Berberine Works But May Very Well Be Harmful

I have been getting a lot of email of late about the supplement Berberine, which appears to be the latest miracle cure being sold to those people with diabetes who believe that completely unregulated herbs imported from countries with long histories of food and drug adulteration are somehow safer and "more natural" than the tightly regulated pharamceuticals.

Berberine does appear to work to lower blood sugar. The problem is that we really know very little about how it does it or what its long term effects are on the body.  I see many mentions on sites promoting berberine supplements of the fact that berberine has a long history of use in Chinese medicine. However, quite a few of the traditional Chinese herbs have turned out to be highly toxic, and it's worth noting that the incidence of kidney and other urinary tract cancer among Chinese herbalists is far greater than that of the population at large. (Details HERE)

You can lower blood sugar by damaging your liver as happens with severe alcoholism.  You can lower blood sugar with drugs that raise the likelihood of heart attack, as is the case with most sulfonylurea drugs. (Details HERE) You can lower blood sugar with drugs that over time damage the pancreas as is the case with the incretin drugs.(Details HERE)  And you can lower blood sugar by taking drugs that turn bone precursor cells into fat cell, as happens with Avandia and Actos, which, over a decade of use of these drugs can lead to your developing bones so brittle that they are prone to breaking. (Details HERE)

Many of these severe, life-ruining side effects did not show up until people had taken these drugs for five to ten years. So the fact that a drug lowers blood sugar for three months in a small population without major harm tells you nothing about its actual safety.

To get a feel for the quality of the research supporting the claims about berberine, scroll down to the Reference section of this page: http://examine.com/supplements/Berberine/ .

Ignore the enthusiastic editorializing by the editors of the site who don't know very much about diabetes or the drugs that berberine is being compared to and pay attention to the quality of the journals publishing these studies. Most are very obscure. Some sound like they are one of the many  "pay to play" journals beloved by supplement sellers--journals that will publish anything as long as they are paid a hefty fee.

Those studies on berberine published in respected endocrinology journals involve small groups of people taking the drug for very short periods. The only one I could find with a large number of subjects is a meta analysis where data from 14 different very small studies was pooled. Meta analyses are only as good as the quality of the underlying studies, which in this case is not very good.

Some studies published in quality journals suggest that berberine's positive effects may stem from the fact that it activates AMP-Kinase, which is what metformin does. If this is the case, you have to ask yourself, why not just take metformin, a safe, very well understood drug that has been in use since the 1950s and which must meet rigorous manufacturing standards before it is sold.

Several mainstream studies claims to have found that berberine inhibits DPP-4 and raises the concentration of the incretin hormone GLP-1 which is the mechanism used by the incretin drugs Januvia,  Onglyza, and Trajenta. As discussed elsewhere, inhibiting DPP-4 can turn off a mechanism the immune system uses to kill cells that have become cancerous, which may make these a poor choice of drug. In addition, accumulating evidence is pointing to the possibility that artificially raising GLP-1 levels over a long period of time leads to the growth of abnormal cells in the pancreas which may grow into the ducts and cause pancreatitis or turn into precancerous tumors.  (Details HERE)

Mainstream research also finds that berberine has a significant impact on your liver. Repeated use downregulates several important enzymes (P450 cytochromes ) that the body uses to eliminate drugs. You can read about that here: http://www.ncbi.nlm.nih.gov/pubmed/21870106.

This means that if you are taking berberine, other drugs you take may not be eliminated properly if they use those enzymes and may build up to toxic levels, while others, which require those enzymes to be working so that the drug can be broken down into the active form of the chemical they contain may not work as expected.

In particular you should not combine repaglinide (Prandin) with berberine as that combination may produce hypos since repaglinide is eliminated from the body by an enzyme that berberine inhibits. Since metformin also inhibits one of these enzymes to some extent, combining berberine and metformin is probably a bad idea, too. (Note I have blogged about the combined effect of metformin and prandin HERE).

Other drugs affected by berberine include cyclosporin (Neoral, Sandimmune), lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and many others.

As always, when you buy an unregulated supplement, you have no way of knowing what is actually in the pill. Herbs grown in third world countries often contain toxic herbicides which are prohibited in the U.S.. And supplements manufactured abroad may also contain lead and other toxic heavy metals, as well as other contaminants. As supplements are completely unregulated in the U.S. and receive no scrutiny unless they kill someone, the assurances of the supplement companies that their supplements are "pure" are worthless. When supplements are taken to the lab by consumer groups, they often turn out to contain different dosages thatn what the label claims and to be contaminated.

With all this in mind, it seems prudent if you are going to use a drug to lower your blood sugar, to stick to drugs that are regulated, provided in pills of known dosage, and which have long track records for safety. Currently, the only drugs that fit that description are: metformin, insulin, prandin, gliclazide (not available in the U.S.)  and acarbose.

I'm Taking a Break from Blogging

I'm taking a break from blogging about diabetes news. If something major occurs, I'll blog about it, but I'm not going to be posting minor tidbits anymore.

Almost all the news items I've been highlighting here over the past few months just reiterate some point made in a previous post or add more data to support an argument already fleshed out on the main site.

The 500+ posts already to be found here and the hundreds of pages available at the main site http://bloodsugar101.com have covered just about everything you need to know about Type 2 diabetes, diabetes drugs, and diet.  

To find information about a diabetes-related topic use the "Search this Blog and its Cites" link located at the top of the right hand column of this page.

To preserve your health if you have been diagnosed with Type 2 diabetes, just do the following:
1. Learn what blood sugars are truly normal.
2. Learn how blood sugar control works and how it stops working.
3. Learn what blood sugar levels cause diabetic complications and heart disease.
4. Learn how to lower your blood sugar to the safe range using dietary changes.
5. Learn what diabetes drugs are safe and what drugs are dangerous.
6. If you are tempted to try supplements read about what they really do HERE and HERE.

Final June Diabetes News Snippet Post

Jenny said...

The FDA is taking another look at Avandia's relationship to heart disease.

http://www.forbes.com/sites/matthewherper/2013/06/04/battleground-fda-how-tomorrows-avandia-panel-could-help-shape-the-future-of-diabetes/

But whatever they conclude about whether or not Avandia causes heart attacks, we know that it, like Actos, also weakens the bones over time and makes them prone to fracture, since it converts that stem cells that should become bone cells into baby fat cells.

It, like Actos, also raises the chances of experiencing retinal edema--swelling in the blood vessels in your eye that can contribute to blindness.

Finally, both Avandia and Actos have been found to cause heart failure in people who had no symptoms of it before taking the drug. Heart failure is different from heart attack, and refers to weakening of the heart muscle that greatly raises the risk of dying within a few years.

Bottom line. The reasons for reviewing Avandia are all about making money for the drug company. There is NO reason for you to be taking this drug--or for that matter, any other new diabetes drug released over the past 6 years.

7:33 AM, June 05, 2013

Chris said...

Am a diabetes newbie here. My recent diagnosis is associated with my second heart attack in six years. Thank you for writing this blog. I'm looking forward to relying on your pointed references in answer to many of my questions, rather than having to scour a dozen websites.

8:36 AM, June 05, 2013

Jenny said...

Scientists find a new medium that allows them to grow ten times the usual number of beta cells in culture. Apparently they are normal cells. This is very good news for those with Type 1 Diabetes who need islet transplants to replace dead beta cells.

Science Daily: Major Hurdle Cleared to Diabetes Transplants

6:08 PM, June 13, 2013

Jenny said...

Good news for ordinary people. The Supreme court ruled that the FTC can sue drug companies that pay generic drug companies not to make their patent-expired drugs so that they can continue to price gouge.

Reuters: Supreme court says FTC can sue over deals that delay generic drug sales

3:15 PM, June 17, 2013

Jenny said...

Dietary fructose causes liver damage in monkeys fed diets that don't cause weight gain. The damage is associated with bacteria leaking into the liver as the fructose seems to modify characteristics of the digestive tract.

Science Daily: Dietary Fructose Causes Liver Damage in Animal Model

9:21 AM, June 20, 2013

Jenny said...

Here's an excellent summary of ALL the studies pointing to serious problems with all the incretin drugs. There are a lot of them from many different kinds of research and they make it crystal clear that the American Diabetes Association's claim that the research is ambiguous is an industry-sponsored lie.

Pharmlot: Troubling New Signals? ? Diabetes Drugs & Adverse Event Reports

9:38 AM, June 20, 2013

Jenny said...

A major study published in the journal Science explains why our understanding of how mitochondria works has been wrong.

At the end of a report about the study we learn, "During the study the team also made the unexpected discovery that the most widely used mouse strain for laboratory genetic analysis is unable to correctly assemble the respiratory supercomplexes. This raises serious questions about the validity of extrapolating results obtained with these mice to humans."

This may explain why so much mouse research comes up with findings that aren't true for people, for example, that eating a high fat diet causes diabetes.

Mitochondria are where cells burn fats and sugars, so when they aren't working properly blood sugar and fat metabolism can be skewed.

Science Daily: Researchers Reformulate the Model of Mitochondrial Function

8:42 AM, July 03, 2013

Jenny said...

Last week was the annual ADA Scientific Sessions, the big conference where diabetes specialists get together to present research findings and be lobbies by drug and device salesforces.

(I am on the mailing list to get the press releases inviting me to discuss various presentations to be given at the conference, so I get a bunch of mail inviting me to learn more about drug company sponsored crap.)

Nothing that advanced the knowledge of anyone not educated by drug companies seems to have come out of this get together. One study found that losing weight doesn't eliminate heart conditions in people with diabetes. Since they lost weight in ways that did not lower their blood sugar below the 150 mg/dl level that solid research links to heart conditions, this did not amaze me, but it was news to doctors. Unfortunately, it is likely to make them prescribe more weight loss surgery which by its nature makes people cut carbs way, way down and can have positive effects on blood sugar.(If it doesn't kill you or leave you nutritionally compromised for life.)

Another study found that eating a low carb diet lowers blood sugar much more than eating a low fat/low cal diet. (We knew that, didn't we?)

I am pretty burnt out on following diabetes research because after 15 years it has become evident that doctors will never pay attention to anything that doesn't enrich drug or device surgeons, or perhaps surgeons--very well funded groups that profit from the suffering of people with diabetes. That it is news that cutting carbs lowers blood sugars 20 years after Dr. Bernstein published on the same subject shows you what we are up against.

And the complete lack of curiosity of doctors, who sheeplike follow whatever they are told by the industry "Thought leaders, a fancy term for " doctors who are paid hundreds of thousands or more by the drug companies to promote their most recent most profitable drugs, ensures nothing will change.

We could cure diabetes were it not that 98% of all research money goes into studies of drugs that counteract symptoms without addressing the cause of those symptoms, and if were not that drug companies would go out of business if we did cure it. It's a 100 billion dollar business making pills and shots that cost $300+ a month which have to be taken every day for decades. Diabetes is the single most widespread costly condition affecting older people.

You'd get fired if you worked for a drug company and came up with anything that actually cured diabetes and your research would go right into the shredder.

8:52 AM, July 03, 2013

Major Breakthrough in Using Stem Cells to Cure A Genetic Form of Diabetes

A study just published in the Journal of Clinical Investigation describes what sounds like a very important advance in the treatment of genetically-caused diabetes.

The study is iPSC-derived β cells model diabetes due to glucokinase deficiency.  Haiqing Hua et. al Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI67638

To better understand what was done here, read Science Daily: Researchers Demonstrate Use of Stem Cells to Analyze Causes, Treatment of Diabetes

The particular form of diabetes that was studied here was MODY-2. This is a monogentic genetic form of diabetes, which means you need have only one copy of the gene to experience its symptoms. MODY-2 involves the glucokinase gene (GCK) which is often described as a "glucose thermostat." It affects the control of fasting blood sugar, and when it is broken people have diabetic-level fasting blood sugars that, in theory, can not be lowered.

This it turns out, is not entirely true. I have heard from several people diagnosed via gene tests with MODY-2 who report that cutting carbs does lower their fasting blood sugar, even though they were told it would not. My guess is that while their base fasting blood sugar is higher than normal eating a high carb diet further stresses their blood sugars as it does in people without the defect, so removing the carb-related stress lowers their fasting blood sugar to a level slightly higher than normal, but not nearly as bad as what they experience while eating a high carb diet.

But because their fasting blood sugar is higher than normal from birth, which in most people leads to post-meal blood sugars that are also higher than normal, People with this gene often die of heart attacks at very young ages, which is why, though it doesn't cause the extremely high post meal blood sugars that produce the classic diabetic complications, MODY-2 is still a very serious condition which requires life-long vigilance on the part of those who suffer from it.

What the researchers did in this study was to take skin cells from people with MODY-2 and using the kind of wizardry that stem cell scientists now routinely pull off, use them to create pluripotent stem cells--cells that can become any kind of tissue.

The researchers then, using even more stem cell magic, turned these pluripotent stem cells into beta cells, implanted them into mice, and three months later confirmed that these cells were in fact beta cells that showed the characteristics of MODY-2.

That's already pretty amazing, but the researchers were just getting going. Next the scientists "repaired the GCK mutation using molecular techniques."  After doing this, "cells with two restored copies of GCK responded normally to the glucose stress test. Unlike other reported techniques, the researchers' approach efficiently repaired the GCK mutation without introducing any potentially harmful additional DNA."

In short, what they did was create perfectly normal beta cells that would have been immunologically identical to those of the skin cell donors that had repaired the flaw that gave these people MODY-2 diabetes. If this is really the case, it should eventually be possible to grow a significant number of these new, repaired beta cells and transplant them back into the people with MODY-2  where they would be able to respond like normal beta cells, secreting insulin when exposed to rising glucose levels. Best of all, these transplants shouldnt require the use of any immunosuppressant drugs.

The part about growing enough cells and transplanting them is still in the future. So even if you have MODY-2  it's going to be a while until there is an actual cure your doctor can prescribe for you. But even so, this is, obviously, extremely good news for anyone who has a genetic form of diabetes which involves damaged beta cells.

And though few people with Type 2 realize it, this would include a lot of people with Type 2, as there are a couple of damaged genes affecting insulin secretion that are very commonly found among Europeans with Type 2 diabetes, for example TCF7L2, which is discussed HERE.

There are other commonly damaged beta cell genes that are found in other ethnic populations too. So in the long run this research could lead to effective beta cell transplants for people with Type 2 that could normalize their blood sugars.

Will it really happen? Hard to say. Sadly, all the money in diabetes treatment lies in creating drugs that have to be taken every day for decades and devices that require very expensive consumable parts that have to be replaced frequently. Since the companies that make those drugs are the companies that fund most research--and the ADA and the JDRF and drive the diabetes research agenda, it may be difficult for the scientists who performed this particular miracle to get the kind of funding it would take to turn beta cell implantation for MODY or Type 2 diabetes into a viable treatment covered by insurance.

Still, if you have a genetic form of diabetes, it's good to know that your children might not have to go through what you did, thanks to the advances made in stem cell research today.

NOTE: Don't confuse this research which is in its early stages with the fake claims of the many scammy  "stem cell clinics" you will find on the web that claim to cure diabetes (and anything else that ails you) with transfusions of your own stem cells. These slimy weasels prey on people who don't understand science and cure them only of having healthy bank accounts. Ignore them.

The exciting stem cell research that may pay off for people with diabetes is still, like the study discussed here, in the preliminary lab-bench stage which is very far from being something you could have done to your body to heal it. But someday, if we're lucky . . .

Big Changes in the Drug Patent World Are Good News for People with Diabetes

Several days ago the Supreme Court of the U.S. issued a decision saying that the FDA could sue drug companies that paid off generic drug makers to keep them from releasing generic versions of drugs that had gone off patent.

A second decision that may be just as important for controlling the costs of drugs for people with diabetes occurred on June 18, 2013. A U.S. appeals court found the patent on Novo Nordisk's Prandin diabetes drug Prandimet, a combination of Prandin with metformin to be invalid, paving the way for introduction of a generic version of the medicine.

MedCity Newsletter: Novo Nordisk’s diabetes drug patent ruled invalid, door open for generic version

Drug companies have been creating combination drugs with two off patent drugs claiming they are new drugs that deserve new patents. Then they convince doctors to only prescribe the expensive, patented combination drug rather than the separate generics. ("So much more convenient." "More effective!" Both lies, of course.)

This is good news not only because it makes the combo drug cheaper, but because if upheld it will dissuade drug makers from marketing these combo drugs, which are a very poor choice for consumers because they make it impossible to dose the individual components correctly.

Some people need 1000 mg of metformin a day for it to be effective. Some need 1500, and some need 2000. However, if you put 1000 mg of metformin in the same pill with a full dose of Prandin, an insulin secretion stimulator, you have to double the Prandin to double the metformin dose. Doubling Prandin can cause hypos in people who are sensitive to it. So with a combo pill the person is likely to end up with an optimal dose of only one component of the pill.

Two generic prescriptions should be the same cost or, more commonly, cheaper than one patented pill, except for people who have top tier health  insurance whose co-pays are low enough that this shouldn't be an issue. Most people with diabetes can handle opening two pill containers and taking two pills if that means they are a) paying less and b) getting more effective doses.

The drug companies are likely to lobby and appeal this one to the top, too, since their failure to come up with effective new drugs drives them to more and more tricks, like bribing generic drug makers or creating these combo pills to keep their expiring patent moneymakers profitable.