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Vitamin C

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102-419: 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

204-438: A starch indicator . Iodine is reduced by ascorbic acid, and when all the ascorbic acid has reacted, the iodine is in excess, forming a blue-black complex with the starch indicator. This indicates the end-point of the titration. As an alternative, ascorbic acid can be treated with iodine in excess, followed by back titration with sodium thiosulfate using starch as an indicator. This iodometric method has been revised to exploit

306-403: A 1,3-diketone: The ascorbate ion is the predominant species at typical biological pH values. It is a mild reducing agent and antioxidant . It is oxidized with loss of one electron to form a radical cation and then with loss of a second electron to form dehydroascorbic acid . It typically reacts with oxidants of the reactive oxygen species , such as the hydroxyl radical . Ascorbic acid

408-446: A blue hue. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it. They secrete two chemicals that aid in the body's defenses: histamine and heparin . Histamine is responsible for widening blood vessels and increasing the flow of blood to injured tissue. It also makes blood vessels more permeable so neutrophils and clotting proteins can get into connective tissue more easily. Heparin

510-445: A cofactor for the following enzymes : 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 . In the eye, ascorbate is thought to protect against photolytically generated free-radical damage; higher plasma ascorbate

612-401: A day. Treatment of scurvy can be with vitamin   C-containing foods or dietary supplements or injection. Chemistry of ascorbic acid Ascorbic acid is an organic compound with formula C 6 H 8 O 6 , originally called hexuronic acid . It is a white solid, but impure samples can appear yellowish. It dissolves freely in water to give mildly acidic solutions. It

714-404: 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 ;

816-481: 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. It is on the World Health Organization's List of Essential Medicines and on

918-400: 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. Plasma vitamin C is the most widely applied test for vitamin C status. Adequate levels are defined as near 50 μmol/L. Hypovitaminosis of vitamin C

1020-573: 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 . 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

1122-573: A multi-vitamin/mineral supplement that included vitamin C, and that for these people total consumption was between 300 and 400 mg/d. 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

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1224-550: A potentially dangerous pro-oxidative compound in certain metabolic contexts. Ascorbic acid and its sodium, potassium, and calcium salts are commonly used as antioxidant food additives . These compounds are water-soluble and, thus, cannot protect fats from oxidation: For this purpose, the fat- soluble esters of ascorbic acid with long-chain fatty acids (ascorbyl palmitate or ascorbyl stearate) can be used as antioxidant food additives. It creates volatile compounds when mixed with glucose and amino acids at 90 °C. It

1326-424: 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 . In plants, synthesis is accomplished through the conversion of mannose or galactose to ascorbic acid. In animals, the starting material is glucose . In some species that synthesize ascorbate in the liver (including mammals and perching birds ),

1428-406: 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. 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). It has also been noted that

1530-423: A similar effect in food despite their lack of efficacy in humans. They include erythorbic acid and its sodium salt (E315, E316). 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 includes enzymes for which vitamin C is a cofactor, with function potentially compromised in

1632-528: A thin strand. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin staining. Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing the dilation of blood vessels . Because they are the rarest of the white blood cells (less than 0.5% of the total count) and share physicochemical properties with other blood cells, they are difficult to study. They can be recognized by several coarse, dark violet granules, giving them

1734-590: A weakened immune system. The name "white blood cell" derives from the physical appearance of a blood sample after centrifugation . White cells are found in the buffy coat , a thin, typically white layer of nucleated cells between the sedimented red blood cells and the blood plasma . The scientific term leukocyte directly reflects its description. It is derived from the Greek roots leuk - meaning "white" and cyt - meaning "cell". The buffy coat may sometimes be green if there are large amounts of neutrophils in

1836-522: Is qualitatively . There are various disorders in which the number of white blood cells is normal but the cells do not function normally. Neoplasia of white blood cells can be benign but is often malignant . Of the various tumors of the blood and lymph , cancers of white blood cells can be broadly classified as leukemias and lymphomas , although those categories overlap and are often grouped together. A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased

1938-448: Is a furan -based lactone of 2-ketogluconic acid . It contains an adjacent enediol adjacent to the carbonyl . This −C(OH)=C(OH)−C(=O)− structural pattern is characteristic of reductones , and increases the acidity of one of the enol hydroxyl groups . The deprotonated conjugate base is the ascorbate anion, which is stabilized by electron delocalization that results from resonance between two forms: For this reason, ascorbic acid

2040-609: Is a cofactor in tyrosine oxidation . The main use of l -ascorbic acid and its salts is as food additives, mostly to combat oxidation. It is approved for this purpose in the EU with E number E300, the US, Australia, and New Zealand. Another major use of l -ascorbic acid is as a dietary supplement . It is on the World Health Organization's List of Essential Medicines . Natural biosynthesis of vitamin C occurs through various processes in many plants and animals. Seventy percent of

2142-448: Is a mild reducing agent . Ascorbic acid exists as two enantiomers (mirror-image isomers ), commonly denoted " l " (for "levo") and " d " (for "dextro"). The l isomer is the one most often encountered: it occurs naturally in many foods, and is one form (" vitamer ") of vitamin C , an essential nutrient for humans and many animals. Deficiency of vitamin C causes scurvy , formerly a major disease of sailors in long sea voyages. It

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2244-523: Is a well-established mechanism of iron reduction and a step obligatory for iron uptake. 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. 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. This biosynthesis

2346-436: Is absorbed in the body by both active transport and passive diffusion. Approximately 70%–90% of vitamin C is active-transport absorbed when intakes of 30–180 mg/day from a combination of food sources and moderate-dose dietary supplements such as a multi-vitamin/mineral product are consumed. However, when large amounts are consumed, such as a vitamin C dietary supplement, the active transport system becomes saturated, and while

2448-470: Is an anticoagulant that inhibits blood clotting and promotes the movement of white blood cells into an area. Basophils can also release chemical signals that attract eosinophils and neutrophils to an infection site. Lymphocytes are much more common in the lymphatic system than in blood. Lymphocytes are distinguished by having a deeply staining nucleus that may be eccentric in location, and a relatively small amount of cytoplasm. Lymphocytes include: Monocytes,

2550-421: Is an important subset of the complete blood count . The normal white cell count is usually between 4 × 10 /L and 1.1 × 10 /L. In the US, this is usually expressed as 4,000 to 11,000 white blood cells per microliter of blood. White blood cells make up approximately 1% of the total blood volume in a healthy adult, making them substantially less numerous than the red blood cells at 40% to 45% . However, this 1% of

2652-657: 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. Most animals and plants are able to synthesize vitamin C through

2754-448: Is associated with lower risk of cataracts. Ascorbate may also provide antioxidant protection indirectly by regenerating other biological antioxidants such as α-tocopherol back to an active state. 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. Ascorbic acid

2856-444: Is at 200–300 μmol/L. 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. Excretion (via urine)

2958-638: Is by lineage: Myeloid cells (neutrophils, monocytes, eosinophils and basophils) are distinguished from lymphoid cells (lymphocytes) by hematopoietic lineage ( cellular differentiation lineage). Lymphocytes can be further classified as T cells, B cells, and natural killer cells. Neutrophils are the most abundant white blood cell, constituting 60–70% of the circulating leukocytes. They defend against bacterial or fungal infection. They are usually first responders to microbial infection; their activity and death in large numbers form pus . They are commonly referred to as polymorphonuclear (PMN) leukocytes, although, in

3060-424: Is defined as less than 23 μmol/L, and deficiency as less than 11.4 μmol/L. 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%. Globally, vitamin C deficiency is common in low and middle-income countries, and not uncommon in high income countries. In

3162-437: 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. Vitamin C chemically decomposes under certain conditions, many of which may occur during

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3264-426: Is less frequently used now. Produced in the bone marrow , white blood cells defend the body against infections and disease . An excess of white blood cells is usually due to infection or inflammation. Less commonly, a high white blood cell count could indicate certain blood cancers or bone marrow disorders. The number of leukocytes in the blood is often an indicator of disease , and thus the white blood cell count

3366-446: Is low, as cells rapidly reduce DHA to ascorbate. SVCTs are the predominant system for vitamin C transport within the body. 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

3468-427: Is most commonly caused by inflammation . There are four major causes: increase of production in bone marrow, increased release from storage in bone marrow, decreased attachment to veins and arteries, decreased uptake by tissues. Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis. Neutrophilia is an increase in the absolute neutrophil count in

3570-413: Is much more acidic than would be expected if the compound contained only isolated hydroxyl groups. The ascorbate anion forms salts , such as sodium ascorbate , calcium ascorbate , and potassium ascorbate . Ascorbic acid can also react with organic acids as an alcohol forming esters such as ascorbyl palmitate and ascorbyl stearate . Nucleophilic attack of ascorbic acid on a proton results in

3672-472: Is not complete. Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity. Treatment is also aimed at the underlying cause of the neutropenia. One severe consequence of neutropenia is that it can increase the risk of infection. Defined as total lymphocyte count below 1.0x10 /L,

3774-536: 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

3876-453: 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

3978-601: Is regulated following a diurnal rhythm . Enzyme expression peaks in the morning to supporting biosynthesis for when mid-day sunlight intensity demands high ascorbic acid concentrations. 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. Vitamin C can be produced from glucose by two main routes. The no longer utilized Reichstein process , developed in

4080-426: Is special because it can transfer a single electron, owing to the resonance-stabilized nature of its own radical ion , called semidehydroascorbate . The net reaction is: On exposure to oxygen , ascorbic acid will undergo further oxidative decomposition to various products including diketogulonic acid , xylonic acid , threonic acid and oxalic acid . Reactive oxygen species are damaging to animals and plants at

4182-446: Is that inhalation of smoke causes oxidative damage, depleting this antioxidant vitamin. 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. 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

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4284-560: Is then discarded." 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 . It may be used as a flour treatment agent used in breadmaking . As food additives, they are assigned E numbers , with safety assessment and approval the responsibility of the European Food Safety Authority . The relevant E numbers are: The stereoisomers of Vitamin C have

4386-428: Is used as a food additive and a dietary supplement for its antioxidant properties. The " d " form can be made via chemical synthesis , but has no significant biological role. The antiscorbutic properties of certain foods were demonstrated in the 18th century by James Lind . In 1907, Axel Holst and Theodor Frølich discovered that the antiscorbutic factor was a water-soluble chemical substance, distinct from

4488-458: Is used in the predominant process used by the ascorbic acid industry in China, which supplies 70% of the world's ascorbic acid. Researchers are exploring means for one-step fermentation. The traditional way to analyze the ascorbic acid content is by titration with an oxidizing agent , and several procedures have been developed. The popular iodometry approach uses iodine in the presence of

4590-553: 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, but these analysis are difficult to measure, and hence not part of standard diagnostic testing. Recommendations for vitamin C intake by adults have been set by various national agencies: In 2000,

4692-418: Is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen. Neutropenia can be acquired or intrinsic . A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. The following list of causes

4794-683: 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. 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

4896-464: The peripheral circulation . Normal blood values vary by age. Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation. Primary causes Secondary causes A normal eosinophil count is considered to be less than 0.65 × 10 /L. Eosinophil counts are higher in newborns and vary with age, time (lower in

4998-683: 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. 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

5100-661: 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. Cigarette smokers and people exposed to secondhand smoke have lower serum vitamin C levels than nonsmokers. The thinking

5202-758: The United States provides rations to international food relief programs, later under the auspices of the Food for Peace Act and the Bureau for Humanitarian Assistance. 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. The report adds: "The stability of vitamin C (L-ascorbic acid)

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5304-460: 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. The same survey stated that about 30% of adults reported they consumed a vitamin C dietary supplement or

5406-603: The World Health Organization's Model Forumulary. In 2021, it was the 255th most commonly prescribed medication in the United States, with more than 1   million prescriptions. 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

5508-408: The ability to internally synthesize vitamin C in either the kidney or the liver. 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. One explanation for

5610-610: 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 . Synthesis does not occur in most bat species, 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. 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

5712-400: The ability was lost separately a number of times in birds. In particular, the ability to synthesize vitamin C is presumed to have been lost and then later re-acquired in at least two cases. The ability to synthesize vitamin   C has also been lost in about 96% of extant fish (the teleosts ). On a milligram consumed per kilogram of body weight basis, simian non-synthesizer species consume

5814-685: 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. 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

5916-603: 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. According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 million years ago. Approximately three to five million years later (58 million years ago), only

6018-607: The bleaching solution. Acid-catalyzed hydrolysis of this product performs the dual function of removing the two acetal groups and ring-closing lactonization . This step yields ascorbic acid. Each of the five steps has a yield larger than 90%. A biotechnological process, first developed in China in the 1960s but further developed in the 1990s, bypassing acetone-protecting groups. A second genetically modified microbe species, such as mutant Erwinia , among others, oxidises sorbose into 2-ketogluconic acid (2-KGA), which can then undergo ring-closing lactonization via dehydration. This method

6120-404: The blood makes a large difference to health, because immunity depends on it. An increase in the number of leukocytes over the upper limits is called leukocytosis . It is normal when it is part of healthy immune responses, which happen frequently. It is occasionally abnormal, when it is neoplastic or autoimmune in origin. A decrease below the lower limit is called leukopenia . This indicates

6222-496: The body against both infectious disease and foreign invaders. White blood cells are generally larger than red blood cells. They include three main subtypes: granulocytes , lymphocytes and monocytes . All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells . Leukocytes are found throughout the body, including the blood and lymphatic system . All white blood cells have nuclei , which distinguishes them from

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6324-406: The cells most commonly affected are CD4+ T cells. Like neutropenia, lymphocytopenia may be acquired or intrinsic and there are many causes. This is not a complete list. Like neutropenia, symptoms and treatment of lymphocytopenia are directed at the underlying cause of the change in cell counts. An increase in the number of white blood cells in circulation is called leukocytosis . This increase

6426-595: 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. The table (right) shows RDAs for the United States and Canada for children, and for pregnant and lactating women, as well as

6528-556: The cofactor FAD+. This reaction produces 2-oxogulonolactone (2-keto-gulonolactone), which spontaneously undergoes enolization to form ascorbic acid. 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. 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

6630-414: The cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature at which they are stored. Cooking can reduce the vitamin C content of vegetables by around 60%, possibly due to increased enzymatic destruction. Longer cooking times may add to this effect. Another cause of vitamin   C loss from food is leaching , which transfers vitamin   C to

6732-522: The cooking water, which is decanted and not consumed. Vitamin C dietary supplements are available as tablets, capsules, drink mix packets, in multi-vitamin/mineral formulations, in antioxidant formulations, and as crystalline powder. 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. Vitamin C molecules can also be bound to

6834-768: The day, seasonally, and during menstruation . It rises in response to allergies, parasitic infections, collagen diseases, and disease of the spleen and central nervous system. They are rare in the blood, but numerous in the mucous membranes of the respiratory, digestive, and lower urinary tracts. They primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and parasitic infections. They secrete chemicals that destroy large parasites, such as hookworms and tapeworms, that are too big for any one white blood cell to phagocytize. In general, their nuclei are bi-lobed. The lobes are connected by

6936-405: 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

7038-469: The disease the damage is reversible, as healthy collagen replaces the defective collagen with vitamin   C repletion. 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

7140-457: The fatty acid palmitate, creating ascorbyl palmitate , or else incorporated into liposomes. Countries fortify foods with nutrients to address known deficiencies. While many countries mandate or have voluntary programs to fortify wheat flour, maize (corn) flour or rice with vitamins, none include vitamin C in those programs. As described in Vitamin C Fortification of Food Aid Commodities (1997),

7242-635: The five main types: neutrophils , eosinophils , basophils , lymphocytes , and monocytes . A good way to remember the relative proportions of WBCs is "Never Let Monkeys Eat Bananas". These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic . Further subtypes can be classified. Granulocytes are distinguished from agranulocytes by their nucleus shape (lobed versus round, that is, polymorphonuclear versus mononuclear) and by their cytoplasm granules (present or absent, or more precisely, visible on light microscopy or not thus visible). The other dichotomy

7344-451: 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

7446-680: The glucose is extracted from glycogen ; ascorbate synthesis is a glycogenolysis-dependent process. 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. 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. A report on goats, sheep and cattle reported ranges of 100–110, 265–270 and 160–350 μmol/L, respectively. The biosynthesis of ascorbic acid in vertebrates starts with

7548-524: The glucose starting point. Researchers are exploring means for one-step fermentation. 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. Cost per metric ton (1000 kg) in US dollars was $ 2,220 in Shanghai, $ 2,850 in Hamburg and $ 3,490 in the US. Vitamin C has

7650-539: The largest type of white blood cell, share the "vacuum cleaner" ( phagocytosis ) function of neutrophils, but are much longer lived as they have an extra role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed. This causes an antibody response to be mounted. Monocytes eventually leave the bloodstream and become tissue macrophages , which remove dead cell debris as well as attack microorganisms. Neither dead cell debris nor attacking microorganisms can be dealt with effectively by

7752-416: The latter, prevalence is higher in males than in females. 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. Vitamin C content in plasma

7854-655: The liver, which become known as Kupffer cells . These cells still serve a role in the immune system. The two commonly used categories of white blood cell disorders divide them quantitatively into those causing excessive numbers ( proliferative disorders) and those causing insufficient numbers ( leukopenias ). Leukocytosis is usually healthy (e.g., fighting an infection ), but it also may be dysfunctionally proliferative. Proliferative disorders of white blood cells can be classed as myeloproliferative and lymphoproliferative . Some are autoimmune , but many are neoplastic . Another way to categorize disorders of white blood cells

7956-679: 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. 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. The principal plant ascorbic acid biosynthesis pathway seems to be via l -galactose. The enzyme l -galactose dehydrogenase catalyzes

8058-489: The molecular level due to their possible interaction with nucleic acids , proteins, and lipids. Sometimes these radicals initiate chain reactions. Ascorbate can terminate these chain radical reactions by electron transfer . The oxidized forms of ascorbate are relatively unreactive and do not cause cellular damage. However, being a good electron donor, excess ascorbate in the presence of free metal ions can not only promote but also initiate free radical reactions, thus making it

8160-448: The morning and higher at night), exercise, environment, and exposure to allergens. Eosinophilia is never a normal lab finding. Efforts should always be made to discover the underlying cause, though the cause may not always be found. The complete blood cell count is a blood panel that includes the overall white blood cell count and differential count, a count of each type of white blood cell. Reference ranges for blood tests specify

8262-504: The neutrophils. Unlike neutrophils, monocytes are able to replace their lysosomal contents and are thought to have a much longer active life. They have the kidney-shaped nucleus and are typically not granulated. They also possess abundant cytoplasm. Some leucocytes migrate into the tissues of the body to take up a permanent residence at that location rather than remaining in the blood. Often these cells have specific names depending upon which tissue they settle in, such as fixed macrophages in

8364-423: 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. Numerous analytical methods have been developed for ascorbic acid detection. For example, vitamin C content of

8466-451: The one that prevented beriberi . Between 1928 and 1932, Albert Szent-Györgyi isolated a candidate for this substance, which he called it "hexuronic acid", first from plants and later from animal adrenal glands. In 1932 Charles Glen King confirmed that it was indeed the antiscorbutic factor. In 1933, sugar chemist Walter Norman Haworth , working with samples of "hexuronic acid" that Szent-Györgyi had isolated from paprika and sent him in

8568-1081: The other blood cells , the anucleated red blood cells (RBCs) and platelets . The different white blood cells are usually classified by cell lineage ( myeloid cells or lymphoid cells ). White blood cells are part of the body's immune system. They help the body fight infection and other diseases. Types of white blood cells are granulocytes (neutrophils, eosinophils, and basophils), and agranulocytes ( monocytes , and lymphocytes (T cells and B cells)). Myeloid cells ( myelocytes ) include neutrophils , eosinophils , mast cells , basophils , and monocytes . Monocytes are further subdivided into dendritic cells and macrophages . Monocytes, macrophages, and neutrophils are phagocytic . Lymphoid cells ( lymphocytes ) include T cells (subdivided into helper T cells , memory T cells , cytotoxic T cells ), B cells (subdivided into plasma cells and memory B cells ), and natural killer cells . Historically, white blood cells were classified by their physical characteristics ( granulocytes and agranulocytes ), but this classification system

8670-478: The overall oxidation to the lactone and isomerization of the lactone to the C4-hydroxyl group, resulting in l -galactono-1,4-lactone. l -Galactono-1,4-lactone then reacts with the mitochondrial flavoenzyme l -galactonolactone dehydrogenase to produce ascorbic acid. l -Ascorbic acid has a negative feedback on l -galactose dehydrogenase in spinach. Ascorbic acid efflux by embryos of dicot plants

8772-461: The presence of potassium iodide and starch. The NBS first oxidizes the ascorbic acid; when the latter is exhausted, the NBS liberates the iodine from the potassium iodide, which then forms the blue-black complex with starch. Leukocyte White blood cells (scientific name leukocytes ), also called immune cells or immunocytes , are cells of the immune system that are involved in protecting

8874-547: The previous year, deduced the correct structure and optical-isomeric nature of the compound, and in 1934 reported its first synthesis. In reference to the compound's antiscorbutic properties, Haworth and Szent-Györgyi proposed to rename it "a-scorbic acid" for the compound, and later specifically l -ascorbic acid. Because of their work, in 1937 two Nobel Prizes : in Chemistry and in Physiology or Medicine were awarded to Haworth and Szent-Györgyi, respectively. Ascorbic acid

8976-475: The product with acetone in the presence of an acid catalyst converts four of the remaining hydroxyl groups to acetals . The unprotected hydroxyl group is oxidized to the carboxylic acid by reaction with the catalytic oxidant TEMPO (regenerated by sodium hypochlorite  – bleaching solution). Historically, industrial preparation via the Reichstein process used potassium permanganate as

9078-498: The pus of wounds. These cells are not able to renew their lysosomes (used in digesting microbes) and die after having phagocytosed a few pathogens. Neutrophils are the most common cell type seen in the early stages of acute inflammation. The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours. Eosinophils compose about 2–4% of white blood cells in circulating blood. This count fluctuates throughout

9180-416: The reaction of ascorbic acid with iodate and iodide in acid solution. Electrolyzing the potassium iodide solution produces iodine, which reacts with ascorbic acid. The end of the process is determined by potentiometric titration like Karl Fischer titration . The amount of ascorbic acid can be calculated by Faraday's law . Another alternative uses N -bromosuccinimide (NBS) as the oxidizing agent in

9282-587: The recommended dietary intake for adult humans is in the range of 1–2 mg/kg. 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

9384-461: 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. 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

9486-436: 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. 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

9588-467: The sample, due to the heme -containing enzyme myeloperoxidase that they produce. All white blood cells are nucleated, which distinguishes them from the anucleated red blood cells and platelets. Types of leukocytes can be classified in standard ways. Two pairs of broadest categories classify them either by structure ( granulocytes or agranulocytes ) or by cell lineage (myeloid cells or lymphoid cells). These broadest categories can be further divided into

9690-450: 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. At non-physiological concentrations achieved by intravenous dosing, vitamin C may function as a pro-oxidant , with therapeutic toxicity against cancer cells. Vitamin C functions as

9792-445: The technical sense, PMN refers to all granulocytes. They have a multi-lobed nucleus, which consists of three to five lobes connected by slender strands. This gives the neutrophils the appearance of having multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules that are pale lilac when stained. Neutrophils are active in phagocytosing bacteria and are present in large amount in

9894-497: The total amount being absorbed continues to increase with dose, absorption efficiency falls to less than 50%. Active transport is managed by Sodium-Ascorbate Co-Transporter proteins (SVCTs) and Hexose Transporter proteins (GLUTs). SVCT1 and SVCT2 import ascorbate across plasma membranes. The Hexose Transporter proteins GLUT1 , GLUT3 and GLUT4 transfer only the oxydized dehydroascorbic acid (DHA) form of vitamin C. The amount of DHA found in plasma and tissues under normal conditions

9996-541: 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

10098-457: The vitamin in amounts 10 to 20 times higher than what is recommended by governments for humans. This discrepancy constituted some of the basis of the controversy on human recommended dietary allowances being set too low. 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. By way of comparison, across several countries,

10200-481: The world's supply of ascorbic acid is produced in China. Ascorbic acid is prepared in industry from glucose in a method based on the historical Reichstein process . In the first of a five-step process, glucose is catalytically hydrogenated to sorbitol , which is then oxidized by the microorganism Acetobacter suboxydans to sorbose . Only one of the six hydroxy groups is oxidized by this enzymatic reaction. From this point, two routes are available. Treatment of

10302-527: Was set at 80 mg in 2011. Although also present in other plant-derived foods, the richest natural sources of vitamin C are fruits and vegetables. Vitamin C is the most widely taken dietary supplement . The following table is approximate and shows the relative abundance in different raw plant sources. The amount is given in milligrams per 100 grams of the edible portion of the fruit or vegetable: Compared to plant sources, animal-sourced foods do not provide so great an amount of vitamin C, and what there

10404-683: 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. 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, as did the Japan National Institute of Health and Nutrition in 2010. For US food and dietary supplement labeling purposes,

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