Jul 16, 2008
Unnatural Approach to Diabetes
As regular readers will be aware, I’m very skeptical of crank claims. Usually, these will claim to cure everything from premenstrual cramps to cancer by way of motor neurone disease and ingrowing toenails, all of them, with one pill. Forgive my flippancy, but the claims of many of those touting such panaceas usually beggars belief.
But some offer quite convincing claims for treating, but not necessarily curing, a specific illness with something novel. One such email arrived recently from a public relations company representing a company selling a herbal supplement. The release discusses the potential of an extract of mulberry leaf to prevent concentration spikes in the blood sugar of patients with Type 2 diabetes mellitus.
This disorder, which is on the increase in the developed world as obesity incidence rises, is characterised by insulin resistance, relative insulin deficiency and hyperglycemia (raised blood sugar levels). Changes in diet and more exercise can often ameliorate the effects in the early stages, but medication and insulin are usually needed in the long term. The main problem is the sharp rises and falls in the concentration of glucose in the blood, which puts a severe strain on the organs, in particular the heart.
The email I received, had the subject line “Type 2 diabetes: a look at natural alternatives to prescription drugs” and seemed innocuous enough. It mentioned the FDA’s pronouncements on diabetes drugs and the need to tighten up on their safety and then went on to highlight mulberry, a natural product that is now being marketed as Glucocil, which can purportedly help prevent those hazardous blood sugar spikes.
According to the press release, mulberry has been used for generations in Chinese medicine and some Indian foods, is showing great promise for Type 2 diabetes sufferers. After seven years of research and development, a medical researcher and scientist from China, Lee Zhong, has discovered a proprietary mulberry leaf extract that has been shown in numerous clinical trials to markedly lower blood sugar levels in Type 2 diabetics, helping them achieve a healthier diet and lifestyle. I asked Zhong for a few details about his work, the efficacy of this food supplement and possible medical issues associated with its use. You can read more about the study in the latest issue of Reactive Reports.
Zhong explains that, “Mulberry leaf
is
a natural
α-glucosidase inhibitorMulberry leaf is a natural α-glucosidase inhibitor. α-glucosidase
inhibitors do not lower blood sugar levels, they reduce and delay the abrupt elevation of blood sugars after meal, therefore stabilize blood sugar levels. π-glucosidase inhibitor drugs, such as Acarbose, are found to 1) reduce diabetic cardiovascular risks 2) be good for weight management 3)
prevent pre-diabetics to become type 2 diabetics.” Zhong and colleagues have published positive results on pure mulberry extract in the journal Diabetes Care, see reference.
It all sounds reasonable so far. But, what is not clearly mentioned in the press release is that Glucocil is not simply mulberry extract. Rather it is a blend of different ingredients:
- Mulberry leaf extract
- Cissus sicyoides (Insulina) leaf extract
- α-lipoic acid
- C. quadrangularis extract
- Banaba leaf extract
- Chromium polynicotinate
- vitamin B1, B6, B9 (folic acid), and B12
I asked Zhong about the presence of that chromium salt, as chromium deficiency has long been suggested to be a factor in the development of diabetes. “Chromium was not included in the extracts that used in our published clinical studies (or the efficacy tests),” he told me, “The ingredients used in the final Glucocil formula have records of many years’ safe human usage.” He adds that, “Glucocil was not developed overnight. We had thousands of tests and have plenty scientific evidence to support the product.”
That’s as maybe, but, I think he missed my point, it’s not the safety of the formulation that concerns me, although chromium picolinate has been linked to liver toxicity (Eur J Intern Med. 2002, 13, 518-520), it’s how it can be marketed as a natural product when it so obviously contains a rather non-natural ingredient in the form of that chromium salt. It seems especially odd given that chromium itself is thought to have an effect on diabetes, although that’s as yet unproven.
Aside from the clinical trials and tests carried out with mulberry in isolation, as far as I know, no double-blind placebo-controlled trials have been carried out on the mixed formulation that includes the chromium salt, which has variously been used as a “natural” slimming aid without serious proof of efficacy. Chris Leonard, Director, Translational Research and Technology at Memory Pharmaceuticals, points Sciencebase readers to what he describes as a “thoughtful and well-referenced discussion on chromium and diabetes.
Pharmacologist and toxicologist Sanjeev Thohan, Research Director at drug discovery company Exelixis, adds that chromium picolinate is quite distinct from the hexavalent form of chromium made infamous by the Erin Brokovich issue. He points out that there have been some clinical trials conducted within the last year that use different derivatives of chromium picolinate and that these are close to finishing and will make their data available in the next year or two. He adds that one must, “Remember that the bioavailability of the picolinate derivative and its action on the beta cells is what will determine if there is a positive effect on insulin. Insulin sensitizer drugs, I believe in some of the clinical trials, are being used with the chromium compounds to see the possibility of synergy.” Thohan highlights an additional UK government PDF resource on chromium. The US government’s PDF document on dietary recommendations for vitamins and trace elements also includes a section on chromium.
Zhong adds that, “This product is being marketed as a dietary supplement (not a food or drug) and is designed to assist those who are trying to manage their condition primarily through changes in lifestyle, primarily diet and exercise.” But, to my mind, something with proven activity in such a potentially debilitating disease should not be marketed as a supplement. Consumers should be made aware of the dangers of diabetes and consult their doctor over possible treatments and outcomes.
Zhong tells me that the marketing does stress that potential users talk to their healthcare workers and that they should monitor their blood sugar carefully. However, one in ten, he concedes, don’t necessarily do so. With diabetes on the rise, one in ten could turn out to be quite large numbers of people using an apparently potent supplement without any clear knowledge of what it might be doing to their bodies and without strictly monitoring the progression of their disease.
“Generally speaking, those who are most interested in this product are those who are newly diagnosed and are not on multiple meds as is the case with those who are more seriously ill,” adds Zhong, “The typical Glucocil consumer is someone who is looking for more natural nutritional support.”
Yes, there are problems with pharmaceutical products. But, maybe its time physiologically active herbal remedies were
brought under
the pharma umbrellamaybe its time physiologically active herbal remedies were brought under the pharma umbrella rather than being sold disguised as food supplements. Indeed, there are calls for this to happen in Europe and elsewhere. This way, not only would they gain acceptance or rejection quickly, but those that are truly effective and worthy, and safe, would reach the patients who really need them and lose the downy feathers of alleged quackery.
UPDATE: There’ll be a post on the regulations debate on Sciencebase, July 23, so grab the site newsfeed to keep up to date or sign up here to get the item delivered by email.
Mudra, M., Ercan-Fang, N., Zhong, L., Furne, J., Levitt, M. (2007). Influence of Mulberry Leaf Extract on the Blood Glucose and Breath Hydrogen Response to Ingestion of 75 g Sucrose by Type 2 Diabetic and Control Subjects. Diabetes Care, 30(5), 1272-1274. DOI: 10.2337/dc06-2120
David Bradley
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Chemgeek said,
July 16, 2008 at 3:54 pm
“But, maybe its time physiologically active herbal remedies were brought under the pharma umbrella maybe its time physiologically active herbal remedies were brought under the pharma umbrella rather than being sold disguised as food supplements.”
The FDA had the opportunity to do this several years ago. But, instead of acting to ensure safety and efficacy we now have “These statements have not been evaluated by the FDA…”
The supplement industry won that battle, but in my opinion they removed themselves from the realm of legitimacy and have become firmly entrenched in the realm of quackery despite the fact that some of these things may hold promise.
David Bradley said,
July 16, 2008 at 5:01 pm
I just had an email from someone telling me about a herbal product that works best if you say a prayer while using it….
Chemgeek said,
July 16, 2008 at 5:34 pm
I bet the prayer increases the effectiveness by at least 100%.
Jo Brodie said,
July 16, 2008 at 8:03 pm
Unfortunately I can’t actually find evidence of the page with the prayer on it. Despite this the
archived pages of the FaithMeds Institute still score very highly on comedic value -
http://web.archive.org/web/20070702085015/www.faithmeds.com/diabalance.html
“Our Standard American Diet (SAD) lacks many necessary fundamental nutrients. To compensate for this, our research scientists applied God’s blue print for optimal health by developing highly effective supplements that help nourish your body as He intended. ”
and
“You know there’s always a “doubting Thomas” in every crowd that says, Oh yeah, well if it’s so good then SHOW ME! Well, for all the doubters, guess what? That’s just what we’ve done! We took the time to scientifically query past users of DiaBalance™ about their results. This is what we found to be true:
98.6% of all people who used DiaBalance™ as directed reported a positive result. ”
You just can’t argue with logic like that ;-)
Bert Ramsay said,
July 17, 2008 at 5:19 pm
Could someone tell me why the Minneapolis Veterans Medical Center is involved in this? If at all. Sounds like an attempt to validate an untested product. Is this product recommned for diabetes 2 people who are already on medication?
Will the posting at this site be used to give credibiliity to this medicine? What are Lee Zhong’s qualifications?
David Bradley said,
July 17, 2008 at 5:31 pm
Bert, you raise an interesting point, I hope my post doesn’t raise expectations for this mulberry extract, I am very skeptical of it having any benefits, especially given that it is being formulated with a chromium salt. Zhong told me that it is aimed at those with early stages, like I said, I’m not sure why such products aren’t controlled properly under drug regulations.
Slevi said,
July 17, 2008 at 9:18 pm
“I just had an email from someone telling me about a herbal product that works best if you say a prayer while using it….”
And here I thought prayer only worsened your chances, RR of complications 1.14 after heart surgery.
But these so called natural products are great of course, but essentially it’s not like it’s all that different from our own basic medicine. Take for example willow bark, sold as a herbal treatment and advertised with uses by the Chinese by some companies and others say the ancient Greeks used it (those which are really accurate say Hippocrates used it).
And how do you get it home? Right, you get a bottle filled with pills. I wouldn’t be surprised if it was even produced in the same pharmaceutical factory as where regular aspirin comes rolling down the line, just got a price tag twice as high slammed on it.
In the end it’s just what most of the ‘natural’ products come down to, they’re just as natural as many other drugs but either untested or with a higher price tag slammed onto it.
David Bradley said,
July 18, 2008 at 7:37 am
Slevi, that’s right, there are something like 60% of prescription and over the counter pharmaceuticals (including aspirin, Taxol, ephedrine, epothilone etc etc) that had a herbal or natural product origin. And, certainly, there are flaws in the drug discovery world because of toxicity, drug promiscuity, inept understanding of mode of action, and the issue of your genes being slightly different from mine so that a drug that works for you may fail me. We could go on.
The difference is very much that those products are regulated, and hopefully there is some professional guidance (in the form of a physician’s expertise and advice) in offering them to a particular patient, whereas anyone could walk into a healthfood shop, buy some pills to pop for diabetes and *if* there is some real activity with the product, cause themselves more harm than good, especially if there are interactions with other medication they may be taking. If the product has no actual activity, then any benefits are nothing more than a placebo effect and they may as well stick with the prayer for all the good it will do them.
Slevi said,
July 18, 2008 at 2:10 pm
Mwuah, picked aspirin because you can just walk into a healthfood shop here and buy it, whether if sold as aspirin or white willow bask. But I take it that’s not the case where you live?
Just like with products like these there is no professional guidance and regulation beyond the leaflets in the package. And as practically nobody reads the leaflets people just buy them and take them without realizing it might be better not to for them as they are familiar with a stomach ulcer for example.
Even with aspirin sold at any random health shop like that of course the side effects and interactions known by health care professionals is much better than when something goes wrong with some herbal product. Take for example Chinese herb nephropathy which has shown how dangerous over the counter herbal medication can be without proper testing. Not just might it give interaction with your other medication, it can actually kill you within a year of usage.
David Bradley said,
July 18, 2008 at 2:20 pm
Slevi, yes we can buy aspirin OTC, I was just highlighting those other drugs to show that a large proportion of OTC and on-scrip products have a natural origin. I entirely agree, it’s probably too easy for people to get hold of stuff that could kill them without them realising there may be serious contraindications for particular medical conditions they have and for other medication they may be using, not to mention toxic contaminants in many products.
Bert Ramsay said,
July 18, 2008 at 7:21 pm
I think the main ingredient in willow bark is salicylic acid - which is a stomach irritant. Aspirin is acetyl salicyic acid which reduces the stomach irritation by blocking the phenolic group.
David Bradley said,
July 18, 2008 at 8:46 pm
That’s right, they use salicylic acid to kill plantar warts (verrucas), but I also heard that grinding an aspirin and making a paste and covering the verruca with the paste and then a plaster will work as the aspirin gets hydrolysed back to the acid on one’s skin. Salicylic acid is the active metabolite of aspirin, I believe, and was used in a herbal remedy obtained from cricket bat willow.
db
Mina said,
July 20, 2008 at 3:14 am
No, please. I totally disagree with placing mainstream herbals under the ‘pharma umbrella.’ It’s not to say I don’t support the notion of thorough research, safety, monitoring and accountability, but to compare the vast majority of herbals to pharmaceutical preparations is misguiding and excessive. I vote stricter regulations but ones that are separate from current pharma protocol/guidelines.
P.S. Speaking of topical aspirin treatments, the ‘aspirin mask’ is a raved about beauty treatment for acne. ;)
David Bradley said,
July 20, 2008 at 9:12 pm
Why keep them separate? If they actually work, then they are physiologically active, and if they’re physiologically active they can have side-effects and contraindications to other drugs and disease states. If they don’t work, then they shouldn’t be being sold in the first place as that’s nothing more than marketing snake oil, surely?
Mina said,
July 21, 2008 at 8:08 am
It’s not so black-and-white though. The vast majority of herbal preparations aren’t viewed to treat disease in the way that pharmaceuticals are presented nor are they presented as ‘cure alls.’ Sure, we all know the stories of dangerous herbs and dubious advertising but I don’t think that warrants all mainstream herbal preparations being subject to the same testing required for pharmaceuticals. Not only that, but the funding simply isn’t there either, particularly given that the treatments don’t have significant effects in the way pharma ones do (generalizing here, of course). Consumers would not have access to many useful herbal preparations if the requirements were on par with pharmaceuticals.
I don’t think that herbals are typically used as a ‘cure’ in the same way that – for example – antibiotics might be used to treat a bladder infection. Herbals are commonly used as preventative and supportive treatments alongside pharmaceuticals.
David Bradley said,
July 21, 2008 at 8:32 am
Mina, but I guess that’s the point. If these herbals aren’t active then why are they being sold? If they’re inactive, then they’re nothing more than placebos, they’re like a crutch for someone with perfectly good legs.
“commonly used as preventative an supportive treatments alongside pharmaceuticals”, sorry but that really just sounds like an evidence-free proposition.
I’m not saying that all herbals are hogwash, some do have physiological effects and because they do, they should be regulated properly. Take St John’s Wort, anyone who feels a bit miserable can buy it OTC and start popping pills in the hope of making themselves better, totally unaware of its latent interactions with certain medications, often made by the same companies via their pharma wing:
http://www.intelihealth.com/IH/ihtIH/WSIHW000/8513/31402/348539.html
More to the point, herbal manufacturers are not allowed to make medical claims about herbal products, so consumers buy these things blindly or having read some anecdotal evidence in lifestyle magazines of non-controlled, non-blinded, quasi clinical trials.
Like I said before, if they have no effects, then they’re a waste of money, if they do have effects then these should be regulated because the effects could be hazardous when mixed with other diseases and pharma products.
Which mainstream herbals do you think are worthy? Echinacea? Ginseng? Maluka honey? None of those have any proven efficacy beyond acting as a poor source of some vitamins and minerals.
Mina said,
July 21, 2008 at 5:49 pm
No, I’ll go back to bladder infections as an example. This is a bit of a deviation from herbals but there is research suggesting that cranberries are useful for preventing bladder infections. Key word is prevention. Once an infection has taken root, no sane doctor is going to recommend cranberry extract or juice. Rather, antibiotics are standard treatment.
To reiterate, I’m not arguing that they should not be regulated. In fact, I’m a huge supporter of increased regulations AND training for anyone who provides information on these types of products. Right now, it’s far too relaxed and pardon my language but some of the ‘advice’ provided along with purchases is daft at best (speaking from personal experience on that one). What I am saying is that pharmaceuticals are far more potentially onerous as a comparative whole and that it seems excessive to subject herbals to the exact same scrutiny and testing. I think a separate category is realistic and would be effective, plus safer than the current wishy washy pseudo-regulations around most herbals.
David Bradley said,
July 21, 2008 at 6:11 pm
Ah, but what about those people taking a daily dose of some particular herbal to stop them getting one disease and repeatedly banging their organs (particularly liver and heart) with a compound that is not safe in its unmetabolised form. The case in point is related to your cranberry example and concerns grapefruit juice and an old antihistamine Triludan. Admittedly, one would have to have drunk an awful lot of grapefruit juice for the Triludan to remain unmetabolised long enough to cause heart damage. However, my point is that many herbals are concentrated versions of such products and so popping a daily pill might provide the equivalent of several glasses of the drink, which could quite easily interfere with a prescribed drug.
A person prescribed antidepressants might imagine that taking St John’s Wort alongside would be safe and helpful. It most likely wouldn’t be, especially if they also have thyroid problems. The fact that there is a serious disconnect between herbals and pharma products could be lethal in some cases, which is why I think there should be better controls.