Tag Archives: diabetes

Berberine – A Nutraceutical for Glucose and Lipid control: An Update

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I was recently reminded of how impressive berberine can be after recently hearing a clinician’s story. The particular patient had Type 2 diabetes and this clinician had been treating him for 15 years. Consistently his glycated hemoglobin was above 9% (aim: to be below 7%). Historically, the patient had been taking 2 grams of Metformin, then recently these meds were lowered to 1 g and berberine was added. Within one month, his glycated hemoglobin was 6.7%. Obviously, this is a single case and other factors may have been involved- lthough the clinician was convinced berberine was a major factor in these results.

We have been following the growing research related to use of the alkaloid compound berberine for almost a decade now and wanted to give a short update for those interested in using this dietary supplement as part of their healthcare protocol for managing glucose, lipids or related cardiovascular outcomes.

Berberine for glucose management in Type 2 Diabetes

Most of the excitement related to the use of berberine for diabetic patients comes from a paper published in early 2010 (Metabolism 59(20)) where a group of Type 2 diabetic patients were given either metformin 1.5 g/d (n=26), rosiglitazone 4 mg/d (n=21) or berberine HCl 1g/day (n=-50) and followed for 2 months. The remarkable results showed drops in fasting blood glucose and glycated hemoglobin for berberine which matched both metformin and rosiglitazone- while only the berberine group saw a statistical drop in TG levels. Furthermore, they followed this study by testing 1g/day of berberine HCl in type 2 diabetic patients who had either hepatitis B or C to detect whether these same outcomes could be confirmed in these patients and what affect berberine may have on liver enzymes in these patients. They found similar benefits in both blood glucose and TG levels as in the non-hepatitis patients, but also a statistical improvement in both AST and ALT enzyme levels.

One of the critiques of this (and most) berberine studies is that they have nearly all been performed in China- on Chinese subjects and most of the published trials are in Chinese- making the data difficult to assess and translate (both linguistically and clinically) into practice here in the US. A recent meta-analysis of these Chinese studies has recently been published (in English) and is available for download online (Evidence-Based Complementary and Alternative Medicine Volume 2012). While showing a consistent positive benefit for berberine in a wide-range of Chinese subjects (14 trials, 1068 subjects), the authors also conclude that many of these trials were poorly conducted and the need for a large, well-controlled and randomized clinical trial is critical. Nonetheless, they found berberine generally safe- listing GI discomfort and constipation (berberine is traditionally used to treat diarrhea in China) as side-effects to treatment in a small number of patients.

Berberine for lipid-altering effects or related cardiovascular outcomes

Years before the glucose-related outcomes were being published, researchers in China had described lipid-altering effects using berberine. Some of these trials are now being performed outside of China in Caucasian subjects. Most recently was a study done at the University of Pavia (Italy) in 144 subjects with low cardiovascular risk (Expert Opin Biol Ther 2013). After a 6-month run-in period of diet and physical activity, patients were randomly given either placebo or berberine (500 mg- twice per day) for 3 months. Patients were taken off their experimental therapy for 2 months (wash-out), and then placed back on berberine or placebo for an additional 3 months. Not only was berberine deemed safe in these individuals, but subjects consuming berberine had reduced total cholesterol, LDL-cholesterol and TG, and increased HDL-cholesterol. All of these benefits were diminished during the washout period but returned once back on berberine.

A small pilot study, done also in Caucasian subjects, was performed here in the US (U. of South Dakota and South Dakota State University) which explored the lipid-lowering effect of berberine (Phytomedicine 2012). Sixteen obese subjects were given berberine (500 mg- 3 times per day) for 12 weeks. As a pilot study, there was no control group. After 12 weeks they saw a modest loss in body weight (avg. 5 lbs/subject) and a significant reduction in total cholesterol (-12.2%) and triglyceride levels (-23%). 2 subjects stopped the protocol due to GI complaints- which may have been due to the higher dose (1.5 grams) over other studies using only 1 gram.

A review and meta-analysis of the Chinese studies looking at the lipid altering effects of berberine is also online (Planta Medica Abstract-2013)

Other Recent Human Studies using berberine

Potential for berberine/drug interactions

“CONCLUSIONS: Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.”

Animal or Mechanism studies of interest

One of the most impressive aspects of the recent berberine studies is the vast number of animal, tissue and mechanistic studies which have been emerging in the past few years. Listed below is just a few recent studies related to metabolic pathways and outcomes. I will only highlight one particular study because it is a fascinating relationship between a nutraceutical agent, the gut microbiome and human physiology.

