JOM Volume 31, Number 1, 2016 1
High Dose Intravenous Vitamin C
Treatment for Zika Fever
Michael J. Gonzalez, NMD, DSc, PhD, FACN;1 Miguel J. Berdie,l MD;2 Jorge R. Miran-
da-Massari, PharmD;2 Jorge Duconge, PhD;1 Joshua L. Rodríguez-López, BS;3 Pedro
A. Adrover-López, BS;
¹University of Puerto Rico, Medical Sciences Campus, Schools of Public Health and Pharmacy, San Juan, PR, 00936-5067
²Berdiel Clinic, Ponce, PR, 00716
3Ponce Health Sciences University, School of Medicine, Ponce, PR, 00716
Abstract e Zika Fever is a viral disease caused by a single-stranded RNA virus from the Fla-
vivirus genus, Flaviviridae family, from the Spondweni group. Its transmission occurs through
mosquito vectors, principally Aedes Aegypti. e most common symptoms of Zika are fever, rash, joint
pain, and conjunctivitis (red eyes). Other common symptoms include muscle pain and headache. As of
now, no vaccine exists for the virus and no oﬃcial treatment has been developed aside from standard
procedures of the use of acetaminophen (paracetamol) and non-steroidal anti-inﬂammatory drugs.
is is a case report of a 54 year-old Hispanic female who arrived at the clinic with symptomatology
congruent with the Zika fever. e patient was treated with high doses of intravenous vitamin C
over three days. e symptoms resolved after the infusions without any side eﬀects at day four. Re-
covery from this viral infection takes normally around two weeks. Based on the positive outcome in
this case, we propose that intravenous vitamin C should be studied further as a potential treatment
for acute viral infections.
Zika virus (ZIKV ) is a member of the
virus family Flaviviridae and the genus
Flavivirus (Knipe et al, 2007). Like other
ﬂaviviruses, Zika virus is enveloped and
icosahedral and has a nonsegmented, single-
stranded, positive-sense RNA genome. It
is spread by daytime active Aedes mosqui-
toes, such as A. Aegypti and A. Albopictus
(Knipe et al, 2007). Its name comes from
the Zika Forest of Uganda, where the virus
was ﬁrst isolated in 1947 (European Center
for Disease Prevention and Control, 2015).
Zika virus is related to dengue, yellow fever,
Japanese encephalitis, and West Nile viruses
(European Center for Disease Prevention and
Control, 2015). As of February 2016, there are
three reported cases indicating that Zika virus
could possibly be sexually transmitted (World
Health Organization, 2016a).
e infection, known as Zika fever, often
causes none or only mild symptoms, simi-
lar to a mild form of dengue fever (Knipe
et al, 2007). e illness cannot be prevented
by medications or vaccines and is treated
mainly by rest (Chen et al, 2016). Zika fe-
ver in pregnant women is associated with
microcephaly but it is unclear whether the
virus is the cause (Knipe et al, 2007; Cable
News Network, 2015; Centers for Disease
High Dose Intravenous Vitamin C for Zika Fever
Control and Prevention, 2016a). ere is a
link between Zika fever and neurologic con-
ditions in infected adults, including cases
of the Guillain–Barré syndrome (World
Health Organization, 2016b; Oehler et al,
2014; Cao-Lormeau et al, 2016). Common
symptoms of infection with the virus in-
clude mild headaches, maculopapular rash,
fever, malaise, conjunctivitis, and joint pains.
Within two days, the rash may start fading,
and within three days, the fever is generally
resolved and only the rash remains.
As of 2016, no vaccine or preventive
drug is available. Symptoms can be treated
with rest, ﬂuids, and paracetamol (acetamin-
ophen), while aspirin and other nonsteroi-
dal anti-inﬂammatory drugs should be used
only when dengue has been ruled out to re-
duce the risk of bleeding (Sikka et al, 2016).
It is diﬃcult to diagnose Zika virus infec-
tion based on clinical signs and symptoms
alone due to overlaps with other arboviruses
that are endemic to similar areas (Centers
for Disease Control and Prevention, 2016b).
In small case series, routine chemistry and
complete blood counts have been normal in
most patients. A few have been reported to
have mild leukopenia, thrombocytopenia,
and elevated liver transaminases (Centers
for Disease Control and Prevention, 2016c;
Waggoner et al, 2016).
Zika virus can be identiﬁed by reverse
transcriptase PCR (RT-PCR) in acutely ill
patients. However, the period of viremia can
be short and the World Health Organiza-
tion (WHO) recommends RT-PCR testing
be done on serum collected within 1 to 3
days of symptom onset or on saliva or urine
samples collected during the ﬁrst 3 to 5 days
(Waggoner et al, 2016; Faye et al, 2008; Ay-
ers et al, 2006).
Later on, serology for the detection of
speciﬁc IgM and IgG antibodies to Zika
virus can be used. IgM antibodies can be
detectable within three days of the onset of
illness (Waggoner et al, 2016). Serological
cross-reactions with closely related ﬂavivi-
ruses such as dengue and West Nile virus as
well as vaccines to ﬂaviviruses are possible
(Waggoner et al, 2016; Faye et al, 2008).
Commercial assays for Zika antibodies are
now available but have not yet been FDA
approved (Centers for Disease Control and
Prevention, 2016). During the ﬁrst seven
days of these illnesses, viral RNA can often
be identiﬁed in serum, and RTPCR is the
preferred test for Zika, chikungunya, and
For many years, it has been widely known
that ascorbic acid (vitamin C) has a variety
of physiological functions with clinical eﬃ-
cacy. Vitamin C is a water-soluble vitamin,
and has been used to prevent many diseases
and/or infections like the common cold and
other viral infections (Mikirova et al, 2012;
Padayatty et al, 2010; Byun et al, 2011; Har-
akek et al, 1990; Zhang et al, 2014). Ascor-
bic acid scavenges reactive oxygen species
(ROS), increases vascular and connective
tissue integrity, improves immune function
(increases interferon) and assists in leuko-
cyte phagocytic functions (increases hydro-
gen peroxide, number and aggressiveness of
white blood cells) (Gonzalez et al, 2014).
Vitamin C supplemented orally has its
limitations in achieving high blood (i.e.,
plasma) levels, whereas the use of intravenous
vitamin C (IVC) can reach blood levels that
possess distinct clinical and pharmacologi-
cal advantages. Oral vitamin C is absorbed
in the gastrointestinal tract, where the body
metabolizes a limited amount and the rest
is excreted through the kidneys. However, if
the vitamin is administered intravenously it
can reach plasma concentrations that are 30
to 70 times higher than the oral route, which
seems necessary for the antiviral activity
(Chen et al, 2016).
Ascorbic acid is also a nutrient for the
immune system. Treatment of ascorbic acid
in vitro resulted in an increase in T-cells and
natural killer (NK)-cells, which constitute one
of the main components of the adaptive im-
mune system, which ﬁghts against viruses and
intracellular bacteria (World Health Organi-
zation, 2016). It has been suggested the same
eﬀect can be achieved by IVC administration.
Here we report a case of Zika fever, treated
with high doses of IVC in a period of three
days without any negative side eﬀects.
High Dose Intravenous Vitamin C for Zika Fever
Case Report Presentation
ree days after suﬀering several mos-
quito bites the patient noted the onset of
intermittent periods of fever and chills (day
one). Two days later, her mouth became sore
and oral blisters developed. On day ﬁve, a
papular rash developed, which spread to her
extremities. e rash lasted three days, and
in conjunction with a retro-orbital headache
and fever and mild non-purulent conjunc-
tivitis, signiﬁcant joint and muscle tender-
ness developed which prompted a visit to the
Blood, nasopharyngeal swab, and urine
samples were collected for investigation of
measles and/or other possible infectious
causes as the diﬀerential work-up. Initial
laboratory investigations showed a hemo-
globin level, leukocyte count, platelet count
and levels of creatinine, electrolytes, alanine
aminotransferase, and alkaline phosphatase
were all within reference ranges.
A reverse transcription polymerase
chain reaction (RT-PCR) described by was
performed resulting positive for ﬂaviviruses.
Since the clinical signs and symptoms of
infection with Zika virus can be easily con-
fused with dengue and/or Chikungunya,
mainly because of the fever, headache, and
generalized rash-like presentation this test
was relevant to diagnosis.
Vitamin C was applied after a G6PD
test in escalating doses of 25g (Day 1 of
Treatment), 50 g (Day 2 of Treatment) and
75 g (Day 3 of Treatment). e symptoms
improved substantially in 24 hours and were
absent by the third day.
Mounting evidence has suggested a close
correlation between oxidative stress and viral
infectious disease. e elevated oxidants in-
duced by viral infection include nitric oxide
radicals, superoxide anions, hydroxyl radicals
and their by-products, which may all con-
tribute to viral pathogenesis, the modulation
of cellular responses, the regulation of viral
replication and the host defense (Epstein &
Weiss, 1989). Many of these oxidants may
be harmful to the host cells if they are re-
leased into the extracellular medium (Smith,
1994; Kim et al, 2013).
Vitamin C is an eﬃcient antioxidant
and possesses anti-viral activity. For ex-
ample, it has been shown that vitamin C is
an essential factor in the production of the
anti-viral immune response during the early
phase of viral infection through the produc-
tion of type I interferons, which up-regulates
NK cell and cytotoxic T-lymphocyte activity
(Madhusudana et al, 2004). Also, studies have
indicated that ascorbic acid can be used as an
inactivating agent for both RNA and DNA
viruses, impacting viral infectivity (Byun et
al, 2011). In addition, ascorbic acid can de-
toxify viral products that produce pain and
inﬂammation (Harakek et al, 1990). All this
evidence conﬁrms the eﬀectiveness of ascor-
bic acid against viral infections, and against
Zika fever, as suggested by the patient’s swift
response to IVC. Furthermore, no negative
side eﬀects resulted during or after the treat-
ment. Based on the positive outcome in this
case, we propose that IVC should be studied
further as a potential treatment for acute vi-
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