Open access peer-reviewed chapter
Abstract
Vitamin C, an essential water-soluble vitamin, is known for its pivotal role in various biological functions. This chapter provides an overview of vitamin C, focusing on its chemical structure and synthesis, its multifaceted biological functions within the body, and its remarkable role as a powerful antioxidant. The significance of vitamin C in maintaining immune function, its contributions to collagen synthesis, and its involvement in cognitive health are explored. Moreover, the dual nature of vitamin C as both a pro-oxidant and an antioxidant is highlighted, emphasizing its broad impact on health and well-being. This comprehensive examination of vitamin C underscores its critical role in safeguarding against oxidative damage-related diseases and supporting overall health.
Keywords
- vitamin C
- ascorbic acid
- deficiency
- antioxidant mechanisms
- immune function
1. Introduction
Vitamins are essential organic compounds that the body does not synthesize on its own. Consequently, it is necessary to obtain vitamins from dietary sources and supplements on a daily basis [1]. These vital nutrients play a crucial role in facilitating carbohydrate, fat, and protein metabolism while also promoting healthy bodily growth, bolstering immune defenses against infections, and aiding digestive functions [2]. The human body relies on vitamins in small amounts to perform crucial functions, such as metabolism, immune response, and cognitive development. Vitamins can be categorized into two groups: fat-soluble vitamins and water-soluble vitamins. One of the water-soluble vitamins is vitamin C [3, 4, 5].
Vitamin C, also known as ascorbic acid, has garnered significant attention in the fields of medicine and nutrition over the years. Its vital biological functions and far-reaching health effects have made it a subject of continuous research and interest among healthcare professionals and scientists. This essential nutrient is naturally present in numerous plants and fruits and plays a crucial role in maintaining overall health. These include collagen synthesis and growth, wound healing processes, bone formation facilitation, immune system enhancement, iron absorption promotion, maintenance of blood vessel integrity, and functioning as an effective antioxidant. The absence of sufficient amounts of this vitamin in the diet can lead to a deficiency condition known as scurvy. Symptoms associated with scurvy may manifest as swollen and bleeding gums, tooth loss or decay due to weakened connective tissues around teeth roots, delayed wound healing processes, and hindered tissue growth [6].
The history of vitamin C research dates back to the eighteenth century, but its isolation and identification as a distinct vitamin occurred in the early twentieth century. Throughout this period, research has delved into the multifaceted roles of vitamin C in various biological functions, ranging from bolstering the immune system to promoting skin health, facilitating tissue repair, and aiding in iron absorption. Furthermore, vitamin C stands out for its remarkable antioxidant properties, effectively mitigating cellular damage induced by free radicals [7, 8].
This chapter aims to consolidate the current body of knowledge and research on vitamin C. Initially, it provides fundamental information about the chemical structure and synthesis of vitamin C and its biological functions within the body. Subsequently, the chapter evaluates the multifaceted role of vitamin C as a powerful antioxidant. Finally, we explore recent research findings concerning vitamin C and identify potential avenues for future investigations. In essence, this chapter offers an overview of vitamin C, contributing to a better understanding of its pivotal role in health and nutrition.
2. Vitamin C: chemical structure and synthesis
Chemically known as ascorbic acid (C6H8O6), vitamin C is a six-carbon lactone synthesized from glucose by many animals [9]. Abundantly present in many fruits and vegetables, vitamin C is essential for robust immune function. It is found in a reduced form as ascorbic acid and in an oxidized form as dehydroascorbic acid [10]. According to the International Union of Pure and Applied Chemistry (IUPAC), the systematic name is “2,3-enediol-L-gluconic acid-β-lactone” [11].
While plants and some animals, mainly in their livers, can synthesize ascorbic acid, humans lack the ability to produce this vitamin internally. Consequently, humans must acquire this vitamin through their diet. Many animals and plants, on the other hand, can synthesize vitamin C using a pathway involving glucuronic acid derived from D-glucose or D-galactose. In certain animals, the synthesis of ascorbic acid occurs in their liver cells (Figure 1) [13]. Similarly, since humans also lack the ability to synthesize vitamin C, it is advisable to supplement with synthetic vitamin C in cases of inadequate or unbalanced nutrition, or obtain it naturally. Most mammals, including mice, are capable of synthesizing vitamin C from glucose, while humans and other primates meet their daily requirements for it through their diet because they lack the L-gulono-g-lactone oxidase enzyme involved in vitamin C synthesis [14, 15, 16].
Figure 1.
L-ascorbic acid [
Vitamin C is transported into cells in its oxidized form, dehydroascorbic acid (DHA), through glucose facilitative transporters (GLUT), and as ascorbic acid via sodium-dependent vitamin C transporters [14, 17, 18]. Specifically, sodium-dependent vitamin C transporters (SVCT) encoded by the SLC23 family consist of two sodium-dependent transporters, SVCT1 and SVCT2. Both SVCT1 and SVCT2 transport ascorbic acid in a sodium-dependent manner with high affinity. SVCT1 is responsible for the absorption of dietary vitamin C along the apical membrane of enterocytes, while SVCT2 plays a role in providing vitamin C to cells for metal ion-dependent enzymatic reactions and protecting cells from oxidative stress [18, 19, 20, 21]. In a study, it was reported that vitamin C transport does not occur in the absence of calcium (Ca) and magnesium (Mg) minerals, even in the presence of sodium, and SVCT2 becomes inactive under such conditions [22].
3. The biological functions of vitamin C
For a healthy adult, an optimal plasma level of approximately 50 μmol/l is considered sufficient. This ratio may vary based on age, gender, and specific circumstances such as pregnancy or lactation. The Recommended Dietary Allowance (RDA) for vitamin C is 75–90 mg/day for adult men and women [23]. While vitamin C tends to be well-tolerated, adults should not exceed the recommended tolerable upper intake levels, which are set at two grams per day [24]. The most common adverse effects of high-dose vitamin C include gastrointestinal discomforts such as stomach pain and bloating, as well as nausea and diarrhea, particularly when administered in a single oral dose of 5–10 g or daily consumption of 2 g. These symptoms typically subside within 1–2 weeks upon reducing the intake [24].
Vitamin C serves numerous important functions within the body. Its physiological roles are largely associated with the oxidation-reduction properties of vitamin C [13]. L-ascorbic acid plays a crucial role in the synthesis of collagen, which is directly related to scurvy etiology [6]. It acts as an electron donor and serves as a cofactor for certain enzymes involved in collagen, carnitine, neurotransmitter, and amino acid synthesis, particularly for Fe and Cu-containing metalloenzymes like hydroxylases and monooxygenases. Vitamin C, in its reduced form, binds to the active center of iron ions, facilitating the optimal activity of hydroxylases and oxygenases. Additionally, its role as an electron donor contributes to its in vivo antioxidant effect [25, 26, 27].
Vitamin C, in addition to its well-known role as an antioxidant, serves various functions in physiological systems of humans and other mammals. It acts as a cofactor in numerous important enzyme reactions, including adrenal steroidogenesis, catecholamine synthesis, carnitine synthesis, collagen synthesis, amino acids, and the synthesis of specific peptide hormones. It has also been reported to be involved in the synthesis of vasopressin released in response to decreased intravascular volume or increased plasma osmolarity [28, 29, 30]. Vitamin C acts as a cofactor in biochemical reactions catalyzed by monooxygenases, dioxygenases, and mixed-function oxygenases [31].
Vitamin C, when combined with LDI-glycerol, promotes osteoblast differentiation [32]. It could expedite the healing process by inducing proline and lysine hydroxylation in the collagen triple helix structure [33]. Deficiency in vitamin C, along with deficiencies in folic acid, vitamin B12, and other vitamins, can lead to issues such as megaloblastic vascular fragility, impaired wound healing, and a weakened immune system [34, 35]. Additionally, vitamin C plays a crucial role in neutralizing free radicals produced at the fracture site [36]. Free radicals disrupt normal cellular activity by affecting body cells and molecules [37]. Vitamin C neutralizes the impact of free radicals, thereby aiding in the reconstruction of damaged cells [38]. Research indicates that vitamin C can enhance the production of genes influencing osteogenesis. For instance, it increases genes like bone morphogenetic protein-2, Runt-related transcription factor 2, and osteocalcin, while decreasing the production of bone-destructive genes such as cathepsin K, tartrate-resistant acid phosphatase, receptor activator of nuclear factor kappa-B, and receptor activator of nuclear factor kappa-B ligand [39]. Considering the positive impact of vitamin C on bone healing, an
Vitamin C stimulates immunity through a range of mechanisms, including macrophage infiltration, cell proliferation, natural killer (NK) cell activity, complement activity, leukocyte phagocytic activity, and the developmental stages of cytokines, including antibody concentrations [41]. Vitamin C has been shown to enhance T-lymphocyte proliferation in response to infection, leading to increased cytokine production and immunoglobulin synthesis [13, 42].
Vitamin C’s importance in various stress conditions involving the immune system, including inflammatory processes, has been noted. It is reported to regulate the secretion of proinflammatory cytokines like TNF-α and IL-6. Vitamin C has also been shown to inhibit the production of intercellular adhesion molecules (ICAMs) induced by TNF-α, reducing leukocyte adhesion and secretion, thereby improving microcirculation flow [43, 44, 45].
Studies have reported that chronic stress in rats leads to a significant decrease in total leukocytes, lymphocytes, and serum immunoglobulin E (IgE), G (IgG), and M (IgM) levels, and vitamin C supplementation significantly mitigates these effects [46]. It is worth noting that the vitamin C levels in leukocytes, which constitute the cellular composition of the immune system, are many times higher than those in plasma [47].
Vitamin C plays a significant role in maintaining the proper functioning of the antioxidant system in the brain and the nervous system [48]. It has been reported to have a therapeutic effect on memory impairments and neurodegenerative changes and plays a crucial role in neuropathological alterations [49, 50]. Numerous studies have shown that vitamin C modulates the activity of receptors such as glutamate and Gamma-Aminobutyric Acid (GABA) [51, 52, 53]. Reports also suggest that vitamin C treatment reduces adverse changes induced by glutamate in immature rat brains [54].
High doses of vitamin C are known to be used in the treatment and prevention of various disorders, including diabetes, cataracts, glaucoma, macular degeneration, atherosclerosis, heart diseases, and cancer [55, 56, 57, 58, 59, 60, 61, 62, 63]. The importance of vitamin C supplements is highlighted by the ability to replenish vitamin C levels during various infections [47]. However, it is worth noting that in individuals with severe infections, vitamin C may not confer a survival benefit [64]. At high concentrations, vitamin C acts as a pro-oxidant, selectively targeting and killing cancer cells through the creation of extracellular hydrogen peroxide [65]. It was observed to trigger apoptotic cell death in different carcinomas, including breast cancer, oral squamous cell carcinoma, multiple myeloma tumor cells, and pancreatic cancer [66, 67, 68, 69, 70]. In a study, high concentrations of vitamin C have been observed to upregulate the expression and activation of p66Shc. Additionally, elevated levels of vitamin C lead to the activation of Rac1 and facilitate apoptotic cell death through the mediation of reactive oxygen species (ROS). Importantly, the activation of Rac1, ROS production, and ensuing cell death induced by vitamin C are dependent on the ser36 phosphorylation of p66Shc. Consequently, the P66Shc/Rac1 pathway emerges as a promising target for vitamin C, presenting potential avenues for exploration in breast cancer therapeutics [66].
It has been reported that high-dose vitamin C can reduce inflammatory reactions, improve oxygen support, and reduce mortality in specific subgroups of critically ill COVID-19 patients and elderly individuals without significant side effects [71]. While antioxidant vitamin supplements are considered safe for physiological systems, many authors have cautioned against high levels of antioxidant vitamins, which can significantly disrupt the physiological balance. It is worth noting that the pro-oxidant effects of ascorbate and other antioxidant vitamins are well recognized by food scientists [72], and these antioxidants may trigger mild oxidative stress due to their pro-oxidant properties [73].
4. The multifaceted role of vitamin C as a powerful antioxidant
Antioxidants constitute molecules capable of impeding or decelerating oxidative harm inflicted upon cells by free radicals. Free radicals, characterized by their instability, pose a threat to cellular integrity and are implicated in the onset of diverse ailments, encompassing cancer, cardiovascular diseases, ovarian damage, and neurodegenerative disorders. Antioxidants function by neutralizing free radicals through the donation of electrons, thereby diminishing their potential to induce harm. The incorporation of antioxidant-rich foods and supplements into one’s diet has been correlated with a myriad of health advantages. Antioxidants play a crucial role in alleviating reactive oxygen species (ROS) and providing protection against oxidative stress [37, 74, 75, 76, 77].
Vitamin C is renowned for its robust antioxidant properties. This vitamin plays a crucial physiological role in safeguarding against various oxidative damage-related diseases, including cancer, atherosclerosis, heart attacks, strokes, arthritis, cataracts, and the aging process. These conditions are primarily driven by the presence of free radicals. One of the most intriguing aspects of vitamin C’s function lies in its in vivo antioxidant effects. Its biochemical structure involves two oxygen atoms bound together by a double bond and three hydroxyl groups connected to its carbon atom. This structure allows vitamin C to act as a powerful antioxidant, protecting our cells from damage caused by free radicals [27].
Vitamin C is part of antioxidant complexes, collaborating with other non-provitamin A carotenoids like vitamin E, β-carotene, lutein, and lycopene, in addition to flavonoids and selenium. However, it is important to note that debates regarding the results of clinical studies in this area persist. Another fascinating characteristic of vitamin C is its dual role-it can act as both a pro-oxidant and an antioxidant within cells, and this dual function depends on the concentration of vitamin C. The antioxidant role of vitamin C is multifaceted, employing various mechanisms to prevent lipid oxidation. It effectively neutralizes superoxide, hydroxyl radicals, hypochlorous acid, and other free radicals and oxygen-derived species by donating electrons to them. Furthermore, vitamin C converts into less reactive semidehydroascorbate and dehydroascorbic acid radicals, effectively reducing oxygen and carbon-centered radicals [78]. Vitamin C is also capable of regenerating essential base antioxidants. Despite being hydrophilic and unable to penetrate the lipid environment of low-density lipoprotein (LDL), vitamin C enhances the action of lipophilic antioxidants by regenerating them. For example, it elevates plasma levels of β-carotene and vitamin E, safeguarding LDL from oxidation by converting tocopherol radicals into their reduced, antioxidative form. Due to these remarkable effects, vitamin C is often lauded as both an anticarcinogen and a protector against atherosclerosis [56, 79].
Vitamin C’s significance extends beyond its antioxidant properties. Its potent electron transfer capability plays a pivotal role in various aspects of cellular function and health [80]. It actively participates in immune responses, cellular metabolism, and enzymatic reactions, while also contributing to the maintenance of the body’s redox balance [81]. The effectiveness of the immune system relies on a resilient and well-protected redox system, in which vitamin C plays an essential role [45]. Furthermore, vitamin C is recognized for its capacity to effectively scavenge free radicals in both plasma and cell membranes. It can also elevate nitric oxide levels through oxidative defense and endothelial nitric oxide synthase activity [82].
Vitamin C’s benefits extend to skin health as well. Studies have shown that both dietary intake and supplementation of vitamin C increase its presence in skin cells and enhance the skin’s antioxidant defense mechanisms [83, 84]. Daily supplementation with 500 mg of vitamin C has been reported to maintain adequate levels of reduced glutathione (GSH) in the bloodstream, enhancing overall antioxidant defense [85].
Several studies have suggested a potential relationship between ascorbic acid and female fertility [86]. Levine and Morita found that ascorbic acid deficiency may contribute to infertility by causing atrophy of ovarian follicular atresia and premature resumption of meiosis [87]. Therefore, maintaining sufficient antioxidant concentrations is crucial to protect oocytes and all follicles from excessive ROS and, consequently, oxidative damage. This is of paramount importance in preserving gamete quality and supporting reproduction within the reproductive systems [88].
5. Conclusion
In conclusion, vitamin C, with its multifaceted antioxidant mechanisms and broad impact on health and cellular function, plays a pivotal role in safeguarding against oxidative damage-related diseases and maintaining overall well-being. Its dual nature as both a pro-oxidant and an antioxidant adds to the intrigue surrounding this essential nutrient.
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