To be honest in vitro studies like this are the least reliable form of evidence, unless they can specifically show the drug concentrations they're using are realistic, that is achievable in the target tissue in the body. In probably 9 out of 10 in vitro studies (or more), the scientists have chosen to use concentrations that show efficacy in the lab, but are far higher than what can be achieved in the body. The scientific literature is therefore full of studies that look interesting on the surface, but have no clinical translatability.
As for vitamin C, there actually is some clinical evidence from a trial of high dose intravenous vitamin C (ascorbate) for GBM.
Thank you, Stephen. I was actually reading this with that other study of IV vitamin C in mind. I’m wondering if using IV vitamin C would have benefit or not.
The thing to remember about vitamin C / ascorbate used as an anti-tumor treatment, is that low doses of vitamin C act as an anti-oxidant and high doses act as a pro-oxidant, and it is the pro-oxidant function that is proposed to have direct anti-tumor effect. A certain threshold level of ascorbate radical is required to further generate hydrogen peroxide which is the active agent that is toxic to tumor cells. I can provide you with in vivo studies to support these statements if you're interested.
The clinical study set the threshold at 20 millimolar (mM) plasma concentration of ascorbate (which is higher than the threshold concentration for hydrogen peroxide generation seen in the mouse studies ~ 8 mM). The clinical study found the 20 mM level was achieved in all patients with an intravenous dose of 87.5 grams, and this was given 3 times a week.
It would be very interesting to study high dose intravenous vitamin C specifically in the context of IDH1-mutant tumors, which are known to be especially vulnerable to pro-oxidant stressors.
It's important to remember that in the mouse studies, no amount of oral vitamin C was sufficient to boost plasma levels above the pro-oxidant threshold level. I would also have great reservations about combining intravenous vitamin C with radiation, because a mouse study showed high dose intrperitoneal vitamin C injections to mice (dose of 1 gram ascorbic acid per kg mouse weight) actually protected the tumors from radiation damage. It's possible that threshold levels of ascorbate are being achieved in the blood but not in the brain tumors in this study? https://www.ncbi.nlm.nih.gov/pubmed/25566497
I’m thinking of IV Vitamin C as a maintain therapy (not during treatment) but I’m challenged to determine how long or how often I’d need to take it. I may have a chance of getting it prescribed in VT but if not it would be expensive.
Hi Maria, here are the in vivo studies I was referring to.
Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo http://www.pnas.org/content/104/21/8749.long
Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice http://www.pnas.org/content/105/32/11105.long
To be honest in vitro studies like this are the least reliable form of evidence, unless they can specifically show the drug concentrations they're using are realistic, that is achievable in the target tissue in the body. In probably 9 out of 10 in vitro studies (or more), the scientists have chosen to use concentrations that show efficacy in the lab, but are far higher than what can be achieved in the body. The scientific literature is therefore full of studies that look interesting on the surface, but have no clinical translatability.
ReplyDeleteAs for vitamin C, there actually is some clinical evidence from a trial of high dose intravenous vitamin C (ascorbate) for GBM.
http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30062-4
The full study is in the Brain Tumor Library -> 1. Therapies - Human studies -> Ascorbate (vitamin C)
Thank you, Stephen. I was actually reading this with that other study of IV vitamin C in mind. I’m wondering if using IV vitamin C would have benefit or not.
ReplyDeleteThe thing to remember about vitamin C / ascorbate used as an anti-tumor treatment, is that low doses of vitamin C act as an anti-oxidant and high doses act as a pro-oxidant, and it is the pro-oxidant function that is proposed to have direct anti-tumor effect. A certain threshold level of ascorbate radical is required to further generate hydrogen peroxide which is the active agent that is toxic to tumor cells. I can provide you with in vivo studies to support these statements if you're interested.
DeleteThe clinical study set the threshold at 20 millimolar (mM) plasma concentration of ascorbate (which is higher than the threshold concentration for hydrogen peroxide generation seen in the mouse studies ~ 8 mM). The clinical study found the 20 mM level was achieved in all patients with an intravenous dose of 87.5 grams, and this was given 3 times a week.
It would be very interesting to study high dose intravenous vitamin C specifically in the context of IDH1-mutant tumors, which are known to be especially vulnerable to pro-oxidant stressors.
It's important to remember that in the mouse studies, no amount of oral vitamin C was sufficient to boost plasma levels above the pro-oxidant threshold level. I would also have great reservations about combining intravenous vitamin C with radiation, because a mouse study showed high dose intrperitoneal vitamin C injections to mice (dose of 1 gram ascorbic acid per kg mouse weight) actually protected the tumors from radiation damage. It's possible that threshold levels of ascorbate are being achieved in the blood but not in the brain tumors in this study?
https://www.ncbi.nlm.nih.gov/pubmed/25566497
Thank you, Stephen. I didn’t see this until now.
DeleteYes, please provide.
I’m thinking of IV Vitamin C as a maintain therapy (not during treatment) but I’m challenged to determine how long or how often I’d need to take it. I may have a chance of getting it prescribed in VT but if not it would be expensive.
Hi Maria, here are the in vivo studies I was referring to.
DeleteAscorbate in pharmacologic concentrations selectively
generates ascorbate radical and hydrogen peroxide
in extracellular fluid in vivo
http://www.pnas.org/content/104/21/8749.long
Pharmacologic doses of ascorbate act as a prooxidant
and decrease growth of aggressive tumor xenografts
in mice
http://www.pnas.org/content/105/32/11105.long