• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Most Clinical Studies On Vitamins Flawed by Poor Methodology

Waverunner

Senior Member
Messages
1,079
Most of us probably read some articles lately, about how useless supplements are. At least this is, what some scientists and the media tell us. But things might look a lot more complex. I can give you an easy example. In order to reach the daily recommended dose of vitamin C, one would "only" have to eat 3 oranges. I don't know anyone who eats 3 oranges a day but you might say, that with salad and other fruits and vegetables, it might be easy to reach this target. But what if someone has fructose malabsorption? What if someone is intolerant to certain foods, that are supposed to be healthy? What if someone can't afford to buy lots of fruit? Well, then it's pretty hard to reach the daily vitamin recommendations, unless you put a lot of effort into it. So maybe supplements might be more useful for certain people, than for others.

"It's fine to tell people to eat better, but it's foolish to suggest that a multivitamin which costs a nickel a day is a bad idea."


http://www.sciencedaily.com/releases/2013/12/131230135106.htm

Dec. 30, 2013 — Most large, clinical trials of vitamin supplements, including some that have concluded they are of no value or even harmful, have a flawed methodology that renders them largely useless in determining the real value of these micronutrients, a new analysis suggests.

Many projects have tried to study nutrients that are naturally available in the human diet the same way they would a powerful prescription drug. This leads to conclusions that have little scientific meaning, even less accuracy and often defy a wealth of other evidence, said Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University, in a new review published in the journal Nutrients.

These flawed findings will persist until the approach to studying micronutrients is changed, Frei said. Such changes are needed to provide better, more scientifically valid information to consumers around the world who often have poor diets, do not meet intake recommendations for many vitamins and minerals, and might greatly benefit from something as simple as a daily multivitamin/mineral supplement.

Needed are new methodologies that accurately measure baseline nutrient levels, provide supplements or dietary changes only to subjects who clearly are inadequate or deficient, and then study the resulting changes in their health. Tests must be done with blood plasma or other measurements to verify that the intervention improved the subjects' micronutrient status along with biomarkers of health. And other approaches are also needed that better reflect the different ways in which nutrients behave in cell cultures, lab animals and the human body.

The new analysis specifically looked at problems with the historic study of vitamin C, but scientists say many of the observations are more broadly relevant to a wide range of vitamins, micro nutrients and studies.

"One of the obvious problems is that most large, clinical studies of vitamins have been done with groups such as doctors and nurses who are educated, informed, able to afford healthy food and routinely have better dietary standards than the public as a whole," said Frei, an international expert on vitamin C and antioxidants.

Vitamin or mineral supplements, or an improved diet, will primarily benefit people who are inadequate or deficient to begin with, OSU researchers said. But most modern clinical studies do not do baseline analysis to identify nutritional inadequacies and do not assess whether supplements have remedied those inadequacies. As a result, any clinical conclusion made with such methodology is pretty much useless, they said.

"More than 90 percent of U.S. adults don't get the required amounts of vitamins D and E for basic health," Frei said. "More than 40 percent don't get enough vitamin C, and half aren't getting enough vitamin A, calcium and magnesium. Smokers, the elderly, people who are obese, ill or injured often have elevated needs for vitamins and minerals.

"It's fine to tell people to eat better, but it's foolish to suggest that a multivitamin which costs a nickel a day is a bad idea."

Beyond that, many scientists studying these topics are unaware of ways in which nutrients may behave differently in something like a cell culture or lab animal, compared to the human body. This raises special challenges with vitamin C research in particular.

"In cell culture experiments that are commonly done in a high oxygen environment, vitamin C is unstable and can actually appear harmful," said Alexander Michels, an LPI research associate and lead author on this report. "And almost every animal in the world, unlike humans, is able to synthesize its own vitamin C and doesn't need to obtain it in the diet. That makes it difficult to do any lab animal tests with this vitamin that are relevant to humans."

Even though such studies often significantly understate the value of vitamin supplements, the largest and longest clinical trial of multivitamin/mineral supplements found a total reduction of cancer and cataract incidence in male physicians over the age of 50. It suggested that if every adult in the U.S. took such supplements it could prevent up to 130,000 cases of cancer each year, Frei said.

"The cancer reduction would be in addition to providing good basic health by supporting normal function of the body, metabolism and growth," he said. "If there's any drug out there that can do all this, it would be considered unethical to withhold it from the general public. But that's basically the same as recommending against multivitamin/mineral supplements."
 
Last edited:

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
There was a huge study some years back in which they examined the nutrient intake in tens of thousands of people. Almost nobody had the RDA of every nutrient in their diet.

When I was at uni I had to analyze my own diet for a day (not a longer time). Pretty good in everything ... except vitamin A. Hmmm.

Its very hard to sustain a balanced diet with just RDA level intake, what if you need more?

There is a need to better research supplements though. There is not enough good data.

A lot of studies also use cheap vitamins, like alpha tocopherol. Anybody who knows much about alpha tocopherol will tell you not to bother anyway. They don't tend to do much research on gamma or mixed tocopherols though, despite these being two of the best ways to take vitamin E.
 

barbc56

Senior Member
Messages
3,657
Even if the methodologies are flawed, doesn't mean that it will show vitamins are necessary. It theoretically could go either way.

Where do scientist get the vitamins for their studies? Since they are not regulated in most countries(?), how can you expect to get a reliable/valid study?

LOL @alex3619 , somehow I missed the comment in your post. Yeah, what kind of vitamins do researchers use? Looks like I need to do some research.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Here is something the other way. We known omega-3 fatty acids from high quality fish oil work, and sometimes better than drugs, for a range of health problems. What type did they use? The very best, the kind I still cannot buy in shops here.

The hype about omega-3 is from research using the very best quality, at over 90% pure and cold distilled to remove anything nasty. What do they sell most places? Minimally purified fish oil at about 30% pure. If you are lucky you can buy somewhat purified fish oil.

The proven stuff is hard to make, most companies don't bother. I think, last time I checked, quality fish oil can be bought in two countries., the USA and France. I have to settle for merely OK fish oil at about 60% pure.
 

barbc56

Senior Member
Messages
3,657
I thought fish oil was not shown to be more beneficial than drugs. Not that it isn't true.

Many pharmaceutical medications are based on the original "natural" ingredient with any extraneous ingredients taken out. An example is Willow Bark. While it's the main ingredient in aspirin, if you get the willow bark as a supplement, it isn't regulated and it may have other ingredients natural to the willow bark which don't do anything for pain or can be detrimental to your health.

I prefer prescription drugs over supplements unless there is a deficiency. I know that prescription drugs have their drawbacks but so do supplements and add to that self medication. It's just not my choice for my health options. Emphasis on the fact that this is MY opinion.

This my analogy. Say you are to descend a cliff and there are two options. One is to climb down by yourself using nothing to help (supplements not backed up by valid studies) and the other option is using a rope and spikes to get to the ground (prescription drugs). It's still not necessarily safe to use the rope and spikes but the odds are a lot better.

We are a pill popping culture for what ails us and that goes for either supplements or prescription medication.

This is my take on not only the supplement issue but also alternative medicine. But that's me.:)
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
I thought fish oil was not shown to be more beneficial than drugs. Not that it isn't true.

Many pharmaceutical medications are based on the original "natural" ingredient with any extraneous ingredients taken out. An example is Willow Bark. While it's the main ingredient in aspirin, if you get the willow bark as a supplement, it isn't regulated and it may have other ingredients natural to the willow bark which don't do anything for pain or can be detrimental to your health.

I prefer prescription drugs over supplements unless there is a deficiency. I know that prescription drugs have their drawbacks but so do supplements and add to that self medication. It's just not my choice for my health options. Emphasis on the fact that this is MY opinion.

This my analogy. Say you are to descend a cliff and there are two options. One is to climb down by yourself using nothing to help (supplements not backed up by valid studies) and the other option is using a rope and spikes to get to the ground (prescription drugs). It's still not necessarily safe to use the rope and spikes but the odds are a lot better.

We are a pill popping culture for what ails us and that goes for either supplements or prescription medication.

This is my take on not only the supplement issue but also alternative medicine. But that's me.:)

I tend to take the opposite view to yours in general. Before considering pharmaceuticals (which are on record for killing many times more people than supplements, although this may be partly due to the (in)efficacy of record-keeping) I look at what I think may be causing the problem, and the most sensible thing to do is to stop doing anything that appears to be causing harm, i.e. to stop hitting your head with a hammer instead of continuing to do it and then taking a drug for the headache! The problem may be dietary, so finding out what component of the diet is causing harm and eliminating it can be very effective.

My second choice will be a supplement or other natural medicine.

If all that fails, I will take a pharmaceutical after reading up on it. If it works and is well tolerated, I will continue to take it as much as necessary.

Re willow bark, a herbalist friend expressed the view that it is often actually better to take a compound in its natural state rather than an isolated chemical or even a synthetic one. There is evidence that this is the case with essential oils, for example. Linalool is a chemical found in many plants, and appears to be much better tolerated in essential oils than when isolated. I think that is because it is the oxidised form that causes, for example, allergic reactions, and the oil contains antioxidants.

Here is a page on willow bark, and there is a list of references at the end.
 

barbc56

Senior Member
Messages
3,657
@MeSci If we all had the same views, it would certainly be a boring world.

Different perspectives are well, different perspectives and by discussing them, problem solving, debating the merits of all sides are good problem solving.

This philosophy is reflected in my signature.
 

biophile

Places I'd rather be.
Messages
8,977
I do not have the available energy to look into the methodology of the studies in the supplement debate, but I would not be surprised if some of those on either side of the debate are soldiering on based on poor evidence.

Good point about the (often poor) quality of supplements and the baseline nutritional status of consumers.

Re supplements causing harm over long periods of time. Some vitamin supplements have sulphites added as a preservative, which can trigger migraines. Additives are not always required to be listed by law if they are under a certain level. So I wonder if additives or even contaminants can also contribute to poor outcomes.

@alex3619. I have done something similar, and yes, vitamin A stood out as being more difficult to get adequately in the diet. Vitamin E was not easy either, but does wheatgerm oil count as a food or a supplement?
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
http://sahs.utmb.edu/pellinore/intro_to_research/omega_3_fatty_acids.pdf

This is the paper that started the omega-3 bipolar debate. Given the risk-benefit ratio I think this is better than drugs. There is still controversy around the use of omaga-3 though.

Ginger is often used to deal with nausea. There is still controversy about its superiority though.

There are indeed bad things being sold as supplements. The debate is raging about folic acid, the oxidized form of folate that is converted by the liver to make methyl folate. There is a growing body of evidence folic acid is toxic, and its been tentatively linked to cancer, dementia and natural killer cell dysfunction. Its more of a problem in old people, or those with common genetic issues, but the debate is now renewed as its been found just two slices of folic acid enriched bread per day overwhelm the liver and folic acid gets into the general circulation, where it might do harm. Folic acid is currently being added to food by regulation in many countries. Methyl folate is not generally used as it is more unstable and more expensive.

Then there is cyanocobalamin, so-called B-12. This is bacterial B-12, not human B-12. Humans have two forms of B-12, and neither is cyanocobalamin.
 
Last edited:

Esther12

Senior Member
Messages
13,774
Balz Frei seems to have some links to those selling supplements, eg:
https://www.centrum.com/expert-corner/the-experts/dr-balz-frei
http://naturals.neutrogena.com/experts/balzfrei

That's not to say his research is poor, but there were things about that press release that raised my eye brows. I'd be a bit sceptical.

Saying that, I've noticed that often the studies claiming to show vitamins/supplements are ineffective seem to be rather poor (although this seems a difficult area to research) and over-hyped. It does seem that there is an ideological opposition to these things from some researchers.

As others have said, that's not to say that there's any good reason to routinely take supplements or vitamins though, and a lot of them are certainly sold with dubious claims about their health benefits... I can understand why some researchers would end up feeling pissed off my the supplement industry, there's a lot of quackery and preying upon desperation there.

I'm too lazy to bother looking into supplements with little research into efficacy... but I've also become more aware of how different people are, and how difficult it is to predict who will respond well/poorly to particular things, so I understand why some people do want to just try out different things for themselves. As long as they are aware of how poor the evidence is, and aren't being mis-sold things, I think that's fine.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,099
Location
australia (brisbane)
I dont think its about one or the other. I say use both. Also depends on what one is trying to accomplish. I dont think thete is anything to compare at the moment to using drugs for viral infections but then for improving immune function there are know meds currently available for most of us so we look into supplements etc. For oxidation there doesn't seem to be any meds available for us so supplements are preferred.

I think its a matter of whats the most effective and best cost to benefit ratio. Also many drug type treatments arent available to us as cfs isnt really seen as a disease so for many issues we only have supplements to choose from.

I think many of us are waiting for big pharma to come up with something and if they could cure 80% with a drug im sure we would all jump at it instead of dicking around with supplements.
 

barbc56

Senior Member
Messages
3,657
BigPharma makes quite a few of the supplements. at least here in the states and if I remember correctly, they also don't have to show efficacy. I need to find the source plus some other sources regarding studies reflecting many sides of the question. I am not saying that pharmaceutical medications are completely safe and as I mentioned above, beig deluged with all the advertisements as well as our culture, it's common to think of taking a pill for what ails you, when it may not be needed.

One reason I don't like to take supplements, except vitamin D as I have a deficiency, is because of the lax oversight vs. the oversight of pharmaceutical medications.. Supplements don't have to have studies before being approved.

An interesting subject is how Orin Hatch et. al., passed the DSHEA. I think I posted something about this but not sure.

I am under the BP's and BS;s influence tonight. I am taking an antibiotic for an abscessed tooth and a probiotic because of the antibiotic. Believe me, I need both!!!!!:jaw-drop: