Clinical uses of IV Vitamin C:
Neurologic illness- Alzheimer’s, Parkinson’s
• Mood disorders- Schizophrenia, Depression, Anxiety
• Infections: Viral infections, bacterial infections, Fungal infections, sepsis
• Chronic inflammation and chronic fatigue
• Cancer

SUMMARY: Vitamin C as a therapeutic treatment offers many potential benefits for patients with complex complicated medical illness. For neurodegenerative disease and psychiatric disorders, evidence suggests that vitamin C has a number of benefits for the neurologic structures of the brain. Vitamin C promotes neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. There is plentiful animal evidence to show that deletion of the vitamin C transport in the brain can lead to widespread cerebral hemorrhage and death, so the brain essentially requires vitamin C for basic functioning. It is suggested that vitamin C use in the course of neurologic diseases and display potential therapeutic roles especially on neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s disease, multiple sclerosis, ALS, psychiatric disorders including mood disorders, and schizophrenia. Vitamin C as an antioxidant directly scavenges reactive oxygen species and nitrogen species that are produced as a byproduct in normal cellular metabolism. Vitamin C inactivates super oxide radicals a major byproduct of mitochondrial metabolism. Vitamin C also helps recycle other antioxidants such as vitamin E. Vitamin C can help lessen the potential oxidative damage induced by vitamin E metabolism; therefore vitamin C is considered very neuroprotective.

VIT C AS AN ANTIDEPRESSANT: Vitamin C modulates neurotransmitter function by binding neurotransmitters to receptors as well as regulating the release from presynaptic vesicles. Vitamin C is a cofactor for the synthesis of catecholamines especially dopamine and norepinephrine. Vitamin C appears to be a substrate for dopamine beta-hydroxylase and catalyses the formation of norepinephrine from dopamine.

Vitamin C also modulates activity of some other receptors such as glutamate and the GABA receptors and therefore can help modulate and lessen damage excitotoxic damage from excess glutamatergic neurotransmission. Vitamin C inhibits the binding of glutamate to the NMDA receptor. Vitamin C also decreases the energy barrier for GABA activation so it promotes GABAergic transmission which ultimately will lessen the beneficial conditions such as anxiety disorders. Vitamin C can also act as a dopamine receptor antagonist which is why it is useful for manic mood disorders such as bipolar and schizophrenia.

VIT C BENEFICIALLY ADJUSTS BRAIN METABOLISM: Vitamin C also promotes optimizing neuronal metabolism by changing the preference for lactate over glucose as the energy substrate to sustain synaptic activity, so when it is released from glial cells and is taken up by neurons where it restrains glucose transport and tubulization so then lactate ends up being the major metabolic substrate for neuronal metabolism as an energy source.

VIT C PROTECTS THE BLOOD/BRAIN BARRIER: Vitamin C is also involved in collagen synthesis which is important for the brain. Collagen is important for regeneration of blood vessels and neuro sheath formation, therefore, it could be said that vitamin C helps optimize and repair the blood brain barrier which is routinely damaged in patients with chronic progressive neurodegenerative illnesses such as Parkinson’s’ and dementia. Vitamin C has been shown to have alleviating effects on seizure activity by the above mechanisms and reduces seizure induced damage on the hippocampus. 

VIT C IS A TREATMENT FOR ALZHEIMERS DEMENTIA: Both in-vivo, animal and in-vitro studies have shown that vitamin C is beneficial for Alzheimer’s.

Murakami et al reported that a six-month treatment of vitamin C can result in reduced A-beta oligomer formation and can significantly decrease in a measurable way brain oxidative damage and can attenuate behavioral decline in an Alzheimer’s mouse model. Studies have shown that also patients with Alzheimer’s have a lower vitamin C plasma level. Other randomized controlled trial involved 276 elderly patients demonstrated that 16-week treatments with vitamin C and beta-carotene significantly improved cognitive function especially with higher doses of beta-carotene.

