Vitamin C (ascorbic acid) is an easy low-molecular-weight carbohydrate with an ene-diol construction that has made it a ubiquitous and important water-soluble electron donor in nature. It’s synthesized by all species aside from higher-order primates, guinea pigs, and a few bat, fish, and chook species. In the entire latter, the gene encoding for i-gulonolactone oxidase—the enzyme catalyzing the ultimate step within the biosynthesis of ascorbic acid—has advanced right into a nonfunctional state as a consequence of accumulation of mutations and/or deletions; consequently, these species depend on an sufficient provide of vitamin C from their food plan.
In all its identified biologic capabilities, vitamin C acts as a reductant, i.e., it donates an electron to a substrate whereas itself being oxidized to an ascorbyl radical, a comparatively secure free radical. Two molecules of ascorbyl free radical can dismutate into 1 molecule of ascorbate and 1 molecule of dehydroascorbic acid, the totally decreased and oxidized types of vitamin C, respectively. To reduce the lack of vitamin C by metabolism and excretion, environment friendly retaining mechanisms have advanced, together with ascorbate recycling, through which dehydroascorbic acid is quickly decreased to ascorbate intracellularly by glutathione (one other mobile reductant) or the selenoenzyme, thioredoxin reductase, and energetic renal reabsorption by the sodium-dependent vitamin C transporter (SVCT)2 1. Vitamin C absorption, tissue distribution, and excretion are tightly managed by tissue-specific, energetic transport by SVCT1 and SVCT2. If vitamin C consumption in people is in extra of ∼400 mg/d, a homeostatic state is reached with maximal plasma steady-state concentrations of ∼60 to 90 μmol/L and intracellular concentrations starting from 0.5 to 10 mmol/L, relying on the tissue. The best concentrations of vitamin C are discovered within the mind, eye, and adrenal gland.
The biologic function of vitamin C is expounded to its decreased kind, ascorbate, and might be separated into enzymatic and nonenzymatic capabilities. One of the best-known enzymatic perform of vitamin C might be as cofactor for the ferrous [Fe(II)] and 2-oxoglutarate dependent dioxygenases in collagen synthesis. These enzymes catalyze the hydroxylation of lysine and proline residues in unfolded procollagen chains, that are the constructing blocks of the triple-helical construction of mature, useful collagen. Ascorbate additionally serves as an electron donor for numerous enzymes catalyzing carnitine and norepinephrine biosynthesis, peptide hormone amidation, and tyrosine metabolism. Ascorbate-mediated hydroxylation of hypoxia inducible issue 1α (HIF-1α) regulates the transcription of a number of genes encoding proteins concerned in iron homeostasis, angiogenesis, and cell proliferation.
Extra not too long ago, a number of research have proven that vitamin C performs an essential function in vascular perform. Ascorbate modulates vasorelaxation by rising NO synthesis or bioavailability in a lot of methods (1). Endothelial NO synthase (eNOS) generates NO, which diffuses to the graceful muscle cell layer of the vascular wall and mediates dilation by its interplay with soluble guanylyl cyclase. Tetrahydrobiopterin is a cofactor for eNOS exercise, and vitamin C seems to recycle tetrahydrobiopterin from its oxidized kind(s), thereby sustaining the enzyme’s exercise. Furthermore, vitamin C might have an effect on NO bioavailability by ascorbate-mediated denitrosylation and phosphorylation of eNOS. Different roles of vitamin C in vascular perform embrace modulating the endothelial cell barrier and regulating the exercise of NADPH oxidases (NOXs) concerned in inflammatory gene response.
Along with its roles within the above enzymatic processes, ascorbate is a strong antioxidant with the flexibility to cut back or “scavenge” many (patho)physiologically related free radicals and reactive oxygen species. As well as, vitamin C can regenerate vitamin E (α-tocopherol) from its oxidized kind (α-tocopheroxyl radical), permitting vitamin C to not directly inhibit lipid peroxidation. Ascorbate may also cut back urate and glutathione radicals as a part of the antioxidant community in cells and extracellular fluids. Though the medical significance of ascorbate’s antioxidant motion is troublesome to evaluate, a substantial experimental literature has proven that vitamin C successfully protects biologic macromolecules from oxidative harm that may in any other case causally contribute to the initiation and development of a number of persistent and acute ailments (2).
Deficiency
The medical hallmark of extreme and extended vitamin C deficiency is scurvy, which is deadly if left untreated. The signs of impaired wound therapeutic, gingivitis, perifollicular hemorrhages, ecchymoses, and petechiae have been identified for hundreds of years and are largely associated to impaired collagen biosynthesis and maybe HIF-1α hydroxylation. Different signs of extreme vitamin C deficiency are malaise and fatigue or lethargy, which can be troublesome to diagnose clinically. These signs might be defined by impaired carnitine biosynthesis leading to decreased fatty acid transport and subsequent β-oxidation in mitochondria required for ATP manufacturing and decreased synthesis of the neurotransmitter norepinephrine. The enzymatic synthesis of each carnitine and norepinephrine entails hydroxylation steps that rely on vitamin C for full enzyme exercise (2). Whereas vitamin C deficiency is principally attributable to poor food plan, a number of extra threat components have been recognized, together with smoking, being pregnant, low socioeconomic standing, genetic predisposition, previous or younger age, strenuous train, and medical circumstances related to metabolic syndrome, reminiscent of hypertension, diabetes, and weight problems.
Dietary Suggestions
Based mostly on the vitamin C consumption required to attain near-saturation of plasma and leukocytes with minimal urinary excretion, and adjusted for physique mass, an RDA of 75 and 90 mg/d for ladies and men, respectively, was established by the U.S. Institute of Drugs (IOM) in 2000. As well as, the RDA for pregnant and breastfeeding girls (≥19 y) was set at 85 and 120 mg/d, respectively. No RDA was established for infants; as a substitute, the Ample Consumption of vitamin C was set at 40 mg/d for infants as much as 6 mo of age, and 50 mg/d for infants as much as 12 mo. For older kids, the advice is predicated on estimated physique mass in relation to an grownup: 15 mg/d for kids as much as 3 y of age, 25 mg/d for kids as much as 8 y, and 45 mg/d for kids as much as 13 y. The RDA for youngsters is predicated on gender: 75 and 65 mg/d for girls and boys 13–17 y of age, respectively (3).
It has lengthy been acknowledged that people who smoke and people uncovered to environmental tobacco smoke (“passive” people who smoke) have a decrease vitamin C standing than nonsmokers. That is believed to be partly as a consequence of poor dietary habits but additionally because of the oxidizing properties of tobacco smoke per se, leading to an elevated turnover of vitamin C. Consequently, the IOM recommends that people who smoke get a further 35 mg/d of vitamin C. No elevated RDA has been established for passive people who smoke, however they’re strongly inspired to make sure that they meet the usual RDA.
Latest knowledge counsel that the present RDA for vitamin C set by the IOM for women and men could also be too low. On the premise of a complete assessment of the scientific proof from human metabolic, pharmacokinetic, and observational research in addition to section 2 randomized managed trials, it was concluded that 200 mg/d is the optimum consumption of vitamin C for almost all of the grownup inhabitants to maximise the vitamin’s potential well being advantages with the least threat of inadequacy or opposed well being results (4).
Meals Sources
Fruit and greens are good sources of vitamin C, and ~90% of the every day consumption within the basic inhabitants comes from these sources. The content material varies between species, however citrus fruit, kiwi, mango, and greens reminiscent of broccoli, tomatoes, and peppers are all wealthy sources of vitamin C. As a result of vitamin C degrades when heated and through storage, the processing and preparation procedures ought to be thought of when estimating dietary consumption of vitamin C. A complete of 5–9 servings of recent, minimally processed, or frozen fruit and greens per day is estimated to equal ~200 mg of vitamin C. The presence of vitamin C in dietary merchandise apart from fruit and greens is usually as a consequence of its addition as a preservative to processed meals to guard in opposition to oxidation. In areas the place vegetation is sparse, such because the arctic areas, individuals have historically relied on various sources of vitamin C, reminiscent of medicinal herbs (natural teas and tinctures from rose hips, pine needles, and tree barks) and animal organs, reminiscent of uncooked liver and whale pores and skin.
