The Controversy of Antioxidants

[Wishful]

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 If you're taking high-dosage antioxidants based on outdated theories (which are still being pushed by manufacturers and marketers), you might want to do a bit more research into more recent findings.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".

 

[gbells]

My experience with strong anti-oxidants like (N-acetyle cysteine, vitamin E) is that they give about 24 hours of symptom relief which lulls one into a false sense of security while you revel in the extra exercise ability but then the extra lactic acid buildup brings a crash. I think they are a bad idea just as excess exercising is bad for ME.

 

[pamojja]

I had nothing more to loose, with a PAD-diagnosis 11 years ago - a 60% walking-disabilities from a 80% stenosis at my abominal aorta - and conventional medicine considering it a mercylessly progressing disease. With only invasive interventions and no hope on recovery.

Therefore I tried it the old way with high-dose antioxidants by Linus Pauling's therapy. Though his hypothesis is a bid more sophisticated, than being based on antioxidant-actions only. And really includes lifestyle-adaptations and comprehensive supplementation with all essential nutrients.

Not only did I experience remission from the walking-disability, but as benefial side-effects also remission from NAFLD, a cystitis circumscripta of the bladder, psoriasis and retinal migraine flare-ups, a CKD stage 1, and ME/CFS symptoms. Beside further minor ailments improving. All conditions conventional medicine has little to offer. Than trying to slow progression.

So my thesis wasn't even antioxidant, nor anything more sophisticated, but 'nothing more to loose', and I gained everything back again. This thesis or that thesis - in the end is really irrelevant - experience of remissions do count. And I found out by trial and error how much is good for me:

A lot. Like 24 g of vitamin C per taken throughout the day for the last 11 years.

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."

Opps. Question not even directed to me... So carry on discussing theories of a small subset of pharmacological actions from so called antioxidants. Of course, as always in pharmacological theory: limiting it to 1 agent at a time (preferably never in such high doses, as real people successfully are taking, as with vitamin C in dozens of grams), while in real life all nutrients work in concert. For me they did much more than ever could be explained by this conventional-medicine model, which actually failed me completely.

 

[godlovesatrier]

For anyone who wants to try vitamin c - who like me may have experimented broadly with umpteen different types and had bad reactions to all of them in the intestine, etc. I found one that works for me 6 months ago and it's been great, but for some reason I never thought to buy it in powder form so I can take say 10g vitc per day.

https://www.luckyvitamin.com/p-7755..._ET7wHhcM2I36iZusCK0N4sGLe8L9hgEaAqRTEALw_wcB

The NOW brand magnesium ascorbate allows you to do this, 1 teaspoon is about 3.2g of vitc, so one tablespoon would be 9.8g of vitc. A tablespoon a day would last about 20 to 30 days I think per tub. Which isn't bad based on the price. So if you have difficulty with ascorbate or buffered vit c (which also didn't work for me) then this is ideal.

 

[stefanosstef]

I did some rigorous exercise (aerobic), short time but intense.I was immediately exausted and the next day I had PEM.Next time I had to do the same I took an antioxidant cocktail just after the exercise:
600mg coQ10 (ubiquinone)
5gr glutamine
1 tsp curcumin
1 tsp liposomal glutathione
2 gr baking soda

I had no PEM afterwards.I tried this combo twice so far, no PEM both times.I think the last one I added some CBD (smoked)

 

[gbells]

There is no need to smoke CBD oil, it has good sublingual absorption.

 

[godlovesatrier]

@stefanosstef This would work for me too but I would be high as a kite and have difficulty sleeping. The effect these high strength nutritional supports have on my mental health is not great. Anxiety, insomnia or being over wired. Still with 5 grams of l-glutamine I am not surprised everything felt good. That would make anyone feel energised.

 

[Wishful]

The problem with 'supplemental antioxidants made me feel better' is that it doesn't actually prove that the antioxidant effect was responsible for the improvement. I'm not sure that any pure chemical has one and only one effect on a human body, and herbal supplements would have even more possible mechanisms for working. Something labelled as an antioxidant might help you by altering your gut microbiome, or it might alter reaction rates of some protein or whatever.

If you try 20 different products that have 'antioxidant' as a property, and they all have a similar effect, that would be statistically significant. If it's only three different products, that's still evidence, but weaker. If it's only one product, you don't know what is the mechanism of its effect.

I'm 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.

 

[pamojja]

The problem with 'supplemental antioxidants made me feel better' is that it doesn't actually prove that the antioxidant effect was responsible for the improvement.

Excactly. The anti-oxidant effect is only one of many other effects. Where many of the later effects actually override the former. Therefore the majority of good experiences reported until now. Nothing to do with anti-oxidation.

 

[JES]

Vitamin C is strange, it actually increases my inflammatory symptoms quickly at dosages above 500 mg. Other antioxidants like ALA, NAC and pycnogenol initially reduce inflammatory symptoms, but after a day or two make flu-like symptoms and hypoglycemia worse.

I think something similar is going on in my case as @gbells describes. Perhaps the relief comes from initially knocking down ROS, but if the immune system is attempting to fight something as is the case for me, then in long-term you might end up doing more damage by high-dose antioxidants. I'm not convinced it's a good idea to take megadoses of antioxidants for any ME/CFS patient.

 

[YippeeKi YOW !!]

I think the last one I added some CBD (smoked)

That would be my preferred method of use ..... well, except for the paranoia that Sativa strains produce. So unless I can be sure I'm getting an Indica strain, or at least a gentle hybrid, I have to regretfully decline ....

There is no need to smoke CBD oil, it has good sublingual absorption.