VIT C IS A TREATMENT FOR PARKINSONS DISEASE: Vitamin C is important in helping patients with Parkinson’s disease. Glutamate mediated excitotoxicity is associated with the pathophysiology of Parkinson’s and this is lessened as a consequence of vitamin C treatment. Vitamin C plays a role in dopaminergic neuron differentiation. Vitamin C also plays a role in alpha synuclein oligomerization, alpha synuclein shown to be produced in the intestine as a consequence of excess LPS production from pathogenic gram negative aerobes in the intestine and the alpha synuclein travels to the brain via the vagus nerve via retrograde axonal transport to promote damage in dopaminergic neurons in the brain leading to the movement disorders associated with Parkinson’s. Human studies have shown that vitamin C deficiency in mild Parkinson’s patients is widespread, however, the plasma level of vitamin C is not as relevant as intracellular vitamin C concentration and this has been confirmed by a study performed Ide et al. It has been shown that lymphocytic vitamin C levels in patients with severe Parkinson’s is symmetrically lower compared to those with less severe Parkinson’s. There is one cohort study involving 1036 Parkinson’s patients showing that dietary vitamin C intake will decrease Parkinson’s risk. There have been multiple case reports showing that IV vitamin C therapy can lessen movement disorders in Parkinson’s patients. Vitamin C also increases L-dopa level which is a precursor for dopamine.

VIT C IS A TREATMENT FOR MULTIPLE SCLEROSIS (MS): For multiple sclerosis, vitamin C has been shown to be useful since it can help lessen oxidative damage and lessen myelin destruction which is characteristic in multiple sclerosis. Multiple sclerosis patients also have a low vitamin C level compared to healthy individuals. Multiple studies have shown that multiple sclerosis patients treated with antioxidants especially vitamin C have decrease in relapse frequency and decreased corticosteroid requirements.

VIT C IS A TREATMENT FOR DEPRESSION & ANXIETY: Because of the effects on neurotransmission, vitamin C has also been shown to be useful for depression modulating catecholamine production, optimizing GABAergic production, GABAergic stimulation and lessening excitotoxicity from NMDA receptor activation. Vitamin C has an antidepressant like effect via potassium channel inhibition and by activation of phosphatidlinositol 3-kinase in the brain. Furthermore, vitamin C deficiency is very common in patients with chronic depression. For its beneficial of anti-GABAergic effects and its anti-glutamate toxicity effects, vitamin C treatments have been shown to be useful for anxiety as well.

A study performed by De Olivera et al examined the effects of short term vitamin C treatments in high school students in a randomized double blind placebo controlled trial. This treatment led to higher vitamin C concentrations associated with decreased anxiety levels and optimized heart rate levels so there was less tachycardia associated with panic disorder and anxiety. A six-week vitamin C treatment led to decreased anxiety measured by patient’s symptom scores. Vitamin C has also been shown to decrease anxiety in diabetic patients. Vitamin C deficiency has been associated with worsened schizophrenia and the studies do show that vitamin C as an antioxidant alleviates the effects of free radicals in the treatment of schizophrenia.

SUMMARY OF NEUROPROTECTIVE EFFECTS OF VIT C: Vitamin C has been useful for Alzheimer’s to by lessening oxidative stress, decreasing amyloid aggregation, decreasing neuronal loss, improving the integrity of the blood brain barrier and lessening phosphrylation of tau protein at Ser-396. Vitamin C has been shown to be helpful for Parkinson’s by lessening alpha synuclein oligomerization, increasing dopaminergic neuron differentiation and protecting against glutamate mediated excitotoxicity and by its beneficial effects on dopamine production. Vitamin C has also been useful for multiple sclerosis by lessening oxidative stress and myelin destruction. For psychiatric disorders such as depression, anxiety and schizophrenia, vitamin C has been shown to be beneficial by modulating catecholamine and GABAergic systems, inhibiting excess NDMA activation, locking potassium channels, decreasing oxidative stress, improving redox mechanisms.

VITAMIN C TREATMENT FOR INFECTIONS

SUMMARY: Data published by the Riordan Clinic has shown that vitamin C has successfully treated polio, diphtheria, Herpes zoster, shingles, Herpes simplex, chickenpox, influenza, measles, mumps and pneumonia.

The mechanism is that the antioxidant property of vitamin C promotes a reducing environment in the blood stream and tissues, enhancing the body’s response to oxidative stress from inflammation thereby helping the immune system to fight microbes and viruses that propagate in stressful situations. Vitamin C therefore functions as an antiviral drug and also enhances immune system function. White blood cells have vitamin C in intracellular level and use vitamin C at the site of infection. Vitamin C also enhances the production of interferon which then helps prevent cells from being infected by viruses and vitamin C stimulates activity of antibodies and cytokines in mega doses and promotes mitochondrial energy production and can help specialize immune cells ingest bacteria such as phagocytes. Vitamin C also interferes with viral DNA and RNA replication; in-vitro experiments have shown that vitamin C can in just isolated way kill influenza viruses.

