Not really enough evidence for NaturEra's "Sugar Crush" diabetes supplements

I will preface this by pointing out that I am not medically trained and that these views are mine alone.

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EDIT: 14 December 2010 - I received earlier today an email from the President of NaturEra with comments from one of the authors of the articles mentioned below, in response to my queries. I've posted their comments below my original post; their text is in blue.

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Response to One Natural Supplement with a Good Rep: Sugar Crush a post by DiabetesMine looking at a new nutritional supplement for people with diabetes which has been advertised (EDIT: this was not a paid-for advert and I mean the word in the colloquial sense, however NaturEra have asked me to make clear that their product and information were not advertised and I am happy to do so) presented at the American Diabetes Association and the American Association of Diabetes Educators.

I started writing this as a comment on the blog but realised it was getting rather long. It's here so I can link to it, prune or refine it, and also to prevent me losing it (also I don't know how to put links in blog comments). These are just some preliminary thoughts and may well change on further reading, or after discussions with others.

I have used the rel="nofollow" command in links to the company's websites, thanks to a helpful explanatory post from @rhysmorgan this means that my linking to these pages shouldn't enhance their market advantage ;)
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Very interesting, although my response is still to be somewhat skeptical.

Who, at the ADA or AADE, determines what research is shared at the conference and what are their criteria for inclusion? I'd always treat research from a conference with interest, but not much more because I'm always a little wary because it perhaps hasn't been through the same degree of peer review* that would happen before (and after) publication. In other words, no offence to either the organisation or the conference, but 'publication' at a conference isn't really sufficient to calm me in my skepticism ;)

*Not that peer review is perfect but that's for another discussion

Why does the company have two websites? There's one under the name of the company and another 'buysugarcrush' one which is linked from the product name website. Also, it's a bit strange that the right click function which normally would let you open something in a new tab or window is disabled, but that's more of a web design criticism than anything against the product of course!

I picked one link at random from the 'NaturEra makes news' but it says "Source: NaturEra" and it seems to be a repost of a press release from the organisation.

Another article - and I may be doing them a disservice by picking these at random - was "American Association of Diabetes Educators (AADE) accepted NaturEra Sugar Crush and Sugar Crush Daily first clinical results" which says that:

"NaturEra today announced that the American Association of Diabetes Educators (AADE) www.diabeteseducator.org has accepted the Sugar Crush line Dietary Supplement Research abstract for poster presentation at the 37th Annual Meeting in San Antonio, Texas August 4th, 2010.

AADE is the premier forum for state-of-the-art education and unmatched value of the biggest event for diabetes education and diabetes related health products. The abstract will be permanently hosted on the AADE archives after the annual meeting and will serve as a great educational and marketing tool for distribution of the Sugar Crush product line.

“This is further proof that the Sugar Crush product line works as a therapy helping diabetics to maintain healthier glucose levels”, said NaturEra’s CEO Oren Cohen. “The purpose of the study was (a) to investigate our novel biologically active food supplement (Sugar Crush) in decreasing blood glucose level in type 2 diabetes mellitus and (b) to determine the impact of improved nutritional status in patients.”"

The "this is further proof" puzzles me as the way it's written implies that the AADE's acceptance (which presumably is not an endorsement any more than a postcard in a newsagents' window endorses a 'man with a van' removal service) lends weight to the evidence. Perhaps they're not really implying this at all and it's just strangely worded.

In passing I note that they also have a product called PlayOn for 'sexual dysfunction in diabetics' - this is ringing alarm bells I have to confess.

The research itself, as indicated in the ADA abstract, note: this is not 'published' and does not appear in PubMed yet) seems a reasonable enough test - although fairly small (51 patients). There isn't really enough information (in two senses, one this is a brief abstract so info is necessarily not included and two, this is one pilot study and I'd expect that more would be needed before a product could be convincingly sold, based on results of tests - I don't think it's quite right to rely on the results of just one or two small tests).

The abstract implies that no other medications were permitted during the trial "No other glucose-lowering medication was allowed except study medication during the course of the study", this would eliminate confounding by people using other medicines to lower their glucose levels, and hopefully people wouldn't suffer if foregoing their medication.

But the full unpublished manuscript says "Fifty‐one (23 males and 28 females) subjects under a diet‐treatment only, diagnosed with T2DM and between the ages of 18 and 70 years who were not pregnant or nursing a child formed the study sample" and "Fifteen patients (29.4%) were being treated by diet therapy alone, six patients by a α‐glucosidase inhibitor, six patients by a sulfonylurea, three patients by nateglinide, and twenty‐one patients (41%) by a biguanaide" which I have to say confuses me a bit.

This might be a consequence of me reading the article by using Ctrl+F to find keywords and not actually reading the full manuscript, so I might be making a silly mistake or being unfair to the product - will need to read stuff properly later.

What else can affect blood glucose levels though, in addition to medications - did the people change their diet or increase their activity levels as well, or did they keep these constant too? There is no mention in the full length manuscript of exercise or activity relating to physical activity (the term appears only in relation to biological activity).

Blood glucose levels can vary quite a bit over a period of weeks - what is the natural variation (within one person) of their fasting blood glucose level? I wonder if HbA1c would be a better test as well.

It's not that there's anything wrong with the research, just that there's not enough of it to warrant using it to underpin an advertising or marketing campaign.

From a search on PubMed the authors don't appear to have published much in diabetes research - I found one article by a JD Schlosser (might or might not be the same as J Schlosser) from 1998, nothing from VK Podichetty on diabetes although an author of the same name has published in other medical areas and nothing from M Weshler.

But to be fair I've not published a bean on diabetes, or anything else, either ;)

I'm not sure if this is sort of trial that would be registered on either the ClinicalTrials.gov or controlled-trials.com websites but in any case it isn't.

How does the research fit in with other published work on the ingredients in the herbal supplement? The ingredients include sage, milk thistle, cinnamon, fenugreek etc., - all of which have had much claimed for them but I don't think the evidence has been particularly impressive?

I shall have to have a look at the 'Russian research manuscript' linked from the company's website too and see if that answers my queries.

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EDIT - comment below included within post because adding it just as a comment makes it harder for me to nest my own comments.

These comments refer to the truncated version (which I posted over at Diabetes Mine) of the blogpost above.

Please pass these comments on to the author of the website. I think its wonderful that these blogs exist to help people get the information they need. This should shed some more light on the credibility of our research.

To better understand what recognition the research has received thus far its a good idea to review the criteria for conference acceptance on the conference abstract submission pages of both the ADA and AADE. The Sugar Crush research was accepted for publication by the ADA for the ADA's 70th Annual Scientific Sessions abstract book. The Diabetes Abstract Book is read by ADA Professional Section Members, subscribers to Diabetes, and attendees of the Scientific Sessions, including physicians, medical researchers, epidemiologists, endocrinologists, psychologists, nurses, diabetes educators, and dietitians. I agree it is not an “endorsement," and certainly is not the same as a publication in a peer review journal. Regardless, it is still quite a feat to get a clinical study accepted for publication by the ADA to their annual scientific sessions, especially a clinical study of a natural product. Each year thousands of studies are submitted to the ADA and a small fraction (estimated at less than 10%) are accepted for publication based on the scientific method used and quality of the results. There is a team of more than 15 scientists that review the research studies and select the most appropriate studies for the annual meeting. You can read about the process on the ADA website.

Fair enough. I don't think it's unreasonable for a conference to accept pilot results but I'm less confident about otherwise 'under'published research being used to support the sale of a product.

In the case of the AADE, the research was again accepted for publication to their annual society meeting. Again, a small percentage of clinical studies submitted are accepted for publication. The clinical study was also accepted for Poster Presentation by the AADE, an additional recognition. If you go on the AADE website and read through their conference newsletter you can see that the AADE chose the Sugar Crush clinical study as one of only 3 to be highlighted. In my opinion, the AADE is equally important to the ADA because diabetes educators count on the AADE to learn about the latest advances in diabetes.

Please note that we did not pay for any of these publications or presentations. They are not something companies can just buy. The publications/presentations are earned on merit. One thing that bothers me is that the author of the blog says that our research was "advertised" at these meetings. We didn't do any advertising. Perhaps she will consider changing that sentence. The research abstract was selected for publication by a team of scientists. Its not something you can buy. Sugar Crush research wasn't just 'displayed' at the society meetings either.

I have made these changes as suggested.

In a world where there are so many bogus products on the market attempting to take advantage of people with diabetes, NaturEra is attempting to prove their products actually benefit people by backing the products with clinical studies. Once our full medical manuscript is published in a peer review journal this will give even more credibility to this study. We will also get the second study, the Russian Ministry of Health clinical study, published once that is completed. Of course clinical studies have significant expense and I am delighted to know that NaturEra plans on completing more studies in the future in addition to the study that was published to society meetings of the ADA and AADE and the Russian Ministry of Health study. Perhaps the author of that blog would be interested in giving us feedback on the protocol for the next study.

This suggests to me that the results are still not published in a peer-reviewed journal. Nothing wrong with that but for the fact that the internet seems to have many pages in which the product is being sold, and sold on the fact that there is evidence for it. If the studies haven't been properly published (they are in press) then this would seem to be putting the cart before the horse somewhat.

I probably don't have the necessary training to comment sufficiently usefully on the protocol for the study but I'll give it a go.

Here are more specific answers to some of the questions you read to me by phone:

1. Criteria for conference acceptance, and how much weight to give conference publication (as opposed to other forms of publication)?

My comments – The author should check “Criteria for conference acceptance” on conference abstract submission page. She is right that conference publication has less weight over a full text journal publication. But you cannot totally discount an abstract. Each society has a team of scientists that review research abstracts and select the most relevant re their own criteria. In the case of the ADA, fewer than 15% of the abstracts are accepted for publication.

This just tells me that the abstract is likely to be a good abstract, it doesn't tell me that the evidence for the product is settled or robust enough to be used to advertise it though.

2. Drawing big conclusions from a small pilot study (anecdotal data is interesting but if we don't know what else that person is doing to manage their blood glucose levels in addition to taking the product then the information is fairly meaningless)?

My comments – The author is correct that subjective bias in clinical studies is unavoidable but type II errors are implied in a statistical equation and you cannot ignore statistically significant results and call them meaningless. If such pilot studies are excluded from mainstream research, there would only be 25% of the studies that will truly enter scientific acceptance. This will lead to no progress in medicine.

I think the commenter has misunderstood me slightly but to be fair my comment as written here isn't very clear - I expanded on this point in the paragraphs beginning "What else can affect blood glucose levels though..."

Pilot studies shouldn't be excluded, but I think more research is needed before this can be used as evidence to support the sale of a product.

3. Slight confusion about the methodology and whether or not other medications were permitted by the 51 trial participants (again, this may be a mistake that I made in my quick skim-reading)?

My comments – Please read the entire study when it’s published. An abstract cannot tell the full study and is concise form as the name suggest. A draft of the full study is available for download at NaturEra.com. The full study will be published in a peer review journal. It is being submitted currently.

Well, to be honest I do find this confusing. Surely if the product is already on sale and reliance is being made on the fact that the research has been accepted (for conference abstracts publication) by prestigious medical conferences then it would seem reasonable for this to be a bit clearer.

This page contains lists of the available research articles. The abstract and manuscript both say that

'No other glucose-lowering medication was allowed except study medication during the course of the study'

in which 51 people participated, but on page 8 of the manuscript it also says

'Fifteen patients (29.4%) were being treated by diet therapy alone, six patients by a α-­‐glucosidase inhibitor, six patients by a sulfonylurea, three patients by nateglinide, and twenty-­‐one patients (41%) by a biguanaide'.
(emphasis added = 51)

Presumably this must mean that the trial participants had been using these treatments before taking part in the trial and that they gave up their medication during the trial - I just think this sentence could be made clearer.

4. Fasting blood glucose is probably a good marker, but HbA1c might have been additionally appropriate as it's often used elsewhere (eg for comparisons to be made with other studies)?

My comments – Completely agreed. This was the first ever study undertaken by the company and our future studies will include and evaluate HbA1c testing.

Incidentally, the trial also included a survey of patient satisfaction.

5. No mention that I could see of the role of physical activity, and what exercise the trial participants were doing - again, might have missed it.

My comments?– There was no role of exercise that was studies as part of the methodology.

That's fine - my query, admittedly not clearly stated here, was more along the lines of - can activity achieve the same effects on blood glucose levels as Sugar Crush.

6. None of the authors appear to have published on diabetes before - although this isn't particularly critical (I haven't either!)?

My comments –The authors have published on a variety of subjects and established researchers in clinical arena although not experts in the field. I'm not sure this is relevant. Isaac Newton never studied gravity before discovering gravity which changed the world forever. :)

Yes, a fair point here too.

7. How does this research fit into other published research on these plants and their hypoglycaemic effects? I don't think the evidence has been particularly impressive. Cinnamon showed promise in a couple of small trials but when looked at as part of the bigger picture the effect is very small.

My comments – Balanced modulation of several targets in the treatment of diabetes can provide superior therapeutic outcome with decreased side effects compared to the action of a single selective ligand. In order to hit the multiple targets implicated in complex clinical disorders such as diabetes, two strategies have been proposed. The first attempts to employ a single compound to hit multiple targets. The second methodology is the use of multiple active ingredients in one preparation. Although this premise has become a common feature in the drug development process, its principle applicability in developing nutritional supplements is still primitive. A unique novel combination of Trigonela foenum-graecum (Fenugreek), Foeniculum vulgare (Fennel), Salvia Officinalis (Sage), Olea europea (Olive), Cinnamon and Silybum marianum and other ingredients with high insulinotrophic properties holds great promise in this direction influencing multiple biological activities with significant physiological effects. We attempted to do just that.

Well... let's hope so. It's difficult to tell until the evidence is properly published and people much cleverer and pickier than me have had a look at it.

Having reviewed (fairly extensively but one can always do better) the evidence for cinnamon as a treatment for diabetes, it's not been wildly impressive. I can see the logic in trying more than one medicinal plant (while being cautious of interactions with other medications and foodstuffs) but I still have the sense that I'm missing something here and that it's a little bit too early to be selling this product based on the currently available evidence.

Edit: 26 June 2012
I had another look at the original post and was interested to see the 'pingbacks' at the end of the comments. Many of them point to different websites and blog posts but almost all have a very similar version, some translated into other languages, of the phrase "...Diabetes Mine (well respected blog about diabetes)". To me this suggests that the blog provided a useful platform, where the product was written about nicely, and enabling other sites to refer to the blog as evidence that the product is viewed favourably. This is an extremely popular strategy, also incidentally used by affilliate marketers of products (although I don't think that's what's going on here).