But the beneficial effects seem to be both more pronounced, more dependable, and more durable than the often misrepresented and dilute effects of various forms of CBD oils. I have yet to find one that does what the seller/producer claims it will ....

 

[gbells]

I think for adults it is a good idea to take absorbable glutathione because it is one of the longevity chemicals that they are naturally becoming deficient in due to age (also ubiquinol, carnosine and nicotinamide riboside). It makes sense to use it as a replacement therapy. This probably will slightly raise their spoons energy capabality and exercise tolerance. However, leaky mitochondria aren't going to magically fix themselves and work normally. In physical therapy I could handle two sets of light anaerobic strength training which minimizes mitochondrial workload by burning mostly glucose. As my ME got better I could increase the weight and repetitions.

 

[gbells]

But the beneficial effects seem to be both more pronounced, more dependable, and more durable than the often misrepresented and dilute effects of various forms of CBD oils. I have yet to find one that does what the seller/producer claims it will

I never vaped it. I use a 24% heated CBD oil concentrate which is lab certified and works well as an antidepressant. I tried a 14% unheated one but the antidep benefits were much weaker and found the pain relieving effect too short lived at 4 hours to depend on.

 

[stefanosstef]

The problem with 'supplemental antioxidants made me feel better' is that it doesn't actually prove that the antioxidant effect was responsible for the improvement. I'm not sure that any pure chemical has one and only one effect on a human body, and herbal supplements would have even more possible mechanisms for working. Something labelled as an antioxidant might help you by altering your gut microbiome, or it might alter reaction rates of some protein or whatever.

If you try 20 different products that have 'antioxidant' as a property, and they all have a similar effect, that would be statistically significant. If it's only three different products, that's still evidence, but weaker. If it's only one product, you don't know what is the mechanism of its effect.

I'm 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.

You are correct.I don't know it was the antioxidant effect.I chose them based on that and the post workout effects and seemed to be a clear success.The reasons are certainly not clear as you pointed out.

@YippeeKi YOW !! @godlovesatrier @gbells
That was a CBD only strain (flower, not oil or extract), supposedly limited to 0.2% THC, that's the only weed that is legal here, and it's not actually weed.I have quite some doubts about that 0.2% THC though, because sometimes there is a high and I think that the label does not match the reality but who knows.I chose that method because of short half life and immediate onset.I do it before sleeping, to initiate sleep.I don't know if it's cheaper, haven't calculated it but it seems so.
I have tried from 17% CBD to 31% CBD.It helps before bed and it's one of the few things my neurologist suggested for CFS, based on a big study (I think it was this one, he suggested I should read it: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919160/ ).
He didn't suggest smoking it though, he meant the oil

 

[pamojja]

Vitamin C is strange, it actually increases my inflammatory symptoms quickly at dosages above 500 mg.

Have you ever tried to titrate to bowel tolerance?

 

[sb4]

@Wishful I think you will like this follow up series to Nick Lanes work on mito. I would recommend reading through the entire Protons blog series if you are interested. It helped explain a lot to me.

 

[gbells]

You are correct.I don't know it was the antioxidant effect.I chose them based on that and the post workout effects and seemed to be a clear success.The reasons are certainly not clear as you pointed out.

@YippeeKi YOW !! @godlovesatrier @gbells

Cannabis isn't legal in my state. I use CBD oil derived from hemp.

 

[godlovesatrier]

Funny if I take CBD oil at anything over 2.5% which is something like 2.5mg per 100ml, no THC. I crash for weeks on end, it's like my immune system de regulates into TH2 dominant or something bizarre and I can barely move, get out of bed, do a damn thing. My main approach to survive ME over the years has been anti virals (herbal ones), I am taking siberian ginseng at the minute. Got a dreadful ME sore throat though at the moment and fairly weak. But I've noticed that if I don't keep my immune system up - which I can only assume is cauisng it to be TH1 dominant, I feel incredibly unwell. I've only been on the ginseng a week, last time I was on it 2-3 weeks before it got a grip on my body and I started to feel better.

I'm just saying whilst it might work for some, low potency CBD oil makes me feel really sick. The higher provocan ones leave me crashed for weeks https://provacan.co.uk/cbd-oils/natural-cbd-oil-600-mg/

 

[Wishful]

I think for adults it is a good idea to take absorbable glutathione because it is one of the longevity chemicals that they are naturally becoming deficient in due to age (also ubiquinol, carnosine and nicotinamide riboside). It makes sense to use it as a replacement therapy.

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."

In other words, they don't know whether glutathione supplementation actually does anything useful for most people. As with antioxidants, simplistic theories don't necessarily apply to human health. I think this needs a properly run large scale study on measurable health indicators.

Also from that paper: "For those looking for a nonsupplemental solution, 500 mL of alcohol-free beer per day raises RBC glutathione 29%!33 There are many other examples of foods that increase glutathione. For example, 83 g/d of almonds increases glutathione in smokers by 16% and decreases their DNA damage by 29%."

That makes me a bit suspicious that the author is merely looking for findings that makes his theory sound good. Maybe the beer or almonds (contains toxins) causes toxic stress that forces the body to create more glutathione in defense. Overall his paper didn't convince me that glutathione supplementation is worthwhile. I can easily imagine the supplement industry pushing these sorts of vague findings to promote marketing it.

 

[YippeeKi YOW !!]

Good info on glutathione, @Wishful ..... I've been circling around it cautiously for quite a while now, but like you, could never come up with any reliable research that indicated any provable potential benefit.

Like you, I came to the conclusion that perhaps it was an energetic, wide-ranging sales pitch from those with big dogs in the fight ...

Which is sad, because on paper, as they say, it looks really promising on a lot of levels ....