The antiviral activity of vitamin C is not virus specific, researches have shown that we can kill any kind of virus whether they are enveloped or non-enveloped, double stranded DNA or single stranded RNA. Multiple in-vivo studies from across the world have shown that vitamin C IV treatments have been useful for complicated viral infections. One study in Germany involved 67 patients with shingles that received 7.5 gm IV vitamin C daily for 2 weeks in addition to standard treatment for shingles and patients that received the vitamin C had less Herpes zoster associated pain, less rashes, and less general complaints. Vitamin C can also treat patients with EBV which is the common cause of chronic fatigue syndrome. EBV is linked to malignancies such as lymphoma and autoimmune diseases. The Riordan Clinic has shown that doses from 7.5 to 50 gm IV can decrease viral antibody levels and the benefits seem to be dependent upon the number of treatments given as patients given 10 or more treatments had greater reduction in viral antibody titers reflecting less viral inflammation. Overall 148 animal studies have been published by 2005 about the benefits of vitamin C as a treatment for infections.

In addition to antiviral effects, vitamin C appears to have an antifungal and antiparasitic effect also. Vitamin C has also been shown to reduce mortality in multiple infections specifically tuberculosis, bacterial sepsis, toxic shock, rabies, Candida, and protozoa, and all the studies have been in animals. Vitamin C has been known to routinely treat the common cold. Multiple studies have also shown the benefits of vitamin C to treat pneumonia, both bacterial and viral pneumonia. There is a study from UK in 1994 performed by Dr. Hunt who carried out a randomized double blind placebo controlled trial on elderly people in the UK, their mean age was 81 years hospitalized for acute bronchitis from pneumonia. Vitamin C treatments reduced the respiratory symptom score in the more ill patients and decreased mortality. Vitamin C appears to have beneficial effects on infections caused by virus, bacteria, Candida, and protozoa. Vitamin C also can decrease the pain associated with oral Herpes.

VIT C IS A CANCER TREATMENT: Many patients have been treated by the Riordan Clinic for cancer with IV vitamin C; the bone, bladder, blood cancers, skin cancers, kidney cancer, pancreatic cancer, lung cancer, prostate cancer, and breast cancers have all been successfully treated with vitamin C either as adjunctive treatments or to lessen mortality. The pathophysiology of its anticancer effect is that continuous perfusion of vitamin C at high doses trigger redox cycling which can lead to a build of hydrogen peroxide in tumor cells which is toxic to tumor cells, essentially leads to tumor cell apoptosis.

The cytotoxic effects can be attenuated by combing vitamin C with lipoic acid. Studies from many laboratories in a variety of animal models including used in hepatoma, pancreatic cancer, colon cancer, sarcoma, leukemia, prostate cancer and mesothelioma confirmed that ascorbate concentrations sufficient for cytotoxicity can be attained in-vivo and that treatments can reduce tumor growth. Vitamin C also is associated with angiogenesis inhibition as ascorbate inhibits endothelial cell tubule formation in a concentration depending fashion.

IV vitamin C is significant anti-inflammatory for cancer patients and can measurably decrease C-reactive peptide. IV vitamin C can also decrease PSA levels. Riordan Clinic has published multiple case reports of patients with multiple types of complicated cancers from stage 3, large B cell lymphoma to grade 4 renal cell carcinoma with lung mass or stage 3C ovarian cancer with these patients improving and going into remission.

Patients must be screened from G6PD deficiency as this is an absolute contraindication for vitamin C treatment as it can induce hemolysis in patients with G6PD deficiency. The Riordan Clinic has administered 40000 IV vitamin C treatments and side effects of high dose IV vitamin C are rare.

Research and experience has shown that therapeutic goal of reaching a peak plasma concentration of 20 mmol which is 350 to 400 mg/dL is efficacious.

Patients can start at 15 gm two to three times a week and escalate to reach that goal therapeutic level to max of 100 gm treatment at any given time. At CCIM, a maximum IV in vitamin C dose would be 100 gm treatment administered 3 times per week, with a goal plasma level of 350-400 mg/dl.

Dushyant Viswanathan, MD, ABIM, ABOIM, AACE

REFERENCES:
1. Journal of Nutrients. 2017 July; 9(7):659
2. Date published by the Riordan Clinic in February 2014.
3. Journal of Nutrients. 2017 April; 9(4):339.
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