Tag Archives: insulin

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:

 

 

 

 

 

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: