, Flis P, Hoang MT, Isaure MP, Lobinski R, Curie C, Mari S (January 2014). "Ascorbate efflux as a new strategy for iron reduction and transport in plants" [archive]. The Journal of Biological Chemistry. 289 (5): 2515–25. doi:10.1074/jbc.M113.514828 [archive]. PMC 3908387 [archive]. PMID 24347170 [archive].
- ↑ 96.0 96.1 96.2 Gallie DR (2013). "L-ascorbic acid: a multifunctional molecule supporting plant growth and development" [archive]. Scientifica. 2013: 1–24. doi:10.1155/2013/795964 [archive]. PMC 3820358 [archive]. PMID 24278786 [archive].
- ↑ 97.0 97.1 97.2 Mellidou I, Kanellis AK (2017). "Genetic control of ascorbic acid biosynthesis and recycling in horticultural crops" [archive]. Frontiers in Chemistry. 5: 50. Bibcode:2017FrCh....5...50M [archive]. doi:10.3389/fchem.2017.00050 [archive]. PMC 5504230 [archive]. PMID 28744455 [archive].
- ↑ Bulley, Sean; Laing, William (2016-10-01). "The regulation of ascorbate biosynthesis" [archive]. Current Opinion in Plant Biology. SI: 33: Cell signalling and gene regulation 2016. 33: 15–22. Bibcode:2016COPB...33...15B [archive]. doi:10.1016/j.pbi.2016.04.010 [archive]. ISSN 1369-5266 [archive]. PMID 27179323 [archive]. Archived [archive] from the original on March 5, 2024. Retrieved February 9, 2024.
- ↑ Eggersdorfer M, Laudert D, Létinois U, McClymont T, Medlock J, Netscher T, Bonrath W (December 2012). "One hundred years of vitamins-a success story of the natural sciences". Angewandte Chemie. 51 (52): 12960–12990. doi:10.1002/anie.201205886 [archive]. PMID 23208776 [archive].
- ↑ "The production of vitamin C" [archive] (PDF). Competition Commission. 2001. Archived from the original [archive] (PDF) on January 19, 2012. Retrieved February 20, 2007.
- ↑ Zhou M, Bi Y, Ding M, Yuan Y (2021). "One-step biosynthesis of vitamin C in Saccharomyces cerevisiae" [archive]. Front Microbiol. 12: 643472. doi:10.3389/fmicb.2021.643472 [archive]. PMC 7947327 [archive]. PMID 33717042 [archive].
- ↑ Tian YS, Deng YD, Zhang WH, Yu-Wang, Xu J, Gao JJ, Bo-Wang, Fu XY, Han HJ, Li ZJ, Wang LJ, Peng RH, Yao QH (August 2022). "Metabolic engineering of Escherichia coli for direct production of vitamin C from D-glucose" [archive]. Biotechnol Biofuels Bioprod. 15 (1): 86. doi:10.1186/s13068-022-02184-0 [archive]. PMC 9396866 [archive]. PMID 35996146 [archive].
- ↑ "Vantage market research: global vitamin C market size & share to surpass $1.8 Bn by 2028" [archive]. Globe Newswire (Press release). November 8, 2022. Archived [archive] from the original on December 21, 2023. Retrieved December 21, 2023.
- ↑ "Vitamin C price trend and forecast" [archive]. ChemAnalyst. September 2023. Archived [archive] from the original on December 21, 2023. Retrieved December 21, 2023.
- ↑ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (March 2012). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases" [archive]. The Cochrane Database of Systematic Reviews. 2012 (3): CD007176. doi:10.1002/14651858.CD007176.pub2 [archive]. hdl:10138/136201 [archive]. PMC 8407395 [archive]. PMID 22419320 [archive].
- ↑ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. hdl:10665/44053 [archive]. ISBN 978-92-4-154765-9.
- ↑ "Ascorbic acid - drug usage statistics" [archive]. ClinCalc. Archived [archive] from the original on January 18, 2024. Retrieved January 14, 2024.
- ↑ Magiorkinis E, Beloukas A, Diamantis A (April 2011). "Scurvy: past, present and future". The European Journal of Internal Medicine. 22 (2): 147–52. doi:10.1016/j.ejim.2010.10.006 [archive]. PMID 21402244 [archive].
- ↑ Hodges RE, Baker EM, Hood J, Sauberlich HE, March SC (May 1969). "Experimental scurvy in man". The American Journal of Clinical Nutrition. 22 (5): 535–48. doi:10.1093/ajcn/22.5.535 [archive]. PMID 4977512 [archive].
- ↑ Pemberton J (June 2006). "Medical experiments carried out in Sheffield on conscientious objectors to military service during the 1939-45 war" [archive]. International Journal of Epidemiology. 35 (3): 556–8. doi:10.1093/ije/dyl020 [archive]. PMID 16510534 [archive].
- ↑ Belsky JB, Wira CR, Jacob V, Sather JE, Lee PJ (December 2018). "A review of micronutrients in sepsis: the role of thiamine, L-carnitine, vitamin C, selenium and vitamin D". Nutrition Research Reviews. 31 (2): 281–90. doi:10.1017/S0954422418000124 [archive]. PMID 29984680 [archive]. S2CID 51599526 [archive].
- ↑ 112.0 112.1 Liang B, Su J, Shao H, Chen H, Xie B (March 2023). "The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials" [archive]. Crit Care. 27 (1): 109. doi:10.1186/s13054-023-04392-y [archive]. PMC 10012592 [archive]. PMID 36915173 [archive].
- ↑ Berger MM, Oudemans-van Straaten HM (March 2015). "Vitamin C supplementation in the critically ill patient". Curr Opin Clin Nutr Metab Care. 18 (2): 193–201. doi:10.1097/MCO.0000000000000148 [archive]. PMID 25635594 [archive]. S2CID 37895257 [archive].
- ↑ Xu C, Yi T, Tan S, Xu H, Hu Y, Ma J, Xu J (April 2023). "Association of oral or intravenous vitamin C supplementation with mortality: A systematic review and meta-analysis" [archive]. Nutrients. 15 (8): 1848. doi:10.3390/nu15081848 [archive]. PMC 10146309 [archive]. PMID 37111066 [archive].
- ↑ Liang H, Mu Q, Sun W, Liu L, Qiu S, Xu Z, Cui Y, Yan Y, Sun T (2023). "Effect of intravenous vitamin C on adult septic patients: a systematic review and meta-analysis" [archive]. Front Nutr. 10: 1211194. doi:10.3389/fnut.2023.1211194 [archive]. PMC 10437115 [archive]. PMID 37599680 [archive].
- ↑ 116.0 116.1 Hemilä H, Chalker E (January 2013). "Vitamin C for preventing and treating the common cold" [archive]. The Cochrane Database of Systematic Reviews. 2013 (1): CD000980. doi:10.1002/14651858.CD000980.pub4 [archive]. PMC 1160577 [archive]. PMID 23440782 [archive].
- ↑ Hemilä H, Chalker E (December 2023). "Vitamin C reduces the severity of common colds: a meta-analysis" [archive]. BMC Public Health. 23 (1): 2468. doi:10.1186/s12889-023-17229-8 [archive]. PMC 10712193 [archive]. PMID 38082300 [archive].
- ↑ Wintergerst ES, Maggini S, Hornig DH (2006). "Immune-enhancing role of vitamin C and zinc and effect on clinical conditions" [archive] (PDF). Annals of Nutrition & Metabolism. 50 (2): 85–94. doi:10.1159/000090495 [archive]. PMID 16373990 [archive]. S2CID 21756498 [archive]. Archived [archive] (PDF) from the original on July 22, 2018. Retrieved August 25, 2019.
- ↑ EFSA Panel on Dietetic Products, Nutrition and Allergies (2009). "Scientific Opinion on the substantiation of health claims related to vitamin C and protection of DNA, proteins and lipids from oxidative damage (ID 129, 138, 143, 148), antioxidant function of lutein (ID 146), maintenance of vision (ID 141, 142), collagen formation (ID 130, 131, 136, 137, 149), function of the nervous system (ID 133), function of the immune system (ID 134), function of the immune system during and after extreme physical exercise (ID 144), non-haem iron absorption (ID 132, 147), energy-yielding metabolism (ID 135), and relief in case of irritation in the upper respiratory tract (ID 1714, 1715) pursuant to Article 13(1) of Regulation (EC) No 1924/2006" [archive]. EFSA Journal. 7 (9): 1226. doi:10.2903/j.efsa.2009.1226 [archive].
- ↑ EFSA Panel on Dietetic Products, Nutrition and Allergies (2015). "Vitamin C and contribution to the normal function of the immune system: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006" [archive]. EFSA Journal. 13 (11): 4298. doi:10.2903/j.efsa.2015.4298 [archive]. hdl:11380/1296052 [archive].
- ↑ Bramstedt KA (October 2020). "Unicorn poo and blessed waters: COVID-19 quackery and FDA Warning Letters" [archive]. Ther Innov Regul Sci. 55 (1): 239–44. doi:10.1007/s43441-020-00224-1 [archive]. PMC 7528445 [archive]. PMID 33001378 [archive].
- ↑ "Vitamin C" [archive]. COVID-19 Treatment Guidelines. April 21, 2021. Archived [archive] from the original on November 20, 2021. Retrieved January 2, 2022.
- ↑ "COVID-19 treatment guidelines" [archive]. U.S. National Institutes of Health. December 26, 2022. Archived [archive] from the original on November 20, 2021. Retrieved December 18, 2023.
- ↑ 124.0 124.1 124.2 124.3 Kow CS, Hasan SS, Ramachandram DS (December 2023). "The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials" [archive]. Inflammopharmacology. 31 (6): 3357–62. doi:10.1007/s10787-023-01200-5 [archive]. PMC 10111321 [archive]. PMID 37071316 [archive].
- ↑ 125.0 125.1 125.2 Huang WY, Hong J, Ahn SI, Han BK, Kim YJ (December 2022). "Association of vitamin C treatment with clinical outcomes for COVID-19 patients: A systematic review and meta-analysis" [archive]. Healthcare. 10 (12): 2456. doi:10.3390/healthcare10122456 [archive]. PMC 9777834 [archive]. PMID 36553979 [archive].
- ↑ 126.0 126.1 126.2 Olczak-Pruc M, Swieczkowski D, Ladny JR, Pruc M, Juarez-Vela R, Rafique Z, Peacock FW, Szarpak L (October 2022). "Vitamin C supplementation for the treatment of COVID-19: A systematic review and meta-analysis" [archive]. Nutrients. 14 (19): 4217. doi:10.3390/nu14194217 [archive]. PMC 9570769 [archive]. PMID 36235869 [archive].
- ↑ Cortés-Jofré M, Rueda JR, Asenjo-Lobos C, Madrid E, Bonfill Cosp X (March 2020). "Drugs for preventing lung cancer in healthy people" [archive]. The Cochrane Database of Systematic Reviews. 2020 (3): CD002141. doi:10.1002/14651858.CD002141.pub3 [archive]. PMC 7059884 [archive]. PMID 32130738 [archive].
- ↑ Stratton J, Godwin M (June 2011). "The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis" [archive]. Family Practice. 28 (3): 243–52. doi:10.1093/fampra/cmq115 [archive]. PMID 21273283 [archive].
- ↑ Heine-Bröring RC, Winkels RM, Renkema JM, Kragt L, van Orten-Luiten AC, Tigchelaar EF, Chan DS, Norat T, Kampman E (May 2015). "Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies". Int J Cancer. 136 (10): 2388–401. doi:10.1002/ijc.29277 [archive]. PMID 25335850 [archive]. S2CID 44706004 [archive].
- ↑ Fulan H, Changxing J, Baina WY, Wencui Z, Chunqing L, Fan W, Dandan L, Dianjun S, Tong W, Da P, Yashuang Z (October 2011). "Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression". Cancer Causes & Control. 22 (10): 1383–96. doi:10.1007/s10552-011-9811-y [archive]. PMID 21761132 [archive]. S2CID 24867472 [archive].
- ↑ Lee Y (November 2023). "Role of vitamin C in targeting cancer stem cells and cellular plasticity" [archive]. Cancers (Basel). 15 (23): 5657. doi:10.3390/cancers15235657 [archive]. PMC 10705783 [archive]. PMID 38067361 [archive].
- ↑ Satheesh NJ, Samuel SM, Büsselberg D (January 2020). "Combination therapy with vitamin C could eradicate cancer stem cells" [archive]. Biomolecules. 10 (1): 79. doi:10.3390/biom10010079 [archive]. PMC 7022456 [archive]. PMID 31947879 [archive].
- ↑ Al-Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, Eres K (March 2017). "Vitamin C supplementation for the primary prevention of cardiovascular disease" [archive]. The Cochrane Database of Systematic Reviews. 2017 (3): CD011114. doi:10.1002/14651858.CD011114.pub2 [archive]. PMC 6464316 [archive]. PMID 28301692 [archive].
- ↑ Chen GC, Lu DB, Pang Z, Liu QF (November 2013). "Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of prospective studies" [archive]. J Amer Heart Assoc. 2 (6): e000329. doi:10.1161/JAHA.113.000329 [archive]. PMC 3886767 [archive]. PMID 24284213 [archive].
- ↑ Ashor AW, Lara J, Mathers JC, Siervo M (July 2014). "Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomized controlled trials". Atherosclerosis. 235 (1): 9–20. doi:10.1016/j.atherosclerosis.2014.04.004 [archive]. PMID 24792921 [archive].
- ↑ Ran L, Zhao W, Tan X, Wang H, Mizuno K, Takagi K, Zhao Y, Bu H (April 2020). "Association between serum vitamin C and the blood pressure: A systematic review and meta-analysis of observational studies" [archive]. Cardiovasc Ther. 2020: 4940673. doi:10.1155/2020/4940673 [archive]. PMC 7211237 [archive]. PMID 32426036 [archive].
- ↑ 137.0 137.1 Guan Y, Dai P, Wang H (February 2020). "Effects of vitamin C supplementation on essential hypertension: A systematic review and meta-analysis" [archive]. Medicine (Baltimore). 99 (8): e19274. doi:10.1097/MD.0000000000019274 [archive]. PMC 7034722 [archive]. PMID 32080138 [archive].
- ↑ Lbban E, Kwon K, Ashor A, Stephan B, Idris I, Tsintzas K, Siervo M (December 2023). "Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomized clinical trials" [archive]. Int J Food Sci Nutr. 74 (8): 814–25. doi:10.1080/09637486.2023.2264549 [archive]. PMID 37791386 [archive]. S2CID 263621742 [archive]. Archived [archive] from the original on January 21, 2024. Retrieved December 23, 2023.
- ↑ Mason SA, Keske MA, Wadley GD (February 2021). "Effects of vitamin C supplementation on glycemic control and cardiovascular risk factors in people With type 2 diabetes: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials" [archive]. Diabetes Care. 44 (2): 618–30. doi:10.2337/dc20-1893 [archive]. hdl:10536/DRO/DU:30147432 [archive]. PMID 33472962 [archive]. Archived [archive] from the original on January 21, 2024. Retrieved December 21, 2023.
- ↑ Nosratabadi S, Ashtary-Larky D, Hosseini F, Namkhah Z, Mohammadi S, Salamat S, Nadery M, Yarmand S, Zamani M, Wong A, Asbaghi O (August 2023). "The effects of vitamin C supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis". Diabetes and Metabolic Syndrome. 17 (8): 102824. doi:10.1016/j.dsx.2023.102824 [archive]. PMID 37523928 [archive]. S2CID 259581695 [archive].
- ↑ DeLoughery TG (March 2017). "Iron deficiency anemia". Med Clin North Am (Review). 101 (2): 319–32. doi:10.1016/j.mcna.2016.09.004 [archive]. PMID 28189173 [archive].
- ↑ Nathan N, Patel P (10 November 2021). "Why is topical vitamin C important for skin health?" [archive]. Harvard Health Publishing, Harvard Medical School. Archived [archive] from the original on October 14, 2022. Retrieved October 14, 2022.
- ↑ Pullar JM, Carr AC, Vissers MC (August 2017). "The roles of vitamin C in skin health" [archive]. Nutrients. 9 (8): 866. doi:10.3390/nu9080866 [archive]. PMC 5579659 [archive]. PMID 28805671 [archive].
- ↑ Al-Niaimi F, Chiang NY (July 2017). "Topical vitamin C and the skin: Mechanisms of action and clinical applications" [archive]. J Clin Aesthet Dermatol. 10 (7): 14–17. PMC 5605218 [archive]. PMID 29104718 [archive].
- ↑ Sanabria B, Berger LE, Mohd H, Benoit L, Truong TM, Michniak-Kohn BB, Rao BK (September 2023). "Clinical efficacy of topical vitamin C on the appearance of wrinkles: A systematic literature review" [archive]. Journal of Drugs in Dermatology. 22 (9): 898–904. doi:10.36849/JDD.7332 [archive] (inactive March 5, 2024). PMID 37683066 [archive]. Archived [archive] from the original on February 25, 2024. Retrieved February 25, 2024.
{{cite journal}}: CS1 maint: DOI inactive as of March 2024 (link) - ↑ Correia G, Magina S (July 2023). "Efficacy of topical vitamin C in melasma and photoaging: A systematic review" [archive]. J Cosmet Dermatol. 22 (7): 1938–45. doi:10.1111/jocd.15748 [archive]. PMID 37128827 [archive]. S2CID 258439047 [archive].
- ↑ Lopes da Silva S, Vellas B, Elemans S, Luchsinger J, Kamphuis P, Yaffe K, Sijben J, Groenendijk M, Stijnen T (2014). "Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta-analysis" [archive]. Alzheimer's & Dementia. 10 (4): 485–502. doi:10.1016/j.jalz.2013.05.1771 [archive]. PMID 24144963 [archive].
- ↑ Li FJ, Shen L, Ji HF (2012). "Dietary intakes of vitamin E, vitamin C, and β-carotene and risk of Alzheimer's disease: a meta-analysis". Journal of Alzheimer's Disease. 31 (2): 253–8. doi:10.3233/JAD-2012-120349 [archive]. PMID 22543848 [archive].
- ↑ Harrison FE (2012). "A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease" [archive]. Journal of Alzheimer's Disease. 29 (4): 711–26. doi:10.3233/JAD-2012-111853 [archive]. PMC 3727637 [archive]. PMID 22366772 [archive].
- ↑ Sideri O, Tsaousis KT, Li HJ, Viskadouraki M, Tsinopoulos IT (2019). "The potential role of nutrition on lens pathology: a systematic review and meta-analysis". Surv Ophthalmol. 64 (5): 668–78. doi:10.1016/j.survophthal.2019.03.003 [archive]. PMID 30878580 [archive]. S2CID 81981938 [archive].
- ↑ Jiang H, Yin Y, Wu CR, Liu Y, Guo F, Li M, Ma L (January 2019). "Dietary vitamin and carotenoid intake and risk of age-related cataract" [archive]. Am J Clin Nutr. 109 (1): 43–54. doi:10.1093/ajcn/nqy270 [archive]. PMID 30624584 [archive].
- ↑ Evans JR, Lawrenson JG (July 2017). "Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration" [archive]. Cochrane Database Syst Rev. 2017 (7): CD000253. doi:10.1002/14651858.CD000253.pub4 [archive]. PMC 6483250 [archive]. PMID 28756617 [archive].
- ↑ Mi N, Zhang M, Ying Z, Lin X, Jin Y (January 2024). "Vitamin intake and periodontal disease: a meta-analysis of observational studies" [archive]. BMC Oral Health. 24 (1): 117. doi:10.1186/s12903-024-03850-5 [archive]. PMC 10799494 [archive]. PMID 38245765 [archive].
- ↑ Tada A, Miura H (July 2019). "The relationship between vitamin C and periodontal diseases: A systematic review" [archive]. Int J Environ Res Public Health. 16 (14): 2472. doi:10.3390/ijerph16142472 [archive]. PMC 6678404 [archive]. PMID 31336735 [archive].
- ↑ Goodwin JS, Tangum MR (November 1998). "Battling quackery: attitudes about micronutrient supplements in American academic medicine". Archives of Internal Medicine. 158 (20): 2187–91. doi:10.1001/archinte.158.20.2187 [archive]. PMID 9818798 [archive].
- ↑ Naidu KA (August 2003). "Vitamin C in human health and disease is still a mystery? An overview" [archive] (PDF). Nutrition Journal. 2 (7): 7. doi:10.1186/1475-2891-2-7 [archive]. PMC 201008 [archive]. PMID 14498993 [archive]. Archived [archive] (PDF) from the original on September 18, 2012.
- ↑ Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson A (March 2013). "Ascorbic acid supplements and kidney stone incidence among men: a prospective study" [archive]. JAMA Internal Medicine. 173 (5): 386–8. doi:10.1001/jamainternmed.2013.2296 [archive]. PMID 23381591 [archive].
- ↑ 158.0 158.1 Jacobs C, Hutton B, Ng T, Shorr R, Clemons M (February 2015). "Is there a role for oral or intravenous ascorbate (vitamin C) in treating patients with cancer? A systematic review" [archive]. The Oncologist. 20 (2): 210–23. doi:10.1634/theoncologist.2014-0381 [archive]. PMC 4319640 [archive]. PMID 25601965 [archive].
- ↑ Shrestha DB, Budhathoki P, Sedhai YR, Mandal SK, Shikhrakar S, Karki S, Baniya RK, Kashiouris MG, Qiao X, Fowler AA (October 2021). "Vitamin C in critically ill patients: An updated systematic review and meta-analysis" [archive]. Nutrients. 13 (10): 3564. doi:10.3390/nu13103564 [archive]. PMC 8539952 [archive]. PMID 34684565 [archive].
- ↑ Holford P, Carr AC, Zawari M, Vizcaychipi MP (November 2021). "Vitamin C intervention for critical COVID-19: A pragmatic review of the current level of evidence" [archive]. Life. 11 (11): 1166. Bibcode:2021Life...11.1166H [archive]. doi:10.3390/life11111166 [archive]. PMC 8624950 [archive]. PMID 34833042 [archive].
- ↑ Abobaker A, Alzwi A, Alraied AH (December 2020). "Overview of the possible role of vitamin C in management of COVID-19" [archive]. Pharmacol Rep. 72 (6): 1517–28. doi:10.1007/s43440-020-00176-1 [archive]. PMC 7592143 [archive]. PMID 33113146 [archive].
- ↑ Lind J (1772). A Treatise on the Scurvy [archive] (3rd ed.). London, England: G. Pearch and W. Woodfall. p. 285. Archived from the original [archive] on January 1, 2016.
- ↑ Ashhurst J, ed. (1881). The International Encyclopedia of Surgery [archive]. Vol. 1. New York, New York: William Wood and Co. p. 278. Archived from the original [archive] on May 5, 2016.
- ↑ Rajakumar K (October 2001). "Infantile scurvy: a historical perspective" [archive]. Pediatrics. 108 (4): E76. CiteSeerX 10.1.1.566.5857 [archive]. doi:10.1542/peds.108.4.e76 [archive]. PMID 11581484 [archive]. Archived from the original [archive] on September 4, 2015.
As they sailed farther up the east coast of Africa, they met local traders, who traded them fresh oranges. Within six days of eating the oranges, da Gama's crew recovered fully
- ↑ Livermore H (2004). "Santa Helena, a forgotten Portuguese discovery" [archive] (PDF). Estudos Em Homenagem a Luis Antonio de Oliveira Ramos [Studies in Homage to Luis Antonio de Oliveira Ramos.]: 623–631. Archived from the original [archive] (PDF) on May 29, 2011.
On returning, Lopes' ship had left him on St Helena, where with admirable sagacity and industry he planted vegetables and nurseries with which passing ships were marvelously sustained. [...] There were 'wild groves' of oranges, lemons and other fruits that ripened all the year round, large pomegranates and figs.
- ↑ Woodall J (1617). The Surgion's Mate [archive]. London, England: Edward Griffin. p. 89. Archived from the original [archive] on April 11, 2016.
Succus Limonum, or juice of Lemons ... [is] the most precious help that ever was discovered against the Scurvy[;] to be drunk at all times; ...
- ↑ Armstrong A (1858). "Observation on naval hygiene and scurvy, more particularly as the later appeared during the Polar voyage" [archive]. British and Foreign Medico-chirurgical Review: Or, Quarterly Journal of Practical Medicine and Surgery. 22: 295–305.
- ↑ Bachstrom JF (1734). Observationes circa scorbutum [archive] [Observations on scurvy] (in Latin). Leiden (Lugdunum Batavorum), Netherlands: Conrad Wishof. p. 16. Archived from the original [archive] on January 1, 2016.
... sed ex nostra causa optime explicatur, que est absentia, carentia & abstinentia a vegetabilibus recentibus, ... ( ... but [this misfortune] is explained very well by our [supposed] cause, which is the absence of, lack of, and abstinence from fresh vegetables, ...
{{cite book}}: CS1 maint: unrecognized language (link) - ↑ Lamb J (February 17, 2011). "Captain Cook and the scourge of scurvy" [archive]. British History in depth. BBC. Archived [archive] from the original on February 21, 2011.
- ↑ Lamb J (2001). Preserving the self in the south seas, 1680–1840 [archive]. University of Chicago Press. p. 117. ISBN 978-0-226-46849-5. Archived [archive] from the original on April 30, 2016.
- ↑ 171.0 171.1 171.2 Baron JH (June 2009). "Sailors' scurvy before and after James Lind--a reassessment". Nutrition Reviews. 67 (6): 315–32. doi:10.1111/j.1753-4887.2009.00205.x [archive]. PMID 19519673 [archive]. S2CID 20435128 [archive].
- ↑ Lind J (1753). A treatise of the scurvy. London: A. Millar. In the 1757 edition of his work, Lind discusses his experiment starting on "A treatise of the scurvy" [archive]. p. 149. Archived from the original [archive] on March 20, 2016.
- ↑ Beaglehole JH, Cook JD, Edwards PR (1999). The journals of Captain Cook [archive]. Harmondsworth [Eng.]: Penguin. ISBN 978-0-14-043647-1.
- ↑ "Copley Medal, past winners" [archive]. The Royal Society. Archived [archive] from the original on September 6, 2015. Retrieved January 1, 2024.
- ↑ Reeve J, Stevens DA (2006). "Cook's Voyages 1768–1780" [archive]. Navy and the nation: the influence of the navy on modern Australia. Allen & Unwin Academic. p. 74. ISBN 978-1-74114-200-6.
- ↑ Kuhnlein HV, Receveur O, Soueida R, Egeland GM (June 2004). "Arctic indigenous peoples experience the nutrition transition with changing dietary patterns and obesity" [archive]. The Journal of Nutrition. 134 (6): 1447–53. doi:10.1093/jn/134.6.1447 [archive]. PMID 15173410 [archive].
- ↑ 177.0 177.1 Squires VR (2011). The role of food, agriculture, forestry and fisheries in human nutrition - Volume IV [archive]. EOLSS Publications. p. 121. ISBN 978-1-84826-195-2. Archived [archive] from the original on January 11, 2023. Retrieved September 17, 2017.
- ↑ Stacey M, Manners DJ (1978). "Edmund Langley Hirst". Advances in carbohydrate chemistry and biochemistry. Vol. 35. pp. 1–29. doi:10.1016/S0065-2318(08)60217-6 [archive]. ISBN 978-0-12-007235-4. PMID 356548 [archive].
- ↑ "Redoxon trademark information by Hoffman-la Roche, Inc. (1934)" [archive]. Archived [archive] from the original on November 16, 2018. Retrieved December 25, 2017.
- ↑ Wang W, Xu H (2016). "Industrial fermentation of Vitamin C" [archive]. In Vandamme EJ, Revuelta JI (eds.). Industrial biotechnology of vitamins, biopigments, and antioxidants. Wiley-VCH Verlag GmbH & Co. KGaA. p. 161. ISBN 978-3-527-33734-7.
- ↑ Norum KR, Grav HJ (June 2002). "[Axel Holst and Theodor Frolich--pioneers in the combat of scurvy]". Tidsskrift for den Norske Laegeforening (in norsk). 122 (17): 1686–7. PMID 12555613 [archive].
- ↑ Rosenfeld L (April 1997). "Vitamine--vitamin. The early years of discovery" [archive]. Clinical Chemistry. 43 (4): 680–5. doi:10.1093/clinchem/43.4.680 [archive]. PMID 9105273 [archive].
- ↑ 183.0 183.1 Zetterström R (May 2009). "Nobel Prize 1937 to Albert von Szent-Györgyi: identification of vitamin C as the anti-scorbutic factor". Acta Paediatrica. 98 (5): 915–19. doi:10.1111/j.1651-2227.2009.01239.x [archive]. PMID 19239412 [archive]. S2CID 11077461 [archive].
- ↑ 184.0 184.1 Svirbely JL, Szent-Györgyi A (1932). "The chemical nature of vitamin C" [archive]. The Biochemical Journal. 26 (3): 865–70. Bibcode:1932Sci....75..357K [archive]. doi:10.1126/science.75.1944.357-a [archive]. PMC 1260981 [archive]. PMID 16744896 [archive].
- ↑ Juhász-Nagy S (March 2002). "[Albert Szent-Györgyi--biography of a free genius]". Orvosi Hetilap (in magyar). 143 (12): 611–4. PMID 11963399 [archive].
- ↑ Kenéz J (December 1973). "[Eventful life of a scientist. 80th birthday of Nobel prize winner Albert Szent-Györgyi]". Munchener Medizinische Wochenschrift (in Deutsch). 115 (51): 2324–6. PMID 4589872 [archive].
- ↑ Szállási A (December 1974). "[2 interesting early articles by Albert Szent-Györgyi]". Orvosi Hetilap (in magyar). 115 (52): 3118–9. PMID 4612454 [archive].
- ↑ 188.0 188.1 "The Albert Szent-Gyorgyi Papers: Szeged, 1931-1947: Vitamin C, Muscles, and WWII" [archive]. Profiles in Science. United States National Library of Medicine. Archived [archive] from the original on May 5, 2009.
- ↑ "Scurvy" [archive]. Online Entymology Dictionary. Archived [archive] from the original on December 15, 2020. Retrieved November 19, 2017.
- ↑ Hirst EL (April 1950). "Sir Norman Haworth". Nature. 165 (4198): 587. Bibcode:1950Natur.165..587H [archive]. doi:10.1038/165587a0 [archive]. PMID 15416703 [archive].
- ↑ Burns JJ, Evans C (December 1956). "The synthesis of L-ascorbic acid in the rat from D-glucuronolactone and L-gulonolactone" [archive] (PDF). The Journal of Biological Chemistry. 223 (2): 897–905. doi:10.1016/S0021-9258(18)65088-4 [archive]. PMID 13385237 [archive]. Archived [archive] from the original on December 3, 2022. Retrieved December 3, 2022.
- ↑ Burns JJ, Moltz A, Peyser P (December 1956). "Missing step in guinea pigs required for the biosynthesis of L-ascorbic acid". Science. 124 (3232): 1148–9. Bibcode:1956Sci...124.1148B [archive]. doi:10.1126/science.124.3232.1148-a [archive]. PMID 13380431 [archive].
- ↑ Henson DE, Block G, Levine M (April 1991). "Ascorbic acid: biologic functions and relation to cancer" [archive]. Journal of the National Cancer Institute. 83 (8): 547–50. doi:10.1093/jnci/83.8.547 [archive]. PMID 1672383 [archive]. Archived [archive] from the original on December 25, 2020. Retrieved March 18, 2020.
- ↑ 194.0 194.1 Saul, Andrew. "Orthomolecular Medicine Hall of fame - Irwin Stone, Ph.D." [archive] Orthomolecular Organization. Archived [archive] from the original on August 9, 2011. Retrieved December 25, 2023.
- ↑ Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N (March 2008). "Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C" [archive]. Cell. 132 (6): 1039–48. doi:10.1016/j.cell.2008.01.042 [archive]. PMID 18358815 [archive]. S2CID 18128118 [archive].
- ↑ Mandl J, Szarka A, Bánhegyi G (August 2009). "Vitamin C: update on physiology and pharmacology" [archive]. British Journal of Pharmacology. 157 (7): 1097–110. doi:10.1111/j.1476-5381.2009.00282.x [archive]. PMC 2743829 [archive]. PMID 19508394 [archive].
- ↑ Cameron E, Pauling L (October 1976). "Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer" [archive]. Proceedings of the National Academy of Sciences of the United States of America. 73 (10): 3685–9. Bibcode:1976PNAS...73.3685C [archive]. doi:10.1073/pnas.73.10.3685 [archive]. PMC 431183 [archive]. PMID 1068480 [archive].
- ↑ Boseley, Sarah (September 12, 2008). "Fall of the vitamin doctor: Matthias Rath drops libel action" [archive]. The Guardian. Archived [archive] from the original on December 1, 2016. Retrieved January 5, 2024.
- ↑ Colquhoun, David (August 15, 2007). "The age of endarkenment | Science | guardian.co.uk" [archive]. Guardian. Archived [archive] from the original on March 6, 2023. Retrieved January 5, 2024.
- ↑ 200.0 200.1 200.2 200.3 Barret S (September 14, 2014). "The dark side of Linus Pauling's legacy" [archive]. www.quackwatch.org. Archived from the original [archive] on September 4, 2018. Retrieved December 18, 2018. Cite error: Invalid
<ref>tag; name ":0" defined multiple times with different content - ↑ Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP (March 2014). "Review of high-dose intravenous vitamin C as an anticancer agent" [archive]. Asia-Pacific Journal of Clinical Oncology. 10 (1): 22–37. doi:10.1111/ajco.12173 [archive]. PMID 24571058 [archive]. S2CID 206983069 [archive].
- ↑ The Vitamins and Minerals 101 Cliff Notes by Chris Masterjohn, PhD
- ↑ The Vitamins and Minerals 101 Cliff Notes by Chris Masterjohn, PhD
- ↑ https://covid19criticalcare.com/covid-19-protocols/i-mask-plus-protocol/ [archive]
- ↑ Joseph Mercola_ Ronnie Cummins - The Truth About COVID-19_ Exposing The Great Reset, Lockdowns, Vaccine Passports, and the New Normal-Chelsea Green Publishing (2021)
- ↑ 206.0 206.1 206.2 206.3 "Vitamin C" [archive]. American Cancer Society.
- ↑ Bad Science, Ben Goldacre
- ↑ Trick Or Treatment, Simon Singh & Edzard Ernst
- ↑ David Gorski [archive], Science Based Medicine, 18 Aug 2008
- ↑ Gropper SS, Smith JL, Grodd JL (2004). Advanced Nutrition and Human Metabolism (4th ed.). Belmont, CA. US: Thomson Wadsworth. pp. 260–275.
- ↑ Yeom CH, Jung GC, Song KJ (2007). "Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration" [archive]. J. Korean Med. Sci. 22 (1): 7–11. doi:10.3346/jkms.2007.22.1.7 [archive]. PMC 2693571 [archive]. PMID 17297243 [archive].
- ↑ Pollock, J. I.; Mullin, R. J. (1987). "Vitamin C biosynthesis in prosimians: Evidence for the anthropoid affinity of Tarsius". American Journal of Physical Anthropology. 73 (1): 65–70. doi:10.1002/ajpa.1330730106 [archive]. PMID 3113259 [archive].
- ↑ R. Eric Miller; Murray E. Fowler (2014-07-31). Fowler's Zoo and Wild Animal Medicine, Volume 8 [archive]. p. 389. ISBN 9781455773992. Retrieved 2016-06-02.
- ↑ Jenness R, Birney E, Ayaz K (1980). "Variation of l-gulonolactone oxidase activity in placental mammals". Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. 67 (2): 195–204. doi:10.1016/0305-0491(80)90131-5 [archive].
- ↑ Vitamin and mineral requirements in human nutrition [archive] (PDF) (2nd ed.). World Health Organization. 2004. p. 138. ISBN 978-9241546126. Retrieved 31 December 2014.
- ↑ Levy, Thomas (2011). Primal Panacea. MedFox Publishing. p. 352. ISBN 978-0983772804.
- ↑ Harri Hemilä (January 2006). "Do vitamins C and E affect respiratory infections?" [archive] (PDF). University of Helsinki. Retrieved 2007-02-21.
- ↑ "Vitamin C (Ascorbic Acid)" [archive]. University of Maryland Medical Center. April 2002. Archived from the original [archive] on 2005-12-31. Retrieved 2007-02-19.
- ↑ "Tolerable Upper Intake Levels For Vitamins And Minerals" [archive] (PDF). European Food Safety Authority. 2006. Archived [archive] (PDF) from the original on March 16, 2016.
- ↑ Dietary Reference Intakes for Japanese 2010: Water-Soluble Vitamins [archive] Journal of Nutritional Science and Vitaminology 2013(59):S67-S82.
- ↑ "Office of Dietary Supplements - Vitamin C" [archive]. ods.od.nih.gov. Retrieved 2016-02-26.
- ↑ "My Love Affair with Vitamin C" [archive] (PDF).
- ↑ Rath M, Pauling L (1990). "Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig" [archive]. Proc Natl Acad Sci USA. 87 (23): 9388–9390. Bibcode:1990PNAS...87.9388R [archive]. doi:10.1073/pnas.87.23.9388 [archive]. PMC 55170 [archive]. PMID 2147514 [archive].
- ↑ Rath M, Pauling L (1990). "Hypothesis: lipoprotein(a) is a surrogate for ascorbate" [archive]. Proc. Natl. Acad. Sci. USA. 87 (16): 6204–6207. Bibcode:1990PNAS...87.6204R [archive]. doi:10.1073/pnas.87.16.6204 [archive]. PMC 54501 [archive]. PMID 2143582 [archive].
- ↑ Rath M, Pauling L (1992). "A unified theory of human cardiovascular disease leading the way to the abolition of this disease as a cause for human mortality" [archive] (PDF). Journal of Orthomolecular Medicine. 7 (1): 5–15.
- ↑ Stone, Irwin (1972). The Healing Factor: Vitamin C Against Disease [archive]. Grosset and Dunlap. ISBN 978-0-448-11693-8. OCLC 3967737 [archive].
- ↑ 227.0 227.1 227.2 227.3 Verrax J, Calderon PB (December 2008). "The controversial place of vitamin C in cancer treatment". Biochem. Pharmacol. 76 (12): 1644–52. doi:10.1016/j.bcp.2008.09.024 [archive]. PMID 18938145 [archive].
- ↑ Rees; Kelsey, Richards (March 1993). "Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency" [archive]. British Medical Journal. 306 (6881): 841–2. doi:10.1136/bmj.306.6881.841 [archive]. PMC 1677333 [archive]. PMID 8490379 [archive].
- ↑ Nankivell, BJ; Murali KM (2008). "Renal failure from vitamin C after transplantation". The New England Journal of Medicine. 358 (4): e4. doi:10.1056/NEJMicm070984 [archive]. PMID 18216350 [archive].
- ↑ "Safety (MSDS) data for ascorbic acid" [archive]. Oxford University. October 9, 2005. Retrieved 2007-02-21.
- ↑ "American Association of Poison Control Centers (AAPCC) - Annual Report" [archive]. aapcc.org.
- ↑ E. B. Henry, A. Carswell, A. Wirz, V. Fyffe & K. E. L. Mccoll (September 2005). "Proton pump inhibitors reduce the bioavailability of dietary vitamin C" [archive]. Alimentary Pharmacology and Therapeutics. 22 (6): 539–45. doi:10.1111/j.1365-2036.2005.02568.x [archive]. PMID 16167970 [archive]. S2CID 23976667 [archive].
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ↑ C. Mowat; A. Carswell; A. Wirz; K.E. McColl (April 1999). "Omeprazole and dietary nitrate independently affect levels of vitamin C and nitrite in gastric juice" [archive]. Gastroenterology. 116 (4): 813–22. doi:10.1016/s0016-5085(99)70064-8 [archive]. PMID 10092303 [archive].
- ↑ Loh HS, Watters K & Wilson CW (1 November 1973). "The Effects of Aspirin on the Metabolic Availability of Ascorbic Acid in Human Beings" [archive]. J Clin Pharmacol. 13 (11): 480–486. doi:10.1002/j.1552-4604.1973.tb00203.x [archive]. PMID 4490672 [archive]. Archived from the original [archive] on 16 March 2007. Retrieved 31 July 2007.
- ↑ Basu TK (1982). "Vitamin C-aspirin interactions". Int J Vitam Nutr Res Suppl. 23: 83–90. PMID 6811490 [archive].
- ↑ "Dietary Supplement Health and Education Act of 1994" [archive]. Food and Drug Administration.
- ↑ Cameron E, Pauling L (October 1976). "Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer" [archive]. Proc. Natl. Acad. Sci. USA. 73 (10): 3685–3689. Bibcode:1976PNAS...73.3685C [archive]. doi:10.1073/pnas.73.10.3685 [archive]. PMC 431183 [archive]. PMID 1068480 [archive].
- ↑ 238.0 238.1 Cabanillas, F (2010). "Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?". Puerto Rico Health Sciences Journal. 29 (3): 215–7. PMID 20799507 [archive].
- ↑ Berger MM (October 2006). "Antioxidant micronutrients in major trauma and burns: evidence and practice". Nutr Clin Pract. 21 (5): 438–49. doi:10.1177/0115426506021005438 [archive]. PMID 16998143 [archive].
- ↑ Greenhalgh DG (2007). "Burn resuscitation". J Burn Care Res. 28 (4): 555–65. doi:10.1097/bcr.0b013e318093df01 [archive]. PMID 17665515 [archive]. S2CID 3683908 [archive].
- ↑ Pham TN, Cancio LC, Gibran NS (2008). "American Burn Association practice guidelines burn shock resuscitation". J Burn Care Res. 29 (1): 257–66. doi:10.1097/BCR.0b013e31815f3876 [archive]. PMID 18182930 [archive]. S2CID 3694150 [archive].
