Vit C & Respiratory
Conditions
Immune-enhancing
role of vitamin C and zinc and effect on clinical conditions- review, Ann Nutr Metab 2006;50(2):85-94. E S Wintergerst et al, https://pubmed.ncbi.nlm.nih.gov/16373990/
A large number of randomized controlled intervention trials
with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available.
These trials document that adequate intakes of vitamin C and zinc ameliorate
symptoms and shorten the duration of respiratory tract infections including the
common cold. Furthermore, vitamin C and zinc reduce the incidence and improve
the outcome of pneumonia, malaria, and diarrhea infections, especially in
children in developing countries.
A combination of high-dose vitamin C plus zinc for the
common cold, J INT MED RES, 2012;40(1):28-42,
S Maggini et al,(1000 mg,10 mg)- less effective than
higher- https://pubmed.ncbi.nlm.nih.gov/22429343/
Extra Dose of Vitamin C Based on a Daily
Supplementation Shortens the Common Cold: A Meta-Analysis of 9 Randomized
Controlled Trials, Biomed Res Int, 2018
Jul 5;2018:1837634. Li Ran et al, https://pubmed.ncbi.nlm.nih.gov/30069463/
administration
of extra therapeutic doses at the onset of cold despite routine supplementation
was found to help reduce its duration , shorten the
time of confinement indoors and relieve
the symptoms associated with it,
The effectiveness of vitamin C in preventing and relieving the
symptoms of virus-induced respiratory infections(1000 mg x3), J
Manipulative Physiol Ther ,
1999 Oct;22(8):530-3. H C Gorton et al, https://pubmed.ncbi.nlm.nih.gov/10543583/
reported
flu and cold symptoms in the test group decreased 85% compared with the control
group after the administration of megadose Vitamin C.
Consumption
of gold kiwifruit reduces severity and duration of selected upper respiratory
tract infection symptoms and increases plasma vitamin C concentration in
healthy older adults, Br J Nutr 2012 Oct;108(7):1235-45.
https://pubmed.ncbi.nlm.nih.gov/22172428/
Gold kiwifruit significantly reduced the severity and
duration of head congestion, and the duration of sore throat. Gold kiwifruit
significantly increased plasma vitamin C, α-tocopherol and lutein/zeaxanthin
concentrations, and erythrocyte folate concentrations, and significantly
reduced plasma lipid peroxidation.
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Bone Health and
Trauma
The Role of Vitamin C in Orthopedic Trauma and Bone Health, Am J Orthop (Belle Meade,
NJ), 2015 Jul;44(7):306-11. A Hart et al; https://pubmed.ncbi.nlm.nih.gov/26161758/
Observational data support the hypothesis that high dietary
intake and supplementation with vitamin C may reduce the risk of hip fractures
in postmenopausal women. Results of 2 high-quality trials support use of
vitamin C 500 mg daily for 50 days as prophylaxis against complex regional pain
syndrome after wrist fracture treated conservatively and operatively.
Observational evidence exists for similar treatment after foot and ankle
surgery. The role of vitamin C in preventing osteoarthritis has tremendous
potential,
Vitamin C and Bone Health: Evidence from Cell, Animal
and Human Studies, Curr Drug Targets,
2018;19(5):439-450. K Y Chin et al, https://pubmed.ncbi.nlm.nih.gov/26343111/
Human studies generally showed a positive relationship
between vitamin C and bone health, indicated by bone mineral density, fracture
probability and bone turnover markers.
Sequential
analysis of oxidative stress markers and vitamin C status in acute bacterial
osteomyelitis, Mediators Inflamm
2014;2014:975061. R Grbic
et al; https://pubmed.ncbi.nlm.nih.gov/25180026/
Compared to 52 healthy controls, in OM group baseline serum
hydroperoxides, MDA and oxidized/reduced vitamin C ratio were higher whilst Asc
and AOA were lower (P < 0.05, resp.). Persistently
high values of oxidized/reduced vitamin C ratio and serum MDA were found in
subacute OM. In conclusion, acute OM was associated with enhanced systemic
oxidative stress and the shift of vitamin C redox status towards oxidized
forms.
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Intravenous
vitamin C in the treatment of allergies: an interim subgroup analysis of a
long-term observational study, J Int Med Res. 2018 Sep;46(9):3640-3655.
C Vollbracht et al; https://pubmed.ncbi.nlm.nih.gov/29950123/
Between the start and end of treatment, the mean sum score of
three disease-specific symptoms decreased significantly by 4.71 points and that
of four nonspecific symptoms decreased significantly by 4.84 points. More than
50% of patients took no other allergy-related medication besides vitamin C.
Conclusions Our observations suggest that treatment with intravenous high-dose
vitamin C reduces allergy-related symptom
Vitamin
C Compound Mixtures Prevent Ozone-Induced Oxidative Damage in Human
Keratinocytes as Initial Assessment of Pollution Protection, PLos One 2015 Aug
13;10(8):e0131097. G Valacchi
et al; https://pubmed.ncbi.nlm.nih.gov/26270818/
this study was able to demonstrate a protective effect of the
tested compounds versus O3-induced cell damage in human keratinocyte
Cardiovascular Health
Effect
of vitamin C on endothelial function in health and disease: a systematic review
and meta-analysis of randomised controlled trials, Atheroscherosis, 2014
Jul;235(1):9-20. A W Ashor et al, https://pubmed.ncbi.nlm.nih.gov/24792921/
Pooling the data from 44 clinical trials showed
a significant positive effect of vitamin C on cardiovascular EF
, with stronger effects in those at higher cardiovascular
disease risk.
Effect
of vitamin E and C supplements on antioxidant defense system in cardiovascular
disease patients in Zahedan, southeast Iran, J Nutr Sci Vitaminol
2010;56(6):436-40. M Karajibani
et al; https://pubmed.ncbi.nlm.nih.gov/21422713/
After intervention, a significant increase in superoxide
dismutase (SOD) activity (61.7%), glutathione peroxidase (GPx) activity
(59.3%), the levels of vitamin E (83.7%), C (145.3%), total antioxidant
capacity (TAC) (62.8%) and a significant decrease in MDA (40%) value were
observed (p<0.0001). There was a significant negative correlation between
MDA and TAC. The results suggest that supplementation with a combination of
vitamins E and C reduced lipid peroxidation and strengthened the antioxidant
defense system. Hence, there will be beneficial effects on the heart by
reducing oxidative stress in CVD patients. (use
natural or full-spectrum E)
a cohort study, Blood Pressure Monitoring: June 2016 - Volume 21 - Issue 3 - p 160-167, Ried, Karin, et al
Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives.
IVC alone (>30 g) reduced the mean BP up to 8–9 mmHg in
prehypertensive patients
Vitamin
C for Type 2 Diabetes Mellitus and Hypertension, 2019 Feb;50(2):11-14. U N
Das,
Supplementation
of vitamin C reduces hyperglycemia and lowers blood pressure in hypertensives and has several benefical actions in type 2 diabetes mellitus and hypertension.
Effects of vitamin C supplementation on blood pressure: a
meta-analysis of randomized controlled trials, Am J Clin Nutr 2012 May;95(5):1079-88. S P Jurascheck et al; https://pubmed.ncbi.nlm.nih.gov/22492364/
In short-term trials, vitamin C supplementation reduced SBP
and DBP.
Effects of vitamin C
supplementation on essential hypertension: A systematic review and
meta-analysis, Medicine (Baltimore), 2020
Feb;99(8):e19274, Y Guan et al, https://pubmed.ncbi.nlm.nih.gov/32080138/
VitC supplementation resulted in a significant reduction of
blood pressure in patients with essential hypertension.
Critically Ill Patients- Vitamin C:
should we supplement? Curr Opin Crit Care, 2018
Aug;24(4):248-255. Spoelstra-de Man AME et al, https://pubmed.ncbi.nlm.nih.gov/29864039/
Older studies showed less organ dysfunction when vitamin C
was administered in repletion dose (2-3 g intravenous vitamin C/day). Recent
small controlled studies using pharmacological doses (6-16 g/day) suggest that
vitamin C reduces vasopressor support and organ dysfunction, and may even
decrease mortality.
Astaxanthin: a novel potential treatment for oxidative stress
and inflammation in cardiovascular disease, Am J Cardiol. 2008 May
22;101(10A):58D-68D. F J Pashkow et
al; https://pubmed.ncbi.nlm.nih.gov/18474276/
Results from multiple species support the
antioxidant/anti-inflammatory properties of the prototype compound,
astaxanthin, establishing it as an appropriate candidate for development as a
therapeutic agent for cardiovascular oxidative stress and inflammation.
Treatment of Chronic Conditions
Effects of vitamin C supplementation on glycaemic
control: a systematic review and meta-analysis of randomised controlled trials, Eur J Clin Nutr , 2017
Dec;71(12):1371-1380.
A W Ashor
et al, https://pubmed.ncbi.nlm.nih.gov/28294172/
vitamin C significantly reduced glucose
concentrations in patients with type 2 diabetes and in
interventions with a duration greater than 30 days (treatment of T2 diabetes)
Vitamin C prevents oxidative damage, Free Radic Res 1996
Aug;25(2):173-9. M K Ghosh et al, https://pubmed.ncbi.nlm.nih.gov/8885335/
The observations substantiate the previous in vitro findings that ascorbate specifically prevents oxidative degradation of microsomal membranes. The results indicate that vitamin C may exert a powerful protection against degenerative diseases associated with oxidative damage and play a critical role in wellness and health maintenance.
Low
vitamin C values are linked with decreased physical performance and increased
oxidative stress: reversal by vitamin C supplementation Eur J Nutr 2016 Feb;55(1):45-53. V Paschalis et al; https://pubmed.ncbi.nlm.nih.gov/25526969/
We show that low vitamin C concentration is linked with
decreased physical performance and increased oxidative stress, and that vitamin C supplementation decreases
oxidative stress and increases
exercise performance in those with low initial concentration of vitamin C.
N-acetylcysteine
(NAC) supplementation increases exercise
performance and reduces oxidative stress in individuals with low levels of
glutathione, Free Radic
Biol Med 2018
Feb 1;115:288-297. V Paschalis et al; https://pubmed.ncbi.nlm.nih.gov/29233792/
Individuals
with low glutathione levels were linked with decreased physical performance,
increased oxidative stress and impaired redox metabolism of erythrocytes. NAC
supplementation restored both performance and redox homeostasis.
[Influence of soccer training on parameters of oxidative stress
in erythrocytes] Nutr
Hosp 2019 Aug 26;36(4):926-930. https://pubmed.ncbi.nlm.nih.gov/31192692/
Conclusions: there is
higher oxidative stress in soccer players than in sedentary players,
and it may be necessary to supplement with antioxidants in this group.
Changes
in vitamin C and oxidative stress status during the treatment of tuberculous meningitis, Int J Tuberc Lung Dis 2013
Nov;17(11):1495-500. D Miric
https://pubmed.ncbi.nlm.nih.gov/24125457/
These results indicate increased local and systemic oxidative
stress, accompanied by impaired redox status, but not total vitamin C
deficiency, which persisted during conventional clinical treatment of TBM.
Vitamin
C protects rat cerebellum and encephalon from oxidative stress following
exposure to radiofrequency(RDF) wave generated by a
BTS antenna model, Toxicol
Mech Methods 2014 Jun;24(5):347-52. https://pubmed.ncbi.nlm.nih.gov/24730455/
The protective role of vitamin C in the treated group
improved antioxidant enzymes activity and reduced MDA compared with the test
group (p < 0.05). It can be concluded that RFW causes oxidative stress in
the brain and vitamin C improves the antioxidant enzymes activity and decreases
MDA.
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Lymphocyte
vitamin C levels as potential biomarker for progression of Parkinson's disease, Nutrition, 2015 Feb;31(2):406-8. K Ide et al; https://pubmed.ncbi.nlm.nih.gov/25592020/
Vitamin C is a major antioxidant and also is known as a neuromodulator in dopaminergic neurons.
Lymphocyte vitamin C levels in patients with severe PD were
significantly lower (odds ratio [OR], 0.87; 95% confidence interval [CI],
0.80-0.97; P < 0.01) compared with those at less severe stages. Plasma
vitamin C levels also tended to be lower in patients with severe PD
Low
plasma vitamin C in Alzheimer patients despite an adequate diet, Int J Geriatr Psychiatry, 1998
Nov;13(11):749-54. S Riviere et al; https://pubmed.ncbi.nlm.nih.gov/9850871/
Plasma vitamin C is lower in AD in proportion to the degree
of cognitive impairment and is not explained by lower vitamin C intake. These
results support the hypothesis that oxygen-free radicals may cause damage.
Vitamin
E Supplements May Decrease the Risk of Lou Gehrig’s Disease (ALS) Linus Pauling Institute- Annals of Neurology on November 4, 2004. They
found that people who reported taking vitamin E supplements regularly for more
than 10 years when the study began were 60% less likely to die from ALS than
those who did not take vitamin E supplements-- https://lpi.oregonstate.edu/vitamin-e-supplements-may-decrease-risk-lou-gehrig’s-disease-als
concussions seem to be a risk factor for ALS; recent
research shows that high doses of supplementation may be able to
slow down the progression of ALS if you already have it. The key is that you
start supplementation before or during early onset (within the first year) of
having .
The research involved treating people with ultra-high-dose
methylcobalamin, the physiologically active form of vitamin B12, according to
one discussing the study.
Multiple Sclerosis
Vitamin C
promotes oligodendrocytes generation and remyelination, Glia
2018 Jul;66(7):1302-1316.
Oligodendrocyte-formed myelin sheaths play important roles in
the neuronal functions in the central nervous system. In demyelinating
diseases, such as Multiple Sclerosis, the myelin sheaths are damaged and the
remyelinating process is somehow hindered. Restoration of the myelin sheaths
requires the differentiation of the oligodendrocyte precursor cells (OPCs) into
mature oligodendrocytes (OLs). To discover small molecule compounds that might
promote the OPC to OL differentiation, a high-throughput screening system is
established and L-ascorbyl-2-phosphate (As-2P), a stable form of Vitamin C
(Vc), is found to greatly enhance the OPC to OL differentiation. As-2P promotes
gradual expression of OL lineage markers, including O4, CNPase and MBP, in a
dose- and time-dependent manner. It also facilitates the formation of myelin
sheaths in OPC-neuron co-culture. As-2P also promotes the repair of the myelin
sheaths in vivo and provides significant therapeutic effect in a
cuprizone-mediated demyelination animal model.
Fatty Acids and Antioxidants in Multiple Sclerosis:
Therapeutic Role of GEMSP, Curr Pharm
Des 2019;25(4):376-380. https://pubmed.ncbi.nlm.nih.gov/30864502/
Although there are some genetic and environmental factors
that have been related to the onset of the disease, these are still not
completely understood and nowadays multiple sclerosis can neither be prevented,
nor its symptom effectively treated due to disease heterogeneity. GEMSP, which consists of a
mixture of functional constituents as fatty acids, antioxidants, free radical
scavengers and amino acids linked individually to poly-L-Lysine (PL), is
emerging as a promising drug for MS treatment. Pre-clinical studies using GEMSP
have demonstrated that this drug strongly inhibits brain leukocyte infiltration
and completely abolishes experimental autoimmune encephalomyelitis. In
addition, in an open clinical trial in humans treated with GEMSP, in 72% of the
cases, a positive evolution of the state of the MS patients treated with GMSP
was observed.
Serum
total antioxidant capacity in patients with multiple sclerosis, Bosn J Basic Med Sci 2011
Feb;11(1):33-6. https://pubmed.ncbi.nlm.nih.gov/21342139/
Our results showed that oxidative stress plays an important
role in pathogenesis of multiple sclerosis. This finding, also, suggests the
importance of antioxidants in diet and therapy of MS patients.
Ascorbic acid acts mainly by decreasing oxidative stress and
reducing the formation of protein aggregates, which may contribute to the
reduction of cognitive and/or motor impairments observed in neurodegenerative
processes. Although several studies support a possible role of ascorbic acid
administration against neurodegeneration, more researches are essential to
substantiate the existing results and accelerate the knowledge in this field.
Lipoprotein
oxidation, plasma total antioxidant capacity and homocysteine level in patients
with multiple sclerosis, Nutr
Neurosci 2003 Jun;6(3):189-96. https://pubmed.ncbi.nlm.nih.gov/12793524/
In multiple sclerosis patients during an attack, a
significant increase in both in vitro lipid oxidizability for plasma and in the
levels of autoantibodies against oxidized low-density lipoproteins, and a
strong decrease in plasma total antioxidant capacity were detected. The present study indicates
that lipoprotein oxidation may be important factor in the course of multiple
sclerosis and in vitro measurements of plasma oxidation kinetics as an
indication for lipoprotein oxidation might be useful as an additional tool for
the clinical diagnosis of multiple sclerosis.
Does Vitamin C Influence Neurodegenerative Diseases and
Psychiatric Disorders?, Nutrients 2017 Jul; 9(7):
659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537779/ (best study I’ve seen)
Vitamin C (Vit C)
is considered to be a vital antioxidant molecule in the brain. Intracellular
Vit C helps maintain integrity and function of several processes in the central
nervous system (CNS), including neuronal maturation and differentiation, myelin
formation, synthesis of catecholamine, modulation of neurotransmission and
antioxidant protection. The importance of Vit C for CNS function has been
proven by the fact that targeted deletion of the sodium-vitamin C
co-transporter in mice results in widespread cerebral hemorrhage and death on
post-natal day one. Since neurological diseases are characterized by increased
free radical generation and the highest concentrations of Vit C in the body are
found in the brain and neuroendocrine tissues, it is suggested that Vit C may
change the course of neurological diseases and display potential therapeutic
roles
Vit C is
important for proper nervous system function and its abnormal concentration in
nervous tissue is thought to be accompanied with neurological disorders.
Alzheimer’s
disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis,
amyotrophic sclerosis, depression, anxiety, schizophrenia
that modulate NMDARs. However, this
issue needs to be further investigated.
7. Conclusions
The crucial role of Vit C in
neuronal maturation and functions, neurotransmitter action as well as responses
to oxidative stress is well supported by the evidences presented in this review
(Figure 2).
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The epigenetic role of vitamin C in health and disease, Cell Mol Life Sci 2016 Apr;73(8):1645-58
Recent advances have uncovered a previously unknown function
of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an
ascorbate anion under physiological pH conditions. Ascorbate was discovered as
a cofactor for methylcytosine dioxygenases that are responsible for DNA
demethylation, and also as a likely cofactor for some JmjC domain-containing
histone demethylases that catalyze histone demethylation. Variation in
ascorbate bioavailability thus can influence the demethylation of both DNA and
histone, further leading to different phenotypic presentations. Ascorbate
deficiency can be presented systematically, spatially and temporally in different
tissues at the different stages of development and aging. Here, we review how
ascorbate deficiency could potentially be involved in embryonic and postnatal
development, and plays a role in various diseases such as neurodegeneration and
cancer through epigenetic dysregulation.
Preventive
and therapeutic potential of ascorbic acid in neurodegenerative diseases, CNS Neurosci Therapy 017
Dec;23(12):921-929. https://pubmed.ncbi.nlm.nih.gov/28980404/
Ascorbic acid acts mainly by decreasing oxidative stress and
reducing the formation of protein aggregates, which may contribute to the
reduction of cognitive and/or motor impairments observed in neurodegenerative
processes. Although several studies support a possible role of ascorbic acid
administration against neurodegeneration, more researches are essential to
substantiate the existing results and accelerate the knowledge in this field.
Treatment with ultra-high-dose methylcobalamin,
the physiologically active form of vitamin B12, may improve the prognosis of patients with amyotrophic lateral sclerosis (ALS) who receive it a year or less
after symptom onset, a long-term study of Japanese
reports. methylcobalamin
was able to decrease homocysteine levels. This molecule’s accumulation has been linked with
motor neuron degeneration in patients with ALS. https://alsnewstoday.com/news-posts/2019/01/17/high-dose-vitamin-b12-helpful-early-diagnosis/
Journal of Neurology, Neurosurgery
& Psychiatry. Jan 17 2019
Vitamin C Status and Cognitive Function: A Systematic Review, Nutrients, 2017 Aug 30;9(9):960., N Travika et al; https://pubmed.ncbi.nlm.nih.gov/28867798/
Studies
demonstrated higher mean vitamin C concentrations in the cognitively intact
groups of participants compared to cognitively impaired groups. qualitative assessment revealed a potential
association between plasma vitamin C concentrations and cognition
A
critical review of vitamin C for the prevention of age-related cognitive
decline and Alzheimer's disease, J Alzheimer’s Dis, 2012;29(4):711-26. F E Harrison, https://pubmed.ncbi.nlm.nih.gov/22366772/
there is a large body of evidence that maintaining healthy
vitamin C levels can have a protective function against age-related cognitive
decline and Alzheimer's disease,
Serum
levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort
of older adults, Exp Gerontol.
2013 Dec;48(12):1428-35. M Kivipelto
et al; https://pubmed.ncbi.nlm.nih.gov/24113154/
Elevated levels of tocopherol and tocotrienol forms are
associated with reduced risk of cognitive impairment in older adults.
Protective
Role for Antioxidants in Acute Kidney Disease,
Nutrients, 2017 Jul 7;9(7):718,
J M Dennis et al; https://pubmed.ncbi.nlm.nih.gov/28686196/
Acute kidney injury is associated with increased oxidative
damage, and various endogenous and synthetic antioxidants that mitigate source
and derived oxidants are beneficial in cell-based and animal studies.
ascorbate (vitamin C), has been shown to be a promising therapeutic
in human renal injury in critical illness and nephrotoxicity.
Vitamin
C improves liver and renal functions in hypothyroid rats by reducing tissue
oxidative injury, Int J Vitam
Nutr Res, 2020 Jan;90(1-2):84-94, M Esmaeilizadeh
et al; https://pubmed.ncbi.nlm.nih.gov/30789800/
Vit C improved liver and renal function of hypothyroid rats
which might be due to its protective effects against tissues oxidative damage.
Entacapone
is an Antioxidant More Potent than Vitamin C and Vitamin E for Scavenging of
Hypochlorous Acid and Peroxynitrite, and the Inhibition of Oxidative
Stress-Induced Cell Death, Med Sci Monit 2016 Mar 1;22:687-96; A Y Chen et al; https://pubmed.ncbi.nlm.nih.gov/26927838/
Entacapone (ENT), a clinical drug for the treatment of
Parkinson's disease, has been shown to have antioxidant effects. ENT is an antioxidant that can scavenge
toxic HOCl and ONOO- species and inhibit oxidative stress-induced cell death
more effectively than vitamin C and vitamin E. ENT may have new clinical
applications as an antioxidant in the treatment of ROS-induced diseases
including cardiovascular disease, cancer, and neurodegenerative diseases.
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(vit C is
effective at reducing pain after injury or operation)
Efficacy of vitamin C in preventing complex regional
pain syndrome after wrist fracture: A systematic review and meta-analysis, Orthop Traumatol Surg Res , 2017
May;103(3):465-470 F Aim et al, https://pubmed.ncbi.nlm.nih.gov/28274883/
Daily supplementation
with 500mg of vitamin C per day for 50 days decreases the 1-year risk of CRPS-I
after wrist fracture.
Prospective randomized study of the vitamin C effect
on pain and complex pain regional syndrome after total knee arthroplasty, Int Orthop 2021 Jan 12, H Jacques et al, https://pubmed.ncbi.nlm.nih.gov/33438072/
Taking 1 g per day of vitamin C during 40 days after a TKA
reduces the risk of CRPS.
Vitamin C revisited,
Crit Care, 2014 Aug 6;18(4):460. Heleen M Oudemans-van Straaten
et al; https://pubmed.ncbi.nlm.nih.gov/25185110/
Vitamin C can restore vascular responsiveness to
vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate
phosphatase and occludin phosphorylation and preventing apoptosis. Finally,
high-dose vitamin C can augment antibacterial defense. These protective effects
against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or
burn seems to mitigate organ injury and dysfunction, and promote recovery after
cardiac revascularization and in critically ill patients, in the latter
partially in combination with other antioxidants
Intravenous
vitamin C in the treatment of shingles: results of a multicenter prospective
cohort study, Med Sci Monit.
2012 Apr;18(4):CR215-24. M Schencking
et al, https://pubmed.ncbi.nlm.nih.gov/22460093/
Mean declines of pain scores (VAS), number of affected
dermatomes and efflorescences, and the presence of hemorrhagic vesicles between
the baseline and follow-up assessments at 2 and 12 weeks were statistically
significant
Vitamin C in the treatment and/or prevention of obesity and co-morbidities of obesity, J Nutr Sci Vitaminol. (Tokyo) 2014;60(6):367-79. https://pubmed.ncbi.nlm.nih.gov/25866299/
It has
been observed that vitamin C intake (ascorbic acid) is negatively associated
with the occurrence of several conditions such as hypertension, gallbladder
disease, stroke, cancers, and atherosclerosis, and also with the onset of
obesity in humans and animals.
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Vitamin
C requirement in surgical patients, Curr Opin Clin Nutr Metab Care, 2010
Nov;13(6):669-76. R Fukushima et al, https://pubmed.ncbi.nlm.nih.gov/20689415/
Vitamin C requirement is increased in surgical patients, and
the potential advantage of supplementation is to increase the plasma and tissue
levels of vitamin C and thereby reduce oxidative stress. Although some clinical
benefits of high-dose vitamin C supplementation have been shown in the
critically ill, the optimal dose for supplementation and the clinical benefits
remain to be investigated in surgical patients.-------------------------------------
Efficacy of vitamin C for the treatment of upper
respiratory tract infection. A meta-analysis in children, Eur J
Clin Pharmacol , 2019 Mar;75(3):303-311.
vitamin C intake reduced the duration of URTI.
[Effect of vitamin C on prognosis of
critically ill patients: a Meta-analysis] Zhoghua wei Zhong Bing Ji Jiu Yi
Xue. 2019 Aug;31(8):942-948. X Du et al, https://pubmed.ncbi.nlm.nih.gov/31537216/
Vit
C can reduce the length of ICU stay and hospital stay. In
addition, vitamin C can reduce mortality of patients with sepsis and septic
shock and reduce the incidence of atrial fibrillation post operation in
patients undergoing cardiac surgery.
Our data indicate that vitamin C is an important independent
antioxidant in protecting cells against death from oxidative stress.
Vitamin
C prevents DNA mutation induced by oxidative stress, J Biol Chem 2002 May 10;277(19):16895-9. https://pubmed.ncbi.nlm.nih.gov/11884413/
We
found that vitamin C loading resulted in substantially decreased mutations
induced by H(2)O(2). Depletion of glutathione led to cytotoxicity and an
increase in H(2)O(2)-induced mutation frequency; however, mutation frequency
was prominently decreased in depleted cells preloaded with vitamin C. The
mutation results correlated with a decrease in total 8-oxo-guanine measured in
genomic DNA of cells loaded with vitamin C and oxidatively stressed. These
findings directly support the concept that high intracellular concentrations of
vitamin C can prevent oxidation-induced mutations in human cells.
Vitamin
C for DNA damage prevention, Mut Res 2012
May 1;733(1-2):39-49. https://pubmed.ncbi.nlm.nih.gov/22178550/
Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with γ-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels>50μmol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels>50μmol/l exposed to higher concentrations of c-PAHs.
Vitamin C- Cancer Treatment
Supplemental ascorbate in the supportive treatment of cancer:
Prolongation of survival times in terminal human cancer, E Cameron, L Pauling,
Proc Natl Acad Sci U.S.A. 1976 Oct;73(10):3685-9 &
Intravenous ascorbic acid: protocol for its application and use, H D Riordon et al, P R
Health Sci J, 2003 Sep;22(3):287-90.
& High
dose concentration administration of ascorbic acid inhibits tumor growth in
BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis, Chang-Hwan Yeom, et al, J Transi Med, 2009 Aug 11;7:70 & Vitamin C uncouples the Warburg metabolic
switch in KRAS mutant colon cancer, O Aguilera
et al, Oncotarget. 2016 Jul
26;7(30):47954-47965. https://pubmed.ncbi.nlm.nih.gov/1068480/
Intravenous
vitamin C in the supportive care of cancer patients: a review and rational
approach, Curr Oncol 2018
Apr;25(2):139-148. E Klimant
et al, https://pubmed.ncbi.nlm.nih.gov/29719430/
The use of IV C is a safe supportive intervention to decrease
inflammation in the patient and to improve symptoms related to antioxidant
deficiency, disease processes, and side effects of standard cancer treatments.
Vitamin C as a Modulator of the Response to Cancer Therapy, Molecules, 2019 Jan 28;24(3):453.
Wiktoria
Blaszczak et al, https://pubmed.ncbi.nlm.nih.gov/30695991/
Experimental studies have shown the ability of
pharmacological doses of vitamin C alone or in combinations with clinically
used drugs to exert beneficial effects in various models of human cancers.
Cytotoxicity of high doses of vitamin C in cancer cells appears to be related
to excessive reactive oxygen species generation and the resulting suppression
of the energy production via glycolysis. A hallmark of cancer cells is a
strongly upregulated aerobic glycolysis, which elevates its relative importance
as a source of ATP (Adenosine 5'-triphosphate). Aerobic glycolysis is
maintained by a highly increased uptake of glucose, which is made possible by
the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and
GLUT-4. These proteins can also transport the oxidized form of vitamin C,
dehydroascorbate, permitting its preferential uptake by cancer cells with the
subsequent depletion of critical cellular reducers as a result of ascorbate
formation. Ascorbate also has a potential to affect other aspects of cancer
cell metabolism due to its ability to promote reduction of iron(III) to
iron(II) in numerous cellular metalloenzymes. Among iron-dependent
dioxygenases, important targets for stimulation by vitamin C in cancer include
prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and
histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C
can be beneficial by itself and can also
promote activity of specific drugs.
Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly, Cancer
Cell, 2018 Nov 12;34(5):700-706.
Two mechanisms of anti-cancer activity with ascorbate have
gained prominence: hydrogen peroxide-induced oxidative stress and DNA
demethylation mediated by ten-eleven translocation enzyme activation.
----------------------------------------------------------------------
The
Role of Oxidative Stress Modulators (Melatonin) in Breast Cancer, Curr Med Chem 2018;25(33):4084-4101. S Suzen et al https://pubmed.ncbi.nlm.nih.gov/28699501/
Our data, in accordance with the literature, suggest an
important role for melatonin in breast cancer prevention and adjuvant therapy.
Melatonin:
the watchdog of villous trophoblast homeostasis against
hypoxia/reoxygenation-induced oxidative stress and apoptosis, Mol Cell Endocrinol 2013 Dec 5;381(1-2):35-45. https://pubmed.ncbi.nlm.nih.gov/23886990/
This study shows that melatonin protects the villous
trophoblast against H/R-induced oxidative stress and apoptosis and suggests a
potential preventive and therapeutic use of this indolamine in pregnancy
complications characterized by syncytiotrophoblast survival alteration.
--------------------------------------------------------------------------------------------------------------------
Does Vitamin C Influence Neurodegenerative Diseases and
Psychiatric Disorders?, Nutrients 2017 Jul; 9(7):
659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537779/ (best study I’ve seen)
Vitamin C (Vit C)
is considered to be a vital antioxidant molecule in the brain. Intracellular
Vit C helps maintain integrity and function of several processes in the central
nervous system (CNS), including neuronal maturation and differentiation, myelin
formation, synthesis of catecholamine, modulation of neurotransmission and
antioxidant protection. The importance of Vit C for CNS function has been
proven by the fact that targeted deletion of the sodium-vitamin C
co-transporter in mice results in widespread cerebral hemorrhage and death on
post-natal day one. Since neurological diseases are characterized by increased
free radical generation and the highest concentrations of Vit C in the body are
found in the brain and neuroendocrine tissues, it is suggested that Vit C may
change the course of neurological diseases and display potential therapeutic
roles
Vit C is
important for proper nervous system function and its abnormal concentration in
nervous tissue is thought to be accompanied with neurological disorders.
Alzheimer’s
disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis,
amyotrophic sclerosis, depression, anxiety, schizophrenia
many
studies have demonstrated that ROS and oxidative stress are implicated in AD disease progression. Aβ peptide was found
to enhance the neuronal vulnerability to oxidative stress and cause an
impairment of electron transport chain, whereas oxidative stress was shown to
induce accumulation of Aβ peptide which subsequently promotes ROS production [16,22,57]. The role of
Vit C in preventing the brain against oxidative stress damage seems to be also
proved by the recent study performed by Sarkar et al. [64]. The researchers share a view that
cerebral ischemia-reperfusion-induced oxidative stress may initiate the
pathogenic cascade leading eventually to neuronal loss, especially in
hippocampus, with amyloid accumulation, tau protein pathology and irreversible
Alzheimer’s dementia. Being the prime source of ROS generation, neuronal
mitochondria are the most susceptible to damage caused by oxidative stress. The
study proved it that l-ascorbic acid loaded polylactide nanocapsules
exerted a protective effect on brain mitochondria against cerebral
ischemia-reperfusion-induced oxidative injury [64]. Kennard and Harrison, in turn, evaluated
the effects of a single intravenous dose of Vit C on spatial memory (using the
modified Y-maze test) in APP/PSEN1 mice. The study was performed on APP/PSEN1
and wild-type (WT) mice of three age spans (3, 9 or 20 months). It was shown
that APP/PSEN1 mice displayed no behavioral impairment as compared to WT
controls, but memory impairment along with aging was observed in both groups.
Vit C treatment (125 mg/kg, i.v.) improved performance in 9-month old APP/PSEN1
and WT mice, but improvements in short-term spatial memory did not result from
changes in the neuropathological features of AD or monoamine signaling, as
acute Vit C administration did not alter monoamine levels in the nucleus
accumbens [65]. Cognitive-enhancing effects of acute
intraperitoneal (i.p.) Vit C treatment in APP/PSEN1 mice (12- and 24-month-old)
were investigated by Harrison et al. Vit C treatment (125 mg/kg i.p.) improved
Y-maze alternation rates and swim accuracy in the water maze in both APP/PSEN1
and wild-type mice; but like in the previous study had no significant effect on
the age-associated increase in Aβ deposits and oxidative stress, and did not
also affect acetylcholinesterase (AChE) activity either, which was
significantly reduced in APP/PSEN1 mice [66]. Murakami et al. [67] in turn reported that 6-month-treatment
with Vit C resulted in reduced Aβ oligomer formation without affecting plaque
formation, a significant decrease in brain oxidative damage and Aβ42/Aβ40 ratio
as well as behavioral decline in an AD mouse model. Furthermore, this restored
the declined synaptophysin and reduced the phosphorylation of tau protein at
Ser396.
Besides the presented
roles, Vit C has also been suggested to prevent neurodegenerative changes and
cognitive decline by protecting blood–brain barrier (BBB) integrity [68]. meta-analysis
performed by Lopes da Silva et al. proved significantly lower plasma levels of
Vit C in AD patients [75]. It seems that
the above discrepancies may result from the fact that not plasma but rather
intracellular Vit C may be associated with AD. randomized control trial involving 276
elderly participants demonstrated that 16-week-co-supplementation of vitamin E
and C with β-carotene significantly improved cognitive function (particularly
with higher doses of β-carotene). Furthermore, the authors suggested that such
a treatment markedly reduced plasma Aβ levels and elevated plasma estradiol
levels [80]. Vit C and E co-supplementation for more
than 3 years was also shown to be associated with a reduced prevalence and
incidence of AD [81]. Moreover, an adequate Vit C plasma level
seems to be associated with less progression in carotid intima-media thickness
(C-IMT)—the greater C-IMT is suggested to be a risk factor in predicting
cognitive decline in the general population, in the elderly population and in
patients with Alzheimer’s disease. Polidori et al. showed significant decrease
(with a linear slope) in Vit C level among old individuals with no or very mild
cognitive impairment from the first to the fourth C-IMT quartile [82].
Parkinson’s
there
are only a few human studies considering the role of Vit C treatment in PD, the
existing ones give some evidences that Vit C treatment may have beneficial
effect in PD course. A cohort study involving 1036 PD patients showed that
dietary Vit C intake was significantly associated with reduced PD risk.
However, it was not significant in a 4-year lagged analysis [109]. Quiroga et al.,
in turn, reported a case of a 66-year-old man with PD, pleural effusion and
bipolar disorder who was found to have low serum Vit C and zinc levels.
Intravenous replacement of both Vit C and zinc resulted in resolution of the
movement disorder in less than 24 h [107]. The other case
report concerned 83-year-old men with dementia, diabetes mellitus,
hypertension, benign prostatic hypertension, paroxysmal atrial fibrillation,
congestive heart failure and suspected PD. The man was treated with Vit C (200
mg) and zinc (4 mg), which resulted in complete resolution of periungual and
gingival bleeding as well as palatal petechiae. Moreover, the man’s orientation
and mental status were found to be markedly improved and no further delusions
or agitations were observed [110].
Huntington’s
Disease
studies performed on cell and animal models of HD appear to
indicate the role of Vit C in HD course,
to the best of our knowledge, in the newest literature there
exists a lack of studies considering the role of Vit C or the effect of its
supplementation in HD human subjects.
MS is
characterized by infiltration of immune cells (in particular T cells and
macrophages), demyelination (loss of myelin sheath that surrounds and protects
nerve fibers allowing them to conduct electrical impulses) and axonal pathology
resulting in multiple neurological deficits, which range from motor and sensory
deficits to cognitive and psychological impairment [131,132]
IT IS suggested that genetic predisposition
associated with environmental factors can lead to expression of the envelope
protein of MS-associated retrovirus (MSRV) and thus trigger the disease [133].
Oxidative/nitrosative stress and
mitochondrial dysfunction are believed to contribute to the pathophysiology of
MS [131,134,135,136,137].
Having regarded the
presented facts, it seems to be justified that Vit C, being a very important
brain antioxidant, may affect MS course. Vit C is known to affect numerous
metabolic processes directly associated with immune system. Furthermore, Vit
C-dependent collagen synthesis has also been linked to formation of the myelin
sheath [7].
existing ones
showed that MS patients displayed significantly lower Vit C level as compared
to healthy individuals [135,136,138]. Besler et al. [138], in turn,
observed an inverse correlation between the serum levels of Vit C and lipid
peroxidation in MS patients. The authors concluded that decreased Vit C level,
observed in MS patients during relapse of the disease, might be dependent on
the elevated oxidative burden as reflected by increased lipid peroxidation.
Hejazi et al. [139],
An efficiency of antioxidant therapy in
relapsing-remitting multiple sclerosis patients (n = 14) treated with complex of
antioxidants and neuroprotectors with various mechanisms of action (oc-lipoic
acid, nicotinamide, acetylcysteine, triovit beta-carotine, alpha-tocopheryl
acetate, ascorbic acid, selenium, pentoxifylline, cerebrolysin, amantadine
hydrochloride) during 1 month, 2 times a year was investigated by Odinak et al.
[140]. The treatment resulted in significant
reduction of relapse frequency, decrease of required corticosteroid courses and
significantly reduced content of lipid peroxide products [140]. However, it should be underlined that
Vit C was only one element of multicomponent treatment. However, in another
study it was shown that intrahippocampal injection of Vit C (0.2, 1, 5 mg/kg, 7
days) improved memory acquisition of passive avoidance learning (PAL) in
ethidium bromide-induced MS in rats. The injection of ethidium bromide caused
significant deterioration of PAL, whereas treatment with Vit C at a dose of 5
mg/kg resulted in significant improvement in PAL [141].
Vit C is also believed
to be involved in anxiety, stress, depression, fatigue and mood state in
humans. It has been hypothesized that oral Vit C supplementation can elevate
mood as well as reduce distress and anxiety.
Depression (DP) is a mental
disorder characterized by a number of basic symptoms like low mood, biological
rhythm disorders, psychomotor slowdown, anxiety, somatic disorders as well
other nonspecific symptoms [151]
believed that
depression is associated with disturbances of serotonin, norepinephrine and
dopamine neurotransmission
GABA level in
plasma and CSF of patients suffering from depression was shown to be reduced [154,155] which points to
its decreased synthesis in the brain. Recent data have suggested that chronic
stress, via initiating changes in the hypothalamic-pituitary-adrenal axis and
the immune system, acts as a trigger for the above-mentioned disturbance. For
example, glucocorticoids and proinflammatory cytokines enhance the conversion
of tryptophan to kynurenine thus leading to a decrease in the synthesis of
brain serotonin
The efficacy of Vit C as an adjuvant agent in the treatment of
pediatric major depressive disorder in a double-blind, placebo-controlled pilot
trial was evaluated by Amr et al. [175]. Patients (n = 12) treated for six months with
fluoxetine (10–20 mg/day) and Vit C (1000 mg/day) showed a significant decrease
in depressive symptoms in comparison with the fluoxetine plus placebo group as
measured by the Children’s Depression Rating Scale and Children’s Depression
Inventory. No serious adverse effects were shown. Zhang et al. [176] in double-blind clinical trial
investigated the effect of Vit C (500 mg twice daily) on mood in non-depressed
acutely hospitalized patients. The applied therapy increased plasma and mononuclear
leukocyte Vit C concentrations and was associated with a 34% reduction in mood
disturbance (assessed with Profile of Mood States) [176]. Similarly, Wang et al. found that
short-term Vit C (500 mg twice daily) treatment was associated with a 71%
reduction in mood disturbance (assessed with Profile of Mood States) and a 51%
reduction in psychological distress (assessed with Distress Thermometer) in acutely
hospitalized patients with a high prevalence of hypovitaminosis C [177]. Khajehnasiri et al. [178] in a randomized, double-blind,
placebo-controlled trial involving 136 depressed male shift workers observed,
in turn, that Vit C administration (250 mg twice daily for 2 months) alone and
in combination with omega-3 fatty acids significantly reduced the Beck
Depression Inventory (BDI) score, however omega-3 fatty acid supplementation
alone was more effective. Moreover, Vit C and omega-3 fatty acids
supplementation alone (but not in combination) decreased significantly serum
MDA levels. Fritz et al. [179] conducted a systematic review of human
and observational studies assessing the efficiency of interventional Vit C as a
contentious adjunctive cancer therapy and reported that it could improve
quality of life, physical function, as well as prevent some side effects of
chemotherapy, including fatigue, nausea, insomnia, constipation and depression.
growing
evidence, which has been recently emerged, suggests that anxiety is associated
with Vit C deficit, whereas Vit C supplementation could help reduce feeling of
anxiety.
existing ones seem to
provide promising results.
De Oliveira et al. [189] examined the effects of short-term oral
Vit C supplementation (500 mg/day, 14 days) in high school students (n = 42) in a randomized, double-blind,
placebo-controlled trial. The treatment led to higher plasma Vit C
concentration that was associated with reduced anxiety levels evaluated with
BIA (Beck Anxiety Inventory). Moreover, the Vit C supplementation had positive
effect on the heart rate. Gautam et al. [171] observed that patients with generalized
anxiety disorder had significantly lower Vit C levels in comparison with
healthy controls, whereas 6-week vitamins supplementation (vitamin C
accompanied with A and E) led to a significant reduction in anxiety scores [171]. Mazloom et al. [190], in turn, showed that short-term
supplementation of Vit C (1000 mg/day) reduced anxiety levels (evaluated basing
on Depression Anxiety Stress Scales 21-item) in diabetic patients. This effect
was exerted through alleviating oxidative damage. Furthermore, recently
performed a systematic review also showed that high-dose Vit C supplementation
was effective in reducing anxiety as well as stress-induced blood pressure
increase [191].
Schizophrenia is
a severe and complex neuropsychiatric disorder that affects 1% of the
population worldwide [192,193,194].
there is the
increasing evidence that several physiological mechanisms such as oxidative
stress, altered one carbon metabolism and atypical immune-mediated responses
may be involved in schizophrenia pathomechanism [192,196].
Hoffer [197] summarized in the review study the
evidence showing that among others Vit C deficiency could worsen the symptoms
of schizophrenia and that large doses of this vitamin could improve the core
metabolic abnormalities predisposing some people to development of this
disease. According to the author, it is probable that the pathologic process
responsible for schizophrenia could increase ascorbic acid utilization.
Sarandol et al. [198] also noted lower levels of serum Vit C as
compared to control group, but this was not regarded as a statistically
significant difference. Moreover, a 6-week-long antipsychotic treatment did not
modify the concentration of this vitamin. The authors explained that other
factors, such as nutrition, physical activity, etc., might be the reason for
the discrepancy between the results of their research and other studies.
Similarly, Young et al. [199] observed only a slight decrease in Vit C
levels in schizophrenic group vs. control one; but interestingly, a highly
significant increase in Vit C level in the control female group as compared to
both control as well as schizophrenic male group was observed. The authors
pointed out that this information might be relevant particularly in the light
of recent reports that the risk of schizophrenia is higher in men than women.
The reduced supply of Vit C with the diet in patients with schizophrenia was
noted by Konarzewska et al. [200].
The review of Magalhães et al.
revealed that the implementation of Vit C as a low-molecular-weight antioxidant
alleviated the effects of free radicals in the treatment of schizophrenia [201]. According to Bentsen et al. [202] membrane lipid metabolism and redox
regulation may be disturbed in schizophrenia. These authors conducted a study
aiming at examination of the clinical effect of adding vitamins E + C to
antipsychotics (D2 receptor
antagonists). Patients with schizophrenia or related psychoses received Vit C
(1000 mg/day) along with vitamin E (364 mg/day) for 16 weeks. Vitamins impaired
the course of psychotic symptoms, especially of persecutory delusions. The
authors pointed to the usefulness of supplementation of antioxidant vitamins as
agents alleviating some side effects of antipsychotic drugs. This was also
confirmed by the next study involving schizophrenia patients treated with
haloperidol [203]. Classical antipsychotics like
haloperidol are suggested to increase oxidative stress and oxidative cell
injury in brain, which may influence the course as well as treatment effects of
schizophrenia. In this study, chronic haloperidol treatment connected with
supplementation of a combination of ω-3 fatty acids and vitamins E and C showed
a significant beneficial effect on schizophrenia treatment as measured by SANS
(Simpson Angus Scale) and BPRS (Brief Psychiatric Rating Scale) scales. BPRS
total score and subscale scores as well as SANS scores were significantly
improved starting from the 4th week of treatment. Moreover, in patients with
schizophrenia after 16 weeks of treatment, serum Vit C levels were almost twice
as high as at the beginning of the study. These results supported the
hypothesis of a beneficial effect of the applied supplementation both on
positive and negative symptoms of schizophrenia as well as the severity of side
effects induced by haloperidol [203]. Heiser et al. [204] also stated that reactive oxygen species
(ROS) were involved in the pathophysiology of psychiatric disorders such as
schizophrenia. Their research demonstrated that antipsychotics induced ROS
formation in the whole blood of rats, which could be reduced by the application
of vitamin C. The aim of their study was to demonstrate the effects of
clozapine, olanzapine and haloperidol at different doses (18, 90 and 180 μg/mL)
on the formation of ROS in the whole blood by using electron spin resonance
spectroscopy. To demonstrate the protective capacity of Vit C the blood samples
were incubated the highest concentration of each drug with Vit C (1 mM) for 30
min. Olanzapine caused significantly greater ROS formation vs. control under
all treatment conditions, while in the case of haloperidol and clozapine only
two higher concentrations resulted in significantly increased ROS formation.
Vitamin C reduced the ROS production of all tested drugs, but for olanzapine
the attenuating effect did not reach a significant level.
A relatively novel
approach as for the role of Vit C in etiology and treatment of schizophrenia
was presented by Sershen et al. [193]. According to the researchers, deficits
in N-methyl-d-aspartate receptor (NMDAR) function are
linked to persistent negative symptoms and cognitive deficits in schizophrenia.
This hypothesis is supported by the fact that the flavoprotein D-amino acid oxidase (DAO)
was shown to degrade the gliotransmitter D-Ser,
a potent activator of N-methyl-d-aspartate-type glutamate receptors, while a
lot of evidence has suggested that DAO, together with its activator, G72
protein, may play a key role in the pathophysiology of schizophrenia. Furthermore,
in a postmortem study the activity of DAO was found to be two-fold higher in
schizophrenia subjects [205]. Sershen et al. [193] showed that acute ascorbic acid dose (300
mg/kg i.p.) inhibited PCP-induced and amphetamine-induced locomotor activity in
mouse model, which was further attenuated in the presence of D-serine (600
mg/kg). The authors suggested that this effect could result from the Vit
C-depended changes in dopamine carrier-membrane translocation and/or altered
redox mechanisms that modulate NMDARs. However, this issue needs to be further
investigated.
The crucial role of Vit
C in neuronal maturation and functions, neurotransmitter action as well as
responses to oxidative stress is well supported by the evidences presented in
this review (Figure 2).
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Normal proteostasis ensures that proteins are produced and folded
appropriately before they are trafficked to precise locations. It also acts to
ensure that abnormal or excess proteins are degraded to prevent the
accumulation of unwanted products.4,5
Building
proteins within the cell is a complex process involving protein
folding. A protein must fold into a specific 3-dimensional conformation to
gain proper function. Because of the critical role proteins play, incorrect
folding can result in diseases such as Alzheimer's and Parkinson's.6
Protein misfolding may occur due to genetic or environmental
factors and often leads to loss of function. Misfolded proteins may accumulate,
form intermediate oligomers or fibrils, and, eventually, mature aggregates, all
of which can be toxic to the cell.3,7
Protein misfolding
Protein
aggregation
Lysosomal
dysfunction
Disease definition
Heat shock proteins exist in normal
circumstances, but their production is induced by stress—and they play a
particularly important role in protecting cells exposed to stress.20
Heat shock
proteins constitute part of the molecular chaperone system of the cell and play
a critical role in protein-folding rescue21
Heat shock
proteins are involved in several processes, such as assisting other proteins to
achieve the correct conformation, and preventing protein misfolding and
aggregation. When the heat shock response is activated, increased heat shock
protein expression is induced.
HSP70
is a key chaperone in protein homeostasis and promotes lysosome membrane
stability and integrity. HSP70 recruits and forms complexes with co-chaperones
to mark proteins for degradation and to guide them to the proteasome or, for
larger aggregates, to the autophagy–lysosome system.
HSP70 production is regulated by key
transcription factors known as heat shock factors (HSFs). In chronic disease,
the heat shock response may be insufficient to cope with prolonged exposure to
a proteotoxic environment. Under times of stress, HSF-1 amplifies the
transcription of HSP70 genes and the production of HSP70 proteins.
The resulting increased levels of HSP70 results
in a heightened response to the stress, protecting cellular proteins from
misfolding errors.
This
allows lipids and other key enzymes to be
chaperoned to the lysosomal membrane