Vitamin C: the known, the unknown, and Goldilocks

Vitamin C, also known as ascorbic acid, abounds in nature and is highly labile. It is a water-soluble vitamin that is lost in large amounts during food processing. It is a vitamin whose prescribed requirement across cultures is not uniform. For example , the prescribed requirement of vitamin C in Great Britain is 30mg/day, while in the U.S.A., it is 60mg/day and 100mg/day in Japan. These variations are unusual and point to the need for further research to establish the acceptable RDAs for diverse populations. The RDA for vitamin C should be more than the amount needed to prevent the occurrence of disease. Vitamin C plays significant functions in the body that enhance its role in the health status of the human body. The biochemical functions of vitamin C include: stimulation of certain enzymes, collagen biosynthesis, hormonal activation, antioxidant, detoxification of histamine, phagocytic functions of leukocytes, formation of nitrosamine, and proline hydroxylation amongst others. Th...

2002

The chemical name for L-ascorbic acid is 2,3-didehydro-L-threo-hexano-1,4-lactone. Carbon 5 of ascorbic acid (Fig. 1.1) is asymmetric, making two enantiomeric forms possible; L-ascorbic acid is the naturally occurring and biologically active form. L-Ascorbic acid is a water-soluble 6-carbon α-ketolactone with two enolic hydrogen atoms (pK a1 at carbon 3 = 4.17 and pK a2 at carbon 2 = 11.57; Fig. 1.1) (1,2). At physiologic pH, >99% of L-ascorbic acid is ionized to L-ascorbate, which can donate a hydrogen atom (H + + e −) to produce the resonance-stabilized ascorbyl radical (Fig. 1.1). The ascorbyl radical can donate a second electron to form the 2-electron oxidation product of ascorbate, dehydroascorbic acid (DHA), or dismutate to form ascorbate and DHA (Fig. 1.1). Alternatively, the ascorbyl radical may be enzymatically reduced back to ascorbate by NADH-dependent semidehydroascorbate reductase or the NADPH-dependent selenoenzyme, thioredoxin reductase. DHA can be reduced back to ascorbate by the glutathione-dependent enzyme, glutaredoxin, or thioredoxin reductase (3). If not recycled to ascorbate, DHA is irreversibly hydrolyzed to 2,3diketo-L-gulonic acid (DKG), which does not function as an antioxidant. Further degradation of DKG results in the formation of oxalic acid and L-threonic acid. Other catabolites include, among many others, L-xylonic acid, L-lyxonic acid, and L-xylose (4). The term vitamin C is generally used to describe all compounds that qualitatively exhibit the biological activity of ascorbate, including ascorbate and DHA (2). Fig. 1.1. Oxidation of ascorbate (AscH −) by two successive one-electron oxidation steps to give the ascorbyl radical (Asc •−) and dehydroascorbic acid (DHA), respectively.

Nutrients

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is r...

Advances in Dermatology and Allergology, 2012

Vitamin C (VC; ascorbic acid, AA) is synthesised from glucose in the liver of most mammals, but not in humans. Synthetic AA supplementation is often necessary to prevent vitamin C deficiency. Intracellularly AA is reversibly oxidized to an ascorbic radical which converts into dehydroascorbic acid (DHA). Ascorbic acid crosses cell membranes with SVCT1, SVCT2 or GLUT1, GLUT3 and GLUT4 transporters. Recommended daily allowance for VC is around 75 mg/day for women and 90 mg/day for men. This seems to be too low in relation to real human body needs and does not ensure true health protection. There are ongoing studies re-evaluating the role of VC in cancer treatment. Therefore, it would be also appropriate to reassess its use as a specific drug in the prevention and therapy of asthma, allergic rhinitis and atopic dermatitis.

Hrana i ishrana, 2020

Although its importance in human biology has been known ever since the emersion of scurvy, it was not until the 20th century that vitamin C was discovered. Scurvy is a disease caused by severe vitamin C deficiency, which was very common among sailors on long sea journeys during the early modern period [1-3]. In 1753 Scottish naval surgeon James Lind identified citrus fruits as an effective cure for scurvy in the first-ever controlled clinical study [1,3,4]. Still, the reason why the citrus fruits had a therapeutic effect was yet to be discovered. The reducing agent responsible for preventing and curing the disease was first found in 1928 by Hungarian scientist Albert Szent-Györgyi. The offwhite crystalline substance that he isolated from plant juices and animal tissues (adrenal glands) and that he named hexuronic acid was thought to be a new hormone similar to simple sugars [5]. Still, a few years later, Svirbely and Szent-Györgyi confirmed that hexuronic acid was, in fact, vitamin C [6]. At the same time, W. A. Waugh and C. G. King isolated a crystalline vitamin C from lemon juice and reported that it had similar physical and chemical properties as hexuronic acid, including the antiscorbutic quality, and that it was identical with the hexuronic acid, which was indeed later confirmed [7]. In 1933 a team led by British chemist Walter N. Haworth defined the molecular structure of vitamin C (i.e., hexuronic acid), renaming it to the ascorbic acid [8]. Albert Szent-Györgyi and Walter N. Haworth were awarded the Nobel Prize in Physiology or Medicine and Chemistry, respectively, for their work on vitamin C.

Oral Diseases, 2016

Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful.

Nutrients, 2013

Research progress to understand the role of vitamin C (ascorbic acid) in human health has been slow in coming. This is predominantly the result of several flawed approaches to study design, often lacking a full appreciation of the redox chemistry and biology of ascorbic acid. In this review, we summarize our knowledge surrounding the limitations of common approaches used in vitamin C research. In human cell culture, the primary issues are the high oxygen environment, presence of redox-active transition metal ions in culture media, and the use of immortalized cell lines grown in the absence of supplemental ascorbic acid. Studies in animal models are also limited due to the presence of endogenous ascorbic acid synthesis. Despite the use of genetically altered rodent strains lacking synthesis capacity, there are additional concerns that these models do not adequately recapitulate the effects of vitamin C deprivation and supplementation observed in humans. Lastly, several flaws in study design endemic to randomized controlled trials and other human studies greatly limit their conclusions and impact. There also is anecdotal evidence of positive and negative health effects of vitamin C that are widely accepted but have not been substantiated. Only with careful attention to study design and experimental detail can we further our understanding of the possible roles of vitamin C in promoting human health and preventing or treating disease.

Ascorbic acid is a cofactor for several enzymes participating in the post-translational hydroxylation of collagen, in the biosynthesis of carnitine, in the conversion of the neurotransmitter dopamine to norepinephrine, in peptide amidation and in tyrosine metabolism. In addition, vitamin C is an important regulator of iron uptake, It reduces ferric Fe 3+ to ferrous Fe 2+ ions, thus promoting dietary non-haem iron absorption from the gastrointestinal tract, and stabilizes iron-binding proteins. Most animals are able to synthesise vitamin C from glucose, but humans, other primates, guinea pigs and fruit bats lack the last enzyme involved in the synthesis of vitamin C (gulonolactone oxidase) and so require the presence of the vitamin in their diet. Thus the prolonged deprivation of vitamin C generates defects in the post-translational modification of collagen that cause scurvy and eventually death. In addition to its antiscorbutic action, vitamin C is a potent reducing agent and scavenger of free radicals in biological systems.

2019

Chemical and Pharmaceutical Bulletin, 2006

Vitamin C (ascorbic acid) (Fig. 1) is a water soluble vitamin that possesses a variety of physiological properties. Ascorbic acid (AA) is an essential micronutrient involved in many biologic and biochemical functions. 1-5) It is an excellent antioxidant in biological systems such as a-tocopherol, and b-carotene. 4) The known functions of AA are accounted for by its action as an electron donor, or reducing agent. 6-8) Its most significant role is seen to be as a reductant that minimizes damage by oxidative processes along with other natural antioxidants. 9) AA seems to affect many enzyme activities and physiologic processes. 1,2,6-8,10) AA efficiently neutralizes reactive oxygen and nitrogen species such as hydroxyl, peroxyl, and super oxide radicals, as well as peroxynitrite, nitroxide radicals, single oxygen, and hypochlorite. This action provides direct antioxidant protection to tissues subjected to high free-radical stress such as phagocytes, eye, brain, stomach, and sperm. 11,12) The biological basis of recommendation for humans should account for absorption and disposition of ascorbic acid which is governed by the following factors: bioavailability and absorption in the gastrointestinal tract, concentration in the circulation, tissue distribution, excretion, and metabolism. Fundamental to all of the issues are the principles of ascorbate chemistry and mechanisms of membrane transport and cellular accumulation. 4) The ascorbate oxidation product; dehydroascorbic acid, is reduced by cells to ascorbate. AA exists in the body in its reduced form. Humans cannot synthesize AA, it must be provided exogenously in the diet and Experimental All chemicals were obtained from Merck. Na 99m TcO 4 was supplied by the