Berberine has come of age as an anti-diabetic nutrient . . .

Take This Dye for Diabetes
From the ancient Silk Road to
the modern nutritional pharmacopeia
By Will Block

The dye of health was beginning to glow on her cheeks;
her eyes sparkled as they had formerly done; and her
light step had regained its elastic firmness.
— Miss Aimwell [pseud.], Good Nature,
or Sensibility and Other Tales

T he greatest discovery of Hungarian explorer, archeologist, and professor Aurel Stein (1862–1943) was made at the Mogao Caves (also known as “Caves of the Thousand Buddhas”), near Dunhuang, China in 1907. Dunhuang is a city in the prefecture of Jiuquan, in the westernmost part of Gansu Province, abutting Mongolia, and a major crossroad stop on the ancient Silk Road. It is the strategic former oasis through which Marco Polo passed on his way to China in the late 13th Century. And it was there that Stein discovered the Diamond Sutra, the world’s oldest, dated, printed text—CE 868, approximately 587 years before the Gutenberg Bible was first printed.

Along with 40,000 other scrolls—all removed by Stein upon winning the confidence of the Taoist caretaker—the great explorer acquired 24 cases of manuscripts, the finest examples of Buddhist art spanning a period of 1,000 years, including 4 cases of paintings and relics. While Stein was knighted for his efforts, to this day he is vilified by the Chinese for what they claim to be the theft of artifacts. One can only wonder … if the equivalent of “grave robbers” or “cultural destructives” had been first, during the chaos of the constant wars and rebellions of the Manchu Qing Dynasty, whether these amazing works would still be intact or even exist today!

Berberine, the Conservator of Thought

Recent research into the methods of the conservation of the Diamond Sutra and other similarly-dyed documents has highlighted the crucial involvement of the alkaloid berberine and its chemistry in preserving this great work.1 What this investigation has found is that the Diamond Sutra, along with some many thousands of other documents from around the world, is dyed yellow with an extract believed to originate form the Amur cork tree, of which berberine is the principal colorant.

Berberine may be likened to
the herbs and oils used to preserve
the mummies of ancient Egypt,
except that it has helped preserve
the thoughts and wisdom of
ancient humans, rather than
merely their bodily residues.

Knowledge of berberine’s chemistry is vital for conservators working in the field of ancient documents, the survival of which is partly dependent on the dye’s protective powers against destruction by insects and its water-repellant properties. Berberine may be likened to the herbs and oils used to preserve the mummies of ancient Egypt, except that it has helped preserve the thoughts and wisdom of ancient humans, rather than merely their bodily residues.

Effective Against The Plague

Berberine is also the major constituent found in the rhizome (among other parts) of the Chinese herb Coptis chinensis, which has been widely used in China for prevention and treatment of infectious diseases, including the plague. This deadly disease is caused by the bacteria Yersinia pestis. The plague has altered the course of history, devastating the world many times, such as between 1347 and 1353 when it wiped out one third of the European population. Known as the Black Death, it is thought to have started in China or Central Asia, before reaching the Crimea, on the Black Sea in South Eastern Europe by 1346.

The plague also ravished China in the 14th century, where it also killed one third of the population, when China’s population was much larger than that of Europe. Berberine’s current use as a therapeutic agent of choice against plague versus conventional antibiotics is owing to its low cost and low toxicity. In a recent study, a total of 360 Y. pestis genes were differentially expressed in response to berberine, indicating its global effects, but not identifying its specific mechanisms.2 As recently as 1865, the Black Death broke out in China and spread to India where it killed as many as 10 million people. The use of berberine may have helped to spare China from the worst of this epidemic.

The Liabilities and Limitations of Hypoglycemic Agents

Aurel Stein, Mogao Cave Grotto, Dunhuang, 1907
For readers of this publication, it comes as no surprise that type 2 diabetes is a worldwide health threat. That is because its principle trigger is obesity, an epidemic in developing countries, and especially the United States. It is also no surprise that treatment of this disease most frequently involves the use of drugs. But these oral hypoglycemic agents are not without their liabilities or limitations, including subsequent failure after long term use. Consequently, any new oral medication or botanical nutrient that can extend the long-term control of blood glucose in patients with type 2 diabetes is welcome. Certain botanical products derived from plants that are generally regarded as safe (GRAS) gives them an initial leg up over new drugs, particularly if these are proven to possess potent antioxidation, antiinflammation, antiobesity, and antihyperglycemia properties.

Wang Yuanlu, Taoist priest whose confidence Sir Aurel Stein won.
Nonetheless, there is a drawback in controlling the quality of botanical supplements because most of these botanical products are mixtures of multiple compounds. So it is a relief to find that a single purified GRAS compound, namely berberine, has been found to possess a glucose-lowering effect in vitro and in vivo. Berberine is the main active component of an ancient Chinese herb Coptis chinensis, which has been used to treat diabetes for thousands of years. As well in China, berberine is sold freely to treat gastrointestinal infections as whole herb, extract, or in molecular form.3 The chemical structure of berberine and related isoquinoline alkaloids are substantially different from other commonly used hypoglycemic agents, such as the drugs biguanides, thiazolidinediones, sulphonylureas, or acarbose. So it follows that if berberine’s efficacy and safety can be confirmed, it can serve as a new class of antidiabetic medication.

Berberine Treats Diabetes

During the last few decades, in vitro and in vivo studies have shown berberine to be beneficial for hyperglycemia, dyslipidemia, and cardiovascular conditions. All of these are associated with obesity, insulin resistance, metabolic syndrome, and diabetes.

During the last few decades, in vitro
and in vivo studies have shown
berberine to be beneficial for
hyperglycemia, dyslipidemia, and
cardiovascular conditions.

Berberis aquifolium
So it is not astonishing that a recent paper has found berberine to be helpful for the treatment of type 2 diabetes.4 In this study—conducted at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China—116 subjects with type 2 diabetes were randomly assigned to take 1 g of berberine or placebo per day for a period of 3 months. In the berberine group, fasting glucose decreased by 20% and postload plasma by nearly 26%. At the same time, glycosylated hemoglobin (HbA1c) was reduced by 12%, along with reductions in triglycerides by 36%, reductions in total cholesterol by 18%, and reductions in LDL-cholesterol (the bad cholesterol) from by 21%. All of these differed significantly from the results of placebo. The authors proclaimed that berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia.

Berberine’s hypoglycemic effect was first reported in 1988 when it was used to treat diarrhea in diabetic patients in China.5 Over the years, berberine has grown in use among Chinese physicians as an antihyperglycemic agent. Indeed, there are many clinical reports about its hypoglycemic action in the Chinese literature. Although most of the previous studies were not well-controlled and experiments were not well-designed, there are now more high-standard studies on the road.

Berberine’s hypoglycemic effect was
first reported in 1988 when it was
used to treat diarrhea in diabetic
patients in China.

Down with Glucose and Bad Lipids

Another recent study was designed to establish the efficacy and safety of berberine in the treatment of type 2 diabetic patients.6 Conducted at Xinhua Hospital, Jiaotong University School of Medicine, Shanghai, 36 newly diagnosed adults with type 2 diabetic were randomly assigned to treatment with berberine or metformin (each at 500 mg, 3-times per day, at the beginning of each major meal) over the course of a 3-month trial. Metformin is a widely used oral antidiabetic drug in the biguanide class and a first-line drug prescribed by doctors for the treatment of type 2 diabetes, particularly in the overweight and obese and those with normal kidney function. Metformin is contraindicated in people with conditions known to increase the risk of lactic acidosis, including kidney disorders (those with high creatinine levels), lung disease, and liver disease.

The researchers were surprised that the glucose-lowering effects of berberine were found to be very similar to that of metformin. It was superior in several ways. There were significant decreases among the berberine group in the following: HbA1c down by 21%, fasting blood glucose down by 35%, postprandial blood glucose down by 44%, and plasma triglycerides down by 21%. Berberine’s effect of decreasing HbA1c was comparable to that of metformin. But it also decreased serum triglyceride and total cholesterol significantly. When compared with berberine, metformin had little effects on these lipid parameters.

It was surprising that the
glucose-lowering effects of berberine
were found to be very similar to
that of metformin, a first-line drug for
the treatment of type 2 diabetes.

In a second leg of the study, 48 adults with poorly controlled type 2 diabetes received the same amount of berberine (1.5 g/day; 500 mg 3-times per day) with equally impressive results. Berberine lowered fasting blood glucose and postprandial blood glucose from the first week until the end of the trial. HbA1c decreased by 10%. Fasting plasma insulin and HOMA-IR (a measure of insulin resistance) were reduced by 28% and 45%, respectively. And total cholesterol and LDL were decreased significantly too. Berberine’s lowering of HOMA-IR represents an increase in insulin sensitivity, an effect that could correspond to fat distribution because waist size and waist/hip ratio of the patients were decreased significantly, even in the absence of weight change. Because these measurements are related to the risk of heart disease, such changes are highly desirable.

There were significant decreases
among the berberine group in
the following: HbA1c down by 21%,
fasting blood glucose down by 35%,
postprandial blood glucose
down by 44%, and plasma
triglycerides down by 21%.

Of further interest, both fasting and postprandial C-peptides increased significantly in patients when berberine was used together with insulin, suggesting that long-term berberine treatment may improve insulin secretion of the patients. During the trial about one third of the subjects suffered transient gastrointestinal adverse effects from combination usage. These side effects included diarrhea (10.3%), constipation (6.9%), and flatulence (19.0%). Yet these side effects dissipated after the first four weeks in most subjects. Reducing the amount of berberine from 0.5 g, 3 times daily (1.5 g), to 0.3 g, 3 times daily (900 mg) in those who did not accommodate the original dose, lessened the gastrointestinal adverse events. None of the subjects suffered from severe gastrointestinal adverse events when berberine was used alone. Also, none of the berberine subjects had pronounced increase in liver enzymes creatinine, unlike the metformin subjects, in whom functional liver or kidney damages were observed in some subjects.

Heart Disease Risk Limits Access to a Diabetes Drug

Avandia, a billion dollar diabetes drug, was dealt a heavy blow this past September when the FDA declared that even after studies—including one done by the FDA—were revealed showing an increased level of heart risk, it would be allowed to stay on the market. But just barely.

Europe will ban its use altogether. However, so great were the restrictions imposed—patients and their doctors must attest that they have tried every other diabetes med and acknowledge that and they are aware of the drug’s substantial risks to the heart—that Avandia use is expected to plummet. One study estimated that in a ten year period ending in 2009, as many as 47,000 people taking Avandia needlessly suffered a heart attack, stroke, or heart failure, or died. Dr. Steven Nisson, the author of one of the critical studies, commented that the restrictions would limit 99% of its use.1

“I think that FDA’s credibility really depends on being able to explain its decisions well,” said Dr. Joshua Sharfstein, FDA’s principal deputy commissioner.2 “We can’t expect people to think that FDA has decided, therefore it’s the right answer.” That’s an interesting confession. Said FDA Director Margaret Hamburg, “As FDA commissioner, my job would be infinitely easier if we had consensus and full scientific clarity.”3 Is that similar to “significant scientific agreement,” the phase barrier which the FDA has used to prevent even mandated nutritional label claims?


  1. Mundy A. Cardiologist Steven Nissen’s reaction to fda decision on Avandia. Wall Street Journal, September, 23, 2010.
  2. Harris G. New F.D.A.: transparence and flexibility. New York Times, September 24, 2010.
  3. Harris G. F.D.A. to restrict Avandia, citing heart risk. New York Times, September 23, 2010.

Mechanisms of Action

The Xinhua Hospital results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. At the same time, according to another study, berberine upregulates the LDL receptor by a mechanism distinct from that of the statins, which involves stabilizing the LDL receptor mRNA.7 Although LDL lowering with statins reduces the mortality and morbidity associated with coronary artery disease, considerable mortality and morbidity remains. When hamsters were fed a high-fat and high-cholesterol diet for 2 weeks, the oral administration of berberine at 100 mg/kg for 10 days reduced total serum cholesterol and LDL by about 44%. Nevertheless, in subjects with hypercholesterolemia, berberine hydrochloride (0.5 g twice daily for 3 months) reduced LDL by 25%, but without any effect on HDL (high density lipoprotein; the good cholesterol). Berberine also caused a reduction in triglyceride levels by 35%.

It is also possible that berberine acts as an alpha-glucosidase inhibitor, thereby braking disaccharidase activities and decreasing glucose transportation cross the intestinal epithelium. This may contribute to the adverse gastrointestinal effects of berberine in some patients.

At the End of the Road

Just as the Silk Road once transported treasures across the ancient world, so berberine—one of its hidden values—can operate to improve and facilitate the transport of insulin along the blood roadways of our bodies. At the same time, berberine can operate as a potent oral hypoglycemic agent while reducing the negative effects of bad lipids. In the final summing up, berberine is safe and the cost of its use is very low. It may prove to be an important addition to treat type 2 diabetes, and also to help prevent it.


  1. Bell SE, Bourguignon ES, Dennis AC, Fields JA, McGarvey JJ, Seddon KR. Identification of dyes on ancient Chinese paper samples using the subtracted shifted Raman spectroscopy method. Anal Chem 2000 Jan 1;72(1):234-9.
  2. Zhang J, Zuo G, Bai Q, Wang Y, Yang R, Qiu J. Microarray expression profiling of Yersinia pestis in response to berberine. Planta Med 2009 Mar;75(4):396-8.
  3. Yin J, Zhang H, Ye J. Traditional chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets 2008 Jun;8(2):99-111.
  4. Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, Ren G, Ning G. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008 Jul;93(7):2559-65.
  5. Ni YX. Therapeutic effect of berberine on 60 patients with type II diabetes mellitus and experimental research. Zhong Xi Yi Jie He Za Zhi 1988;8:711-3.
  6. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008 May;57(5):712-7. 7.
  7. Doggrell SA.Berberine—a novel approach to cholesterol lowering. Expert Opin Investig Drugs 2005 May;14(5):683-5.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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