Medical Makes use of – “vitamin c ncbi”
The present RDA for vitamin C largely exceeds the quantity crucial to stop scurvy (~10 mg/d). Nonetheless, given the doable severity of occasions related to scurvy, pressing substitute remedy is recommended when medical indicators or signs of vitamin C deficiency are recognized. Oral supplementation with 500 mg/d will likely be sufficient in milder instances, however parenteral remedy could also be required in extreme instances and in instances of impaired intestinal perform or lack of compliance. Subclinical vitamin C deficiency is troublesome to detect as a result of the everyday signs, fatigue and lassitude, are nonspecific. Overt vitamin C deficiency might be seen in malnourished populations, together with these with persistent circumstances, poor dietary habits, malabsorption, or chemical dependencies.
A substantial epidemiologic literature has discovered associations between poor vitamin C standing and elevated threat of growing cardiovascular ailments (CVDs), together with coronary coronary heart illness, ischemic stroke, and hypertension (5). These with near-saturated plasma vitamin C concentrations seem to have the bottom CVD threat, suggesting that intakes larger than the RDA are required to attain these well being advantages. Nonetheless, correctly designed randomized managed trials haven’t but been carried out to both verify or reject a causal hyperlink between vitamin C standing and CVD. Thus, prophylactic supplementation of high-risk people is just not presently beneficial by the medical group. In distinction, a substantial variety of giant intervention research have confirmed that supplementation of already well-nourished people has no extra well being advantages.
One other medical use of vitamin C is to extend nonheme-iron absorption. Within the small gut, vitamin C reduces dietary iron and permits for environment friendly transport throughout the intestinal epithelium. Meals sources of vitamin C or dietary supplements, when consumed with iron, might result in elevated hemoglobin manufacturing in anemic sufferers. Latest work on the NIH and the College of Iowa has recommended that gram-doses of intravenously administered vitamin C might have advantage in most cancers remedy along with customary chemotherapy. This helpful impact of intravenous vitamin C could also be as a consequence of ascorbate autooxidation and the era of hydrogen peroxide, which is selectively poisonous to most cancers cells.
Toxicity
Vitamin C is mostly secure and nicely tolerated, even in giant doses. The IOM set the Tolerable Higher Consumption Degree for oral vitamin C ingestion at 2 g every day for adults primarily based on gastrointestinal disturbances noticed in some people at increased doses. Excessive quantities of vitamin C consumption have been related to an elevated threat of kidney stones, though the proof is combined and inconsistent. The present suggestion is to keep away from vitamin C supplementation in these prone to kidney stone formation. Vitamin C consumed with iron might improve the chance of iron overload in prone people. Sufferers with these circumstances mustn’t keep away from consuming fruit and greens however restrict their consumption of iron as a substitute. Vitamin C has been reported to trigger hemolysis in people with glucose-6-phosphate dehydrogenase deficiency, however these reviews haven’t been substantiated.
Latest Analysis
The so-called antioxidant speculation of the Nineteen Eighties promising an extended and wholesome life from an ample consumption of antioxidants, together with vitamin C, has lengthy been changed by the view that the well being advantages of vitamin C are derived from its function in a lot of key reactions inside immune perform, metabolism, and different enzymatic and nonenzymatic reactions (see above). Thus, rising proof signifies that even marginal vitamin C deficiency might impair regular perinatal neurogenesis, have an effect on fetal programming of grownup illness threat, and improve the chance of cardiovascular and all-cause mortality. A number of genetic variants have been recognized in SVCTs, haptoglobin, and glutathione S-transferases that will affect plasma vitamin C standing or uptake into tissues. Newer research have investigated how these polymorphisms might work together with low dietary vitamin C concentrations to extend persistent illness threat (6).
“vitamin c ncbi”