Considerations In High Dose IV Vitamin C (Ascorbic Acid)

I have been getting consistent requests to weigh in on this for folks - is high dose vitamin c iv therapy good or bad ? My response usually centers around - its not good or bad in general, but it would be wise to understand some of the mechanisms of action involved and assess if its appropriate for the particular individual's situation.

VITAMIN C SCAVENGES THE FREE RADICAL SUPER OXIDE & PEROXYNITRITE

Ascorbic acid is an effective reducing agent, and also an effective agent for scavenging peroxynitrite and super oxide - which are a damaging free radicals produced in various bodily processes, particularly associated with Nitric Oxide uncoupling, iNOS / NOS2 upregulation, or NOS3 downregulation. If you have nitric oxide issues you can almost bank on it you have a super oxide issue and oxidative stress. If you neurotransmitter issues read on - it may be slightly more complicated, but you will need BH4 regardless - and its oxidized by peroxynitrite. [5,6,7,8,9]. There are many other scavengers of peroxynitrite and super oxide as well - and for those with high levels of oxidative stress it is probably worthy of exploration. However, one word of caution - those with nitric oxide issues (too much) often suffer from both vasodilation and low blood pressure - the vast majority of free radical scavengers are in fact vasodilators, causing many to "feel worse".

VITAMIN C HELPS PROTECT BH4

Peroxynitrite is not only important given the oxidative stress it induces generally, but in particular, it oxidizes BH4 (tetrahydrobiopterin - which is an important cofactor in creating serotonin and dopamine) into BH3, an intermediary before being oxidized into BH2. As BH4 levels drop - this reduces your ability to produce neurotransmitters (serotonin and dopamine). Vitamin C can help this by scavenging super oxide and peroxynitrite. [5,6,7,8,9]

VITAMIN C RECYLCLES 5-MTHF (WHICH IS ALSO A PEROXYNITRITE SCAVENGER)

Vitamin C also protects and recycles 5-MTHF (methyltetrahydrofolate) which is used not only in methylation, but also is a potent pyroxynitrite scavenger itself. When 5-MTHF gets oxidized it turns into 5-MDHF which is suspected to have toxic by products. So, in another way, vitamin c protects us from the toxic by products of 5-MDHF by reducing it back into a the peroxynitrite scavenger 5-MTHF.

ME/CFS FOLKS HAVE LOW TOLERANCE FOR METHYL FOLATE - VITAMIN C HELPS THIS

Most chronically ill folks have low tolerance for 5-MTHF, one theory being that as it gets oxidized, especially in the gut - it just creates more toxic by products (5-MDHF)without reducing agents to support its recycling. With Vitamin C supplementation, higher dosing of 5-MTHF can be tolerated as it gets recycled. I have consistently seen immune and inflammation functional markers on stool tests stabilize after consistent dosing of vitamin c (1,000-2,500 2-3x per day).

VITAMIN C RECYCLES BH4 AFTER IT GETS OXIDIZED TO BH3

Vitamin C recycles (reduces) BH3 back to BH4 so that the neurotransmitter pathways can be supported. BH4 is one of the most precious substances in the body, and serves both nitric oxide production but also neurotransmitter support. Vitamin C recycles BH3 back into BH4 - supporting functional levels of BH4 and neurotransmitter cofactors. [7]

VITAMIN C CAN REDUCE MOLECULAR OXYGEN TO HYDROGEN PEROXIDE

Super high dose vitamin c, > 30grams, can reduce molecule oxygen to hydrogen peroxide which has been used as an effective agent against certain bacteria and viruses. However, hydrogen peroxide is ALSO very oxidative, and can cause oxidative stress in the body. This oxidative stress can stimulate the gene NRF2 in the body, and can also be neutralized by glutathione in the body, in particular the GPX genes (GPX1-7) and Catalase [1,2]. Catalase is expressed mostly in the liver, however catalase supplementation has helps folks deal with gut based oxidative stress. GPX2 is expressed in the gut - folks mutated here almost always have gut issues. If your glutathione GPX genes are compromised and / or your glutathione recycling gene (GSR) is compromised - this can spell trouble [2]. For these folks, their system can be over whelmed by lots of hydrogen peroxide and be unable to neutralize all the oxidative stress. These are the folks who end up in bed for 1-4 weeks after a high dose IV Vitamin C therapy or a 3,000 mg Glutathione IV, or ozone therapy - will write another article on that. On the flip side, the high levels of hydrogen peroxide in the body can stimulate the rate limiting enzyme for producing BH4 - its called GTPCH1. This is good news for more BH4 potentially. However, GTPCH1 is also modulated by HSP90 (heat shock protein 90) which is activated during sauna therapy, so sauna helps increase BH4 production too! Another blog article coming on sauna therapy.

VITAMIN C & OXALATES

There is conflicting research on this topic related to high dose vitamin and oxalates causing kidney stones. I will leave it here - lots of arguments on both sides of the fence. However, if you have genetics making you vulnerable to high oxalate levels, or you have had a diet high in oxalates (spinach, beets, nuts, greens, raw veggies, etc), i encourage you to use caution. [10]

So what does all this mean ? It means if your anti oxidant systems are running smoothly and are not compromised, Vitamin C therapy can be supportive - it can trigger your antioxidant systems to jump into high gear and also wipe out various viruses and bacteria. However, if your anti oxidant systems are already stressed, and compromised genetically, be very very careful. If you have a history of kidney stones and or oxalate issues do your own research to get comfortable.

If you have high oxalic acid on an organic acids test, you almost certainly have nutrient absorption issues. Liposomal formats in supplements will work better for you in the interim to bypass the gut issues, and a steady longer term oxalate lowering diet and protocol will be supportive for nutrition, fatigue, and inflammation. When i see mutations in the key oxalate genes, more often than not it spells trouble.

SUMMARY

What does all this tell us in the context of IV therapies like Myers cocktails and vitamin c ? Certainly the combination of methyl folate in myers cocktails and vitamin c will be helpful in increasing BH4 levels, as well as reducing the oxidative stress from peroxynitrite and super oxide free radicals. The magnesium sulfate in Myer's cocktails also has benefits for lowering coagulation in the blood and enabling better blood flow and oxygen delivery to the brain [12].

A POOR MAN'S MYER'S COCKTAIL

If you want to do an at home poor mans version of a Myers cocktail - consider this:

1) Epsom salt bath for magnesium sulfate

2) Quicksilver Scientific Ultra Vitamin for all your B's and others (A, C, D, E, K) - liposomal [3]

3) Quicksilver liposomal Vitamin C and R Lipoic Acid (upregulates NRF2) [3]

4) Consider sauna therapy 1-3x per week in gradual increments to raise BH4, or add in some royal jelly (YS Ecco Bee Farms) and or Ecological Formula's PTeredin-4.

The above gives you many of the same benefits, and you can do it regularly. You can modulate your methylation and Vitamin C appropriately. For folks dealing with nitric oxide uncoupling, upregulated NOS2 or downregulated NOS3, low levels of BH4 and/or neurotransmitters (e.g. anxiety and depression), this can be a cost effective low risk alternative. You wont get the calcium and potassium in the above, but those are easily found in various electrolyte drinks. The liposomal format bypasses all the gut absorption issues, and just as importantly perhaps bypasses the oxidation that could occur in the gut too. I am a fan of Quicksilver Scientific products, and my favorite place to get them is www.digestivewarrior.com - they ship with ice packs.

[1] First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid O.M. Ighodaro a,b,⇑ , O.A. Akinloye b. Alexandria Journal of Medicine. Available online 13 November 2017

[2] Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism Agnieszka Loboda, Milena Damulewicz, Elzbieta Pyza,Alicja Jozkowicz, Jozef Dulak, Cell. Mol. Life Sci. (2016) 73:3221–3247 DOI 10.1007/s00018-016-2223-0 Cellular and Molecular Life Sciences

[3] www.digestivewarrior.com is my favorite source for quicksilver products, they ship with ice packs

[5] Free radicals, natural antioxidants, and their reaction mechanisms . Satish Balasaheb Nimse and Dilipkumar Pal. DOI: 10.1039/C4RA13315C (Review Article) RSC Adv., 2015, 5, 27986-28006.

[6] Ascorbate Prevents the Interaction of Superoxide and Nitric Oxide Only at Very High Physiological Concentrations. Terence S. Jackson, Aiming Xu, Joseph A. Vita and John F. KeaneyJr. Originally published 2 Nov1998. https://doi.org/10.1161/01.RES.83.9.916Circulation Research. 1998;83:916–922

[7] Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols IMPLICATIONS FOR UNCOUPLING ENDOTHELIAL NITRIC-OXIDE SYNTHASE* Received for publication, March 4, 2003, and in revised form, April 5, 2003 Published, JBC Papers in Press, April 10, 2003, DOI 10.1074/jbc.M302227200 Nermin Kuzkaya‡§, Norbert Weissmann‡, David G. Harrison, and Sergey Dikalov. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 278, No. 25, Issue of June 20, pp. 22546–22554, 2003 © 2003 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A

[8] Free radical scavengers, vitamins A, C, and E, plus magnesium reduces noise trauma

Colleen G. Le Prell,a Larry F. Hughes,b and Josef M. Millera,cFree Radic Biol Med. Author manuscript; available in PMC 2007 Aug 20.Published in final edited form as: Free Radic Biol Med. 2007 May 1; 42(9): 1454–1463. Published online 2007 Feb 20. doi: 10.1016/j.freeradbiomed.2007.02.008 PMCID: PMC1950331 NIHMSID: NIHMS21361PMID: 17395018

[9] Vitamin C revisited. Heleen M Oudemans-van Straaten, Angelique ME Spoelstra-de Man & Monique C de Waard Critical Care volume 18, Article number: 460 (2014).

[10] Total, Dietary, and Supplemental Vitamin C Intake and Risk of Incident Kidney Stones. Pietro Manuel Ferraro, MD, Gary C. Curhan, MD, ScD, Giovanni Gambaro, MD, PhD, and Eric N. Taylor, Am J Kidney Dis. Author manuscript; available in PMC 2017 Mar 1. Published in final edited form as:Am J Kidney Dis. 2016 Mar; 67(3): 400–407. Published online 2015 Oct 14. doi: 10.1053/j.ajkd.2015.09.005 PMCID: PMC4769668 NIHMSID: NIHMS725119 PMID: 26463139

[11] Key role of singlet oxygen and peroxynitrite in viral RNA damage during virucidal effect of plasma torch on feline calicivirus. Risa Yamashiro, Tatsuya Misawa & Akikazu Sakudo . Scientific Reports volume 8, Article number: 17947 (2018)

[12] Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery, measured by rotational thromboelastometry. H. S. Na, H. J. Shin, S. B. Kang, J. W. Hwang, S. H. Do. First published: 05 August 2014. https://doi.org/10.1111/anae.12684. Association of Anesthesia. Volume69, Issue12. December 2014. Pages 1314-1321