Need help debunking Vitamin C megadosing

[fls]

Huh? A double blind placebo study on bronchial function isn't testing efficacy and effectiveness?

Right. "Double blind placebo study" describes the experimental design. Whether or not that experimental design is testing efficacy or whether it is testing something else depends upon the study population and what is being measured. The experimental design mostly affects internal validity - the extent to which the results reflect the effect of the intervention. The choice of population and what to measure affects external validity - the extent to which the results are relevant to the questions asked in the real world. In the case of efficacy and effectiveness, those questions are "does this intervention make me better", where better refers to clinically relevant outcomes - reduction in disease, clinically relevant improvements in symptoms, avoidance of death, prevention of disease and impairment, etc. In the case of allergic rhinitis, better means non-trivial improvement in symptoms and improvement in impairment (missed work, avoidance of triggers, etc.). For diabetes, symptoms are almost immaterial compared to reductions in heart and kidney disease.

Now, we don't always measure the outcome of interest. In the case of diabetes, waiting for kidney disease to show up (or not) is not only much more expensive and onerous (this would need a much longer and much bigger study) than monitoring blood sugar, it's also unethical. Instead, we look at whether an intervention leads to tight blood sugar control, even though elevated blood sugar by itself is not a clinically relevant outcome - it doesn't cause symptoms or in the short term lead to any sort of impairment. But what it is is a critical intermediary step in the process whereby diabetes leads to kidney disease. And because we have also shown that high blood sugar leads to kidney disease and that control of blood sugar prevents kidney disease, we can reasonably make assumptions about treatments for diabetes based on their effects on blood sugar. Even so, additional studies are often done in order to confirm that this process is intact - that we do actually go on to see reductions in kidney disease with the use of a drug which controls blood sugar.

The outcome of interest in an allergic rhinitis study on efficacy is whether symptoms and impairments are improved. It isn't the result of a blood test, or the result of a test measuring something unrelated to the perception of those symptoms. Some people with allergic rhinitis also demonstrate airway hyper-reactivity. But air way hyper-reactivity is not responsible for the manifestations of allergic rhinitis. So demonstrating some alterations in airway reactivity does not tell you whether you have made someone's allergic rhinitis better. On the other hand, look at the outcomes measured in the homeopathy study - symptom severity, degree of impairment - exactly the outcomes we need to know if we want to know whether someone has been made better.

That is why the homeopathy studies are efficacy/effectiveness studies and the vitamin C studies are not.

At a quick browse, none of those articles support the assertion that, for example, the study on vitamin c and bronchial function I cited has "low reliability and validity"

It would be the article on what studies are useful to assess interventions.

Who gets to define "feeling better in a way that is somewhat substantial"?

The person who has the condition. Nobody defines feeling better as "a 10 percent drop in my CRP level", for example.

I'd suggest it's the person feeling better, not you. (unless of course it is you in that particular case!)

Exactly. And that's how we know what to look for - people want to live longer, suffer less impairment, have their symptoms reduced to a tolerable level, etc. They don't care about blood test results which are unrelated to their level of impairment, or care about trivial changes in their symptoms. Who is satisfied with a pain-killer which moves your pain from "excruciating" to "somewhat excruciating"?

Oh come off it. You dismissed a quality study because there were other studies in the area that showed something similar and no effect, or something similar from something that should have no effect.

Do you really believe that "pretty much all of medicine" is based on science that has never had studies that were inconclusive or negative?

That's not what I said. Negative and inconclusive studies are as much a part of the picture as conclusive or positive studies.

Ignorance of the substances mostly. If you can show me stuff that

(a) may plausibly be beneficial to health
(b) has little or no evidence to indicate it is risky to health
(c) has some supporting science, even if equivocal, that it may be beneficial to health
(d) has minimal other risk or cost
(e) my personal experience indicates it's beneficial to me

Then yeah, I'll give it serious consideration!

PS (e) isn't even necessary, given the potential long term benefits eg something like resveratrol, or heck, olive oil

You obviously missed the Tumeric thread.

I could turn you into my parents. I haven't made a strict count, but they take about 40 or 50 supplements every morning on the basis of (a) to (e). And of course, the number would be much higher if Canada's Therapeutic Health Directorate wasn't watching out for them. Much as I cringe to watch them, at least their approach is consistent, as opposed to those who only pick out one or two on the basis of happenstance.

Linda

 

[icerat]

In the case of allergic rhinitis, better means non-trivial improvement in symptoms and improvement in impairment (missed work, avoidance of triggers, etc.).

Your missing the point. You claimed the homeopathy study showed efficacy, but not the Vitamin C study, and used that to dismiss the Vitamin C study. That's the problem I have with your approach.

So demonstrating some alterations in airway reactivity does not tell you whether you have made someone's allergic rhinitis better. On the other hand, look at the outcomes measured in the homeopathy study - symptom severity, degree of impairment - exactly the outcomes we need to know if we want to know whether someone has been made better.

That's like claiming the number of toes lost in accident isn't a measure of severity if you haven't asked the victim how they feel about it. Bronchial responsiveness, is a proxy for airway inflammation, symptom severity and degree of impairment

It would be the article on what studies are useful to assess interventions.

Not a primary source for the claim made about the study under discussion.

The person who has the condition. Nobody defines feeling better as "a 10 percent drop in my CRP level", for example.

I find it ironic, given your usual perspective, that you're defending self-report as an accurate measure of efficacy or a treatment, but not an objective measurement of actual impairment.

Who is satisfied with a pain-killer which moves your pain from "excruciating" to "somewhat excruciating"?

Few would be "satisfied", but most would take it as "better than nothing". People take pain killers all the time that don't completely remove the pain but alleviate it. I sure do. Heck, I've got a headache right now (not this thread's fault ) and about to take some paracetamol. I don't expect it to help, but not completely alleviate it.

That's not what I said. Negative and inconclusive studies are as much a part of the picture as conclusive or positive studies.

Your attitude on this thread has been to (or at least come across as) dismiss positive studies if there's been negative studies.

You obviously missed the Tumeric thread.

sure did. Can you give a 2 line summary?

I could turn you into my parents. I haven't made a strict count, but they take about 40 or 50 supplements every morning on the basis of (a) to (e). And of course, the number would be much higher if Canada's Therapeutic Health Directorate wasn't watching out for them. Much as I cringe to watch them, at least their approach is consistent, as opposed to those who only pick out one or two on the basis of happenstance.

Their approach is also entirely logical, though I'd be surprised if there were 40 to 50 supplements that fit that criteria.

 

[fls]

Your missing the point. You claimed the homeopathy study showed efficacy, but not the Vitamin C study, and used that to dismiss the Vitamin C study. That's the problem I have with your approach.

I may have given you a false impression. I'm simply pointing out that pre-clinical studies, such as the vitamin c study, tend to have low validity and reliability. That is, when we go on to perform efficacy and effectiveness studies on substances which passed preclinical studies, many of them fail (more fail than pass, in general). And even if they pass, there are still circumstances under which you are still more likely to be wrong than right (the homeopathy study was one example of those circumstances).

That's like claiming the number of toes lost in accident isn't a measure of severity if you haven't asked the victim how they feel about it. Bronchial responsiveness, is a proxy for airway inflammation, symptom severity and degree of impairment

Bronchial responsiveness is not a proxy measure for the severity of allergic rhinitis. In order to establish something as a proxy measure, it is important to go through the process of establishing a close correspondence between the two, and for justifying why you would fail to measure the outcome of interest by substituting another. To go back to your toe example, if people feel differently about having their toenails clipped vs. getting their toes cut off, we will perceive a pedicure as different from an industrial accident.

Not a primary source for the claim made about the study under discussion.

At issue is whether we can reasonably expect to be right if we make recommendations based on the kind of study under discussion.

I find it ironic, given your usual perspective, that you're defending self-report as an accurate measure of efficacy or a treatment, but not an objective measurement of actual impairment.

I'm defending self-report as an accurate measure, not of treatment efficacy, but of whether a relevant outcome is present or absent. It varies widely, of course, whether or not self-report is able to identify the presence or absence of that outcome. For example, we depend upon self-report for pain, but not for the presence of a gastric ulcer. Similarly self-report tells us whether or not someone stayed home from school or work, with respect to impairment.

Few would be "satisfied", but most would take it as "better than nothing". People take pain killers all the time that don't completely remove the pain but alleviate it. I sure do. Heck, I've got a headache right now (not this thread's fault ) and about to take some paracetamol. I don't expect it to help, but not completely alleviate it.

Whether a change would be considered trivial is based on studies. So it would be like asking you to rate your headache before and after you took the paracetomol and also asking you if it helped. Then we would discover that even though you rated your pain a half a point better, you didn't call that helping. But when you rated your pain a point and a half better, you also were willing to say that it helped.

Your attitude on this thread has been to (or at least come across as) dismiss positive studies if there's been negative studies.

I think I gave you a false impression, then. I was pointing out that not only do you lack positive studies, you don't get any help from somewhat related studies, since they are negative.

sure did. Can you give a 2 line summary?

It satisfies the requirements of (a) to (e), so we'll ignore that it failed clinical trials.

Linda

 

[icerat]

I may have given you a false impression. I'm simply pointing out that pre-clinical studies, such as the vitamin c study, tend to have low validity and reliability. That is, when we go on to perform efficacy and effectiveness studies on substances which passed preclinical studies, many of them fail (more fail than pass, in general). And even if they pass, there are still circumstances under which you are still more likely to be wrong than right (the homeopathy study was one example of those circumstances).

Never disagreed with that. I've said all along more research is needed. Still there's plenty of reason to think it may help, and little or no risk. So, like your parents, worth a shot to see if it helps.

Bronchial responsiveness is not a proxy measure for the severity of allergic rhinitis.

Not quite what I said, but with further research I see there is a problem with what I did say. Mea culpa., though I'm consoled I'm not alone in having made the same mistake!

At issue is whether we can reasonably expect to be right if we make recommendations based on the kind of study under discussion.

It's not exactly the only study to support a link between C and inflammation.

I'm defending self-report as an accurate measure, not of treatment efficacy, but of whether a relevant outcome is present or absent. It varies widely, of course, whether or not self-report is able to identify the presence or absence of that outcome.

So your defending it as an accurate measure while simultaneously stating that it varies wildly whether it can accurate measure something.

In any case we're getting overly pedantic. I'm not against self-report as a metric. I prefer objective measurements where possible, as I'm sure you do too.

I think I gave you a false impression, then. I was pointing out that not only do you lack positive studies, you don't get any help from somewhat related studies, since they are negative.

Au contraire, there is no lack of studies showing a link between C and inflammation.

It satisfies the requirements of (a) to (e), so we'll ignore that it failed clinical trials.

clinical trials for what? and tested how?

Tumeric (or more specifically curcumin), like Vitamin C, has been linked, very strongly, to inflammation mediation, and there's a whole load of research on links between inflammation and various health issues.

But we're almost certainly talking about long-term cumulative effects. You wouldn't expect a clinical trial lasting weeks or months or even a few years to necessarily have any strong effect on disease outcomes. The best you could expect is some open to interpretation epidemiological studies, potential mechanisms from in vitro studies, and some clinical trials showing effects on various biomarkers - in other words, exactly what we have for a lot of potential nutritional interventions.

 

[fls]

Never disagreed with that. I've said all along more research is needed. Still there's plenty of reason to think it may help, and little or no risk. So, like your parents, worth a shot to see if it helps.

Okay, so when that "may" is at 1%, to you it's worth the bother. Is there any point at which that "may" isn't worth the bother? After all, there's some weeds in my parents' yard they haven't tried yet.

It's not exactly the only study to support a link between C and inflammation.

So what? We're not interested in whether some in vitro or pre-clinical effects can be demonstrated. We want to know if it has a useful effect. If pre-clinical effects usually meant clinical effects, then that information would be useful. But since most of the time it doesn't, those studies don't really give us the information we need.

So your defending it as an accurate measure while simultaneously stating that it varies wildly whether it can accurate measure something.

What varies from condition to condition is which outcomes are important. For migraines, the relevant endpoint is the presence or absence of pain. For diabetes, the relevant endpoints are the prevention of life-threatening complications. When the relevant endpoint is pain, then individual reports on the presence or absence of pain (in the setting of an interventional trial) are how we discover whether a treatment is effective. But the same kind of report would be useless if the condition we were looking at was diabetes.

In any case we're getting overly pedantic. I'm not against self-report as a metric. I prefer objective measurements where possible, as I'm sure you do too.

Actually, I prefer relevant metrics. These are often not objective.

Au contraire, there is no lack of studies showing a link between C and inflammation.

I'm not talking about what happens in a test tube, but what happens in people with respect to health.

clinical trials for what? and tested how?

Tumeric (or more specifically curcumin), like Vitamin C, has been linked, very strongly, to inflammation mediation, and there's a whole load of research on links between inflammation and various health issues.

But we're almost certainly talking about long-term cumulative effects. You wouldn't expect a clinical trial lasting weeks or months or even a few years to necessarily have any strong effect on disease outcomes. The best you could expect is some open to interpretation epidemiological studies, potential mechanisms from in vitro studies, and some clinical trials showing effects on various biomarkers - in other words, exactly what we have for a lot of potential nutritional interventions.

I realize that there are excuses given for why research fails to show effectiveness. However, this presents a problem for you. If the kinds of mechanisms present in pre-clinical trials were responsible for the clinical effects, then these studies would be able to demonstrate effectiveness if it were present. If you want to propose that real effectiveness is present, but it is unable to be demonstrated in these effectiveness trials, then it means the mechanism is different. That is, your pre-clinical trials are not evidence for the effects that you are claiming because they are not evidence for a mechanism which would fail clinical trials.

Linda

 

[icerat]

Okay, so when that "may" is at 1%, to you it's worth the bother. Is there any point at which that "may" isn't worth the bother? After all, there's some weeds in my parents' yard they haven't tried yet.

Now you're not being entirely honest. Colour me skeptical but somehow I doubt those weeds satisfy (a) to (e)

So what? We're not interested in whether some in vitro or pre-clinical effects can be demonstrated. We want to know if it has a useful effect. If pre-clinical effects usually meant clinical effects, then that information would be useful. But since most of the time it doesn't, those studies don't really give us the information we need.

The problem is you are assuming too hard or too expensive to test = doesn't work, no matter what evidence there is to suggest it would, and does, work.

Actually, I prefer relevant metrics. These are often not objective.

Now you're just being silly. Relevance is obviously a priority.

I'm not talking about what happens in a test tube, but what happens in people with respect to health.

So am I. The difference is your only interested in easily measurable short-term effects. If it hasn't yet been clinically demonstrated, then dismiss it. Fortunately in fields where there may be a short-term clinical benefit, real live scientists continue to research and establish what is going on.

For stuff that's too hard or too expensive to test in clinical trials, most people accept that in vitro and epidemeological studies actually have some worth and can contribute to decision making.

I realize that there are excuses given for why research fails to show effectiveness.

There are also reasons why research fails to show effectiveness - like it's bad research. Take omega-3. Let's say omega-3 truly is an effective anti-inflammatory. What are the odds of a clinical trial demonstrating effect if the trial does not control for high omega-6 intakes? Now find me some omega-3 trials that control for omega-6 intake.

However, this presents a problem for you. If the kinds of mechanisms present in pre-clinical trials were responsible for the clinical effects, then these studies would be able to demonstrate effectiveness if it were present.

Sure, if the studies were designed in such a way. For the sake of argument, assume that inflammation over many many years, decades in fact, is a contributing factor in alzheimers. Let's say Vitamin C helps mediate that inflammation, and that's shown in vitro.

Why on earth would you believe that giving someone Vitamin C for a few weeks, months, or years would help prevent or alleviate alzheimers?

While there's a chance it may, and it's worth testing for that chance, you simply wouldn't expect it to.

Clinical trials (at least in the real world of requiring funding) simply aren't going to establish an effect. The best you can realistically expect is accumulated non-clinical studies, with all their flaws, to give you some idea.

If you want to propose that real effectiveness is present, but it is unable to be demonstrated in these effectiveness trials, then it means the mechanism is different.