One of the main historical uses for berberine (Coptis chinensis and its extracts) within Traditional Chinese Medicine is for intestinal infections and diarrhea. This has led some to wonder if consuming berberine regularly for cardiometabolic outcomes might promote an imbalance within the gut bacteria (microflora). As it turns out, the answer might be yes, but in a very helpful way. In a study published in PLoS ONE (Full Article Free online), researchers show that the prevention of obesity and insulin resistance which occurs in rats fed a high-fat diet are partially mediated by changes to the gut microflora. This mechanism adds to the long list of known metabolic influences that berberine has on metabolic pathways and links to the growing evidence we now have of the relationship between obesity and gut microflora in humans. While the paper is quite technical, it gives some interesting background information and highlights the type of research that will continue to be done to decipher the benefits of berberine and other nutraceutical agents. It also shows us that some agents have activities which don’t even require absorption to result in a clinical outcome.

Here are more studies on berberine that might interest you:

 

 

 

 

 

Take a stroll after a meal for best glycemic control

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I have often suggested that taking a walk a short time after eating a meal is a good way to improve overall glycemic control by directly impacting the post-prandial (after-meal) effects of glucose and insulin. A new study from Mayo Clinic has done a great job of showing how large an impact this might actually have. In order to get this data, however, they required volunteers (healthy controls and Type 1 diabetic subjects) to wear special suits and monitors that recorded their every move and calorie expended for three days in a laboratory/clinic setting.

 

I will focus my attention on the control subject for this report. These subjects were normal weight (avg. BMI-25.6) and in their late 30’s (5 men, 7 women). Before testing the effects of walking on post-prandial glucose, they first recorded the energy expenditure of these subjects based on their activity- something that is important to note.

 

At rest (Basal metabolic rate/BMR):     0.84 kcal/h/kg

Standing                                               1.17 (40% increase over BMR)

Walking 1 mph                                                2.41 (186% increase over BMR)

Walking 2 mph                                                3.08 (266% increase over BMR)

Walking 3 mph                                                4.02 (378% increase over BMR)

 

Notice how much more energy is expended just when they begin to walk even at 1 mph, compared to being sedentary. For me, this data alone made the paper worth reading and another confirmation of why I am planning to install my new treadmill desk soon! Now back to the rest of the data.

 

Each of the 3 meals they consumed for the 3 days was virtually identical and contained 33% of their daily caloric needs. Meals consumed at 7 AM, 1 PM and 7 PM were 30% carbohydrate, 40% fat and 40% protein (no food was permitted outside these meals). Each day, one of the meals was followed by complete sedentary activity (lying in bed for 6 hours) and the other two meals were followed by bouts of walking (averaging 90-95 minutes before the next meal). While these activity levels seem a bit extreme, the metabolic differences were quite dramatic. When measuring the glucose excursion for 270 minutes after these meals, the amount was over twice us much (113% higher) when the subjects had no physical activity, compared to when they were walking (at only 1.2 mph!).

 

What does this mean for the average person? Well, the total distance walked after these meals was actually less than 2 miles. Most people can walk this in 40 minutes (at 3 mph) which is much more practical with a busy schedule. But more to the point, it tells us that any amount of physical activity, especially after a meal, improves glucose tolerance and reduces the level of blood glucose after eating. These numbers are likely to be even more striking in patients with insulin resistance eating higher carbohydrate meals than those tested here (i.e. the average American).

 

Think about how you can change your regular eating habits to allow for a walk afterward, or perhaps schedule your physical household chores to be accomplished right after eating supper so you can avoid plopping down on the couch or in front of the computer for several hours of sitting.

 

Here are some other similar recent studies you might find interesting:

 

Vegetable and plant oil rich diet protects against oxidative damage in diabetics

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Oxidative stress is a culprit in the development of many chronic diseases and may be one reason why those with diabetes are more vulnerable to developing cancer. A healthy diet rich in antioxidants has long been known to prevent cellular damage from oxidation and radiation and now a new study sheds some more light on its protective effects on health. According to a recent study, subjects who consumed 300 g of vegetables and 25 ml of plant oil for 8 weeks raised their serum antioxidants levels and reduced their levels of HgBA1C, a marker which indicates damage to DNA strands. Those who followed a healthy diet but did not consume the 300 g of vegetables reduced their glycated hemoglobin but did not get the important benefits of improved antioxidant status. Click to read more: http://www.foodconsumer.org/newsite/2/Diabetes/vegetables_pufa_diabetes_mellitus_1119120735.html

The Diabetes drugs pipeline

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November is Diabetes Awareness Month and there are some interesting facts you might want to be aware of. According to the latest data released by the CDC, diabetes rates have been increasing at an alarming rate over the past two decades; but not to worry; over 200 new drugs are currently in the pipeline to save us. If you didn’t detect my sarcasm, let me be clear: these two ”unrelated” pieces of information show that we still have much more to be aware of before we can make any headway in our current diabetes crisis.

The CDC released data this month that shows that the number of diagnosed cases of diabetes between 1995 and 2010 grew by 50% or more in 42 states (in the US), and by 100% or more in 18 states. States with the largest increases over the 16-year period were Oklahoma, up 226%; Kentucky, up 158%; Georgia, up 145%; Alabama, up 140%, Washington, up 135%, and West Virginia, up 131%.

And our “hope” to slow this colossal devastation of our health and healthcare system? More drugs, of course. According to the Pharmaceutical Research and Manufacturers of America (PhRMA) there are no less than 221 drugs in clinical trials or in the process of FDA approval for diabetes (Type 1, type 2, or diabetes complications) [See News Report here]. Billions of dollars will be spent so a few of these can make it to market; and if I can make a prediction, 10 years from now the diabetes rates will continue to increase and many of these drugs will have been approved and recalled by FDA due to their sides effects. (I can’t help from thinking that the rampant use of statin drugs in the past decade has played a significant role in driving the diabetes numbers in the previous story- but I digress)

While it is agreed upon by most researchers that 70-80% of the cases of diabetes (Type 2) are preventable with lifestyle prevention/intervention; the vast majority of research dollars are still spent on finding solutions which avoid this solution! This is the type of “awareness” that is desperately needed if we are truly to reverse this, and most of the chronic diseases that are plaguing us today- and also the reason I wrote the Original Prescription in the first place. Our solutions must address the root cause if we hope to change the numbers the CDC reports a decade from now.

Should you eat breakfast like a king?

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We have all heard the old adage that “Breakfast is the most important meal of the day,” but can such an adage be proven scientifically? And if so, by what criteria do we measure the importance of one meal over another, and perhaps most importantly, would this be true for everyone?

 

In the dietary principles we lay out in chapter 8 of The Original Prescription, principle #3 reads: “Unless purposely fasting, don’t skip meals. Start each day with a balanced breakfast containing both protein and fiber.” I mention, among other things, that the glycemic dynamics after the morning meal have a powerful impact on hunger signals throughout the day. I also mention how the diurnal rhythm of the stress hormone cortisol, which peaks in the morning just after awakening, is supposed to steadily drop during the time one normally consumes breakfast. Of course, cortisol is one the body’s modulators of glucose and insulin action and, I believe, one of the reasons that stress, insulin sensitivity, eating breakfast and risk for obesity and metabolic disorders are related. Skipping breakfast, as most of you know, is linked with increased risk for obesity, insulin resistance, diabetes and heart disease. Among other things, the need for our bodies to maintain higher cortisol to sustain our glucose levels when we skip our breakfast meals (remember cortisol is a gluco-corticoid), diminishes our insulin sensitivity and increases the overall catabolic effect of cortisol- driving more metabolic dysfunction.
 

As we discuss in the book in detail, our bodies are designed to take in the “signals” of our life(style) and convert this into health. As with many of the signals that follow a circadian rhythm like cortisol, researchers have now identified that insulin secretion and action follows a pattern based on a diurnal pattern of pancreatic beta cell function. And would you believe, glucose tolerance and insulin sensitivity is highest after breakfast. Researchers at the Mayo Clinic measured a number of parameters of beta-cell function and insulin and glucose metabolism and discovered that total beta cell responsiveness was over 20% higher after breakfast than after either lunch or dinner [Pub Med Link]. Overall, this pattern was maintained amongst most of the participants, but it was not so in every person measured (they studied “healthy” normal weight volunteers with normal fasting glucose). They found, that in a few individuals, morning insulin sensitivity and beta cell function was dramatically lower after breakfast than after lunch or dinner. What is going on in these individuals?
 

The authors speculate that individual responses may be influenced by sleep-wake cycles, age, gender, shift work or jet lag. Of course, my first question was “What are the cortisol levels in these individuals?” The author emailed me that cortisol, among other hormones, was monitored in these individuals and the data is being studied for a future publication (we will have to wait). I think this information will help us understand why some individuals responded differently to the group as a whole. I can tell you, as someone who attempted a similar study; that performing a glucose/insulin test after breakfast without controlling for wake time and shift work will dramatically influence the individual responses.
 

How I read this data with what we know already:

  • Insulin sensitivity follows a diurnal rhythm- corresponding with the normal sharp drop in cortisol in the AM (the hypothalamus is controlling all of this).
  • After an 8-12 hour fast, the body appears to be designed to dispose of a larger meal by increasing beta-cell function and peripheral insulin action.
  • Eating breakfast helps to ensure the normal drop off in cortisol levels after awakening.
  • Skipping breakfast means we miss the window when our body is designed to most efficiently deal with a meal and, among other things, triggers cortisol production and a subsequent increased desire for comfort foods.
  • This pre-programmed increase in insulin and beta cell action after breakfast can be eliminated by improperly timing the first meal of the day due to awakening time (shift work, jet lag, poor sleep) or HPA axis stress.
  • The link between elevated stress, skipping breakfast and a wide-range of metabolic disorders is not a coincidence.

In my next post, I will discuss how exercising before breakfast might affect your metabolism.
 
Here are few more related articles to ponder: