The worldwide adult population of diabetics has more than doubled since 1980. It now stands at 347 million. This is a 133% increase according to an international team of researchers. You can read their paper in the medical journal The Lancet.1 This figure is a far larger number than previously thought. This strongly suggests that costs of treating diabetes will soon explode. With all the economic problems of the world economy, this is a disaster in the making. Especially in the U.S., which now has the fastest rate of diabetes increase in men, and the third fastest in women. We will show you how berberine can be a major part of fixing this.
Too Many People Are Diabetic
A previous recent projection had put the estimated number of diabetics at 285 million worldwide. But the new study has found that figure woefully short. The research team evaluated the worldwide FPG (fasting plasma glucose) records from 2.7 million individuals ≥25 years of age. The estimated prevalence using advanced statistical methods. Of the 347 million people with diabetes, 138 million are in China and India. There are another 36 million in the United States and Russia.
Led by Professor Majid Ezzati, from the School of Public Health at Imperial College London, and Dr. Goodarz Danaei, from the Harvard School of Public Health, the authors of the new study attribute 70% of this increase to longer lifespans. As it turns out, the older you are, the greater your risk is for developing diabetes. Obesity and other risk factors account for the remaining 30%.
According to Professor Ezzati:
Diabetes is one of the biggest causes of morbidity and mortality worldwide. Our study has shown that diabetes is becoming more common almost everywhere in the world. This is in contrast to blood pressure and cholesterol, which have both fallen in many regions. Diabetes is much harder to prevent and treat than these other conditions.2
To which Dr. Danaei added:
Unless we develop better programs for detecting people with elevated blood sugar and helping them to improve their diet and physical activity and control their weight, diabetes will inevitably continue to impose a major burden on health systems around the world.2
Diabetes mellitus is a group of metabolic diseases that have some commonalities and some differences. In both of the two principal varieties, type 2 diabetes (about 90–95% of all “diabetes” in the U.S.) and type 1 diabetes (5–10% of the “diabetes” population) high blood sugar is the common feature. High blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). However, in type 2 diabetes, cells do not respond to the insulin. And in type 1 diabetes, the body does not produce enough insulin.
Other differences include the presence of insulin resistance. This is a condition in which cells fail to use insulin properly. It is sometimes combined with an absolute insulin deficiency in type 2 diabetes (this is why it was previously called non-insulin-dependent diabetes mellitus) and the need to inject insulin in type 1 diabetes (this is why it used to be called insulin-dependent diabetes mellitus).
Berberine Benefits Both Principal Types of Diabetes
A surprising new study conducted in Taiwan has found that berberine administered to non-obese diabetic (NOD) mice protects pancreatic islets and serum lipids.3 In type 1 diabetes, pancreatic islets can incur damage by auto-antibodies. This misdirects the immune system is to attack proteins, gradually causing chronic complications. This momentous study examined the effects of berberine on type 1 diabetes in vivo. The NOD mice were grouped and given 50, 150 or 500 mg of berberine/kg of body weight per day* over a 14 weeks week period. During the span of the investigation, the following measurements were made:
- Changes in pancreatic islets
- Serum insulin levels
- Berberine levels
- Lipid levels
- LDL/TC (low density lipoprotein
- HDL (high density lipoprotein cholesterol)
- HDL/TC (high density lipoprotein cholesterol/total cholesterol)
- LDL/TC (low density lipoprotein
* The amounts given to the mice, respectively are the human equivalent of 344, 1033, or 3443 mg per day for a 187 lb person.
The results showed that berberine supplementation significantly increased pancreatic islets cells while raising serum levels in dose-dependent manners. As well, supplementation also increased insulin levels, but decreased the ratio of LDL-C/TC. (Oftentimes folks refer to LDL-C as the bad cholesterol.) Furthermore, as serum levels of berberine increased, so did HDL-C (the good cholesterol) levels along with the HDL-C/TC ratio. This study suggests that berberine administration protects pancreatic islets and serum lipids in NOD mice.
Berberine administration may alleviate cardio-metabolic complications in diabetes via improving serum lipid profiles.
Possible Mechanism of Activity
Unfortunately, the new paper did not perform any tests necessary to clarify the mechanism of action. However, a previous study shows the ability of berberine to act both as an insulin sensitizer and an insulin secretagogue (releaser), which may be due to its modulation of several signaling pathways and targets.4 This paper choose to investigate berberine’s function as a ligand (binder) of a fatty acid receptor GPR40 (G protein-coupled receptor 40), which stimulates glucose dependent insulin secretion. They also found that berberine stimulates calcium mobilization in the GPR40 cell line. Furthermore, berberine stimulated glucose-dependent insulin secretion from rat pancreatic beta cell line. Together, this data suggests that it functions as an agonist (trigger) of fatty acid receptor GPR40. It also might be a novel antidiabetic mechanism of action for berberine.
Berberine Inhibits H1N1 Influenza AIn another new study,1
Researchers tested whether berberine can inhibit the growth of influenza A. The results showed strong inhibition of the growth of 2 strains of H1N1 influenza A (PR/8/34 and WS/33) in macrophage-like cells, human lung epithelial-derived cells, and murine bone-marrow-derived macrophages. The authors suggest that the mechanism of berberine underlying these effects occurs after chemical translation to inhibit virus protein trafficking/maturation which in turn inhibits virus growth.
Berberine was also assessed for its ability to inhibit production of TNF-α (tumor necrosis factor-alpha, a cytokine mediator involved in systemic inflammation) and PGE2 (prostaglandin E2, a mediator with strong physiological effects, including the regulation, contraction, and relaxation of smooth muscle tissue) from PR/8/34 infected-macrophage-like cells. What the researchers found revealed strong inhibition of the production of both mediators. This effect is probably distinct from the anti-viral effect.
Finally, berberine-containing ethanol extracts of goldenseal at high concentrations also strongly inhibited the growth of influenza A and production of inflammatory mediators. However, diluted extracts were somewhat less effective than purified berberine. The results indicate that berberine may indeed be useful for the treatment of infections with influenza A.
|Cinnamon and Berberine: Better Together Researchers investigated the pharmacokinetics of a mixture of cinnamon granules and berberine from Rhizoma coptidis granules in healthy male volunteers. The concentration of berberine in the plasma of healthy male volunteers was determined directly by high performance liquid chromatography (HPLC) after an oral administration of Rhizoma coptidis granules alone or combined with cinnamon granules.
The plasma concentration-time curves of berberine were plotted. Based on the finding, the authors suggest berberine granules combined with cinnamon granules could increase the plasma concentration of berberine, promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers. Cinnamon would appear to make berberine work better, longer, and harder.
Islet Cells Protected
Returning to the current study, the central idea was to evaluate the long-term effects of berberine supplementation on type 1 diabetes. Using a normal species control for the NOD mice, controls were shown to have markedly higher islet cell numbers than those of NOD mice, and this continued throughout the experimental period. Nonetheless, supplementation increased the islet cell numbers in a dose dependent manner. And the higher the doses of berberine, the higher the counts compared to the control group. This suggested that it protected islet cells from spontaneous injury in NOD mice.
The serum levels in berberine-administered groups significantly increased in a dose-dependent manner.
Using HPLC (high-performance liquid chromatography, a technique that can analyze the content of mixture), the Taiwan researchers calculated the berberine levels in individual mice and compared these to the reflected peak standard. It was shown that the serum berberine levels in berberine-administered groups significantly increased in a dose-dependent manner. This provides persuasive evidence that it is readily absorbable via the digestive tract. Oral supplementation enriched the body and serum concentrations, indicating that the bioavailability of berberine supplementation was proven. Yet, the relative distribution in different body organs remains to be further clarified.
Berberine Altered Serum Insulin Levels
When the changes in insulin levels were determined, it was found that the controls had markedly higher levels of insulin than the groups receiving berberine. Yet the insulin levels of the NOD mice increased throughout the experiment. But berberine reversed the lower levels of insulin in NOD mice, allowing the researchers to conclude that it increases insulin secretion levels via a reawakened use of pancreatic islets. Unfortunately, serum insulin levels were up just slightly, but not significantly through the 14-week experimental period. Thus the scientists thought that berberine administration at the indicated concentrations in this study could not fully reverse the spontaneous injury to pancreatic islet β-cells in the NOD mice. But NOD mice were designed to finish their days with type 1 diabetes.
Berberine Changes Serum Lipids Mostly for the Better
Berberine administration did not significantly influence serum lipid levels, including serum triglycerides (TG), TC, HDL-C, and LDL-C levels. Nevertheless, NOD mice had significantly higher ratios of LDL-C/HDL-C and LDL-C/TC compared to the controls throughout the study. This argues that relatively higher LDL-C levels existed initially in the NOD mice. Of importance, the different doses of berberine markedly decreased the raised LDL-C/TC ratio.
Evidently, a decrease in TG, TC, LDL-C serum levels with an increase in HDL-C (good cholesterol) in vivo is favorable to good health and avoids diabetic complications, at least for type 2 diabetes. In summary, the results propose that berberine administration improved serum lipid profiles in NOD mice principally through relatively decreasing LDL-C serum levels.
Correlating Berberine levels, Islet Cell Numbers, and Lipid Levels
It is important to understand the relationship among berberine, pancreatic islet cell numbers, and lipid levels. To do so in the experimental NOD mice, the correlations between these factors were determined using a technique called Pearson’s correlation coefficients (a measurement of the correlation between two variables). The results demonstrated a significantly positive correlation between berberine and HDL-C levels. Also, there was a significantly positive correlation between it and HDL-C/TC ratios.
The researchers hypothesize that berberine inhibited pancreatic islets cell death, particularly through its potent anti-inflammation potential.
Berberine Benefits for Cholesterol
At the same time, a significantly negative correlation between berberine serum levels and the LDL-C/HDL-C ratios was found. Also, there was a slightly positive correlation between the serum levels and pancreatic islet cell numbers. These results further suggested that berberine administration, whatever the level of ingestion, could not fully protect pancreatic islets from spontaneous injury.
Serum fasting glucose levels and oral glucose tolerance test (OGTT) were determined and showed that NOD mice developed type 1 diabetes, notwithstanding berberine absorption via the digestive tract. Berberine is an alkaloid with moderate water soluble property, and this characteristic may have enhanced its bioavailability in the study.
And the higher the berberine serum levels the greater the protective effects from spontaneous pancreatic islet cell injury. Accordingly, these higher levels raised the decreased islet cell numbers in a dose dependent manner. As they have been designed to do, the NOD mice spontaneously developed type 1 diabetes, accompanied by chronic inflammation resulting in apoptosis (cell death), especially in their pancreatic islet β cells.
B-Cells and Berberine
It is reasonable to assume that the prevention of pancreatic islet insulin-producing β cells from selective destruction—such as through anti-apoptotic effects on the islets in the early stage—may cure or delay type 1 diabetes. Regrettably, the researchers did not determine the pancreas β cell mass in this study. Moreover, it is difficult to directly diagnose β-cell abnormalities in vivo. This is because of their small size, as well as the fact that they are deeply and sparsely dispersed in the pancreas. However, techniques are currently in development to do that. Scientists believe that islet cell numbers correlate closely with b cell mass in the pancreas.
Taiwan Research of Berberine
In the Taiwan researchers’ previous studies,5 berberine was found to possess potent anti-inflammation potential. It was also show to inhibit streptozotocin-induced apoptosis in mouse pancreatic islets. The researchers did not doubt that it can protect β cells from cell death in NOD mice. Once absorbed via the digestive tract, berberine can enter pancreatic islet β cells and exert its anti-apoptotic effect possibly using its potent anti-inflammatory and antioxidant activities, not to mention its ability to down-regulate the Bax/Bcl-2 gene expression ratio (which helps govern apoptosis).
The researchers hypothesized that berberine inhibited pancreatic islets apoptosis, particularly through its potent anti-inflammation potential. They found that appropriate insulin secretion levels were produced by the increased pancreatic islet β cells. However, insulin levels did not see a significant change through the experimental period. Also, they found that NOD mice showed significantly higher LDL-C/HDL-C and LDL-C/TC ratios, compared to those of controls, suggesting that relatively higher LDL-C levels exist in NOD mice.
Berberine’s versatility for combating a wide range of diabetic consequences, now includes protection of pancreatic islets and the reduction of serum lipids.
Surprisingly, berberine administration at different doses for 14 weeks markedly decreased the raised LDL-C/TC ratio. This demonstrates that it improves serum lipid profiles in NOD mice. Further analysis also showed a significantly positive correlation between berberine and HDL-C levels, as well as a significantly positive correlation between serum levels and HDL-C/TC ratios, but a significantly negative correlation between serum levels and LDL-C/HDL-C ratios in NOD mice.
Research results indicate that berberine administration improved serum lipid profiles in NOD mice via relatively increasing serum HDL-C, and decreasing LDL-C levels. The results further clarify that it may alleviate cardio-metabolic complications in diabetes via improving serum lipid profiles. In another study, berberine was found to inhibit fatty acid synthesis via decreasing the acetyl-CoA carboxylase activity in 3T3-L1 adipocytes (fat cells).6 Nonetheless, this regulatory mechanism of berberine on serum lipid levels and profiles requires more study.
Berberine Study Limits
Unfortunately, they did not complete cell and tissue analysis of the liver, pancreas and lung. Doing so could have provided insight into the protective effects of berberine on type 1 diabetes-induced organ fibrosis. However, it decreased the ratios of pro-/anti-inflammatory cytokine gene expressions in the liver and kidney of NOD mice. This suggests an anti-inflammatory protection of berberine on visceral organs.
When taken together, the findings of this study are promising. They support a growing body of scientific literature, which—along with anecdotal evidence—show berberine’s versatility for combating a wide range of diabetic consequences. This notably includes protection of pancreatic islets and the reduction of serum lipids.