Not necessarily - it may simply mean you've got the dose wrong, or failed to control for something (like omega-6), or there's some nutrigenomic effect, or you haven't allowed enough time ... or or or ...

Take a group of patients with scurvy and anemia. Treat them with iron supplements. Gee, it may not work so well. Does that mean iron deficiency isn't a cause of anemia and iron supplementation isn't a valid treatment?

Of course not. Ascorbic acid is crucial to effective iron absorption.

This isolate an active chemical, stick it in a clinical trial "silver bullet" approach simply isn't realistic for preventive medicine and lifestyle diseases.

 

[fls]

Now you're not being entirely honest. Colour me skeptical but somehow I doubt those weeds satisfy (a) to (e)

They may...

The problem is you are assuming too hard or too expensive to test = doesn't work, no matter what evidence there is to suggest it would, and does, work.

No. I'm assuming that it is no more likely to work than any other substance which hasn't failed in vitro testing and hasn't passed clinical testing.

Now you're just being silly. Relevance is obviously a priority.

You're the one who keeps referring to a vitamin C study with an outcome which isn't relevant to allergic rhinitis.

So am I. The difference is your only interested in easily measurable short-term effects.

Huh? I said the opposite of that.

If it hasn't yet been clinically demonstrated, then dismiss it. Fortunately in fields where there may be a short-term clinical benefit, real live scientists continue to research and establish what is going on.

For stuff that's too hard or too expensive to test in clinical trials, most people accept that in vitro and epidemeological studies actually have some worth and can contribute to decision making.

Who are you talking about? Obviously not these people. http://www.theannals.com/cgi/content/full/39/12/2073?ijkey=c9ca48832fdd59730f269ff41d6ce1804a260e7b

There are also reasons why research fails to show effectiveness - like it's bad research. Take omega-3. Let's say omega-3 truly is an effective anti-inflammatory. What are the odds of a clinical trial demonstrating effect if the trial does not control for high omega-6 intakes? Now find me some omega-3 trials that control for omega-6 intake.

That's the point of randomization. In addition to stuff that we know will influence the outcome, we can guess that there may be unrecognized factors, as well. Randomization means that unrecognized factors won't be distributed systematically, but will instead will likely be present in both groups, giving the intervention the opportunity to demonstrate a difference.

Sure, if the studies were designed in such a way. For the sake of argument, assume that inflammation over many many years, decades in fact, is a contributing factor in alzheimers. Let's say Vitamin C helps mediate that inflammation, and that's shown in vitro.

Why on earth would you believe that giving someone Vitamin C for a few weeks, months, or years would help prevent or alleviate alzheimers?

While there's a chance it may, and it's worth testing for that chance, you simply wouldn't expect it to.

Clinical trials (at least in the real world of requiring funding) simply aren't going to establish an effect. The best you can realistically expect is accumulated non-clinical studies, with all their flaws, to give you some idea.

This is untrue. Reliable and valid research has been used to establish effects in related and unrelated areas of prevention. That is, failure to establish an effect does not occupy a special place in this particular case. However, even if what you said was true, we are still left with the problem that a lack of relevant research does not serve to make a proposition more likely to be true.

Not necessarily - it may simply mean you've got the dose wrong, or failed to control for something (like omega-6), or there's some nutrigenomic effect, or you haven't allowed enough time ... or or or ...

Take a group of patients with scurvy and anemia. Treat them with iron supplements. Gee, it may not work so well. Does that mean iron deficiency isn't a cause of anemia and iron supplementation isn't a valid treatment?

The study you describe lacks external validity. The conclusion which could reasonably drawn is that iron supplementation is not effective for anemia in a population of people with scurvy. The conclusion which would not be reasonable is your conclusion that this study demonstrates that iron supplementation is effective in those without scurvy.

Of course not. Ascorbic acid is crucial to effective iron absorption.

This isolate an active chemical, stick it in a clinical trial "silver bullet" approach simply isn't realistic for preventive medicine and lifestyle diseases.

I agree, but this is hardly relevant. These issues are studied in a multitude of ways which reflect the realities of what we are trying to demonstrate.

Linda

 

[icerat]

They may...

irrelevant, since the criteria requires knowing about it in order to make educated decisions

No. I'm assuming that it is no more likely to work than any other substance which hasn't failed in vitro testing and hasn't passed clinical testing.

So let me get this straight. A substance has a plausible mechanism to induce some physiological change. In vitro testing shows it induces physiological change.

But because it hasn't passed clinical testing, you assume that it is no more likely to work than any other substance. Why would you bother doing a clinical test then? Why not test powdered granite stuck in the ear canal?

You're the one who keeps referring to a vitamin C study with an outcome which isn't relevant to allergic rhinitis.

No, you're the one who keeps claiming it's not relevant when it is. Heck, the fact it has "allergic rhinitis" in the title might give you a hint. Some more for you -

Relationship between nasal and bronchial responsiveness in perennial allergic rhinitic patients with asthma.

Early bronchial airflow impairment in patients with persistent allergic rhinitis and bronchial hyperreactivity.

Huh? I said the opposite of that.

You've said no such thing. Indeed you've confirmed it above where you essentially state you believe a substance that hasn't passed a clinical trial should be assumed worthless. This means that any treatment that can't reasonably be expected to be assessed by clinical trial (because of cost/duration/ethics/whatever) is of no interest.

Who are you talking about? Obviously not these people.

obviously not. I'm talking about you.

