Vitamin C: update on physiology and pharmacology

Km: 65–237 µM) ascorbate transporter and is largely present in epithelial tissuesnHighlight:the prevention of scurvy. However, intake of as little as 10 mg·day−1 of vitamin C is appropriate for this purposenHighlight:In normoxia, HIFs are inactive because of the oxygen- (and ascorbate-) dependent hydroxylation and subsequent degradation of the α-subunitnHighlight:GLOnHighlight:is retained and converted to insoluble oxalate, which can accumulate in various organsnHighlight:An elevated level of ascorbate in the intestinal lumen led to down-regulation of SVCT1 mRNA in enterocytes (MacDonald et al., 2002). A similar self-regulatory role for ascorbate was demonstrated for SVCT2 in plateletsnHighlight:Iron in these enzymes is maintained in the active Fe(II) form by ascorbatenHighlight:vitamin C enters mitochondria as dehydroascorbic acid (DHA)nHighlight:The maintenance of the intramitochondrial ascorbate level seems to have a notable anti-apoptotic effectnHighlight:sepsisnHighlight:it has been suggested that the GSH-dependent reduction of DHA is one of the major ascorbate-producing reactions in mammalian mitochondrianHighlight:DHA is taken up by low-affinity (Km∼0.8 mM) sodium-independent facilitated diffusionnHighlight:elevated level of ROS can induce the collapse of the mitochondrial membrane potentially leading to apoptosisnHighlight:ascorbate- dependent mono- and dioxygenationsnHighlight:renal failure due to the widespread deposition of calcium oxalate crystalsnHighlight:Two separate dioxygenations of HIF-1α have been identified: proline hydroxylation and asparagine hydroxylationnHighlight:vitamin C and other antioxidants, resulted in significantly faster recovery of organ function based on a prospective, randomized, controlled, double-blind clinical trial with 55 patients (nHighlight:ascorbate is regarded as a reducing agentnHighlight:The two major forms of vitamin C in the diet are L-ascorbic acid and L-DHAnHighlight:Glucose inhibits ascorbate uptake but not that of DHAnHighlight:Activity of HIF-1α can be regulated by hydroxylation, which needs ascorbatenHighlight:high-dose vitamin C therapy should be avoided in patients with renal failure or renal insufficiency, and in patients undergoing dialysisnHighlight:release of cytochrome c was also prevented and the mitochondrial membrane potential was stabilized by vitamin CnHighlight:Both ascorbate and DHA are absorbed along the entire length of the human intestinenHighlight:hydroxylationnHighlight:able to reduce redox-active metals such as copper and iron, thereby increasing the pro-oxidant chemistry of these metalsnHighlight:The transport protein responsible for the intestinal absorption of DHA has not yet been identified.nHighlight:a decrease in plasma vitamin C levels has been observed in both type I and type II diabetesnHighlight:these events led to a decreased activation of caspase-9 and caspase-3 with resultant inhibition of apoptosisnHighlight:deficiency in glucose-6-phosphate dehydrogenase, intravascular haemolysis occurred after high-dose vitamin C administrationnHighlight:More than 100 HIF target genesnHighlight:SVCT2 is a low-capacity, high-affinity transporter (Km: 8–62 µM). It is widely expressed in metabolically active and specialized cells and tissuesnHighlight:Thus ascorbate can act as both a pro-oxidant and an antioxidantnHighlight:rate of uptake of both ascorbate and DHA is saturablenHighlight:Plasma concentrations of vitamin C are tightly controlled when the vitamin is taken orallynHighlight:mitochondrial vitamin C is a major component in the maintenance of the mitochondrial membrane potential, and that vitamin C exerts its anti-apoptotic effect through its ability to scavenge ROSnHighlight:systemic iron overloadnHighlight:extracellular ascorbate selectively kills cancernHighlight:vitamin C enters mitochondria in its oxidized state via GLUT-1nHighlight:pharmacological plasma concentrations of vitamin C can only be reached through the intravenous administration of the vitaminnHighlight:HIFs are heterodimers, consisting of oxygen-sensitive HIF-α and HIF-β. In hypoxia, the induced HIF-α is translocated to the nucleusnHighlight:reduced form, L-ascorbic acid, is imported by an active mechanism requiring two sodium-dependent vitamin C transporters (SVCT1 and SVCT2)nHighlight:high doses of vitamin C is contraindicative for patients with oxalate kidney stones or hyperoxalurianHighlight:Plasma levels of vitamin C are not only limited by absorption, but also by reabsorption in the kidneys by SVCT1.nHighlight:DHA is very unstablenHighlight:L-Gulonolactone oxidase (GLO), a microsomal enzyme, catalyses the aerobic conversion of gulonolactone tonHighlight:the capacity of the transporters is limitednHighlight:In patients with renal failure, vitamin CnHighlight:SVCT1n]]>

Picture of About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.


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