Potential of ascorbic acid in human health against different diseases: an updated narrative review

ABSTRACT

Ascorbic acid (vitamin C) is the most crucial antioxidant for the body. The biochemical capabilities of ascorbic acid are still being studied. It acts as a cofactor for many enzymes participating in various physiological functions. This review presents how ascorbic acid is a cofactor for multiple enzymes involved in numerous human activities. Ascorbic acid protects the immune system, reduces allergic reaction severity and assists the fight against infections and other disorders. Ascorbic acid is metabolized by several procedures in the gastrointestinal tract. Eukaryotes produce ascorbic acid via L-galactose (L-Gal) and GDP-D-mannose as part of its metabolic process. It is disseminated throughout the body cells after being readily absorbed by the digestive system. This review will uncover ascorbic acid’s biological functions and metabolism in humans.

KEYWORDS:

• Ascorbic acid
• metabolism
• biological functions
• cofactor
• antioxidant
• diseases

Introduction

Vitamins are highly complex organic compounds that are present in traces in various foods and drinks, are essential for normal metabolism, and their deficiency causes multiple types of diseases^[1]. However, resupply of these nutrients cures symptoms caused by their deficiency. Vitamins are diverse, just like fats, proteins, and carbohydrates. Ascorbic acid, commonly named vitamin C, is popular for certain qualities like acting as a potent antioxidant and a free-radical scavenger.^[2] Acorbic acid is present in optimum amounts in the diet. A slight amount of ascorbic acid is enough to maintain normal body functions. It is also widely acknowledged as the most important hydrophilic antioxidant, and for the different types of enzymatic reactions, it acts as a specific cofactor.^[3] Several animals and plants may use d-galactose and D-glucose to make ascorbic acid. But as GLO (L-gulonolactone oxidase) is not present in humans naturally as well as in other species of animals like birds, bats, pigs, monkeys, etc., because they cannot produce endogenous forms of ascorbic acid.^[4] Acorbic Acid is naturally present among animals and plants in abundant quantities, and it is a promising nutraceutical present naturally in food, reporting different medical or health benefits. L-ascorbic acid, often vitamin C, is a potent antioxidant that safeguards cellular membranes. DNA and tissues from the oxidative damage.^[5] Ascorbic acid possesses free radical characteristics, allowing it to interact with free oxygen ions, superoxide ions, and hydroxyl ions while also inhibiting the formation of inflammation, carcinogens, and other factors that exacerbate photoaging in the skin.^[6] L-ascorbic acid, dehydro-L-ascorbic acid, and L-ascorbic acid salts are all popular names for the substance known as vitamin C. (such as potassium, calcium L-ascorbate and sodium). About 80% to 90% of the vitamin C in food comprises L-ascorbic acid.^[7] Ascorbic acid is commonly present in citrus fruits, blackcurrants, and rose hips and can also be produced from glucose. About its antioxidant properties, acorbic acid can help to minimize oxidizing agents like hydrogen peroxide.^[8] Ascorbic acid performs several functions in the maintenance of good health as well as to combat illness and infection. Hypovitaminosis C can trigger low mood symptoms. Numerous clinical symptoms might be linked to its severe deficiency.^[9] Prolonged and severe ascorbic acid deficiency can result in some specific clinical syndromes, such as scurvy, a medical illness that requires hospitalization. Ascorbic acid plays countless functions in providing optimal health as well as in the prevention of diseases. Low mood symptoms may be caused by infection, moderate insufficiency, or hypovitaminosis C.^[10]

There are several clinical manifestations that its severe deficit can be connected to. Prolonged and painful deficiency of Ascorbic acid (vitamin C) can result in some specific clinical syndromes. One of them is scurvy, a medical illness still recognized in people and sporadically in global health epidemics today.^[11] And if left untreated, this condition, called scurvy, can become a lethal disease. The balanced ingestion of ascorbic acid and its amount are a subject of debate and recommended values are not universal. Based on a wide range of ascorbic acid benefits, several global authorities have adjusted their dietary guidelines for ascorbic acid from their earlier suggested levels for avoiding scurvy.^[12]

Dietary intake of ascorbic acid is crucial for determining body status, whose amount, regularity, serum state, and occurrence of insufficiency are all related. Due to the high link between fruit consumption and plasma ascorbic acid status, vegetables and fruits are substantial nutritional suppliers of ascorbic acid.^[13] Papayas, melons, cranberries, kiwifruit, tomatoes, guavas, oranges, strawberries, asparagus, spinach, cantaloupe, mangoes, and Brussels sprouts are among the foods high in ascorbic acid. Along with the preceding supplies, cereals, e.g. rice, starchy roots, maize, eggs, meat, dairy and wheat items, also have minor levels of ascorbic acid.^[14] From a therapeutic perspective, another significant role of ascorbic acid results in lowering mortality rates in some groups. Numerous prospective studies demonstrate an inverse relationship between ascorbic acid plasma content and death for all reasons, encompassing a range of cardiac syndromes, such as ischemic cardiac disorder.^[15] The ascorbic acid content in the body relies on several factors listed as food ingested, recycling, renal reuptake, and effective absorption in the digestive tract. The levels of ascorbic acid in tissues and serum may be precisely controlled by specific sodium-dependent vitamin C transporters or sodium vitamin C cotransporters (SVCTs).^[16] The differing ascorbic acid requirements of distinct organs and tissues are reflected in the level of ascorbic acid. Brain, adrenal, and pituitary gland tissues have higher ascorbic acid concentrations than other tissues. One of ascorbic acid’s primary functions can be imitated by its potential to serve as a cofactor for a variety of regulatory and biosynthetic enzymes, including those involved in the production of catecholamines and peptide hormones.^[17] Depending on ingestion, an adult’s body typically has 1500–3000 mg of vitamin C; anything less than 900 mg is considered undesirable. The range of 36.1–79.4 mumol/l and 0.50 to 1.80 mg/dl is likewise regarded as usual for blood ascorbic acid content. The recommended daily amount (RDA) for ascorbic acid in the United States and Canada is 90 mg for males and 75 mg for females.^[18]

Morphological Hallmarks

Ascorbic acid is a water-soluble vitamin. They give the appearance of a slightly yellow or white crystal, or even powder contains a slightly acidic taste. It is an antiscorbutic product. Based on their exposure to light, they gradually change it to darken. It oxidizes fast when mixed in a mixture but is quite durable in the air when dried.^[19] Ascorbic acid is easily and quickly dissolved in water but is moderately dissolved in alcohol and insoluble in benzene, ether, and chloroform. The empirical formula for ascorbic acid is C6H806, and its molecular mass is 176.13. Reichstein was the first to synthesize ascorbic acid effectively in 1933, and Roche followed two years later with the first commercial production of ascorbic acid. Ascorbic acid production is being done on a substantial industrial basis. Wheat or corn is the primary raw material for ascorbic acid.^[20] Specialized businesses transform this through starch into glucose and subsequently to sorbitol. Through several stages, we convert sorbitol into the pure final product. The chemical structure of vitamin C is shown in Figure 1.

Figure 1. Chemical structure of Ascorbic acid and conversion of D-sorbitol to L-Ascorbic acid via 2-keto-L-gulonic acid.

Ascorbic acid in aqueous solution is a potent reducing agent. It is oxidized to dehydroascorbic acid using a range of oxidizing agents such as halogens, quinones, iodate ions, phenol indophenol, molecular oxygen, and a suitable catalyst metal ion and activated charcoal. This oxidation reaction is readily reversible.^[21] The two chiral centers at positions 4 and 5 of ascorbic acid, which resemble a planar five-member ring, determine its four stereoisomers. The oxidized form of ascorbic acid, dehydroascorbic acid, can appear as a hydrated hemiketal or dimer and retain some ascorbic acid action. L-ascorbic acid breaks in aqueous medium according to various factors, such as oxygen concentration, temperature, pH, and the existence of metals.^[22]

Ascorbic acid, one of the least expensive therapeutic alternatives, may prevent and cure infections, toxins, autoimmune disorders, and cancer development. Ascorbic acid is a marvel for people with aesthetic preferences amid its role as an anti-aging agent that maintains skin tone and texture. Although our bodies do not naturally generate it, it is widely distributed.^[23] It may be connected to sugars, prevalent molecules in various species used to make ascorbic acid. Plant species, counting photosynthetic protists and algae, have been shown to synthesize ascorbic acid.^[24]

Along with additional minor roles, ascorbic acid serves three key functions in plants: donor or acceptor in electron transport in either the chloroplasts or the plasma membrane, radical scavenger, cofactor for the enzyme. Additionally, potatoes and soft beverages, particularly juices, contribute significantly. Fungi, in addition to plants and mammals, can biosynthesize acorbic acid. However, it is often quite low in both wild and domesticated fungi.^[25] Due to its various medical benefits, ascorbic acid is becoming more and more renowned. Higher blood levels of ascorbic acid can serve as an excellent dietary indicator for general health; nonetheless, it has been the most contentious vitamin in recent years. This is attributable to claims that mega-doses of ascorbic acid may cure everything from an ordinary cold to cancer.

Ascorbic acid is necessary for optimal human development and growth.^[26] Numerous citrus fruit types from the Rutaceae family, as well as a variety of vegetables, are high in ascorbic acid (Table 1). Oranges, strawberries, tomatoes, lemons, amla, Mausami, and amla are the most common plant sources. Ascorbic acid is abundant in low-cost fruits such as guava and amla twenty times more. Regarding ascorbic acid concentration, one or two oranges are comparable to one or two amla fruits. Generally, the destruction of most or all of the ascorbic acid occurs due to the heating or drying of fresh fruits or vegetables, which are initially present inside fruits and vegetables. Amla stands out among fruits for its high ascorbic acid concentration and compounds that partially shield the vitamin from deterioration during drying and heating.^[27] The primary sources of ascorbic acid include Indian gooseberries, citrus fruits including lemon, orange, and lime, papaya, potatoes, tomatoes, kiwifruit, cantaloupes, strawberries, and red and green peppers. Other significant sources of Vitamin C are broccoli, like green leafy vegetables, and fortified cereals. Animals are another source of ascorbic acid because they typically produce this vitamin independently, particularly in the liver.^[28]

Table 1. The ascorbic acid content in fruit and vegetables.^[29].

Source	Ascorbic acid content (mg/100 g of Product)
Watercress	68–79
Acerola	1300
Pear	3–4
Broccoli	113
Potato (Dec.)	15
Apricot	7–10
Brussels sprouts	87–109
Avocado	15–20
Gourd	8
Apple	2–10
Blackberry	15
Pepper (green)	128
Loganberry	30
Damson	3
Pineapple (canned)	12
Tomato	20–25
Cranberry	12
Passion fruit	25
Grapefruit	40
Potato (Jan., Feb.)	10
Horseradish	120
Kale	186
Quince	15
Cauliflower	64–78
Banana	10–30
Cauliflower(cooked)	55
Carrot	6
Blackcurrant	200–210
Redcurrant	40
Peach (canned)	6
Cherry	5–8
Potato (new)	30
Guava	230–300
Kiwi	60
Rosehip	1000
Spinach	51
Lime	25
Potato (boiled)	16
Lychee	45
Melon	10–35
Orange	50
Orange (juice)	50
Tangerine	30
Peach	7–31
Spinach (cooked)	28
Kale (cooked)	62
Plum	3
Strawberry	59–60
Tomato (juice)	16
Pineapple	12–25
Broccoli (cooked)	90
Pea	25
Lemon	50
Gooseberry	40
Pomegranate	6
Cabbage (raw)	46–47
Potato (Oct., Nov.)	20
Lettuce	15
Potato (Mar.–May)	8
Raspberry	25

Biosynthesis

It is essential to comprehend ascorbic acid production for two main reasons. First, it is an integral part of the plant’s antioxidant system and has several other hypothesized physiological functions. Second, plants are humans’ main nutritional supply of acorbic acid.^[30] Unlike humans, most plants and animals can synthesize ascorbic acid via D-mannose/L-galactose pathway, for its multifunctional roles in plant cells amid redox characteristics. This biosynthesis route, hypothesized by Wheeler, continues through steps of eight reactions with D-fructose-6P, with (L-Gal) and GDP-D-mannose serve as representative intermediates.^[31] The constitutive enzymes of the pathway, including GDP-D-Mannose-3′,5′-Epimerase (GME), L-Galactose-1-Phosphate Phosphatase (GPP), Phosphomannose Mutase (PMM), Galactono-1,4-Lactone Dehydrogenase (L-GalLDH), GDP-D-Mannose Pyrophosphorylase (GMP), Phosphomannose Isomerase (PMI), and L- GDP-L-Galactose Phosphorylase (GGP), play a pivotal role in this biogenesis. Other alternate pathways for ascorbate biosynthesis have been found via D-Galacturonic Acid, L-Gulose, and D-Glucuronic Acid, but with limited research available.^[32] light levels, Temperature, and Jasmonic acid, a hormone that triggers ascorbic acid production, all influence how ascorbic acid is synthesized.^[33]

Metabolic profile and pharmacodynamics

Studying the metabolic pathway of ascorbic acid in the human body is as crucial as its importance. This is because less absorption leads a human body to take vitamin C supplements, which also has specific health impacts.^[12] Knowing how ascorbic acid is absorbed and used in the human body can enhance its bioavailability and close the dollar industry of ascorbic acid supplements. For a quick review of ascorbic acid functions, the immune support and the acorbic acid are often used interchangeably. This vitamin does more than make one feel good. This satiety feeling starts with the absorption of ascorbic acid in the small intestine, from where the absorption of ascorbic acid starts ^[38].

This is the distinct feature of ascorbic acid that it can be synthesized by most mammals, except human beings, via the glucuronic acid pathway in the liver. This is because they lack enzyme L-gulonolactone oxidase, which is essential for ascorbic acid synthesis. Human beings are bound to take vitamin C from their dietary sources. When ascorbic acid is popped, the ileum and jejunum are two important sites of ascorbic acid absorption.^[34] Ascorbic acid bioavailability is dose-dependent. In humans, 200–400 mg daily doses cause transport saturation. An oral dose of 500 mg is absorbed at about 70%. However, 50% of the absorbed dosage is nonmetabolized and eliminated in the urine. Only 50% of a dose of 1250 mg is absorbed, and the majority (85%) of that amount is excreted. In Western cultures, ascorbic acid plasma concentrations range is 54 to 91 mmol.^[35]

Ascorbic acid and DHAA (dehydro-L-ascorbic acid) are the oxidized & reduced forms of vitamin C. The micronutrient is a scavenger of free radicals and a cofactor in various biochemical processes. Research has shown that intestinal absorption of ascorbic acid involves a concentrative, Na±dependent, carrier-mediated mechanism.^[36] Passive sodium-independent, carrier-mediated mechanisms are a part of the DHAA absorption. Despite the discovery and study of two ascorbic acid uptake systems, the sodium-dependent vitamin C transporter-1 (SVCT-1; a protein generated from the SLC23A1 gene) appears to be the predominant mechanism in the digestive system. The GLUT3, GLUT1, and GLUT4 are glucose transporters which have also been discovered, and the processes responsible for DHAA intestinal absorption have been identified molecularly.^[37] The intestinal ascorbic acid absorption mechanism seems regulated by an intrinsic PKC-mediated route. In addition, the extracellular substrate quantities tend to control the procedure dynamically, while the molecular process behind this control is unclear.^[38] The principles underlying the intracellular trafficking and membrane targeting of the human SVCT-1 mechanism are shown by modern laser scanning of human intestinal cells. The SVCT-1 polypeptide is released at the basolateral membrane and in various intracellular structures with distinctive, temperature – and microtubule-dependent dynamic characteristics. A 10 amino acid segment of the polypeptide has been found to include the targeting signal that regulates the ascorbic acid transporter’s apical membrane expression. The basolateral membrane region of intestinal epithelial cells seems to express SVCT-2.^[39]

In the body, ascorbic acid is converted into ascorbates, a reducing chemical that gives vitamin C its antioxidant properties. It is implied that ascorbic acid is an antioxidant since its electrons may neutralize oxidants, although this nomenclature is inaccurate.^[40] The ascorbate electrons could oxidize metals such as iron and copper, producing hydrogen peroxide and superoxide along with other reactive oxidant molecules as a response. Ascorbate can generate oxidants under specific circumstances because of its function as a reducing agent. When pharmacologic ascorbate quantities in the mill molar level are found in the blood and extracellular fluids, this chemistry occurs in vivo. It can also happen when metals are involved in the growth medium.^[41] Electrons are sequentially lost by ascorbate. The ascorbate radical is the earliest outcome of an electron loss. Just under one millisecond is the lifespan of the significant oxidizing agents. The ascorbate radical has an odd half-life since it can last for many seconds or even minutes based on the availability of oxygen and electron acceptors, especially iron. Only specific techniques can quantify ascorbate radicals in serum and extracellular space specimens. A more stable species is produced when a second electron is lost compared to the ascorbate free radical. The result is dehydroascorbic acid (DHA), which can be found in both anhydrous and hydrated forms. DHA is delivered via the range of facilitated glucose transporters (GLUTs), which have an affinity for it.^[42] DHA and ascorbate radical undergoes bidirectional conversion to ascorbate. Due to hydrolytic ring fragmentation, DHA has a short half-life of a few minutes. If the ring structure is destroyed, the final result 2, 3-diketogulonic acid cannot recreate its predecessors DHA, ascorbate radical, and ascorbate.^[43] Ascorbic acid is a vital nutrient because it is an antioxidant and a cofactor in many enzymatic processes. It plays a positive role in health by combating neurogenerative syndromes, cardiovascular disease, obesity and autoimmune disorders (Figure 2, Table 2). Despite being significant, ascorbic acid uptake has not received adequate research^[44]

Figure 2. Ascorbic acid absorption and recycling

Table 2. Multiple effects of ascorbic acid against chronic diseases.

Administration	Diseases	Outcomes	Source
N.A	HIV-infected subjects	High oxidative stress in hospitalized HIV-infected adults; ASC (p < .0001) and albumin (p < .01) were lower in HIV-patients relative to controls.	^[Citation48]
Not applicable (N.A)	Infection diseases	Low levels of ASC were proportional to infection disease severity	^[Citation49]
Intravenous administration	COVID-19	Large doses of ASC (10,000–20,000 mg/d) led to a shorter mean hospital length of stay compared with untreated patients with COVID-19 and no incidences of death	^[Citation50]
High-dose intravenous administration	Advanced cancer	Improved QoL in cancer patients	^[Citation51]
N.A	Hepatitis virus C	Oxidative stress was independently associated with recurrence of hepatitis virus C infection.	^[Citation52]
Intravenous administration	Metastatic and node-positive pancreatic cancer	Data suggested pharmacologic ascorbate administered concurrently with gemcitabine were well-tolerated. Initial data from this small sampling suggested some efficacy.	^[Citation53]
High-dose intravenous administration	Advanced cancer patients	Ascorbic acid administered i.v. at 1 g/min for 4 consecutive days/week for 4 weeks produced up to 49 mM ascorbic acid in patient’s blood and was well tolerated. The recommended dose for future studies is 70–80 g/m^2	^[Citation54]
Oral administration	HIV	Exogenous antioxidant supplementation with ACS did not increase the antioxidant status in patients with HIV	^[Citation52]
Intravenous administration	Metastatic pancreatic cancer	The initial safety data did not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients.	^[Citation54]
Oral administration	Diabetic patients	ASC increased HDL cholesterol and reduced systolic and diastolic blood pressure	^[Citation55]
Intravenous administration	Acute and chronic viral infectious	Protective effects with improvement of oxidative damage	^[Citation56]
Oral administration of orange juice	Hepatitis C under antiviral therapy	The serum levels of total cholesterol, LDL-cholesterol, c-reactive protein (CRP) and parameters of oxidative stress decreased in patients receiving orange juice. Moreover, alanine aminotransferase (AST) levels decreased significantly after oral administration of orange juice.	^[Citation57]
Oral administration	Patients with CVD	ASC prevented decline in endothelial function during sitting	^[Citation58]

The (SVCT) actively absorbs ascorbic acid (SVCT). The sodium electrochemical gradient induced by sodium-potassium ATPase facilitates this active transport. Afterward, ascorbic acid diffuses into capillaries and eventually reaches the systemic circulation. The body’s most prevalent form of vitamin C is ascorbic acid.^[45] Since it is a water-soluble vitamin, it does not build up in the body. Nonetheless, researchers have discovered that it builds up in specific body tissues and is 100 times more abundant than in serum. The in vivo kinetics of ascorbic acid in terms of storage and consumption remains mostly unclear.^[41] However, it is well acknowledged that ascorbic acid concentration varies differently in different organs. It is 40–50 mg/100 ml in the pituitary gland, 25–31 mg/100 ml in the eye lens, 13–15 mg/100 ml in the brain and 3–4 mg/100 g in skeletal muscles, respectively.^[46]

Therapeutic Strategies of Ascorbic Acid in Biological Events

Ascorbic acid is an essential human micronutrient due to its vital biological functions for human health. Ascorbic acid is needed mainly for the synthesis of collagen. Irregular or imperfect collagen synthesis is the first sign of scurvy, a medical condition due to ascorbic acid deficiency.^[47] Since it was discovered that vitamin C, also referred to as L-ascorbic acid, is necessary for treating scurvy. L-dehydroascorbic acid is its oxidized form, which the body can readily transform to L-ascorbic acid^[7] (Figure 3).

Figure 3. Positive Health effect of ascorbic acid.

Adjuvant therapy in cancer

The ability of ascorbic acid to undergo reversible oxidation and reduction is one of the critical properties underlying its biological activity. Ascorbate ensures the catalytic activity of metal ions by reducing them, such as iron or copper. The execution of many iron-dependent enzymatic processes, notably those that are crucial for DNA synthesis or epigenetics, is ensured by this reduction of Fe3+ to Fe2+ iron. One of these is the post-translational modification of collagen, proline, and lysine hydroxylase, which, because of the Fe2+ ion present in the active center, disrupts the functioning of connective tissue, notably the walls of blood vessels.^[5] Ascorbate-rich diets have several positive health effects. Ascorbate has been suggested as a therapy for several cancers through various processes, including causing oxidative stress in cancer cells or boosting the effectiveness of specific chemical therapies.^[59] Vitamin C can also effectively provide electrons to Fe³⁺ to regenerate Fe²⁺. This could trigger ferroptosis by increasing ferrous iron levels in colorectal cancer cells and promote the lethal metabolic cell death program induced by ATP depletion and oxidative stress, as shown in Figure 4. Ascorbic acid seems to enhance chemo-sensitivity and is also helpful in reducing the toxicity of chemotherapeutic drugs in many types of cancer cells.^[60] Due to its potential to prevent cancer, ascorbic acid has recently attracted much interest. It is the most important water-soluble antioxidant in vegetable and fruit sources and may prevent cancer by reducing oxidative DNA degradation, such as DNA mutations.^[61] According to dose-response analyses, increasing ascorbic acid consumption by 50–100 mg per day has directly been linked to a lower risk of all-origin mortality, esophageal cancer, lung cancer, gastric cancer, cervical cancer, and cardiovascular disease (CVD).

Figure 4. Ferroptosis generation through ascorbic acid in tumor microenvironment.

Additionally, positive relationships have been shown for outcomes in ophthalmologic, renal, respiratory, neurological, dental health and musculoskeletal. Taking vitamin C supplements has been linked negatively to kidney stones and breast cancer.^[62] It is also evident from experimental research that ascorbic acid can fight cancer through various methods. Some may require intravenous delivery of pharmaceutical doses, such as those with cytotoxic effects. In contrast, others may be effective even at physiological levels, such as those made possible by oral administration.^[63] There are mounting indications that ascorbic acid may be an effective anti-cancer treatment when administered intravenously and in large doses. Intravenous ascorbic acid is safe and effective in killing tumor cells of several cancer types in early-stage clinical trials. It is widely used as adjuvant therapy, as shown in Table 3.^[64]

Table 3. Clinical status of vitamin C as adjuvant in chemotherapy and radiotherapy.

Drug	NCT	Cancer type	Status	Phase	Combination therapy
Ascorbic acid	NCT04801511	Rectal Cancer	Recruiting	Phase 2	Preoperative/Neoadjuvant Radiotherapy
IV Ascorbic Acid	NCT04516681	Colorectal Cancer	Recruiting	Phase 3	FOLFOXIRI Protocol
Vitamin C	NCT04033107	Hepatocellular, Pancreatic, Gastric and Colorectal Cancer	Recruiting	Phase 2	metformin
Vitamin C (IV route)	NCT03146962	Pancreatic,Gastric and Colorectal Cancer	Recruiting	Phase 2	Resectable surgery
Vitamin C	NCT04150042	Metastatic cancer	Recruiting	Phase 1	autologous hematopoietic stem cell infusion
Ascorbic Acid (Vitamin C)	NCT04553666	older survivors of cancer	Recruiting	Phase 2	Epigallocatechin-3-Gallate (EGCG)
Pharmacological ascorbate	NCT02905578	Pancreatic Cancer	Recruiting	Phase 2	Gemcitabine, nab-paclitaxel
Ascorbate	NCT02905591	Non-Small Cell Lung Cancer	Recruiting	Phase 2	Radiation Therapy and Paclitaxel
ascorbic acid	NCT03624270	Acute Promyelocytic Leukemia	Recruiting	Phase 2	Oral arsenic Trioxide, ATRA
vitamin C	NCT03999723	Acute Myeloid Leukemia	Recruiting	Phase 2	azacitidine

Antioxidative potential against metabolic disorders

Antioxidants are essential elements naturally found in vegetables and fruits. Raising the ingestion of raw or even processed vegetables & fruits in the diet can help reduce the development of chronic illnesses in people. Some of the fruits and vegetables like grapefruit, dates, lime, pomegranates, lemon, banana, orange, apples, grapes, yellow and green vegetables such as cabbage, peppers, carrots, strawberries, and dark leafy greens are well known for having ample amount of antioxidants.^[65] Ascorbic acid has antioxidant properties. The effects of ascorbic acid might be more pronounced when oxidative stress is increased. The stimulation of phagocytes is caused by several pathogens that produce oxidizing substances like reactive oxygen species (ROS). These creatures are necessary to get rid of germs and neutralize viruses.^[66] Deficiency of Vitamin C and its clinical syndrome scurvy are related to vulnerability to infections, particularly respiratory tract infections and pneumonia. During infection, due to increased oxidative stress, the antioxidant role of vitamin C may be more prominent.^[56] The elevated need for antioxidants and utilization by leukocytes could describe the alleviation in vitamin C amounts generally examined throughout infections, particularly during lung infections,^[67] and in severely sick patients.^[68] In addition to an antioxidative effect, the essential functionality of vitamin C in pneumonia is established to act across signaling pathways of inflammation restriction and immunoregulation elevation.^[12]

In addition to act as a scavenger of free radicals and being a necessary component for collagen formation and stability, ascorbic acid must be acquired through dietary sources.^[69] L-ascorbic acid is an essential antioxidant for vegetable and animal metabolism.^[65] Additionally, it works as an enzyme cofactor. Ascorbate may be produced in the liver or kidneys of many animals, such as non-human primates, guinea pigs, humans, and several varieties of bats and birds. However, other animals, including non-human primates, humans, guinea pigs, and other species, have lost this capacity due to a buildup of abnormalities in the coding sequence of L-gulono-1,4-lactone oxidase, the final committed enzyme of the pathway. The decrease in selection pressure to maintain the route function results from dietary modifications that include plenty of fruits and vegetables. As a result, this component must be included in the diet, with fruits and vegetables serving as the significant suppliers of ascorbate.^[70] Antioxidants can reduce the chance of developing chronic diseases through additive and synergistic effects. Because of this, fruits and vegetables help to prevent long-term disorders such as heart, neurological, cerebral, and blood-related illnesses, as well as hypertension, diabetes, cancer, and strokes. Different studies which are conducted on animal species also highlighted that the consumption of fruits and vegetables that are rich in ascorbic acid would help protect the body against cardiovascular disorders, gastrointestinal disorders, cancer, skin infections and diabetes through the reduction of insulin glycation and by increasing glucose homeostasis.^[71] Therefore, the most crucial characteristic of ascorbic acid is its antioxidant activity, which also aids in treating several ailments, including cataracts, age-related muscle damage, malignancy, and cardiac disorders.^[72]

Vitamin C and CVD

CVD is multifaceted, containing several notable risk factors, including diet, tobacco smoking, diabetes, and hypertension.^[56] Much of the literature has documented that vitamin C-rich foods utilization, mainly fruits and vegetables, is linked with a decreased risk of CVD. Contradictory results have also been reported in the literature. Increased consumption of dietary vegetables and fruits alleviates the risk of heart disease.^[73] This connection is partially linked to antioxidants, such as vitamin C and vitamin E, in these foods, protecting from oxidative damage by preserving biological molecules. Captivating verification has supported that oxidative damage caused by ROS is linked with an elevation of CVD.^[74] In numerous epidemiological studies observational studies and randomized controlled trials, the association between antioxidants and incidence of CVD have been inspected. However, the outcomes and evidences of the literature are unstable. While few of the observational studies have documented an inverse relationship between dietary intake of vitamin C alone, or with other antioxidant vitamins and the probability of cardiovascular impediments,^[75] however has not been observed in randomized controlled trials.^[76]

Vitamin C and gastrointestinal diseases

Conflicting data is available on the protective effect of vitamin C and other antioxidants on pancreatic cancer in one of the largest cohorts from the Netherlands containing 120,000 participants with 16 years of follow-up with no demonstration of benefit,^[77] in contrast to recent another large cohort study exhibiting that patients taking the highest three quartiles of all of vitamins C, E and selenium collectively, has a lower risk of pancreatic cancer.^[78] A meta-analysis by Kubo et al.^[79] containing 10 observational studies shows that vitamin C intake is inversely related to the risk of esophageal adenocarcinoma without gastric cardia carcinoma.

A potential protective effect of vitamin C on the production of gallstones, clinical and experimental data has been documented in the late ninety’s.^[80] This might be related to the alleviation in bile acid biogenesis and the supersaturation of bile-containing cholesterol because of insufficient cholesterol 7α-hydroxylation in ascorbic acid deficiency. In an observational study containing 2129 participants, the participants documenting regular vitamin C supplementation showed remarkably less frequency of gallstone disease than those not taking vitamin C.^[81]

Role of vitamin C in skin

Vitamin C is responsible for the production of the skin barrier and collagen in the dermis and performs a physiological role in the skin versus skin oxidation, in the antiaging of wrinkles, and cell signal pathways of cell growth and differentiation, correlated with the prevalence and development of different skin diseases.^[82] Vitamin C is also responsible for UV-induced oxidative stress resistance, hindrance of melanogenesis, and assistance of the differentiation of keratinocytes and has been utilized as a clinical treatment reagent for a long time. Many systemic diseases in humans induce scurvy in the world’s navies due to Vitamin C deficiency.^[83]

A familiar type of porphyria, Porphyria Cutanea Tarda (PCT), is present in humans. It is identified clinically by acute and chronic skin blistering upon exposure to sunlight. It typically causes considerable distress among patients in the middle and late stages of the disease.^[84] The antioxidant ability of ascorbic acid hinders the catalytic oxidation of CYP1LA2, making vitamin C an excellent potential drug for PCT treatment. The disease’s prevalence and development are associated with iron content: the higher the iron content, the more the disease severity.^[85]

Atopic dermatitis (AD) is another chronic and deteriorating inflammation of the skin correlated with allergies. Lesions containing erythematous papules with itching or scaling affect 15–30% of children.^[86] Essential determinants of the human skin barrier are keratinocytes and their intercellular lipids and keratinocyte differentiation and the formation of interstitial material is enhanced by vitamin C.^[87] Ceramide production in keratinocytes and enhancement of overall epidermal barrier function is also stimulated by Vitamin C.^[88] With an elevation of clinical symptoms of AD, vitamin C and ceramide levels have been reduced, which has determined the positive correlation between vitamin C and ceramide levels.^[89] Vitamin C may impact the functionality and quantity of melanocytes, alleviating their formation as a result.^[90] Vitamin C indirectly causes hindrance in the action of tyrosinase due to its antioxidant capability, lowering melanogenesis.

Vitamin C and diabetes

Oxidative stress related to hyperglycemia and pancreatic β cell function and reduction in diabetic complications mainly appears to be reduced by vitamins C and E.^[91] Furthermore, the impact on free radicals, reducing oxidative damage, and the crucial role in enhancing antioxidant-related defense in patients with diabetes are the main processes involved in the antioxidant activity of vitamins C and E.^[92] Supplementation of vitamin C in diabetes mellitus patients may also be favorable.

Scavenging oxidative stress in neurodegenerative diseases

There are a variety of illnesses known as neurodegenerative diseases, which are characterized by the gradual degeneration of the central or peripheral nervous system’s anatomical and functional state. There are almost 600 diseases, which also include Huntington’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis. The human body’s many physiological processes and central nervous system, which are concentrated in the brain, depend on ascorbic acid, or vitamin C. (CNS) homeostasis.^[57] The brain is a type of organ particularly vulnerable to oxidative stress and the activity of free radicals, which are connected to high quantities of unsaturated fatty acids and rapid cell metabolism. Ascorbic acid is an antioxidant by directly scavenging reactive oxygen and nitrogen species produced during ordinary cell metabolism. Ascorbic acid manufactures molecules like collagen, carnitine, tyrosine, and peptide hormones as an enzymatic co-factor, performing non-oxidant actions inside the (CNS).

Additionally, it has been suggested that ascorbic acid might encourage myelin growth in Schwann cells. Further, ascorbic acid functions as a co-factor in the synthesis of neurotransmitters, notably dopamine and norepinephrine, which are catecholamines.^[93] Vitamin C is a key antioxidant, co-factor for many enzymes, and a necessary nutrient. Our immunological, neuron, and bone cells, in particular, require a lot of ascorbic acid to function at their best. It plays a role in synthesizing neurotransmitters, neuropeptides, carnitine, collagen, and other substances essential for wound healing, energy metabolism, and nervous system function.^[94] The brain and neuroendocrine tissues have high ascorbic acid levels. Because ascorbic acid concentrations in the brain are higher than in other organs, as has already been noted, it is likely to help preserve cognitive processes [79]. In newborns, ascorbic acid deficiency can lead to memory impairments due to decreased hippocampus neurons.^[95] Optimal ascorbic acid levels in older persons may help minimize the severity of numerous degenerative illnesses, including Parkinson’s disease, by regulating dopamine.^[96] Because of this, ascorbic acid is well known for helping to prevent various diseases, particularly those linked to oxidative stress, like cardiovascular and neurological dysfunctions.

Prooxidant in viral disorders

The coronavirus disease (COVID-19) pandemic is one of numerous significant infectious illness epidemics that have emerged in the twenty-first century, severely impacting people’s lives and means of livelihood everywhere. Several viral diseases have caused high rates of mortality & morbidity and have spread across borders to infect people in numerous countries.^[97] As a powerful antioxidant with high therapeutic concentrations, ascorbic acid is now widely acknowledged to paradoxically have pro-oxidant effects (like free radical production) through the reduction of transition metal. Leucocytes, lymphocytes, and macrophages are exceptionally high in quantities of ascorbic acid. It aids in enhancing chemotaxis, neutrophil phagocytic capability, oxidative killing, and lymphocyte proliferation in addition to supporting these processes. Ascorbic acid restores cellular antioxidants including tetrahydrobiopterin and -tocopherol, while directly scavenging oxygen-free radicals.^[98] Due to its various benefits, ascorbic acid is an essential therapeutic agent for respiratory infections, a potent antioxidant with anti-inflammatory and immune-supporting qualities. Coronaviruses like influenza viruses and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase oxidative stress in the body, which in turn can cause cellular and tissue damage. It has been demonstrated to be a safe and effective treatment for severe respiratory viral infections to deliver large amounts of vitamin C (in the form of ascorbic acid or ascorbate) in combination to traditional supportive therapies. High dosages of antibacterial, corticosteroids, and antiviral medications that might be toxic, immunosuppressive, and adrenal depressive, aggravating the course of the condition, could be considerably reduced with high-dose vitamin C treatment. Antiviral and immune system-boosting effects of ascorbic acid are significant. Ascorbic acid is crucial for generating type I interferons during the antiviral immune response.^[88] Treatment of viral diseases presents a perplexing to the physician and frequently an unrewarding problem, specifically since some of the 50 different diseases of man are of viral etiology. It is commonly known that vitamin C helps connective tissue remain stable and tensile strong. This trait encourages, among other things, the construction of a barrier to ward against contagious diseases. Capillary resistance gradually declines and sensitivity to the effects of some toxins appears to rise when ascorbic acid stocks are significantly depleted during infectious illnesses. It has been proposed that modifying cells’ susceptibility to viral invasion could give a mechanism for both controlling and avoiding infection.

Vitamin C is both an antioxidant and prooxidant

Vitamin C is a strong free radical scavenger in the plasma, protecting cells against oxidative damage created by (ROS) at physiological concentrations.^[99] Because of ascorbic acid’s antioxidant property, it can potentially alleviate the damaging ROS, producing a comparatively stable ascorbyl free radical. Ascorbate can act as a reducing agent. One electron’s donation by ascorbate gives rise to ascorbyl radical, monodehydroascorbate (MDHA) or semi-dehydroascorbate (SDA). Further oxidization gives rise to DHA. DHA is unstable and promptly breaks down, forming diketo-L-gulonic acid, which breaks down to oxalic and L-chronic acid. In vitro tests executed under physiological conditions manifest greater feasibility of ascorbic acid pretreated cells, which might result in ascorbic acid prevention of oxidant-induced apoptosis.^[100] However, vitamin C hampers the production of 8-oxodG in refined DNA, exposing it to peroxynitrite or UV light in the unavailability of added metal ions.^[101] Moreover, the study of Pournaghi-Azar and Ojani,^[102] has manifested alleviated strand breakage, as established by the comet analysis in lymphocytes. Results of cytotoxicity tests in S. demonstrating a protective effect of ascorbic acid^[103] concerning intracellular oxidation when cerevisiae cells firstly treated with ascorbic acid and later treated with Cr(VI).

Ascorbic acid supplies free radicals by donating hydrogen atoms that can pair up with unpaired electrons on free radicals. Ascorbic acid gives rise to an ascorbyl radical, which is comparatively non-reactive to biomolecules in this process.^[104] Non-reactive means that ascorbyl radical is relatively inactive enough to cause biomolecule impairment. However, in the availability of transition metals, ascorbic acid can also act as a pro-oxidant, relying on the presence of molecules in the environment.^[105] The reaction of ascorbic acid with transition metal ions could enhance their reduction, followed by elevated H2O2 formation^[106] and, therefore, OH˙ formation. The ascorbate acts as a reducing agent to iron and other transition metals, allowed by the standard redox potentials (Fe3+ -ferritin/ferritin, Fe2+ :SRP = −0.19 V; ascorbate˙-, H+/ascorbate– : SRP = .28 V).

Ascorbic acid alleviates Fe(III) to Fe(II), which decreases oxygen to hydroxyl radical.^[107] Cells contain low-molecular-mass intracellular »pools« of iron. Pro-oxidant effects may take place if these appear to be in proximity with ascorbate. The ability of ascorbic acid to increase transition metals’ release from protein complexes and their alleviation to catalytic forms indicates this compound also acts as a prooxidant.^[108] Also, vitamin C, which contains high body iron stores, exhibits prooxidant properties.^[109] In the availability of elevated body iron stores, vitamin C is especially hazardous, which makes vitamin C extremely prooxidant.^[110]

VITAMIN C ESTIMATION by NON-SPECTROPHOTOMETRIC METHODS

For the analysis of such modified commodities, the literature is loaded with the various types of methods, and attempts to search for efficient methods are in process. These attempts to estimate ascorbic acid in these samples have followed many methods. The colorimetric methods have been reviewed repeatedly, so various non-spectrophotometric methods promptly increased their number and kind. Different non-spectrometric methods are titrimetric, electrochemical, chemiluminescent, kinetic, chromatographic, and fluorometry.^[111]

Titrimetric methods

Numerous titrimetric methods have been documented using different titrants, briefly explored below.

2,6-Dichlorophenolindophenol (DCIP) has been a renowned reagent for the direct titration of ascorbic acid. In an acidic solution, this method is established to alleviate DCIP with ascorbic acid. This dye has been frequently referred to as “Tillimans Reagent.” Officially, the ca. 2 mg of ascorbic acid solution 5 ml of a combination of metaphosphoric acid and acetic acid is titrated with a standard solution of DCIP. The titrant is considered a self-indicator. However, as an official method, it is not significant for numerous pharmaceutical preparations containing Fe(II), Sn(II), Cu(I), SO₂, SO₃²⁻ and S₂O₃²⁻ ions generally linked with mineral or liver preparations. Moreover, the dye oxidizes tannins and sulfhydryl compounds, typically in fruits or biological materials. This method is appropriate only when the amount of dehydroascorbic acid is unsubstantial. The determination of the sample is also hampered due to its alkalinity.

Different titrimetric reagents containing iodine/bromine have been used to estimate ascorbic acid. To evaluate ascorbic acid with iodine, potassium iodate, potassium bromate and iodine monochloride, employing starch as many employees have documented a standard. However, it has been noticed in the final case that starch cannot be used in such titrations because it reduces the reaction rate between ascorbic acid and iodine. Few other reagents such as variamine blue, carbon tetrachloride or chloroform containing mercuric chloride and p-ethoxychrysoidine as standards and their utilization in ascorbic acid have been suggested.

Electrochemical methods

Various polarographic methods that have been established on the reduction waves taken from the condensation products of dehydroascorbic acid with o-phenylene diamine have been mentioned for the determination of Vitamin C. Reductones, diketogluconic acid and reduced sulfhydryl compounds do not probe where equimolar use or fewer concentration of o-phenylene diamine gives a dominant wave for dehydroascorbic acid. The methodology was later altered to include another oxidant, viz. 2,6-DCIP instead of silver nitrate and has been employed for the analysis of preserved fruits,^[112] fried potatoes^[113] and orange juices.^[114]

Voltammetric analysis using various electrodes (conventional electrodes, microdisk electrodes^[115] microband and multiple microband electrodes^[116] and carbon paste electrodes^[111] has been put forward for the estimation of Vitamin C. However the accuracy of the extensive relevancy of these electrodes reduces with repetition because of electrode smearing by oxidation commodities. Pournaghi-Azar et al.^[102] have described the analysis of pharmaceutical preparations and fresh fruit juices by utilizing electrogenerated ferriciniumcarboxylic acid as an intermediary, including electrocatalytic oxidation of ascorbic acid in homogenous formula. Due to this method, ascorbic acid (15–45 mg/100 ml) can be estimated in the samples of intensely colored, viscous and turbid fruit juices. For the catalytic determination of ascorbic acid in buffer solutions (pH 4.0), these employees promptly used a polypyrrole/hexacyanoferrate(II)-modified glassy carbon electrode. However, this procedure is not suitable for the Vitamin C analysis of fruit juices. On a glassy carbon electrode, analysis of fruits and vegetables has also been brought out by stripping voltammetry.^[117] This method contains the origination of ferroin when adding ascorbic acid to a mixture of iron(III) and 1,10-phenanthroline. Ferroin adsorption occurs on the electrode, followed by stripping voltammetric measurement in the cathodic route.

Chemiluminescent methods

For the foundation of many chemiluminescent methods for ascorbic acid, various systems are involved, including Cu(II) – luminol, Ce(IV) – rhodamine 6 G, Fe(II) – luminol – O₂, KMnO₄–luminol, H₂O₂–hemin – luminol and H₂O₂–luminol – peroxidase CL form.^[118] The identification boundary lies between 1.0–6.2 × 10⁻⁷ mol l⁻¹ and the higher-level boundary of the linear response range differs from 2.0 × 10⁻⁶ to 6.0 × 10⁻⁵ mol l⁻¹ ascorbic acid. These processes have been employed in analyzing fruits, juices, vegetables, etc. Based on the obstruction of the CL reaction of the luminol – Fe²⁺–O₂ system by ascorbic acid, a highly sensitive CL^[119] method for the determination of ascorbic acid (1 × 10⁻⁹–1 × 10⁻⁶ g ml⁻¹) in tablets and vegetables containing reagent flow injection analysis (FIA) is documented. However, another flow injection CL method has built on the sensitized photo-oxidation of ascorbic acid^[120] for its estimation in between 1 × 10⁻⁹–3 × 10⁻⁴ M. Qin and coworkers^[121]after immobilizing luminol and iron(II)/permanganate on an ion exchange resin column and evading with HCl – Na₂SO₄ solutions has created CL-based flow sensors for Vitamin C in vegetables and beverages. The calibration graph is linear, ranging between 1 × 10⁻⁹–1 × 10⁻⁶ g ml⁻¹ with a mid-range comparative to standard deviation of 2.3%. CL methods are actually highly vulnerable but for making measurements, they need modified spectrophotometer.

Kinetic methods

Kinetics in analytical chemistry has shown less significance except where reaching equilibrium in a reaction is lagging. Therefore, only a few kinetic techniques have been elaborated for the estimation of Vitamin C. By employing the reducing effect of ascorbic acid on DCIP^[122] (λ_max = 522 nm) or toluidine blue^[123] (λ_max = 600 nm), kinetic spectrophotometric methods with or without the application of hindered flow have been formulated. However, these procedures are time-consuming, consuming at least 20 minutes for one determination. The procedures containing DCIP alleviation, ascorbic acid (2 × 10⁻⁶–5 × 10⁻⁵ M) can be determined in samples of orange juice, parsley and potato containing recoveries of 98.0, 95.0 and 90.0%, accordingly. Homogeneous kinetic methods were evaluated either by measuring the reduction in absorbance of Co(III) – EDTA in a reaction mixture involving 20% ethanol and 0.08 M Britton – Robinson buffer (pH 5.5), at 540 nm or employing 5-[N-(3,5-dichloroquinoneimine)]-8-hydroxyquinoline. Zhang et al. have used catalytic kinetic spectrophotometry for determining ascorbic acid up to 0.6 μg ml^−s (λ_max = 555 nm) in a hydrochloric acid – potassium dihydrogen phosphate buffer containing rhodamine B, vanadium ion and potassium bromate solution. Catalytic estimations, however, suggest the benefit of elevated sensitivity, but they need reproducibility of blending the analyte with the reagent and an absolute reaction time. Kinetic methods can manifest harmful errors because of complex matrices and a slow reaction rate in samples.^[111] Analyses of synthetic samples, urine and soft drinks using chloramine T-KI-starch or KBr-methyl red as standard or Ce(IV) as a titrant in 0.1 M sulfuric acid and as a self-indicating system have been employed by titrimetric FIA^[124] which is dependent on the redox characteristics of ascorbic acid. Although, the procedure has been put forward by Sultan [124] using Ce(IV) as a titrant which needs strong acidity control.

Chromatographic methods

Liquid chromatography (LC) has generally been utilized to separate and determine ascorbic acid. For ascorbic acid analysis, different LC methods^[125]employing highly polar columns and mobile phases containing several proportions of acetonitrile and methanol, including dilute phosphate – citric acid – acetic acid buffers or an aqueous solution of citric acid are described. By LC, using acetonitrile – water (pH 4.2; 10 mM phosphate buffer) (4:1) or acetonitrile – dilute potassium dihydrogen phosphate (3:1/1:1) as mobile phases^[126] and by observing the UV absorbance at 210 or 254 nm, the oxidized and reduced forms of ascorbic acid have been determined in various samples. After alleviating dehydroascorbic acid with homocysteine,^[127] tin(II) chloride^[111] or dithiothreitol, utilizing a blend of methanol–0.25% potassium dihydrogen phosphate (1:1) acetonitrile – water as mobile phases with UV detection at 244 nm,^[127] the estimation of total Vitamin C in orange drinks and other food samples has been documented. For the concurrent determination of ascorbic acid and dehydroascorbic acid in beverages, fruits and biological fluids by LC with UV (300 or 254 nm) or electrochemical detection, extremely sensitive and selective procedures^[111] have been suggested. The sample of fruits, vegetables and animal tissues have been examined for amounts of ascorbic acid employing 1.8% THF–0.3% metaphosphoric acid^[128] and a mixture of acetonitrile – acetic acid – water^[129] as mobile phases followed by UV detection at 244 nm. Preventive strategies are required when examining citrus fruit juices because citrate is seemingly responsible for creating gaps in the column. Although acetonitrile has generally been utilized as a mobile phase, holding of its solution needs precautionary measures to avert from evaporating its vapors (Figure 5).

Figure 5. Column chromatography.

Fluorometry methods

For ascorbic acid analysis of several samples involving fruits, vegetables and human serum, fluorometric analysis^[130] has been used. The production of a fluorescent commodity by the reaction of dehydroascorbic acid with o-phenylene diamine is the foundation of such procedures,^[111] containing the (AOAC) official method of analysis which includes the oxidation of ascorbic acid with several oxidants such as activated charcoal and diluted iodine solution. Hongyong and Sanhe reported an upgraded microfluorometric procedure utilizing DCIP as an oxidizing agent despite being acid-washed, excluding the filtration and transfer operation steps. Despite metaphosphoric acid – acetic acid for releasing the sample, Weiquian has suggested utilizing an oxalic acid – acetic acid solution, which is inexpensive. However, Bourgeois and Mainguy^[111] examined fluorescence quenching by contaminants. Moreover, dehydroreductic acid, dehydroreductones, and alloxan interference have been reported. According to Augustein et al.,^[131] when this method is employed in the analysis of manufactured potato commodities, it gives an elevated value of Vitamin C.

Future prospective

Considering the above discussion, this paper shows that ascorbic acid insufficiency is widespread and especially prevalent in low- and middle-income nations. Until today, people’s daily ascorbic acid intake levels in many countries have not been evaluated. Therefore, further study is needed to examine the significance of this vitamin in various parts of the world, and through this work, more perspectives on this vitamin will become available. For now, ascorbic acid may be utilized directly in the field to determine the global vitamin C status [14]. As the metabolism process of ascorbic acid is not transparent yet, there are still many things to discover about this vitamin. There is still a need to highlight the health benefits of this vitamin, for more consumption of healthy and cheap sources, and for getting ample amounts of ascorbic acid that is beneficial from a health point of view. Numerous research has examined the possibility of using ascorbic acid supplements to lower a variety of non-communicable illnesses and infections [88]. However, there is still substantial dispute over the effectiveness of supplementation, partly because studies are poorly organized and do not consider the subjects’ baseline ascorbic acid level [89]. In addition, local data on deficiencies concerning changing food intake and other risk factors are considered by national and local governments. These risk factors must be considered when reviewing and revising the global recommendations for vitamin dietary intakes. Additionally, healthcare professionals need to be on the lookout for hypovitaminosis C and vitamin deficiencies in the at-risk populations that have been widely publicized [17].

Conclusion

In conclusion, ascorbic acid (vitamin C) is the body’s most crucial antioxidant, containing ample health-related benefits. A balanced amount must be taken in a daily diet and from raw and fresh fruits and vegetables rather than processed ingredients. These citrus fruits and vegetables contain all those sources that are cheap and easily accessible for all individuals. Low- and middle-income countries experience a greater deficit of ascorbic acid than high-income or developed countries. Vitamin C supplements are also beneficial in certain amounts and conditions. Chronic illnesses, neurological disorders, viral infections, and other conditions can all be prevented by ascorbic acid. Due to its anti-inflammatory, anti-cancer, anti-viral, anti-oxidant, immunosupportive properties, it prevents humans from diseases.

Acknowledgments

We are thankful to Food and Nutrition Society, Gilgit Baltistan, Pakistan for providing us with access to the publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).