Chapter 16

Ascorbic acid
Bharti Mittu1, Zahid Rafiq Bhat5, Ashish Chauhan1, Jasmeet Kour2, Anindita Behera3 and Mahaldeep Kaur4
1
National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Sangrur, Punjab, India; 2Department of Food Engineering and
Technology, Sant Longowal Institute of Engineering and Technology, Sangrur, Punjab, India; 3School of Pharmaceutical Sciences, Siksha ‘O’
Anusandhan Deemed to be University, Bhubaneswar, Odisha, India; 4Department of Microbial Biotechnology, Panjab University, Chandigarh, India;
5
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Sangrur,
Punjab, India

16.1 Introduction
Ascorbic acid is commonly known as Vitamin C. In 1928 Szent-Gyorgyi isolated ascorbic acid from the adrenal cortex. He
also demonstrated the reducing property of ascorbic acid and named this compound “hexuronic acid” (Szent-Gyorgyi,
1928). The chemical structure of vitamin C being hexonic acid aldono-1,4-lactone with an enediol group on C2 and C3 was
achieved by Norman Haworth in 1933 (Haworth & Hirst, 1933). It is also called L-ascorbic acid, a powerful antioxidant,
and free radical scavenger that protect our tissues, cell membranes, and DNA from oxidative damage. It is found to be
stable in its dry condition but it quickly oxidizes in solution form on exposure to heat or light. It is an essential micro-
nutrient and a key element for the metabolism of almost all living organisms. It is abundantly available among animals and
plants naturally as they have the capability to biosynthesize ascorbic acid. Vertebrates such as mammals, reptiles, and birds
are capable of synthesizing ascorbic acid; only a few species of animals such as guinea pigs, human beings, and primates
require ascorbic acid in their diet (Hornig et al., 1975). Humans are unable to synthesize vitamin C endogenously due to the
lack of an enzyme, L-gulono-gamma-lactone oxidase (Sheraz et al., 2011). It acts as an essential cofactor and electron
donor during collagen hydroxylation that boosts the maturation of intracellular and extracellular collagen production. It
also protects the body against environmental stress and is used for repairing and growth of bodily tissues and is also
involved in protein metabolism. Its deficiency causes scurvy and capillary fragility, which results in weakness of the tissues
and collagens an essential dietary component (Li et al., 2007).

16.2 Sources/derivatives
The human body is unable to synthesize and store ascorbic acid. Ascorbic acid must be consumed in the diet. Therefore, it
is important to include an adequate amount of ascorbic acid in our daily diet from exogenous supplements or sources. The
current daily value (DV) for vitamin C is 90 mg. The bioavailability of ascorbic acid from food is assumed to be very high;
Kakadu plums being the richest source contain 5300 mg of ascorbic acid per 100 g. The other sources include red acerola
cherries, rose hips, fruits and vegetables, citrus fruits, tomatoes, and potatoes. Other food sources include red and green
peppers, kiwifruit, broccoli, strawberries, brussels sprouts, and cantaloupe. It is not naturally present in grains instead it is
added to some fortified breakfast cereals. Consuming five varied servings of fruits and vegetables a day can provide more
than 200 mg of vitamin C. According to the Food and Drug Administration (FDA), one serving of any of the foods
mentioned above contains more than 20% of the recommended DV of vitamin C. Along with this, it is also found in dietary
supplements in the form of nutraceutical. Nutraceuticals are oral dietary components naturally found in foods believed
to have medical or health benefits. The global vitamin C production is currently estimated at 11,000 tons annually.
Supplements typically contain vitamin C which has equivalent bioavailability to that of naturally occurring ascorbic acid
in foods, such as orange juice and broccoli (Segall & Mayono, 2008; Carita et al., 2020). Other forms of vitamin C
supplements include sodium ascorbate, calcium ascorbate, other mineral ascorbates, ascorbic acid with bioflavonoids,
and combination products, such as Ester-C, which contains calcium ascorbate, dehydroascorbate, calcium threonate,

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290 Nutraceuticals and Health Care

TABLE 16.1 Sources of ascorbic acid and its content.

S. No. Source Content per 100 gm

1 Kakadu plums 5300 mg (Richest source)
2 Red acerola cherries 1677 mg
3 Rose hips 426 mg
4 Green chili peppers 242 mg
5 Guavas 228 mg
6 Yellow peppers 183 mga
7 Blackcurrants 181 mg
8 Thyme 160 mg
9 Parsley 133 mg
10 Mustard spinach 130 mg
11 Kale 120 mg
12 One medium kiwi 71 mg
13 Broccoli 89 mg
14 Brussels sprouts 85 mg
15 Lemons 77 mg
16 Lychees 72 mg
17 American persimmons 66 mg
18 Papaya 62 mg
19 Strawberries 59 mg

20 Oranges 53 mg
a
The highest vitamin C content.

xylonate, and lyxonate. The vast applications of ascorbic acid in the food industry, pharmaceutical industry, and
cosmetic industry have led to quantification, identification, and qualification of ascorbic acid and enhanced its
importance among researchers, pharmaceutical, and food industries as well. Content of ascorbic acid per 100 gm of sources
has been calculated in Table 16.1 (Nermin et al., 2018).
Ascorbic acid cannot be synthesized in the human body due to the absence of an enzyme that converts glucose to
ascorbic acid. Ascorbic acid can be easily oxidized to form dehydroascorbic acid (DHAA) while can also be reversed
easily (Groff et al., 1995). Thus, it is more important to derivatize the ascorbic acid and few such derivatives of ascorbic
acid are mentioned in Table 16.2.

16.3 Methods of extraction and characterization

Ascorbic acid is a water-soluble vitamin having the chemical formula C6H8O6. It plays a crucial role in human health and
involving several physiological functions of the human body. It is associated with health risks considering its deficiency
and excess in the body. Thus it is important to establish the approaches for monitoring the concentrations of vitamins in
different matrices. This vitamin is not formed in the human body due to the absence of an enzyme that converts glucose to
vitamin C. This vitamin can be easily oxidized to form DHAA while can also be reversed easily (Groff et al., 1995). As
vitamin C requirement can’t be fulfilled by the human body, it needs to be supplied from diet or supplements (Nermin
et al., 2018; Shrikhande et al., 1974). However, an overdose of vitamins is also not recommended and can be toxic as well.
In order to take vitamins in an adequate amount, it is necessary to have some methods in place for the extraction and
characterization of different vitamins. Different methods have been developed for the extraction and characterization of
vitamins.
Sample preparation for analysis of water-soluble vitamins involves extraction using diluted HCl solution or methanol.
Ascorbic acid was found to be highly soluble in methanol than in an aqueous solution. Liquid chromatography has been
employed for the quantification of total vitamin C in several food samples. The method is employed for ascorbic acid
 Ascorbic acid Chapter | 16 291

TABLE 16.2 Various derivatives of ascorbic acid.

S.No. Derivatives Functions References

1 Ascorbic acid (AA)
2 Sodium ascorbyl phosphate
(SAP)
3 Magnesium ascorbyl
phosphate (MAP)
4 Ascorbylpalmitate (AA-PAL)
5 3-O-Ethyl ascorbate (EAC)
Strong reducing agent, antioxidant agent, synthesize collagen Elmore (2005)
Used in cosmetic products for UV protection, collagen production, Tsao et al. (1990)
antioxidant action, and skin lightning and brightening effects also
enhance hepatocyte growth factor production
For suppression of skin pigmentation, whitening of dark skin, boost Kameyama et al.
collagen synthesis of skin as antiaging agent, exfoliating effect (1996)
Antimutagenic, antineoplastic, antioxidant role Shimpo et al.
(1996)
Antioxidant activity, reducing skin darkening after UV exposure, Sitren (1987)
promotion of growth of nerve cell decreases the damage due to
chemotherapy

6 Ascorbylglucoside (AA-2G) Inhibits the melanin production, helps in production of collagen Butwong et al.
(2020)

extraction using 3% metaphosphoric acideacetic acid and relatively its oxidation to DHAA. Ultrasound-assisted extraction
is employed for the extraction of vitamin C. It is a less time-consuming method that gives the highest yield (Hong & Van,
2012; Verma et al., 2020). Moreover, supercritical fluid extraction is yet another beneficial approach for its extraction. It
works on the solvent power and density relation of the solute and the solvent. Moreover, it is also beneficial for ther-
molabile substances (Pellicano et al., 2019). Similarly, dispersive liquideliquid microextraction (DLLME) has also been
employed for the extraction of ascorbic acid after oxidationereduction reaction with methylene blue (Zhang et al., 2018)
(Fig. 16.1).

FIGURE 16.1 Methods of extraction of ascorbic acid.

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TABLE 16.3 Methods of characterization of ascorbic acid.

S.No. Characterization technique Features References

1 Capillary electrophoresis Analytical and quantitative method, separates sample Voeten et al.
components according to their sizes and charge, fast, (2018)
high separation efficiency
2 High-performance liquid chromatography Analytical method, high selectivity and sensitivity, used Noh et al.
for quantification of different vitamins (2020)
3 Reversed-phase high-performance liquid Determination of water-soluble vitamins Noh et al.
chromatography (2020)
4 High-performance liquid chromatography Detection of vitamins Noh et al.
etandem mass spectrometry (2020)
5 Microbiological assays Perceived by global authority who established this Zhang et al.
method as the best quality level for a long time, (2018)
improved precision, and accuracy

6 Biosensors Excellent tool for detecting vitamins in different matrices Zhang et al.
is optical biosensors. This technique has been associated (2018)
with simplicity, low cost, and its application in field
analysis

Ascorbic acid is most often characterized by reversed-phase HPLC. The mobile phase system used for water-
soluble vitamins involves combinations of methanolewater in various ratios along with triethylamine or ion-pair
reagents (sodium heptylsulfonate, sodium octylsulfonate, or sodium dodecyl sulfate). However, it involves
several drawbacks in resolution, dead retention volume, and low pH that causes increased degradation and
dissolution of the silica-based analytical column. Thus, it is necessary to adjust the pH of the mobile phase below
the pKa of L -ascorbic acid, i.e., 4.17, to stop the column degradation (Zhang et al., 2018). Likewise, ultrahigh-
performance liquid chromatography has also been employed for the quantification of vitamin C in fruits and
vegetables which is a rapid, sensitive, and reproducible method (Noh et al., 2020). Moreover, the other analytical
and quantitative method like capillary electrophoresis is used to quantify ascorbic acid according to their sizes and
charges. This technique is fast, associated with high separation efficiency. It can analyze several samples
concurrently in multicapillary systems (Voeten et al., 2018). Moreover, an excellent tool for detecting vitamins in
different matrices is optical biosensors. This technique has been associated with simplicity, low cost, and its
application in field analysis (Zhang et al., 2018). Electrochemical method and microfluidic device are the two
detection methods of vitamins and traces of vitamins B1, B2, and C, respectively. One such example of this method
is an electrochemical synthesis of poly(3,4-ethylenedioxythiophene)ezirconia nanocomposite for the examination
of vitamins B2, B6, and C (Baghizadeh, 2015). Different characterization techniques used for ascorbic acid are
enlisted in Table 16.3.

16.4 Chemistry
The generic name of L-ascorbic acid is vitamin C which is a freely water-soluble vitamin (300 g/L at 20
C). It has
numerous chemical names such as ascorbate. It is made up of asymmetrical six-carbon atoms (C6H8O6) which is
structurally correlated to glucose. The molecular weight of this vitamin is 176.12 g/mol having a melting point of
190e192
C and having a density of 1.65 g/cm3. It shows a density of approximately 1.65 g/cm3. It is difficult to solubilize
in alcohol (20 g/L at 20
C) and is not soluble in chloroform, ether, and benzene. It has two pKa values: 4.2 and 11.6. The
pH of a 5% (w/v) solution in water is 2.2e2.5. It acts as an antioxidant due to its high reducing power. It is also used as
food additives, thereby preventing the deterioration of food, and is also used to improve the color and baking property of
flour or dough by acting as an additive (Fig. 16.2).
This vitamin is not formed in the human body due to the absence of an enzyme that converts glucose to vitamin C. This
vitamin can be easily oxidized to form DHAA while can also be reversed easily (Groff et al., 1995). Thus, it is more
important to derivatize the ascorbic acid and few such derivatives of ascorbic acid are mentioned in Fig. 16.3.
 Ascorbic acid Chapter | 16 293

FIGURE 16.2 Conversion of ascorbic acid to dehydroascorbic acid.

FIGURE 16.3 Important derivatives of ascorbic acid.

16.5 Mechanism of action

Vitamin C has remarkable actions with a broad spectrum of mechanisms. It holds a unique position among the vitamins.
The roles of vitamin C are getting more transparent and clear with advanced research and have delineated its significance in
biological systems. Vitamin C facilitates the structural process of tissue repair along with collagen formation, involved in
oxidationereduction reactions as well as other metabolic reactions. Vitamin C exerts its reducing action due to the
presence of the enediol group (Harris, 1953). Endothelial cells contain a sodium-dependent transport system across the
membrane that carries ascorbate ions into these cells while DHAA is transferred through facilitative glucose that is further
reduced to ascorbate. However, the efflux of ascorbate could be enhanced by the calcium-dependent mechanisms which are
able to retain intracellular concentration at a much higher rate than the extracellular one. Reports suggest that during sepsis
inflammatory cytokines resist ascorbate uptake in endothelial cell culture. Moreover, ascorbate deficiency is also caused in
endothelial cells due to acute level of hyperglycemia in septic patients and impairs endothelium-based modulation.
Ascorbic acid has key roles to play in the brain, immune system, sepsis, and bone (Wilson, 2009). All the concerned organs
occupied different modes of action (Wolbach & Howe, 1926). Interestingly, cessation in bone formation and new tooth
formation was first reported on guinea pigs (Harris, 1953). Similarly, in human beings, the impact of ascorbic acid is more
on the cessation of osteogenesis. Aghajanian et al. (2015) analyzed several epidemiological studies and genetic mouse
models regarding the effect of vitamin C show a positive effect on bone health (Aghajanian et al., 2015). There are well-
known functions of an ascorbic acid described in Table 16.2 (Kuiper & Vissers, 2014). Certain kinds of recurrent infections
result from the genetic disorder of neutrophil function such as rare autosomal deficiency syndrome, defective leukocyte
294 Nutraceuticals and Health Care

FIGURE 16.4 Mode of action of ascorbic acid.

generation, and ChediakeHigashi syndrome. The dosage of ascorbic acid stabilizes the microtubules via the mechanism of
phagocytosis as represented in Fig. 16.4 (Boxer et al., 1979).

16.6 Bioavailability of ascorbic acid

Like ADME (absorption, distribution, metabolism, excretion) and toxicology of a drug or an active pharmaceutical or
nutrient, the bioavailability of an active constituent is increasingly gaining importance in therapeutic efficacy. This is one
of the prime factors in drug development and drug discovery. As per the definition by US FDA, bioavailability is “the rate
and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available
at the site of drug action.” Generally, bioavailability is measured by determining the area under a curve, or AUC. AUC is a
technique of quantitative measurement of the bioavailability of a drug and determined with a plot of concentrations of the
drug in blood analyzed at frequent intervals. AUC and concentration of unaltered drugs in the patient’s blood are directly
proportional (Allam et al., 2011; Veber et al., 2002).
The bioavailability of vitamin C in humans is highly complex. As vitamin C is a micronutrient, its bioavailability (in
drug, dietary forms, or formulations) can be represented by the amount absorbed by the intestines and available for
different metabolic processes in the human body. Vitamin C levels in vivo are majorly influenced by its pharmacokinetic
processes. Active transport of vitamin C into the body has been found to occur via SVCT1 and SVCT2 which are the two
sodium-dependent vitamin C transporters (Łukawski et al., 2020; Savini et al., 2008). Interestingly, SVCT1 and SVCT2
also exhibit different affinity for their distribution in various tissues and expressions which influence the rate of uptake of
vitamin C. Moreover, one of the transporters (SVCT1) found in epithelial cells/tissues is accountable for uptake by the
intestine and renal reabsorption of vitamin C when ingested orally. It helps in maintaining the homeostasis of body ho-
meostasis by preventing excess urinary loss (Savini et al., 2008; Wohlrab et al., 2017). In addition, another transporter,
SVCT2 shows different expression and distribution patterns, i.e., specialized and metabolically active tissues. SVCT2
delivers ascorbic acid at the sites where the requirement of this vitamin is for some enzyme-mediated reactions or to protect
the tissues from oxidative stress (Savini et al., 2008). Ascorbic acid acts as a reducing agent and for the antioxidant activity;
it undergoes one- and two-electron oxidations and gets converted to ascorbyl radical and DHAA. Accumulating shreds of
 Ascorbic acid Chapter | 16 295

evidence have reported that DHAA can be transported to the small intestine by the facilitative glucose transporters GLUT2
and GLUT8 (Corpe et al., 2013). Whereas, DHAA is internalized into the cells by GLUT1 and GLUT3 followed by
reduction to ascorbate intracellularly (Corti et al., 2010).
Interestingly, the pharmacokinetics has shown variations in the level of vitamin C in blood and rate of excretion by
urine after intake of the vitamin Cecontaining test substance. Maximal plasma levels (Cmax) of vitamin C are attained
about 2 h after ingestion. Moreover, an early animal study has reported that Cmax of vitamin C provided in citrus fruit
media is delayed as compared to synthetic source but the bioavailability of vitamin C in citrus fruits is more than the
synthetic source (Lykkesfeldt & Tveden-Nyborg, 2019). In addition to this, a comparable trend was observed in a clinical
trial where the subjects are supplemented with 500 mg of vitamin C with or without a citrus fruit extract (Vinson & Bose,
1988; Padayatty et al., 2004). The citrus fruit extract showed a much similar trend in the fact that it achieved the maximal
plasma levels late by 1 h but the bioavailability of vitamin C increased by 35%. The citrus fruit extract increased the
urinary excretion of vitamin C by 24 h in the presaturated but decreased in nonsaturated patients than the patients treated
with only a synthetic source of vitamin C. So the baseline status of vitamin C affects the bioavailability of vitamin C. In
two other studies, the urinary excretion of vitamin C is increased in presaturated patients with a source of fruit juice (Levine
et al., 1998; Lykkesfeldt & Tveden-Nyborg, 2019). Another presaturation study showed the effect of bioflavonoids on the
plasma levels and 24 h urinary excretion of vitamin C (Johnston & Luo, 1994). The intestinal bioavailability of a dose of
500 mg of vitamin C is lesser as the same quantity cannot be available through a normal daily diet (Padayatty et al., 2004).
Pharmacokinetic studies have indicated that the relative availability of vitamin C from synthetic sources or natural form
in foods or fruit juices (Kondo et al., 2012; Uchida et al., 2011). An intestinal triple lumen tube perfusion model was
chosen by Nelson et al. for a comparative study of absorption of vitamin C from the synthetic origin and a natural source
like orange juice solution. The study measured the intraluminal events and no difference was found between the two test
solutions (Nelson et al., 1975). Some pharmacokinetic studies have reported the decreased Cmax and urinary excretion of
vitamin C in presence of food and fruit juices but the differences are minimal (Kondo et al., 2012; Uchida et al., 2011).
A study suggests that the bioavailability (plasma levels) of synthetic versus a natural source of vitamin C from kiwifruit
in nine nonsmoking male individuals of 18e35 years had optimized levels of plasma vitamin C (>50 mM) (Carr et al.,
2013). The individuals were given either a chewable tablet of vitamin C (200 mg) or an equal dose of crude kiwifruit. After
an intervention, fasting blood and urine levels of vitamin C were checked after half an hour, then an hour, and subsequently
for 8 h. Ascorbate level in plasma increased after 30 min from the intervention but no significant differences in the AUC
were observed between the two interventions. The net increase in the level of vitamin C ensures the indicated complete
absorption of the ingested ascorbate tablet and vitamin C derived from kiwifruit. Similarly, there was a proportional in-
crease in excretion of vitamin C by urine as compared to creatinine after 2 h. A significant difference between these two
groups was found with respect to the amount of excretion of ascorbate in the urine. About w40% of the ingested dose of
the tablet and w50% of the vitamin C derived from kiwifruit were reported. So the pharmacokinetic parameters showed
comparable bioavailability of vitamin C from the natural source and synthetic source (Carr et al., 2013; Lykkesfeldt &
Tveden-Nyborg, 2019).
For general consumption dose of vitamin C up to 2000 mg/day is considered safe (Hathcock et al., 2005). However,
smaller doses of vitamin C are better than taking larger doses as the reports from pharmacokinetic studies indicated that the
bioavailability of a single dose of ascorbic acid greater than 200 mg has lesser bioavailability (Levine, 1996). So ingestion
of the number of smaller doses is more bioavailable than a single larger dose. The bioequivalence study established that the
relative bioavailability of vitamin C from different tablet formulations is different as the slow-release formulations provide
superior vitamin bioavailability than the immediate release (Padayatty et al., 2004). The sodium and calcium salt forms of
vitamin C are also being evaluated. Interestingly, in preclinical studies, the calcium form was absorbed more rapidly and
excreted slowly as compared to natural vitamin C (Bush & Verlangieri, 1987). Additionally, the calcium form is better
tolerated in individuals sensitive to acidic foods (Gruenwald et al., 2006) (Fig. 16.5).

16.7 Stability, safety, and toxicology

The ascorbic acid content in different sources like fruits, vegetables, pharmaceutical products, and cosmetics decreases
with an increase in temperature and pH (Emese & Nagymate, 2008). The third most commonly consumed vitamin C has
been taken in the form of a supplement by a majority of adults. Thus it is necessary to regulate the stability of vitamin C in
foods and supplements. It is added to food in its salt forms. It is majorly used in several formulations like creams, cosmetic
products with alpha-tocopherol.
A substantial content of vitamin C in food gets diminished while storage and preparation. The stability of this vitamin
in different formulations is a critical issue and should be taken care of while manufacturing and while storage of products.
296 Nutraceuticals and Health Care

FIGURE 16.5 Bioavailability of ascorbic acid.

TABLE 16.4 Physical factors influencing stability of ascorbic acid.

Physical
factors Influence References
Moisture Moisture shows a key role in affecting degradation rates of ascorbic Tsao et al. (1996)
acid, and also causes discoloration of solid form of ascorbic acid
Air and light Upon exposure to air and light, ascorbic acid converts to dehydroascor- Sheraz et al. (2015)
bic acid
pH Alkaline environment have been rapidly affecting the oxidation of ascor- Yuan and Chen (1998), Buettner and
bic acid Jurkiewicz (1996)

Temperature Temperature fluctuations affected the concentration Jeney-Nagymate & Fodor (2008)

Major factors influencing the stability of ascorbic acid and degradation patterns are temperature, sunlight, moisture,
oxygen, pH, and viscosity. It is also catalyzed by metal ions, particularly Cu2þ, Fe2þ, and Zn2þ. Ascorbic acid breaks
down with time in tablets and syrups and even in the pure powder during storage. All the formulations of ascorbic acid
including the pure powder under the various storage conditions demonstrate that the concentration of ascorbic acid in the
various products reduced with time. Storage under refrigeration gave the highest stability, and minimized breakdown.
Physical factors affecting the stability of ascorbic acid have been discussed in Table 16.4.

16.7.1 Toxicity
Ascorbic acid has low toxicity and is not associated with any serious adverse effects even at a higher level of consumption.
The common adverse effects are due to the osmotic effect of unabsorbed vitamin C in the gastrointestinal tract, thus
causing diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances (Jacob & Sotoudeh, 2002). The
highest limit of intake of vitamin C is 2000 mg/day. Vitamin C worsens the state of patients having high iron load (Slivaka
et al., 1986; Nermin et al., 2018), thereby resulting in tissue damage (Jacob & Sotoudeh, 2002). The other adverse effects
that are associated with the high intake of this vitamin include reduced vitamin B12 and copper levels, metabolism, and
allergic responses (Wyngaarded, 1987; Nermin et al., 2018). Enamel erosion resulted in the usage of the unbuffered form
of ascorbic acid (Flemming et al., 2002). Vitamin C also acts as a prooxidant, thereby causing oxidative damage under
certain conditions. Earlier reports suggested as a prooxidant it results in chromosomal and/or DNA damage, thereby
causing cancer development (Lee et al., 2001). An intake of 1 g/day for a period of 3 months resulted in the generation of
 Ascorbic acid Chapter | 16 297

the stones in kidney (Alkhunaizi and Chan, 1996; Baxmann et al., 2003). High vitamin C intakes can also increase urinary
oxalate and uric acid excretion, thus causes to the formation of kidney stones in patients with renal disorders (Nermin et al.,
2018).

16.8 Applications of L-Ascorbic acid and its health benefits

16.8.1 Clinical and pharmacological relevance
16.8.1.1 Role in cardiovascular disease
Ascorbic acid protects the cardiovascular system by decreasing the systolic blood pressure, thus improving heart func-
tioning (Chen et al., 2013; Roberts, 2009; Sesso, 2008). It keeps the arteries flexible and strengthens the blood vessel wall.
It prevents damage by a heart attack, peripheral artery disease, and stroke by decreasing the chances of atherosclerosis
(Ashor et al., 2014).

16.8.1.2 Role in biosynthesis

L-Ascorbic acid is essential for the body to synthesize collagen for the cartilage as reported by Ballaz and Rebec (2019).
Ascorbic acid promotes wound healing by stimulating the formation of the epidermal barrier. It increases collagen syn-
thesis, wound closure time, and decreases the inflammatory responses of the wound in a healthy person (Charlesworth,
2019; D’Aniello, 2017; Sato, 2017).

16.8.1.3 Role as antioxidants

L-Ascorbic acid performs an important role in protection against oxidative stress in numerous tissues as discussed
(Abraham, 2014). It acts as an antioxidant and resists the damage caused by free radicals. Intake of diets rich in vitamin C
reduces the risk of arthritis. It has been observed that higher content of ascorbic acid in joints shows higher protection level
against the damage (Carr & Frei, 1999). Ascorbic acid is a strong antioxidant that can increase blood antioxidant levels in
the body. This process can lessen the risk of chronic diseases like heart disease (Ljiljana et al., 2015).

16.8.1.4 Role as an antiaging agent

The antiaging effect of ascorbic acid pertains to its potent antioxidant effect that stimulates collagen formation and refrains
damage and wrinkles (Harrison, 2012). Vitamin C in combination with other antioxidants like beta-carotene, vitamin E,
and zinc protects the eyes and vision from degeneration that leads to blindness. Maintaining a healthy level of vitamin C
shows a protective function against age-related cognitive dysfunction, Alzheimer’s disease, gout, inflammation, and pre-
and postsurgery pain (Hansen et al., 2014; Marzocchella et al., 2011). Aging of the skin is a very common problem, which
can be seen by signs such as wrinkles, sagging of skin, uneven skin tone, and dryness. In a recent evaluation improvements
in skin integrity, aging, pigment appearance on the skin have been seen with the synergistic antiaging effects of vitamin C
and other ingredients. Topical products vitamins C with E have shown protective effects in the process of aging as human
skin needs water-soluble as well as lipid-soluble nutrient components (Pattarawan et al., 2020).

16.8.1.5 Role as an anticancer

Population-based studies evaluated that intake of foods rich in vitamin C lowers the rate of cancer associated to the skin,
cervical dysplasia, and breast. Vitamin C plays an eminent role in protecting cellular integrity as a scavenger, preventing
oxidation of cellular protein, lipid, and DNA. L-Ascorbic acid is one of the nutritive nonenzymatic antioxidants (Cadeau,
2016).

16.8.1.6 Role in immunity

Ascorbic acid participates in immune defense by improving the cellular functions of both the innate and adaptive immune
systems. It controls the epithelial barrier layer against pathogens. It is accumulated in the phagocytic cell-like neutrophils to
enhance chemotaxis, phagocytosis, reactive oxygen species that kill microbes. It is also required for apoptosis and
clearance of macrophages. Ascorbic acid deficiency renders impaired immunity and higher susceptibility to infections
(Schmidt et al., 2011). In a recent study on COVID-19 patients, the administration of ascorbic acid increased the chances of
survival of COVID-19 patients by attenuating increased activation of the immune response. Ascorbic acid enhances
antiviral cytokines and free radical formation, suppressing viral yield. It also attenuates maximum inflammatory responses
298 Nutraceuticals and Health Care

and hyperactivation of immune cells. Vitamin C is considered an antiviral agent as it increases immunity. A daily
allowance of vitamin C can enhance nutritional defense that can be beneficial in patients at risk of or diagnosed with
coronavirus disease 2019 (Minkyung & Hyeyoung, 2020).

16.8.1.7 Role in lipid metabolism

L-Ascorbicacid has a great influence on the lipids existing either in intra- or extracellular form. Vitamin C improves the
metabolism of the lipid by restricting the oxidation of the unsaturated lipids and lipoproteins (Alul et al., 2003).

16.8.1.8 Role in protection from heavy metals toxicity

L-Ascorbic acid facilitates the heavy metal absorption from the intestine such as iron while lowering levels of lead in blood
(Dawson et al., 1999). It plays a significant role in the synthesis of carnitine, an enzyme that acts as a cofactor to increase
the absorption of nonheme iron in the gastrointestinal tract. It also increases the formation of reduced iron favorable for
absorption (Teucher et al., 2004).

16.8.1.9 Role in endocrinology system

L-Ascorbic acid contributes to the development of several hormones like adrenaline, endogenous serotonin, and hy-
droxylation of aromatic compounds in the liver (Anderson et al., 1980; Schmidt et al., 2011).

16.8.1.10 Role in preventing health disorders

L-Ascorbic acid, if taken orally, improves a genetic disorder in newborns in which blood levels of the amino acid tyrosine
are too high. Vitamin C supplements also help in managing anemia in people undergoing dialysis. Vitamin C supports
reduction in symptoms of exercise-induced asthma, eczema, and allergic rhinitis (Finkelsteinn et al., 2011; Frikke-Schmidt
et al., 2011; Michiels et al., 2010).

16.8.1.11 Deficiency disorders of ascorbic acid

Ascorbic acid has immense health benefits (Fig. 16.6). Scurvy is a deficiency of ascorbic acid that results in absence of
healing of a wound and fractured bones due to collagen deformation. Other symptoms of scurvy are body weakness, legs,
and arms edema, nose, skin, and gums hemorrhage, infections, vasculitis, bone and cartilage damage, internal bleeding,
anemia (Finkelsteinn et al., 2011; Frikke-Schmidt et al., 2011; Michiels et al., 2010).

FIGURE 16.6 Health benefits of ascorbic acid.

 Ascorbic acid Chapter | 16 299

16.8.2 Other commercially viable applications

16.8.2.1 Role in bakery
L-Ascorbic acid is widely used as an additive to the flour. It enhances a number of desired features such as strengthened
gluten, greater loaf volume, finer crumb, tenderness to the crumb, a faster-rising loaf for quicker baking. The utilization of
ascorbic acid in bakery contributes to higher profit yields (Sahi, 2014; Zhou et al., 2014).

16.8.2.2 Role in water treatment and purification

L-Ascorbic acid combination with sodium ascorbate serves as a useful means to neutralize chlorinated water than other
sulfur-based chemical methods and makes chlorinated water safe for drinking (Urbansky et al., 2000; Gao et al., 2020).

16.8.2.3 Role as a beverage and health drink

L-Ascorbic acid as a natural additive in juice and beverage enhances the nutritional value of the beverage without inter-
ference to its taste while abstaining from its spoilage (Maryam et al., 2012).

16.8.2.4 Role in the meat industry as a preservative

L-Ascorbic acid’s primary function in the meat environment is to prevent its oxidation (Kanatt et al., 2018; King et al.,
2016; Lee et al., 2018).

16.8.2.5 Role in fruit preservation

The use of ascorbic acid slows down the oxidation with its low pH. The ascorbic acid helps in the prevention of microbial
growth. Ascorbic acid resists browning, which preserves the freshness of fruits as studied by Nagy and Smoot (1977) and
Roig et al. (1995).

16.8.2.6 Role in personal care and cosmetics

L-Ascorbic acid regulates the synthesis of the structural protein collagen and hydroxylation of collagen molecules. It has been
shown to stabilize collagen mRNA for collagen protein synthesis of the damaged skin. It plays a vital role in photoprotection,
wrinkling, and wound healing so it is preferred in skin care lotions, creams, and cosmetics (Soledad et al., 2019).

16.8.2.7 Role in the manufacturing industry

L-Ascorbic acid is used in a wide range of industrial applications. It helps in masking the taste of iodine in sterilized and
potable water. It is used in manufacturing plastic (Oster & Fechtel, 2012; Pizzocaro, 1993; Rahman, 2007).

16.9 Conclusion
L-Ascorbic acid is an abundant multifunctional molecule that serves as an essential nutrient for the growth and devel-
opment of plants and animals including man. It is a naturally occurring, water-soluble, potent reducing, and antioxidant
agent that has numerous commercial, biological, and nutraceutical applications. The role of vitamin C in providing better
esthetics exhibits immense significance. Due to its protective role, the supplementation of vitamin C serves as a prereq-
uisite to sustaining life with a significant rise in pollution. It is vital in improving immunity by fighting infections and
detoxifying reactions. It renders the formation, maintenance, and repair of collagen in fibrous tissue, teeth, bones, con-
nective tissue, skin, and capillaries. It is a cofactor for enzymes biosynthesis of collagen, carnitine, and neurotransmitters
that can quench a variety of reactive oxygen and nitrogen species in aqueous environments.
The therapeutic use of ascorbic acid includes prevention of ascorbic acid deficiency in a patient at risk, in infants,
treatment of scurvy, anemia, and acidifying the urine in urinary tract infection. It acts as a hypertensive and hypo-
cholesterolemic agent. It helps in the reduction of cold and age-related health problems. Adequate amount intake of vitamin
C prevents from breast, cervix, and colon cancers. It is recommended to have an intake of 40 mg per day as per India
National Institute of Nutrition, Hyderabad, and 45 mg per day or 300 mg per week as per the World Health Organization.
Vitamin C gets destroyed by heat and light. Smokers, patients with kidney disease, heredity iron overload disorder patient
should use ascorbic acid wisely. L-Ascorbic acid has immense potential in the biomedical application that still remains
unnoticed. It is speculated that young scientists would take up ascorbic acid as challenge for research to explore and
expedite remarkable achievements.
300 Nutraceuticals and Health Care

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