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Veterinary Quarterly

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L-Ascorbic acid (vitamin C) supplementation to


optimize health and reproduction in cattle

R. Ranjan , A. Ranjan , G.S. Dhaliwal & R.C. Patra

To cite this article: R. Ranjan , A. Ranjan , G.S. Dhaliwal & R.C. Patra (2012) L-Ascorbic acid
(vitamin C) supplementation to optimize health and reproduction in cattle, Veterinary Quarterly,
32:3-4, 145-150, DOI: 10.1080/01652176.2012.734640

To link to this article: https://doi.org/10.1080/01652176.2012.734640

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Veterinary Quarterly
Vol. 32, Nos. 3–4, September–December 2012, 145–150

REVIEW ARTICLE
L-Ascorbic acid (vitamin C) supplementation to optimize health and reproduction in cattle
R. Ranjana*, A. Ranjanb, G.S. Dhaliwala and R.C. Patrac
a
Department of Teaching, Veterinary Clinical Complex, Guru Angad Dev Veterinary and Animal Sciences University,
Ludhiana, Punjab, India; bDepartment of Veterinary Pharmacology and Toxicology, Guru Angad Dev Veterinary and Animal
Sciences University, Ludhiana, Punjab, India; cDepartment of Veterinary Medicine, College of Veterinary Sciences,
Orissa University of Agriculture and Technology, Bhubaneswar, Odisha, India
(Received 2 July 2012; final version received 24 September 2012)

Cattle can synthesize L-ascorbic acid (or Vitamin C) from either D-glucose or D-galactose through glucuronic acid
pathway in the liver. L-Ascorbic acid present in cattle diet is almost totally destroyed by rumen microorganisms
making them essentially dependent on its endogenous synthesis, which is assumed sufficient to meet the
physiological requirement. Therefore, the role of vitamin C in cattle health and disease has remained widely
overlooked. However, there is mounting evidence that the level of L-ascorbic acid in blood and other tissues
decreases in association with stress and disease, and Vitamin C supplementation revealed favorable response as
evident from early recovery. The present review is an attempt to summarize the existing literature pertaining to
the physiological role of L-ascorbic acid and the scope of its supplementation in the prevention and treatment of
diseases in cattle. It should be realized that the aqueous solution of vitamin C is highly acidic and subcutaneous
or intramuscular administration may cause tissue irritation and inflammation, whereas the sodium ascorbate
solution is less acidic and might be used for intramuscular administration.
Keywords: L-ascorbic acid; cattle; bovine; disease; health; vitamin C

1. Introduction milk production in cattle is not associated with


Animals have the ability to biosynthesize L-ascorbic decrease in the plasma Vitamin C level.
acid through glucuronic acid pathway in liver (in Only L-isomer of vitamin C (Figure 1) and its
mammals) or kidney (in reptile and birds) using either oxidized derivative L- dehydroascorbic acid has vita-
D-glucose or D-galactose (Basu and Schorah 1982). min C activity. L-Dehydroascorbic acid is readily
Cattle are essentially dependent on this endogenous reduced back to the active form L-ascorbic acid in
synthesis as dietary vitamin C is almost totally the body. The D-isomer, also called iso-ascorbic acid or
destroyed by rumen microorganisms (Nockels 1988a). erythroboric acid, does not have vitamin C-like activity
No published dietary requirement data of vitamin C (Basu and Schorah 1982).
are available for adult cattle since endogenous synthe-
sis is assumed sufficient to meet the requirement
(Nockels 1988b; Hemingway 1991). However, several 2. Biosynthesis, distribution, and tissue
studies have conclusively documented the decrease of concentrations
vitamin C level in the blood during stress and diseases All ruminants including cattle have high endogenous
in cattle and other ruminants (Palludan and Wegger capacity for the synthesis of L-ascorbic acid. However,
1984; Ali 2000; Ranjan et al. 2005a). Decrease in the calves are unable to synthesize vitamin C until two–
vitamin C level during stress and diseases may be the three weeks of age, hence are totally dependent upon
end result of decreased endogenous synthesis or its supply through colostrum and milk. Fresh and
increased demand or a combination of both. Any frozen colostrums are satisfactory sources of vitamin
condition that decreases the availability of vitamin C C, but stored unfrozen colostrums rapidly lose their
precursors, i.e. glucose and galactose, may result in vitamin C content (Hemingway 1991).
insufficient endogenous synthesis. For example, high Vitamin C circulates freely in plasma, leukocytes,
milk-producing dairy cows have an elevated demand and red blood cells and enters into all tissues and body
for glucose by the mammary gland in order to produce fluids in human beings (Iqbal et al. 2004). It has been
lactose, hence they may synthesize less vitamin C recorded that vitamin C is actively transported into
(Macleod, Zhang, Ozimeck, et al. 1999). However, few human blood leukocytes, thereby maintaining a high
authors do not approve this hypothesis. Padilla et al. vitamin C concentration unless vitamin C deficiency
(2005) observed that even ketotic cows have the ability occurs (Washko et al. 1989). High vitamin C concen-
to produce sufficient vitamin C and concluded that tration can be recorded in pituitary and adrenal glands,
vitamin C synthesis is possibly given a high-metabolic followed by spleen, liver, brain, and kidneys of adult
priority. Santos et al. (2001) also reported that high cattle (Kolb et al. 1989). Thymus, corpus-luteum,

*Corresponding author. Email: Rakesh_ranjan3@rediffmail.com

ISSN 0165–2176 print/ISSN 1875–5941 online


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146 R. Ranjan et al.

levels by preventing free radical-induced damage


(Englard and Seifter 1986). Vitamin C concentration
in the aqueous humor of cattle is several times
higher than its plasma concentration and the level is
maintained both by active transport (Helbig et al.
1990) and regeneration by ciliary body (Bode
et al. 1993).
Vitamin C is regarded to have critical functions in
the brain including its role as a cofactor of dopamine
-hydroxylase, and is thereby involved in catechol-
Figure 1. Chemical structure of L-ascorbic acid.
amine biosynthesis. Vitamin C inhibits peroxidation of
membrane phospholipids and acts as a scavenger of
free radicals in the brain (Englard and Seifter 1986)
Table 1. Plasma concentration (mg/L) of ascorbic acid in and is required for the synthesis of several hormones
healthy cattle and other domestic ruminants. and neurotransmitters. It acts as a true co-substrate for
dopamine beta-monooxygenase for the biosynthesis of
Species Concentration (range) Reference norepinephrine from dopamine in bovine granulosa
Cattle 2.85–4.81 Ataman et al. (2010) cells (Dhariwal et al. 1991). It also acts as a reducing
2.97–3.63 Padilla et al. (2006) agent for the synthesis of aldosterone in the adrenal
5.42–5.99 Mohamed et al. (2004) gland (Yanagibashi et al. 1990) and oxytocin in
5.7–6.2 Chanda (1958) granulosa cells of corpus luteum (Luck and Jungclas
Buffalo 5.3–5.5 Chanda (1958) 1988). Vitamin C regulates oxytocin secretion through
Sheep 4.67–4.77 Mohamed et al. (2004)
4–8 Mac-Pherson (1983) direct interaction with catecholamines (Luck and
Goat 1.75–1.92 Sivakumar et al. (2010) Jungclas 1987). In humans, vitamin C is required for
the biosynthesis of carnitine and the catecholamines
that regulate the nervous system (Iqbal et al. 2004). In
in vitro cell culture, vitamin C has been demonstrated
retina, testicles, thyroid glands, lymph nodes, pancreas, to play a critical role in the production and release of
and salivary glands also have high vitamin C concen- corticosteroids in the bovine adrenal glands (Finn and
tration (Hediger 2002). In a study in mice, it was found Johns 1980).
that L-ascorbic acid does not cross the blood–brain In myeloid leukemia cell culture, the addition of
barrier, but L-dehydroascorbic acid easily crosses the Vitamin C in high doses has been reported to induce
blood–brain barrier through glucose transporters oxidative damage inside the cell, suggesting that
(Agus et al. 1997). vitamin C in high concentration may play a pro-
Measurement of vitamin C levels has been largely oxidant role (Osiecki et al. 2010).
confined to different biological fluids, plasma, and
whole blood. Vitamin C concentration in leukocytes
seems to be an accurate index of body status in man
(Washko et al. 1989). Normal vitamin C concentra- 4. Ascorbic acid and immunity
tion in the blood of cattle and other ruminant Vitamin C is required for collagen synthesis and hence
species as reported by different authors is given in maintenance of skin and epithelial linings of the body
Table 1. Blood vitamin C level does not change in orifices (Gaby and Singh 1991). Neutrophils contain
response to lactation or the number of lactations about 40–60 times higher vitamin C concentration than
(Santos et al. 2001). However, certain other factors plasma. Motility and phagocytic capacity of neutro-
such as season in bulls (Kolb et al. 1991), stage of phils are enhanced following vitamin C supplementa-
oestrus cycle and pregnancy in cows (Ataman et al. tion (Roth and Kaeberle 1985). Vitamin C
2010), and the type of housing system in calves concentration in neutrophils is rapidly depleted in
(Cummins and Brunner 1991) may have significant acute disease, infection, corticosteroid administration,
influence. and trauma in human beings (Basu and Schorah 1982).
Vitamin C protects neutrophils from oxidative damage
and promotes oxidative killing of bacteria inside
3. Biochemical functions neutrophils (Goldschmidt et al. 1988; Wang et al.
Vitamin C is a powerful reducing agent required in 1997). Vitamin C also supports normal lymphocyte
the hydroxylation of proline and lysine for the proliferation, stimulates interferon production (Gerber
biosynthesis of collagen in human beings (Gaby 1975), and reduces the suppressor activity of mononu-
and Singh 1991). Collagen and hence vitamin C clear leukocytes (Gaby and Singh 1991). Low blood
support wound healing and the formation of blood vitamin C level in camels may compromise their
vessels, bone, and teeth. In addition, vitamin C plays resistance against infectious diseases (Mohamed
a protective role at many cellular and sub-cellular et al. 2011).
Veterinary Quarterly 147

5. Ascorbic acid in cattle diseases months old (Cummins and Brunner 1989) and IgM in
5.1. Heat stress calves older than two months (Hidiroglou et al. 1995).
The plasma vitamin C level in cattle declines during
heat stress (Padilla et al. 2006). Few research reports
also document the beneficial effects of Vitamin C 5.3. Reproductive problems
supplementation in goats (Kobeisy 1997; Sivakumar Perhaps, the first use of vitamin C supplementation for
et al. 2010). Supplementation of ascorbic acid polypho- therapeutic purposes in adult ruminant was for the
sphate along with salts (sodium bicarbonate and treatment of infertility. Subcutaneous administration
potassium carbonate) was found effective in reducing of 2.2–4.4 mg/kg BW vitamin C on every third–fourth
heat stress in buffaloes (Kumar et al. 2011). In goats, day claimed to improve the performance of bulls with
vitamin C supplementation has been reported to poor breeding records (Daykin 1960). Similar dosages
ameliorate the stress-induced hemolysis of erythrocytes were also recommended in cows to improve the
after road transportation for 12 hours during hot-dry conception rate. The administration of vitamin C
season (Minka and Ayo 2010). during the period of hormonal stimulation in women
has showed a positive though statistically insignificant
impact in terms of higher number of pregnancies (Crha
et al. 2003). Vitamin C concentrations vary according
5.2. Neonatal diseases
to the follicle size, functional status, and the stage of
Milk is a poor source of vitamin C as the average estrous cycle, suggesting a role in the process of
concentration in whole milk of cow and goat is about follicular development during the estrous cycle in
1–2 mg/100 mL (Renner 1983), which is inadequate to buffalo (Khan and Das 2011). In ovaries collected
fulfill the requirement of newborn animals. The from slaughterhouse, it was found that small- and
recommended level of vitamin C in dry milk replacer medium-sized follicles of acyclic buffaloes had lower
for calves is 2000 mg/kg. Endogenous vitamin C vitamin C concentrations than the corresponding size
production in the calf does not start until two–three estrogen-active follicles of their cyclic counterparts
weeks of age and does not reach a maximum until 8–16 (Khan and Das 2012). Addition of vitamin C in the
weeks (Palludan and Wegger 1984). As a consequence, in vitro culture medium has been reported to increase
vitamin C level in blood decreases after birth up to the rate of buffalo embryo development (Saikhun et al.
three months of age (Kolb 1992). Furthermore, vita- 2008). However, the exact mechanism by which vita-
min C level in blood is also influenced by several min C supplementation improves breeding perfor-
factors, such as genetic potential of the individual mance in cattle still remains inconclusive. Beneficial
animal to produce vitamin C (Palludan and Wegger effects of vitamin C supplementation on male fertility
1984), the presence of environmental stressors in humans have also been investigated by several
(Cummins and Brunner 1989), and management fac- researchers. It prevents sperm agglutination, resulting
tors (Cummins and Brunner 1991). into poor fertility in men (Dawson et al. 1983). Bull
Decrease in vitamin C level has been noted in calves semen also has little endogenous antioxidants.
in association with many diseases. Dermatosis in calves Addition of optimum quantity of vitamin C to semen
commencing on the ears and spreading to neck and extender can help protect spermatozoa from damages
chest has been associated with low level of vitamin C during storage and handling induced by free radicals
(Radostits et al. 1994). Scurvy-like disease has also (Foote et al. 2002). However, vitamin C is also
been reported occasionally in adult cattle (Duncan reported to enhance iron-induced oxidative damage
et al. 1944). Several studies have documented signifi- to spermatozoa (Dawra et al. 1983) and impairing the
cant decrease in plasma vitamin C level in pneumonia success rate of bovine in vitro fertilization (Daivit et al.
(Jagos et al. 1977) and enteric infections (Hemingway 1998). Thus, debate continues over its role in male
1991; Seifi et al. 1996) in calves. It has been hypoth- fertility.
esized that the demand of vitamin C increases in In females, vitamin C has multiple roles in repro-
various infections due to increased tissue requirements ductive physiology. During ovarian folliculogenesis, it
(Hemingway 1991). Beneficial effects of vitamin C plays an important role in collagen biosynthesis,
supplementation on calf diarrhea cases further consol- steroidogenesis, and apoptosis (Luck and Zhao
idate this hypothesis (Cummins and Brunner 1989; 1993). In vitro study has highlighted the role of vitamin
Sahinduran and Albay 2004). It may also be possible C in the maintenance of ovarian follicle health and
that the decrease in vitamin C concentration leads to basement membrane remodeling in bovines (Thomas
compromise in immunity and predisposes the animal et al. 2001). As discussed earlier, ascorbate regulates
to various diseases. An immune-stimulatory effect of the biosynthesis and release of oxytocin. Of interest,
vitamin C supplementation has already been reported low vitamin C level in placental tissues has been
in dairy calves (Cummins and Brunner 1991). reported in retained placenta cases (Kankofer 2001).
Response of vitamin C supplementation on immune Significant decline in plasma total vitamin C concen-
function, however, varies with age. It increases the tration in dairy cows has been reported during the
plasma concentration of IgG in calves less than two periparturient period (Tanaka et al. 2011).
148 R. Ranjan et al.

5.4. Mastitis 7. Conclusion


Several research reports document decreased vitamin C Ascorbic acid is a strong antioxidant nutrient present
concentration in milk and plasma in bovine and in blood plasma, neutrophils, and other body tissues. It
caprine mastitis (Steffert 1993; Gupta et al. 1999; has diverse physiological functions and plays an
Ranjan et al. 2005a). Parenteral administration of important role in the regulation of immune function
vitamin C alone or along with intramammary antibi- and offers protection from oxidative damage at many
otics improves the cure rate in spontaneous cases of cellular and sub-cellular levels. Though cattle can
bovine mastitis (Chaiyotwittayakun et al. 2002; Naresh synthesize vitamin C from D-glucose or D-galactose,
et al. 2002; Ranjan et al. 2005b). Vitamin C along with several reports suggest the decrease in its tissue
cupric ions as teat dip or intra-mammary infusion also concentrations during various diseases and stress and
helps in the prevention and treatment of mastitis in beneficial effects of its supplementation on the main-
dairy cows (Upton 1988). Weiss et al. (2004) observed tenance of health and fertility. However, extensive
large decrease in vitamin C level in Escherichia coli- research is required to explore the need and effect of
induced mastitis. However, in another study, intrave- ascorbic acid supplementation to cattle. Alleviation of
nous administration of vitamin C in cows that received heat stress, management of calf diarrhea, mastitis, and
an intramammary challenge of endotoxin had limited infertility are some of the potential conditions in
positive effects on clinical signs (Chaiyotwittayakun which vitamin C supplementation may be helpful.
et al. 2002). Santos et al. (2001) reported that plasma Development of rumen stable vitamin C supplements
vitamin C concentrations in dairy cows do not corre- and dose standardization is essential for its large-scale
late with somatic cell counts in milk. use regarding preventive and therapeutic purposes.

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