As for that study, if alzheimer's is at least partially a result of long-term inflammation (and I for one are under no illusion that it would be any more than a contributing factor), why on earth would you expect 3 or 4 year trials to come up with useful, consistent results?

That's the point of randomization. In addition to stuff that we know will influence the outcome, we can guess that there may be unrecognized factors, as well. Randomization means that unrecognized factors won't be distributed systematically, but will instead will likely be present in both groups, giving the intervention the opportunity to demonstrate a difference.

I don't need a lesson on randomization. You apparently need a lesson in the metabolism of EFAs and current dietary habits. I'm not going to go into it here except to say that it's completely predictable that even if Omega-3 is a fantastic anti-inflammatory, it's not going to be effective in the presence of high levels of Omega-6, and it's almost certain that in any normal western sample the latter will be true.

Yet we see clinical trials on omega-3 again and again that never address this issue. It's like testing the mileage of different cars, all of which have broken axles. It's pointless.

However, even if what you said was true, we are still left with the problem that a lack of relevant research does not serve to make a proposition more likely to be true.

I entirely agree. The difference is I believe in vitro and epidemiological studies to be "relevant research". You apparently do not. We've had this same discussion before.

The study you describe lacks external validity. The conclusion which could reasonably drawn is that iron supplementation is not effective for anemia in a population of people with scurvy. The conclusion which would not be reasonable is your conclusion that this study demonstrates that iron supplementation is effect in those without scurvy.

You've misunderstood the point, whether deliberately or not I'm not sure. Pretend you don't know the samples have scurvy and C status was not tested for. You're entirely correct the study lacks external validity. But you wouldn't know it without the knowledge of C status, and the study would be reported as evidence iron supplementation is not a viable treatment for anemia.

But I see this type of thing in nutritional studies all the time. Try this absolutely absurd study on Omega-3 and how it's reported - "The finding raised questions about the benefits of omega-3"

Not that it raised questions about the benefits of omega-3 when delivered via margarine!

Now you might say that's just the reporting .... but why on earth would you even do the study in the first place?

And then someone like the Cochrane folk will come along and include studies like this in a Meta.

 

[fls]

irrelevant, since the criteria requires knowing about it in order to make educated decisions

So let me get this straight. A substance has a plausible mechanism to induce some physiological change. In vitro testing shows it induces physiological change.

But because it hasn't passed clinical testing, you assume that it is no more likely to work than any other substance.

...which shows in vitro changes.

Why would you bother doing a clinical test then?

To find out if it works?

Why not test powdered granite stuck in the ear canal?

That strategy has an even lower yield. And we already have a higher false-positive rate than we would like.

No, you're the one who keeps claiming it's not relevant when it is. Heck, the fact it has "allergic rhinitis" in the title might give you a hint.

I don't think it's relevant because I know a lot about allergic rhinitis, not because the title looks vaguely relevant on a google search.

Some more for you -

Relationship between nasal and bronchial responsiveness in perennial allergic rhinitic patients with asthma.

Early bronchial airflow impairment in patients with persistent allergic rhinitis and bronchial hyperreactivity.

Exactly. As those studies show, bronchial hyper-responsiveness is not consistently present and symptoms are not consistently related to bronchial hyper responsiveness, which means that measuring changes in bronchial hyper responsiveness doesn't tell you whether you have effected a change in someone's allergic rhinitis.

You've said no such thing. Indeed you've confirmed it above where you essentially state you believe a substance that hasn't passed a clinical trial should be assumed worthless. This means that any treatment that can't reasonably be expected to be assessed by clinical trial (because of cost/duration/ethics/whatever) is of no interest.

I didn't actually say that. I have pretty much been saying the opposite. Clinical trials should be performed on substances which show in vitro effects if we are interested in discovering which of them are efficacious and effective. What I said was that until we perform clinical trials, we don't know which of the few substances within that larger pool have that efficacy.

obviously not. I'm talking about you.

You made reference to "most people" who were able to recognize the value of epidemiological and in vitro testing. Who are these "most people" who form conclusions different from those experts working within the field?

As for that study, if alzheimer's is at least partially a result of long-term inflammation (and I for one are under no illusion that it would be any more than a contributing factor), why on earth would you expect 3 or 4 year trials to come up with useful, consistent results?

That would depend upon the time period over which we see changes due to inflammation, would it not?

I don't need a lesson on randomization. You apparently need a lesson in the metabolism of EFAs and current dietary habits. I'm not going to go into it here except to say that it's completely predictable that even if Omega-3 is a fantastic anti-inflammatory, it's not going to be effective in the presence of high levels of Omega-6, and it's almost certain that in any normal western sample the latter will be true.

Yet we see clinical trials on omega-3 again and again that never address this issue. It's like testing the mileage of different cars, all of which have broken axles. It's pointless

And yet, studies on omega-3 are able to demonstrate benefit, which confirms what I said and contradicts what you said.

I entirely agree. The difference is I believe in vitro and epidemiological studies to be "relevant research". You apparently do not. We've had this same discussion before.

Well, I am hampered by a detailed understanding of epidemiology and research methods.

You've misunderstood the point, whether deliberately or not I'm not sure. Pretend you don't know the samples have scurvy and C status was not tested for. You're entirely correct the study lacks external validity. But you wouldn't know it without the knowledge of C status, and the study would be reported as evidence iron supplementation is not a viable treatment for anemia.

Hence the attention paid to population selection when designing studies.

But I see this type of thing in nutritional studies all the time. Try this absolutely absurd study on Omega-3 and how it's reported - "The finding raised questions about the benefits of omega-3"

Not that it raised questions about the benefits of omega-3 when delivered via margarine!

How would you know? You've quoted a newspaper article as though they ever give anything other than a gross misrepresentation about how it is perceived by those working in the field.

Now you might say that's just the reporting .... but why on earth would you even do the study in the first place?

To find out if it works?

Linda

 

[icerat]

...which shows in vitro changes.

Well that's a change in your stated position. Remember this discussion evolved out of comparing a vitamin C study with a homeopathy study. At no time have you indicated an in vitro backing for the homeopathy study. We can now safely cross out at least two thirds of this discussion.

ies show, bronchial hyper-responsiveness is not consistently present and symptoms are not consistently related to bronchial hyper responsiveness, which means that measuring changes in bronchial hyper responsiveness doesn't tell you whether you have effected a change in someone's allergic rhinitis.

"not consistently" does not mean "not related". I alas no longer have easy access to full articles so am having to rely on abstracts alone, which is always problematic, but I quote -

nasal function is strictly related with bronchial calibre and BHR grade

may support the viewpoint that allergic rhinitis and asthma represent a continuum of inflammation involving one common airway

So you can understand why I might think there's a relationship between bronchial function and allergic rhinitis.

That would depend upon the time period over which we see changes due to inflammation, would it not?

yes, and on the degree and type of changes. There's little reason to believe 3 to 4 years is likely to be long enough for consistent significant clinical outcome.

And yet, studies on omega-3 are able to demonstrate benefit, which confirms what I said and contradicts what you said.

Swap "never" for "inconsisently". Many of the "positive" trials have used fish rather than supplemention. Eating more fish invariably means eating less of something else, such as meat, which will influence O-6 intake. Other supplement studies for example have found no influence, but it was on subjects who already had high intake. Others have looked at issues unrelated to inflammation altogether.

The point is that it's going to be all over the place and would significantly reduce the accuracy and power of meta-analysis that don't address it.

Hence the attention paid to population selection when designing studies.

To quote the poet Rumsfield -

As we know,
There are known knowns.
There are things we know we know.
We also know
There are known unknowns.
That is to say
We know there are some things
We do not know.
But there are also unknown unknowns,
The ones we don't know
We don't know.

Many studies exhibit not only issues with the unavoidable unknown unknowns, but, like the omega-3 margarine study, known unknowns are not addressed.

How would you know? You've quoted a newspaper article as though they ever give anything other than a gross misrepresentation about how it is perceived by those working in the field.

Here's the study. Again, I don't have full access but there's no mention of controlling for Omega-6. The quote about raising questions of benefit originates from the original press release, ie from the researchers themselves (or at least their funder). How those working in the field perceive it is a different matter, but I'm concerned more with public health, so public perceptions are ultimately what matter.

Either way, a silly experimental design.

To find out if it works?

Wouldn't it be better to spend the time and money on a study that has a better chance of working?

 

[fls]

Well that's a change in your stated position. Remember this discussion evolved out of comparing a vitamin C study with a homeopathy study. At no time have you indicated an in vitro backing for the homeopathy study. We can now safely cross out at least two thirds of this discussion.

The point about the homeopathy study was that it had already distinguished itself from the pool of substances showing in vitro changes by passing studies looking at efficacy. That is, it wasn't coming from the pool of very weak evidence, but from the pool of good evidence. However, homeopaths do also perform in vitro studies and claim success.

"not consistently" does not mean "not related". I alas no longer have easy access to full articles so am having to rely on abstracts alone, which is always problematic, but I quote -

So you can understand why I might think there's a relationship between bronchial function and allergic rhinitis.

Yeah, one of the hazards of Google U.

yes, and on the degree and type of changes. There's little reason to believe 3 to 4 years is likely to be long enough for consistent significant clinical outcome.

Presuming that you know better than researchers working in the field.

To quote the poet Rumsfield -

As we know,
There are known knowns.
There are things we know we know.
We also know
There are known unknowns.
That is to say
We know there are some things
We do not know.
But there are also unknown unknowns,
The ones we don't know
We don't know.

Many studies exhibit not only issues with the unavoidable unknown unknowns, but, like the omega-3 margarine study, known unknowns are not addressed.

Hence the point of randomization.

Here's the study. Again, I don't have full access but there's no mention of controlling for Omega-6. The quote about raising questions of benefit originates from the original press release, ie from the researchers themselves (or at least their funder). How those working in the field perceive it is a different matter, but I'm concerned more with public health, so public perceptions are ultimately what matter.

Either way, a silly experimental design.

Wouldn't it be better to spend the time and money on a study that has a better chance of working?

Oh, I'm sure you'll find some way in which it was screwed up when it doesn't return the result you want.

Linda

 

[icerat]

The point about the homeopathy study was that it had already distinguished itself from the pool of substances showing in vitro changes by passing studies looking at efficacy. That is, it wasn't coming from the pool of very weak evidence, but from the pool of good evidence. However, homeopaths do also perform in vitro studies and claim success.

And published in quality peer-reviewed journals? Colour me skeptical.

Yeah, one of the hazards of Google U.

Are you saying the abstracts were inaccurate reflections of the articles and fields?

Presuming that you know better than researchers working in the field.

No presumption necessary. Some of them are friends. The problem is many of the researchers working in the field are, understandably, lacking in cross-disciplinary knowledge. For example you might get alzheimer's researchers studying EFAs and alzheimers. They're not necessarily going to be experts in EFA metabolism or for that matter dietary habits.

Hence the point of randomization.

(a) Pointless if a problem is ubiquitous
(b) the bigger the problem is, the more it dilutes real effects
(c) even more so when you're talking about multiple interfering interactions.

Oh, I'm sure you'll find some way in which it was screwed up when it doesn't return the result you want.

I never would have done that study in the first place and would have been stunned if it had a replicable, significant effect. Delivering omega 3 via margarine is just downright bizarre. It's bizarre when I see it on the supermarket shelf, it's bizarre when I see it in a journal. I'm guessing nothing more than somebody with a market budget throwing money at researchers either in ignorance or the blind hope of a random chance effect that would boost sales.

The point is, as I've stated before, research in this area is hard with so many interactions and there's a lot of very very poor studies out there (with findings in both directions) even when they might superficially have good experimental design.

Heck, it's only been in recent years we've even become aware of the significance of genomic issues.

The end result is that you are predictably going to get a variety of contradictory studies, which is exactly what we keep getting in the field. But ... I maintain that overall you're much more likely to get these contradictory results if there is a real underlying effect than if there is no real underlying effect.

So we just have to keep trying to learn and improve the studies and work out what is going on.

 

[fls]

And published in quality peer-reviewed journals? Colour me skeptical.

. Well, they are similarly dismissive of criticisms of their fabulous positive studies and scathing in the idiocy of the negative studies.

Are you saying the abstracts were inaccurate reflections of the articles and fields?

No. The abstracts also contain the information about the inconsistency between bronchial hypersensitivity and allergic rhinitis symptoms/impairments.

No presumption necessary. Some of them are friends. The problem is many of the researchers working in the field are, understandably, lacking in cross-disciplinary knowledge. For example you might get alzheimer's researchers studying EFAs and alzheimers. They're not necessarily going to be experts in EFA metabolism or for that matter dietary habits.

(a) Pointless if a problem is ubiquitous
(b) the bigger the problem is, the more it dilutes real effects
(c) even more so when you're talking about multiple interfering interactions.

I'm not sure where you're going with this. How is the complexity of the process of performing good research of relevance? Unless you are suggesting that we should forego good research and use poor, more easily obtained, information instead?

I never would have done that study in the first place and would have been stunned if it had a replicable, significant effect. Delivering omega 3 via margarine is just downright bizarre. It's bizarre when I see it on the supermarket shelf, it's bizarre when I see it in a journal. I'm guessing nothing more than somebody with a market budget throwing money at researchers either in ignorance or the blind hope of a random chance effect that would boost sales.

Because the idea of evaluating the claims manufacturers make for their products is bizarre?

The point is, as I've stated before, research in this area is hard with so many interactions and there's a lot of very very poor studies out there (with findings in both directions) even when they might superficially have good experimental design.

Heck, it's only been in recent years we've even become aware of the significance of genomic issues.

The end result is that you are predictably going to get a variety of contradictory studies, which is exactly what we keep getting in the field. But ... I maintain that overall you're much more likely to get these contradictory results if there is a real underlying effect than if there is no real underlying effect.

So we just have to keep trying to learn and improve the studies and work out what is going on.

Okay, but what has that got to do with the issue which started this discussion?

Linda

 

[icerat]

. Well, they are similarly dismissive of criticisms of their fabulous positive studies and scathing in the idiocy of the negative studies.

So? Your smart enough to know the poor logic you're following on that path

No. The abstracts also contain the information about the inconsistency between bronchial hypersensitivity and allergic rhinitis symptoms/impairments.

Welcome to working with humans.

I'm not sure where you're going with this. How is the complexity of the process of performing good research of relevance? Unless you are suggesting that we should forego good research and use poor, more easily obtained, information instead?

no, indeed mostly the exact opposite. I am suggesting that research based on flawed or incomplete assumptions, no matter how good the actual experimental design, should be avoided. Both in the doing and the interpretative use of

In the absence of good, relevant research, you make do with what you have when decision making.

And you continue to encourage better research. But just as you shouldn't blindly accept something based on flawed research, you shouldn't blindly reject something based on flawed research either.

Because the idea of evaluating the claims manufacturers make for their products is bizarre?

I'm not aware if they made any claims or not. They funded the research. Why not fund research that you have reasonable reason to believe might find something useful?

Okay, but what has that got to do with the issue which started this discussion?

Because the jury is still out on vitamin C and inflammation. The OP was looking to debunk it, but there's a number of contradictory studies, of varying quality, and not really enough information to come to a hard conclusion either way. Given there is some evidence to support it may help some people and it's low cost and low risk, there's no reason not to give it a try.

 

[fls]

So? Your smart enough to know the poor logic you're following on that path

Huh? I'm not the one suggesting that decisions be made in the absence of good, reliable research as though unreliable research serves as a substitute.

Welcome to working with humans.

Huh? What does that have to do with what I said?

no, indeed mostly the exact opposite. I am suggesting that research based on flawed or incomplete assumptions, no matter how good the actual experimental design, should be avoided. Both in the doing and the interpretative use of

So what does that have to do with this discussion?

In the absence of good, relevant research, you make do with what you have when decision making.

What do you mean? Pre-clinical research does not magically gain reliability and validity just because good, relevant research is absent.

And you continue to encourage better research. But just as you shouldn't blindly accept something based on flawed research, you shouldn't blindly reject something based on flawed research either.

What does that have to do with this discussion?

I'm not aware if they made any claims or not. They funded the research. Why not fund research that you have reasonable reason to believe might find something useful?

Why make omega-3 margarine if it's not in response to the idea that it will benefit health?

Because the jury is still out on vitamin C and inflammation. The OP was looking to debunk it, but there's a number of contradictory studies, of varying quality, and not really enough information to come to a hard conclusion either way. Given there is some evidence to support it may help some people and it's low cost and low risk, there's no reason not to give it a try.

There is a tendency for DIM proponents to treat less than adequate information as though it were adequate when adequate information hasn't been obtained (or has been obtained but is not flattering). Your characterization of the information on omega-6 fatty acids and that of vitamim C would be an example of this. You sort of throwaway that last bit, but it's of the most importance. Is there a reason to give something a try if we don't have information which tells us it will help (or avoid when we don't have information on harm)?

Linda

 

[icerat]

True. The choice is to supplement or not supplement. Absent good, relevant research showing a benefit, why bother?

Agreed. But there is good relevant research showing a benefit.

Vitamin C supplementation in excess of normal requirements is not low risk.

Neither study you cite supports that assertion for "normal" people, indeed one contradicts it. The study on postmenopausal women with diabetes, says "Vitamin C intake was unrelated to mortality from cardiovascular disease in the nondiabetic subjects at baseline."

So one was on postmenopausal women with diabetes, the other was a study on the children of pregnant women at risk of preeclampsia who supplemented. It was also a combined C/E supplement and at leaves of E that have previously shown problems in other groups.

So again, we're left with nothing at all on C supplementation in an otherwise healthy group, and someone using it as evidence such use was risky - even though one of the studies said the exact opposite!

 

[fls]

Agreed. But there is good relevant research showing a benefit.

What criteria do you use for "good" and "relevant"?

Linda

 

[icerat]

Huh? I'm not the one suggesting that decisions be made in the absence of good, reliable research as though unreliable research serves as a substitute.

Huh? What does that have to do with what I said?

So what does that have to do with this discussion

What do you mean? Pre-clinical research does not magically gain reliability and validity just because good, relevant research is absent.

What does that have to do with this discussion?

Clearly we are arguing at cross-purposes. I'm not understanding your points and you're not understanding mine.

I really don't have the time to clear that up.

Why make omega-3 margarine if it's not in response to the idea that it will benefit health?

It's nothing but marketing. There is no reason at all to believe that "omega-3 margarine" would benefit health, but because "omega-3" is a marketing buzz word, they slap it on to increase sales.

Nothing to do with health at all, all to do with marketing.

There is a tendency for DIM proponents to treat less than adequate information as though it were adequate when adequate information hasn't been obtained (or has been obtained but is not flattering).

Sorry, don't know what DIM is?

However, in my probable misunderstanding of your view I certainly get a very strong impression that you "treat less than adequate information as though it were adequate when adequate information hasn't been obtained (or has been obtained but is not flattering)"

Is there a reason to give something a try if we don't have information which tells us it will help (or avoid when we don't have information on harm)?

Oh good grief Linda, I don't think for one moment you believe "will help" (ie 100% certainty) is your criteria.

 

[fls]

It's nothing but marketing. There is no reason at all to believe that "omega-3 margarine" would benefit health, but because "omega-3" is a marketing buzz word, they slap it on to increase sales.

Nothing to do with health at all, all to do with marketing.

So clinical studies showing that supplementing with omega-3 FA's benefits health are not relevant to whether supplementing with omega-3 FA's benefits health, but studies showing that cells change in the presence of vitamin C is highly relevant to whether vitamin C benefits health. Got it.

Sorry, don't know what DIM is?

That's why I put an explanatory link in my sig.

However, in my probable misunderstanding of your view I certainly get a very strong impression that you "treat less than adequate information as though it were adequate when adequate information hasn't been obtained (or has been obtained but is not flattering)"

What information would you consider less than adequate which I have treated as adequate?

Oh good grief Linda, I don't think for one moment you believe "will help" (ie 100% certainty) is your criteria.

Huh? Where do you get 100% certainty? All I mentioned was "more likely to be right than wrong". That's not so awful, is it?

Linda

 

[icerat]

So clinical studies showing that supplementing with omega-3 FA's benefits health are not relevant to whether supplementing with omega-3 FA's benefits health

Never said anything remotely like that.

, but studies showing that cells change in the presence of vitamin C is highly relevant to whether vitamin C benefits health.

Never said that either.

Got it.

Clearly you haven't "got" it at all

That's why I put an explanatory link in my sig.

I rarely read sigs. Again though, poor (and insulting) logic does not become you.

What information would you consider less than adequate which I have treated as adequate?

You seem to think the omega-3/margarine study is "adequate", which does nothing more than show you have less than adequate knowledge of the topic.

Huh? Where do you get 100% certainty? All I mentioned was "more likely to be right than wrong". That's not so awful, is it?

It's not that hard Linda. I even quoted you directly - "will help". Not "might help" or "probably help" or is "shown to help 80% of people". "will help".

Is there a reason to give something a try if we don't have information which tells us it will help (or avoid when we don't have information on harm)?

My mother-in-law is currently undergoing cancer treatment. She's had her uterus, ovaries, appendix, and half her colon removed. They're not at all certain where the cancer originated but are working on the basis it's colon cancer.

They think they removed it all.

They are however recommending she undergo chemotherapy. She may not have cancer any more. If she does, the chemo may or may not help. There are serious potential side effects.

We don't know if it will help.

You ask - "Is there a reason to give something a try if we don't have information which tells us it will help"

Yes, there is.