- ↑ Baker, W. L; Coleman, C. I (2016). "Meta-analysis of ascorbic acid for prevention of postoperative atrial fibrillation after cardiac surgery". American Journal of Health-System Pharmacy. 73 (24): 2056–2066. doi:10.2146/ajhp160066 [archive]. PMID 27806938 [archive].
- ↑ Polymeropoulos, Evangelos; Bagos, Pantelis; Papadimitriou, Maria; Rizos, Ioannis; Patsouris, Efstratios; Toumpoulis, Ioannis (2016). "Vitamin C for the Prevention of Postoperative Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis" [archive]. Advanced Pharmaceutical Bulletin. 6 (2): 243–50. doi:10.15171/apb.2016.033 [archive]. PMC 4961983 [archive]. PMID 27478787 [archive].
- ↑ Hu, Xiaolan; Yuan, Linhui; Wang, Hongtao; Li, Chang; Cai, Junying; Hu, Yanhui; Ma, Changhua (2017). "Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials" [archive]. International Journal of Surgery. 37: 58–64. doi:10.1016/j.ijsu.2016.12.009 [archive]. PMID 27956113 [archive].
- ↑ 245.0 245.1 Hemilä, Harri; Suonsyrjä, Timo (2017). "Vitamin C for preventing atrial fibrillation in high risk patients: A systematic review and meta-analysis" [archive]. BMC Cardiovascular Disorders. 17 (1): 49. doi:10.1186/s12872-017-0478-5 [archive]. PMC 5286679 [archive]. PMID 28143406 [archive].
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ↑ Hemilä, Harri (2017). "Publication bias in meta-analysis of ascorbic acid for postoperative atrial fibrillation". American Journal of Health-System Pharmacy. 74 (6): 372–373. doi:10.2146/ajhp160999 [archive]. hdl:10138/312602 [archive]. PMID 28274978 [archive].
- ↑ Hemilä, Harri (2014). "The effect of vitamin C on bronchoconstriction and respiratory symptoms caused by exercise: A review and statistical analysis" [archive]. Allergy, Asthma & Clinical Immunology. 10 (1): 58. doi:10.1186/1710-1492-10-58 [archive]. PMC 4363347 [archive]. PMID 25788952 [archive].
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ↑ Hemilä, Harri (2013). "Vitamin C may alleviate exercise-induced bronchoconstriction: A meta-analysis" [archive]. BMJ Open. 3 (6): e002416. doi:10.1136/bmjopen-2012-002416 [archive]. PMC 3686214 [archive]. PMID 23794586 [archive].
- ↑ Ashor, Ammar W; Lara, Jose; Mathers, John C; Siervo, Mario (2014). "Effect of vitamin C on endothelial function in health and disease: A systematic review and meta-analysis of randomised controlled trials". Atherosclerosis. 235 (1): 9–20. doi:10.1016/j.atherosclerosis.2014.04.004 [archive]. PMID 24792921 [archive].
- ↑ 250.0 250.1 Hemilä, Harri; Chalker, Elizabeth (2013). "Vitamin C for preventing and treating the common cold" [archive]. Cochrane Database of Systematic Reviews. 2013 (1): CD000980. doi:10.1002/14651858.CD000980.pub4 [archive]. PMC 1160577 [archive]. PMID 23440782 [archive].
- ↑ Hemilä, Harri (2017). "Vitamin C and Infections" [archive]. Nutrients. 9 (4): 339. doi:10.3390/nu9040339 [archive]. PMC 5409678 [archive]. PMID 28353648 [archive].
- ↑ Hickey S, Roberts H (27 September 2005). "Misleading Information on the Properties of Vitamin C" [archive]. PLOS Medicine. 2 (9): e307. doi:10.1371/journal.pmed.0020307 [archive]. PMC 1236801 [archive]. PMID 16173838 [archive].
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ↑ 253.0 253.1 "The Vitamin C Foundation – 514071 – 04/17/2017" [archive]. U.S. Food and Drug Administration. 2019-04-23. Retrieved 2019-06-07.
- ↑ Nabzdyk CS, Bittner EA (October 2018). "Vitamin C in the critically ill – indications and controversies" [archive]. World Journal of Critical Care Medicine. 7 (5): 52–61. doi:10.5492/wjccm.v7.i5.52 [archive]. PMC 6201324 [archive]. PMID 30370227 [archive].
- ↑ Jacob RA, Sotoudeh G (March 2002). "Vitamin C function and status in chronic disease". Nutrition in Clinical Care. 5 (2): 66–74. doi:10.1046/j.1523-5408.2002.00005.x [archive]. PMID 12134712 [archive].
- ↑ Institute of Medicine (US) Panel on Dietary Antioxidants Related Compounds (2000-04-11). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. doi:10.17226/9810 [archive]. ISBN 9780309069359. PMID 25077263 [archive].
- ↑ Ohno S, Ohno Y, Suzuki N, Soma G, Inoue M (March 2009). "High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer" [archive]. Anticancer Research. 29 (3): 809–815. PMID 19414313 [archive].
- ↑ Marik, Paul E.; Khangoora, Vikramjit; Rivera, Racquel; Hooper, Michael H.; Catravas, John (2017). "Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock". Chest. 151 (6). Elsevier BV: 1229–1238. doi:10.1016/j.Chest.2016.11.036 [archive]. ISSN 0012-3692 [archive]. PMID 27940189 [archive]. S2CID 3509326 [archive].
- ↑ "The Marik Protocol: Have We Found a "Cure" for Severe Sepsis and Septic Shock?" [archive]. Rebel EM – Emergency Medicine Blog. 2017-04-07. Retrieved 2021-07-22.
- ↑ "Vitamin C Drug Cocktail for Sepsis" [archive]. HealthManagement. July 9, 2019. Retrieved 2021-09-24.
- ↑ 261.0 261.1 Rubin R (July 2019). "Wide Interest in a Vitamin C Drug Cocktail for Sepsis Despite Lagging Evidence". JAMA. 322 (4): 291–293. doi:10.1001/jama.2019.7936 [archive]. PMID 31268477 [archive]. S2CID 195788169 [archive].
- ↑ ""Ethically and morally unacceptable": Reaction to vitamin C for sepsis trial" [archive]. Dietary supplements, Nutraceuticals, Functional foods, Health ingredients, Herbals. 2020-01-28. Retrieved 2021-07-22.
- ↑ Lee YR, Vo K, Varughese JT (May 2021). "Benefits of combination therapy of hydrocortisone, ascorbic acid and thiamine in sepsis and septic shock: A systematic review". Nutr Health. 28 (1): 77–93. doi:10.1177/02601060211018371 [archive]. PMID 34039089 [archive]. S2CID 235215735 [archive].
- ↑ 264.0 264.1 Carr AC, Cook J (2018-08-23). "Intravenous Vitamin C for Cancer Therapy – Identifying the Current Gaps in Our Knowledge" [archive]. Frontiers in Physiology. 9: 1182. doi:10.3389/fphys.2018.01182 [archive]. PMC 6115501 [archive]. PMID 30190680 [archive].
- ↑ 265.0 265.1 Vissers MC, Das AB (2018-07-03). "Potential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence" [archive]. Frontiers in Physiology. 9: 809. doi:10.3389/fphys.2018.00809 [archive]. PMC 6037948 [archive]. PMID 30018566 [archive].
- ↑ 266.0 266.1 Verrax J, Calderon PB (December 2008). "The controversial place of vitamin C in cancer treatment". Biochemical Pharmacology. 76 (12): 1644–1652. doi:10.1016/j.bcp.2008.09.024 [archive]. PMID 18938145 [archive].
- ↑ 267.0 267.1 267.2 Fritz H, Flower G, Weeks L, Cooley K, Callachan M, McGowan J, et al. (July 2014). "Intravenous Vitamin C and Cancer: A Systematic Review" [archive]. Integrative Cancer Therapies. 13 (4): 280–300. doi:10.1177/1534735414534463 [archive]. PMID 24867961 [archive].
- ↑ Carpenter KJ (2012). "The discovery of vitamin C". Annals of Nutrition & Metabolism. 61 (3): 259–264. doi:10.1159/000343121 [archive]. PMID 23183299 [archive]. S2CID 37436503 [archive].
- ↑ 269.0 269.1 "Intravenous Vitamin C: The Historical Progression" [archive]. PaulingBlog. 2017-10-18. Retrieved 2019-05-20.
- ↑ "The Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C" [archive]. www.seanet.com. Retrieved 2019-05-20.
- ↑ "Clinical Guide to the Use of Vitamin C" [archive]. www.seanet.com. Retrieved 2019-05-20.
- ↑ 272.0 272.1 272.2 272.3 Cameron E, Pauling L (October 1976). "Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer" [archive]. Proceedings of the National Academy of Sciences of the United States of America. 73 (10): 3685–3689. Bibcode:1976PNAS...73.3685C [archive]. doi:10.1073/pnas.73.10.3685 [archive]. PMC 431183 [archive]. PMID 1068480 [archive].
- ↑ 273.0 273.1 Mikirova N, Casciari J, Riordan N, Hunninghake R (August 2013). "Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients" [archive]. Journal of Translational Medicine. 11: 191. doi:10.1186/1479-5876-11-191 [archive]. PMC 3751545 [archive]. PMID 23947403 [archive].
- ↑ Pauling L (January 1973). "Ascorbic acid and the common cold". Scottish Medical Journal. 18 (1): 1–2. doi:10.1177/003693307301800101 [archive]. PMID 4577802 [archive]. S2CID 28875346 [archive].
- ↑ Harakeh S, Jariwalla RJ, Pauling L (September 1990). "Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells" [archive]. Proceedings of the National Academy of Sciences of the United States of America. 87 (18): 7245–7249. Bibcode:1990PNAS...87.7245H [archive]. doi:10.1073/pnas.87.18.7245 [archive]. PMC 54720 [archive]. PMID 1698293 [archive].
- ↑ Rath M, Pauling L (August 1990). "Hypothesis: lipoprotein(a) is a surrogate for ascorbate" [archive]. Proceedings of the National Academy of Sciences of the United States of America. 87 (16): 6204–6207. Bibcode:1990PNAS...87.6204R [archive]. doi:10.1073/pnas.87.16.6204 [archive]. PMC 54501 [archive]. PMID 2143582 [archive].
- ↑ 277.0 277.1 Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, Rubin J, Frytak S (September 1979). "Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial". The New England Journal of Medicine. 301 (13): 687–690. doi:10.1056/NEJM197909273011303 [archive]. PMID 384241 [archive].
- ↑ 278.0 278.1 Tschetter L, Creagan E, O'Fallon J (1983). "A community-based study of vitamin C (ascorbic acid) in patients with advanced cancer". Proceedings of the American Society of Clinical Oncology. 2: 92.
- ↑ 279.0 279.1 279.2 Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, Ames MM (January 1985). "High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison". The New England Journal of Medicine. 312 (3): 137–141. doi:10.1056/NEJM198501173120301 [archive]. PMID 3880867 [archive].
- ↑ Klimant E, Wright H, Rubin D, Seely D, Markman M (April 2018). "Intravenous vitamin C in the supportive care of cancer patients: a review and rational approach" [archive]. Current Oncology. 25 (2): 139–148. doi:10.3747/co.25.3790 [archive]. PMC 5927785 [archive]. PMID 29719430 [archive].
- ↑ Cabanillas F (September 2010). "Vitamin C and cancer: what can we conclude – 1,609 patients and 33 years later?". Puerto Rico Health Sciences Journal. 29 (3): 215–217. PMID 20799507 [archive].
- ↑ Parrow NL, Leshin JA, Levine M (December 2013). "Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics" [archive]. Antioxidants & Redox Signaling. 19 (17): 2141–2156. doi:10.1089/ars.2013.5372 [archive]. PMC 3869468 [archive]. PMID 23621620 [archive].
- ↑ Fritz H, Flower G, Weeks L, Cooley K, Callachan M, McGowan J, et al. (July 2014). "Intravenous Vitamin C and Cancer: A Systematic Review" [archive]. Integrative Cancer Therapies. 13 (4): 280–300. doi:10.1177/1534735414534463 [archive]. PMID 24867961 [archive].
- ↑ Tetef M, Margolin K, Ahn C, Akman S, Chow W, Leong L, et al. (1995). "Mitomycin C and menadione for the treatment of lung cancer: a phase II trial". Investigational New Drugs. 13 (2): 157–162. doi:10.1007/BF00872865 [archive]. PMID 8617579 [archive]. S2CID 10086469 [archive].
- ↑ Margolin KA, Akman SA, Leong LA, Morgan RJ, Somlo G, Raschko JW, et al. (1995). "Phase I study of mitomycin C and menadione in advanced solid tumors". Cancer Chemotherapy and Pharmacology. 36 (4): 293–298. doi:10.1007/BF00689046 [archive]. PMID 7628048 [archive]. S2CID 7283959 [archive].
- ↑ Borst P (December 2008). "Mega-dose vitamin C as therapy for human cancer?" [archive]. Proceedings of the National Academy of Sciences of the United States of America. 105 (48): E95, author reply E96. Bibcode:2008PNAS..105E..95B [archive]. doi:10.1073/pnas.0809328105 [archive]. PMC 2596258 [archive]. PMID 19033231 [archive].
See also
- Big Pharma
- Bill Gates
- Bioweapon
- Experimental coronavirus vaccines
- HIV/AIDS
- HPV vaccine
- Immune system and COVID-19
- Impact of the COVID-19 pandemic on religion
- Pharmedia
- Smallpox
- Tablighi Jamaat coronavirus hotspot in Delhi
- Vaccine
- Vitamin A
- Vitamin C
- Vitamin D
- Western medicine
- World Health Organization
- Zinc
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- https://www.dailymail.co.uk/health/article-10776301/Taking-vitamins-liquid-form-means-theyre-absorbed-worth-it.html [archive]
- Quackwatch article critical of megadosing for cold prevention [archive], Charles W. Marshall, Ph.D. Accessed 2016-06-02.
https://chrismasterjohnphd.substack.com/p/cancer-iv-drips-and-the-glutathione [archive]
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