Thursday, June 28, 2007

06/28/07 - Randomized Clinical Trials; cGMPs posted


1. RCT (Randomized Clinical Trials) and nutrients
2. New cGMPs now available on net
4. CRUSH media release: Silver Safety Standard

1. RCT (Randomized Clinical Trials) and Nutrients

This article by Dr. Melton is cogent and worth reading. The article goes to the heart of the coming cGMPs – how will you substantiate the claims you make about your products? How will you prove the identity and quality of the ingredients? If you have the time to think about what your company will be doing in two years when the cGMPs become effective for small companies, this is something you need to think about… and, yes, you do need to start thinking now…

Clinical trials - gold standard or white elephant?

25/06/2007 - Randomised clinical trials are the ultimate. Forget what the observational studies tell us, if the RCT gives us an answer it must be the final word, right? Wrong.

The value of such trials for the food industry is undeniable, but too often nutrients are pulled out of context, following the same methodology as used for the testing of drugs.

But let's not forget that by following the drug model we are supplementing the diet with one or two nutrients, each at a single dose, for a set period of time. Can a time-constrained randomised trial really capture a lifetime of consumption with respect to chronic disease?

Randomised clinical trials work by randomly assigning a group of volunteers to receive an active compound, be it a drug or nutrient(s), or a non-active comparison, be it an inactive form of the active compound or a placebo. Observational studies, as the name suggests, observe a population and relate dietary intakes of food and nutrients to the occurrence of disease.

We need to consider the science as a whole and not blinker ourselves with results of one big clinical trial, regardless of how much money it costs and what universities were involved.

For food items that do not normally form part of the usual food chain, randomised clinical trials are the best of the best because such compounds can be tested and retested successfully.

Phytosterols, probiotics, or botanical supplements, for example, fit into this category.
Indeed, clinical trials on phytosterols have shown time and again that daily consumption of 1.5 to 3 grams of phytosterols/-stanols can reduce total cholesterol levels by eight to 17 per cent, representing a significant reduction in the risk of cardiovascular disease.

Studies looking at how these results transfer into real free-living populations have backed up the clinical trials, showing a stabilisation of cholesterol levels in certain populations.

So we know the benefit of clinical trials. But when we start using this approach for vitamins, minerals, antioxidants and other nutrients, we come a little unstuck.

Some may say that I'm over-reacting, but let's just look at the report published in the New Scientist magazine that slammed antioxidant supplements as myth.

Despite a vast body of observational/ epidemiological studies linking an increased dietary intake of antioxidants from fruits and vegetables to reduced risks of a range of disease, including cancer, cardiovascular disease and diabetes, when such antioxidants have been extracted and put into supplements, the results, according to RCTs, do not produce the same benefits and may even be harmful.

So the author of the article, Dr. Lisa Melton from the London-based registered charity, the Novartis Foundation, concluded that antioxidant supplements are too good to be true.

Is this really the answer or is it due to poor study design? Would a two-year trial of vitamin E, let's say, really produce a reduction in the risk of a chronic disease?

To illustrate this point further, we only need to go back to last year's Women's Health Initiative (WHI) trial that followed 18,176 post-menopausal women taking calcium (1000 mg) and vitamin D (400 IU) supplements. A similar population (N=18,106) was given a placebo. The subjects were followed for about seven years and the researchers reported that the supplements 'had no effect' on the risk of colorectal cancer.

None of the women had the cancer at the start of the study and colorectal cancer has a long latency period of 10 to 20 years, which begs the question - could we really have expected to see an effect?

We also need to remember that nutrients often work in synergy with one another and exert effects on multiple body tissues, unlike pharmaceuticals.

Additionally, many randomised clinical trials look at the effect of nutrients in diseased populations. Surely the damage of a lifetime's poor nutrition has already been done. When we obtain negative or null results from such trials, should we really be surprised?

The power of nutrients is in the prevention, not cure, of disease.

So what should we do? I don't pretend to have any answers. These are for ladies and gentlemen with infinitely bigger brains than me.

Realistically, there are no viable alternatives out there at present. Randomisation is the best way of limiting bias that creeps into every study, and controlling, specifically with placebo, is the best way to make comparisons.

For those times where randomised trials clearly aren't the best option, then we probably need to look at the observational studies and mechanistic studies in greater depth, and place more value on them.

The research community as a whole must work together to re-evaluate how to get the most from research into nutrition. Lots of different types of studies are out there. Let's make the most of what we already have.

Stephen Daniells is the Food Science Reporter for and He has a PhD in Chemistry from Queen's University Belfast and has worked in research in the Netherlands and France.

If you would like to comment on this article please contact stephen.daniells'at'


2. FDA publishes Current Good Manufacturing Practices for Dietary Supplements

I’m reading them, but so can you, at: (467 pages when downloaded to MS Word; the actual rule doesn’t start until page 426, after 359 comments…).

Here are some comments by FDA, from the commentary preceding the new rule, that tell us a lot about where the present administration of FDA is taking us: “…we disagree with the comments asserting dietary supplements have a track record of safety such that dietary supplement CGMP requirements are unnecessary. Section 402(g) of the act does not require us to establish a ‘bad’ track record of safety in the manufacture of dietary supplements before we may issue a dietary supplement CGMP rule. Furthermore, we disagree with the comments comparing dietary supplement safety to drug safety; there are different statutory requirements, different regulatory requirements, and different safety evaluations for dietary supplements and drugs.”

We can hope there will be a change of Agency attitude when the Administration changes in about a year and a half; especially if the good doctor from Texas replaces the current Texan occupying the White House. I’ll provide more tidbits as I read the materials.


3. Health Freedom Blog

The Vitamin Lawyer Health Freedom Blog is now at The address is:

I just posted a link there to an 8 minute presentation I taped for Natural Solutions Foundation, for use with health-friendly delegates at next week’s Codex Commission meeting in Rome.


4. CRUSH Silver Safety Standard

The Committee on the Responsible Use of Silver in Health (of which I am a member) is releasing the final version of its Silver Safety Standard (The “12 for 25 Rule). The media release will be posted on PRWeb shortly and can be seen at or on my Blog.

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