The Controversy of Antioxidants

[pamojja]

24 grams is definitely a LOT. Enough to become a prooxidant, which is how it often works w/difficult cancer cases, and may be how it helped you.

Ascorbic acid til now only has been found pro-oxidant in-vitro to cancer cells with concentrations only attainable by infusions. Never in-vivo.

One study found with intakes of about 20 g throughout a day plasma levels rise to about 9 mg/dl. Still very far from IV ascorbate plasma peaks.

 Table 9.312 Human tissue & fluid ascorbic acid concentrations1

Organ/Tissue   Vitamin C Concentration*
 
Pituitary Gland            40-50 
Adrenal Gland             30-40 
Eye Lens                     25-31 
Liver                           10-16 
Brain                           13-15 
Pancreas                     10-15 
Spleen                        10-15 
Kidneys                       5-15  
Lungs                              7
Skeletal Muscle            3-4
Testes                              3
Thyroid                           2
Cerebrospinal Fluid        3.8
Plasma                      0.4-1
Saliva                        0.1-9.1

* mg/100 g wet tissue, mg/100 mL fluids

However, if one assumes already pro-oxidants effects of plasma-levels at 9 mg/dl, one also would have to assume this pro-oxidant environment is how the pituitary, adrenals, eye-lens, liver, brain, pancreas, speen and kidneys work day-in-day-out.

Which beside no such in-vivo finding, I find very unlikely.

 

[dannybex]

Ascorbic acid til now only has been found pro-oxidant in-vitro to cancer cells with concentrations only attainable by infusions. Never in-vivo.

One study found with intakes of about 20 g throughout a day plasma levels rise to about 9 mg/dl. Still very far from IV ascorbate plasma peaks.

 Table 9.312 Human tissue & fluid ascorbic acid concentrations1

Organ/Tissue   Vitamin C Concentration*

Pituitary Gland            40-50
Adrenal Gland             30-40
Eye Lens                     25-31
Liver                           10-16
Brain                           13-15
Pancreas                     10-15
Spleen                        10-15
Kidneys                       5-15
Lungs                              7
Skeletal Muscle            3-4
Testes                              3
Thyroid                           2
Cerebrospinal Fluid        3.8
Plasma                      0.4-1
Saliva                        0.1-9.1

* mg/100 g wet tissue, mg/100 mL fluids

However, if one assumes already pro-oxidants effects of plasma-levels at 9 mg/dl, one also would have to assume this pro-oxidant environment is how the pituitary, adrenals, eye-lens, liver, brain, pancreas, speen and kidneys work day-in-day-out.

Which beside no such in-vivo finding, I find very unlikely.

My brain is only working at about 50%, so take what I say with a grain of salt. But it's my understanding that vitamin C works selectively, so perhaps one shouldn't assume that it works the same way in every environment or even cell.

This study was in-vivo, and found it had prooxidant effects (if given by IV) in tumors, but not in the blood of rats. And this study in humans, found the same -- that it was selective -- but worth noting that it also was given by IV.

Anyway, the reason I replied to this thread is not because I don't think antioxidants aren't important -- or critical to health -- but because it may just be possible that some of us have been or may be interfering with the body's natural response to infections, etc., by taking too much, too many, too often.

 

[pamojja]

I don't think antioxidants aren't important

As already said, each nutrient falling under the anti-oxidant umbrella, has much more important functions, than being just anti-oxidant only.

... or may be interfering with the body's natural response to infections, etc., by taking too much, too many, too often.

Not in my experience taking all nutrients, also with not-so-important antioxidant activity, at mega-doses for the last 11 years. Only remissions.

As you now found too, pro-oxidant effects occure with cancer-cells at levels attainable with IVs only.

This study was in-vivo, and found it had prooxidant effects (if given by IV) in tumors, but not in the blood of rats. And this study in humans, found the same -- that it was selective -- but worth noting that it also was given by IV.

The first study in mice, the second in rats.

 

[ebethc]

From ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/ ): "Glutathione administered intravenously, inhaled, and ingested intranasally increases systemic levels.27 IV glutathione has a short half-life but has shown at least short-term efficacy in several diseases. Oral administration is controversial; while most research shows that oral glutathione does not increase RBC glutathione, there are a few studies that show efficacy.28 My opinion is that unmodified oral glutathione is unlikely to consistently elevate cellular levels. Oral and transdermal liposomal glutathione show promise, but research is early."

do you know if intranasal glutathione can cross the blood-brain barrier?

 

[Wishful]

do you know if intranasal glutathione can cross the blood-brain barrier?

Nope. You'll have to dig through research papers for that.

 

[dreamydays]

In my opinion, antioxidants are a the old way of thinking and don't work. NMN and resveratrol (with fat as its not very bioavailable) are the latest thinking from the longevity community. This guy https://www.youtube.com/user/bsta045 is excellent and goes through the research and his indenpendant suggestions. I suggest there is great evidence for sulphoraphane (Jarrow BrocooMax) and NMN and resveratrol. Antioxidants are basically ineffective and great for selling foods and supplements, but don't work. Watch Rhonda Patrick's videos regarding sulphoraphane on youtube. I have looked into growing broccoli sprouts but its too much work, so the Jarrow supplement is the only affordable way of taking it.

 

[pamojja]

In my opinion, antioxidants are a the old way of thinking and don't work.

Experienced too many benefits to be able to agree. Where I wholeheartedly agree, and already explained in my former post: to even categorise as 'antioxidants', despite their manyfold, not overlaping and much more important functions, is indeed an old and not well thoughtout way of thinking.

 

[dreamydays]

Thanks for your reply pamojja, I just feel there was a rush to exaggerate and sell foods and supplements but I have never felt any benefits. Watch Dr Brad Stanfield on Youtube, he examines what works and what doesn't have the evidence. Obviously all supplements and foods have their own benefits. There is definitely a role for antioxidants and Vitamin C, Glutathione, etc. I just think there is so much hype and bullshit around and a lot of the evidence has moved on. Some of these newer ideas improve antioxidant activity. A lot of the longevity post I agree with. I take piracetam, which I think is so underrated and underused in ME. Its about sorting through the hype and finding out what actually works.

 

[Wishful]

It's kind of hard to personally figure out whether taking antioxidants will make you live longer. How do you know when you would have died if you weren't taking them? I'm sure marketers love that kind of inability to disprove their claim.

For that matter, once you're dead, you won't be around to think about the issue.

 

[pamojja]

It's kind of hard to personally figure out whether taking antioxidants will make you live longer.

Though I think it really isn't accurate to speak of 'antioxidants', I had usually mercilessly progressing conditions, which conventional medicine thinks irreversible. But experienced remission of a 60% walking-disabilty (from PAD), COPD, ME/CFS symptoms and other minor ails (NAFLD, cystitis, retinal migraines, psoriasis..). As a bonus I don't get sun-burned anymore (without suncream)

Healthspan compared to lifespon is pretty obvious, once it manifests.

 

[lateM98]

The body recycle kilograms worth of antioxidant molecules per day. Some of these molecules goes through irreversible pathways that end with none re-usable products, such as detoxification of drugs and cellular debris, and this is where exogenous antioxidant supplementation may help (NAC for Paracetamol overdose for example), other than that, the best thing antioxidant supplementation can do is to saturate the rate of enzymatic reactions that involve said antioxidants. But that is not enough for people with serious enzymatic defects such as in G6PD. The body may recycle a kg worth of glutathione per day.. no one will take a one kg infusion of glutathione per day.. In the same way the body recycle 60 kg of ATP per day, 10-20 kg of NAD+ per day..etc

 

[xploit316]

Are there any natural immunosuppressants?

For some reason I personally dont do well with high antioxidants (Be it plant based diet, supplements, spices (Esp turmeric and cloves) etc). I suspect its a genetic liver issue which I inherited from my paternal side (Grandmother died from colon cancer, grandfather had Alcoholic fatty liver).

High starch and medium protein, low fat/fructose/fiber is the diet which is working well for me and keeps my body and mind at peace.

 

[Wishful]

Are there any natural immunosuppressants?

I'm not sure, but another question is what part of the immune system are you trying to suppress? I tried cyclosporin, a quite potent immunosuppressant, but it had no effect on my symptoms. Afterwards I learned that it doesn't pass the BBB easily, so it wouldn't suppress neuroinflammation.

 

[frozenborderline]

A lot of people seem to follow the old theories about ROS being 'bad for us' and antioxidants 'being good for us'. Apparently, it's not quite that simple, especially for mitochondria. In mitochondria, superoxide is a signalling molecule essential for proper function; electron leakage is part of the feedback mechanism. In response to increased demand for ATP, more superoxide is produced, which interacts with certain proteins in a way that increases mitochondrial capacity and number of mitochondria per cell. Increasing antioxidant levels can actually reduce ATP production, by preventing this adaptive function. If levels of superoxide increase enough (due to damage or whatever), it triggers cell death, which will hopefully result in replacement by a fresh healthy cell; antioxidants might keep defective cells around longer.

Early proponents for antioxidant supplementation claimed that this would reduce cellular damage and thus increase lifespan. Multiple trials showed that this was incorrect, and that taking high-dose antioxidants actually increased the risk of earlier death. Furthermore, pro-oxidants can increase lifespan.

There's also the problem that the level of antioxidants in the body are carefully regulated; taking high dosages may only increase cellular levels slightly, with the rest flushed down the toilet.

These challenges to the old theories about ROS and antioxidants are something I found in "The Vital Question", by Nick Lane. Fascinating theories for how life initially started, and how it developed how it did. Mitochondria play a critical role in life more advanced than bacteria, so several chapters are about them. I haven't verified all the references and study results. I just thought it was worthwhile pointing out that the question of antioxidant supplements is not simple. If you're taking high-dosage antioxidants based on outdated theories (which are still being pushed by manufacturers and marketers), you might want to do a bit more research into more recent findings. I highly recommend "The Vital Question", but I'm sure there are other resources out there. A quick googling showed plenty of papers about the controversy, with the common conclusion being "We don't know how much is good for you." I think the safe assumption is that moderate levels in diet are probably good for you, and moderate supplementation might be a good idea if for some reason you can't get moderate amounts of fruits and veggies in you diet. For ME, I think you have to experiment to see whether supplementation provides any noticeable benefits for you as an individual. Just don't assume that "more is better".

I've started skimming this book ... I'm severe so I can only get thru a bit at a time without crashing. Its very interesting, I find the whole field of bioenergetics and ideas about entropy and thermodynamics of biological life and self organizing systems and the origin of life so fascinating. I would say that just bc antioxidants aren't a panacea doesn't mean they wouldn't help in me/cfs, as we don't know if what's wrong in this illness is similar to other diseases like cancer or aging. Paul Cheney seemed to think there was some kind of oxidative stress going on. Otoh , reductive stress is very much a problem in many diseases , and maybe in me/Cfs. If pyruvate dehydrogenase is truly partially impaired as fluge and mella showed, one part of the cellular respiration cycle would be shunting pyruvate away from oxidative metabolism , away from feeding the Krebs cycle , and into being reduced to lactate. Now I don't know if redox reactions or states can be generalised across cell types and the whole body , is it possible for cells in one organ or system to be doing anaerobic metabolism /reductive stress and ones in another part of the body to be doing the opposite ...?? I don't know. Metabolism and bioenergetics is clearly so so so complex , that's my main takeaway from nick lanes book as a midwit who has brain fog and is so sick I'm bedridden. Well , other main takeaway is that metabolism and the structures that evolved to support efficient metabolism , is possibly as important or more important than genes In evolution, in survival and disease ... The optimismi have from skimming that book comes from thinking we are due for a kuhnian paradigm shift (a buzzword or very saturated signifier I know , but I do know what it means ) in cellular biology and medicine and that this will involve less focus on top down ideas of genetic determinism and more on the intricacies of metabolism and how mitochondria and other parts of the eukaryotic cell respond to threats . a centering of bioenergetics where genetics has been dominant. maybe the anomalies of chronic diseases we cant solve with current biological theories will reach a tipping poing where a scientific revolution is needed to ecplain fhem since the facts cant easily be made to fit existing theory. And a sort of dialectical synthesis btwn mechanism and vitalism .... that is needed. Both are very reductive . of course there is no vital essence within living things , as vitalists postulate , but living matter has self organizing autopoetic tendencies and uses energy in a way that animates it, even if this electromagnetic energy /proton and electron flux isn't an essence but rather a force

 

[frozenborderline]

Are there any natural immunosuppressants?

Oh yeah. Chinese medicine uses licorice as a hardcore corticosteroid replacement. It raises cortisol and aldosterone a lot iirc. Natural isn't better always tho and in this case it's probably worse and more dangerous than just getting on some kind of targeted treatment for autoimmune disease or mcas or whatever you got going on.

There's also adrenal supplements containing animal adrenal glands which I think have actual epinephrine/norepinephrine or some kind of catecholamines in them. That stuff amps you up. And yeah it does broadly suppress "inflammation" but so does dexamethasone and that doesn't cure me/Cfs. Anyway yes there are natural things for that. No they aren't necessarily safer.

There are more targeted immunomodulators in nature too, like chaga , !maybe baicalein, but my point is natural doesn't mean better automatically. It depends on the individual herb /drug.

 

[frozenborderline]

not trying to convince people to not try antioxidants; I think experimentation is good. However, I do think that there are many people who take supplemental antioxidants because of an outdated--and incorrect--theory and who might actually be harming their health unknowingly, as well as wasting money. I doubt that government regulators are in a hurry to question old approvals of marketing claims.

Again all nick lane was saying was that antioxidants and oxidative stress or free radicals aren't an importsnt factor in aging or a panacea. But with cfs a lot of responses to things --meds, exercise , chemicals , mold, is all different than normal people or even people with unrelated illnesses.

I don't think that anti oxidants are that important for this illness although I have had some interesting beneficial effects from tocovit (mixed tocopherols and tocotrienols), but I'm just saying what Nick lane says about anti oxidants doesn't necessarily apply for our illness

 

[sb4]

I think that in general exogenous antioxidants aren't good and we should be relying on our body making it's own anti oxidants through things like glutathione. Of course that is from the perspective of a healthy person, a sick person might have extra oxidants to deal with thanks to the immune system / pathogens.

I have been following Brad Marshal for some time, who has been building on the work by Peter @Hyperlipid. They are coming at it from the perspective that ROS is good when it comes to cell signalling of energy and preventing obesity.

Brad Mashal has been recently writing about how reductive stress causes oxidative stress. I think that could be applicable to this illness. The basic gist of it is, if your metabolism isn't working well (for various reasons, they focus on polyunsaturated fatty acids but I also think things like CFS could contribute) then you get a build up of NADH, relative to NAD. Too much fuel is building up but not being burnt / oxidized. I think PDH inhibition could cause something similar. When this happens you are not using NNT enough to regenerate GSH which should be used to mop up ROS (and burn off excess calories).

I'm probably not explaining it well but here is a video that does a better job:

 

[sb4]

@frozenborderline Also in the accompanying blog post he mentions things like vit C and E reducing the NADH pool which is good and is inline with your experience with tocopherols.

 

[Wishful]

is it possible for cells in one organ or system to be doing anaerobic metabolism /reductive stress and ones in another part of the body to be doing the opposite ...??

Seems possible to me. Different cell lines evolved for different purposes, so for escaping a predator, your muscles might boost mitochondrial function in response to stress hormones, while your gut cells might go into holding pattern to conserve energy.