The Incredible Health Effects of Berberine

Berberine has been found to work as an antibiotic, and anti-fungal/anti-candida agent, reduce LDL cholesterol and triglycerides, support the cardiovascular system, works as an anti-inflammatory, reduces fatty liver disease, reduces leaky gut syndrome, acts as an antidepressant, and has anti-cancer effects.  It also lowers blood sugar and reduces insulin resistance, in one study as effectively as metformin.

Because people with diabetes are at risk for candida, high cholesterol and triglycerides, heart disease, inflammation, fatty liver, intestinal problems, mood disorders and cancer, they may want to consider taking berberine to not only assist in lowering blood sugar, but in protecting their body from all the risks associated with diabetes.

(SpringTree Glucose Balance has 500 mg of berberine with each serving.)

Berberine is a strongly yellow colored compound found in plants such as Oregon grape, Barberry, Goldenseal and others.  It has been used for centuries for both its medicinal properties and as a natural dye.
 
Berberine is a nucleic acid-binding isoquinolone alkaloid with wide potential therapeutic properties.  Berberine prevents and suppresses proinflammatory cytokines, E-selectin, and genes, and increases adiponectin expression.

Antibiotic properties
Berberine has long been used as an antibiotic, such as in Goldenseal.  Studies have shown that it has effectiveness against Staphylococcus Aureus, and possibly against MRSA. 

Antifungal and antiyeast properties
Berberine has shown some activity against fungal infections, Candida albicans, yeast, parasites, and bacterial/viral infections. Berberine seems to exert synergistic effects with fluconazole (an anti-fungal medication) even in drug-resistant C. albicans infections. 


Support of the cardiovascular system
During the last few decades, many studies have shown berberine has various beneficial effects on the cardiovascular system.  Berberine lowers elevated blood total cholesterol, LDL cholesterol, triglycerides and atherogenic apolipoproteins (Apo B).  It seems to improve arterial endothelial function.  Clinical and experimental studies show that berberine may be useful in congestive heart failure.

Anti-inflammatory properties
 Berberine has significant anti-inflammatory activities.  It restores cellular redox by inhibiting gp91phos expression and enhancing SOD, the body's super anti-oxidant.  It suppresses pro-inflammatory cytokines and reduces pro-inflammatory gene expression.

Profoundly positive effects in diabetes
Exciting new research is showing that berberine has been shown to lower elevated blood glucose as effectively as metformin.  Using 500 mg. three times per day, there were significant decreases in hemoglobin A1C, fasting blood glucose, after meal (postprandial) blood glucose, and triglyceride levels.  The mechanisms of action include inhibition of aldose reductase, inducing glycolysis, preventing insulin resistance through increasing insulin receptor expression and acting like incretins.  A new study suggested berberine may overcome insulin resistance via modulating key molecules in insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells.

Fatty liver disease
Berberine reduces hepatic fat content in the rats of nonalcoholic fatty liver disease. Berberine also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury.

Cancer
Berberine has drawn extensive attention towards its antineoplastic effects. It seems to suppress the growth of a wide variety of tumor cells, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma. Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, clastogenesis, tumor promotion, tumor invasion, prostate cancer, neuroblastoma, and leukemia.

Brain and Mental Health
Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders.  As berberine is a natural compound that has been safely administered to humans, preliminary results have been found in clinical trials in patients with depression, bipolar affective disorder, schizophrenia, or related diseases in which cognitive capabilities are affected, with either the extract or pure berberine.   It increases noradrenaline and serotonin levels in the brain (rats) while inhibiting dopaminergic activity.  It may increase the number of serotonin transporters available in the brain, enhacing the reuptake of serotonin.  The half-life of berberine in vivo seems to be three to four hours, thus suggesting administration three times a day if steady levels are to be achieved.

New experimental results suggest berberine may have a potential for inhibition and prevention of Alzheimers Disease(AD), mainly through both cholinesterase (ChEs) inhibitory and β-amyloids pathways, and additionally through antioxidant capacities.

Intestinal Disorders
As an antibiotic and antifungal berberine reduces intestinal dysbiosis (abnormal gut bacteria and yeast).  Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage (which causes "leaky gut syndrome") in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states.

Consider Berberine as one of your regular supplements, especially if you have pre-diabetes or diabetes.

Until we meet again,
Dr. Judi

Are Statins Beneficial in Preventing Heart Disease?

If you are taking a statin drug to prevent heart disease even though your cholesterol levels may be normal, think again.

The following is quoted from Family Practice News, Volume 40, Issue 12, Pages 10-11 (July 2010):

Studies Dispute Statins Benefits for Prevention

The only large clinical trial to find that statins reduce mortality in patients taking them for primary prevention—a group that comprises 75% of statin users—was so seriously flawed that its conclusions were termed “clinically inconsistent” and invalid by one group of researchers and “extreme and exaggerated” by another, according to separate reports.

In the first critique of the 2008 JUPITER (Justification for the Use of Statins in Primary Prevention) trial, Dr. Michel de Lorgeril of Université Joseph Fourier and Centre National de la Recherche Scientifique, Grenoble, France, and his associates, analyzed the methods and findings of this only major study to claim that rosuvastatin produced a striking decrease in mortality in low-risk patients who have no evidence of coronary heart disease. These findings, which immediately provoked controversy, “have undoubtedly propelled many healthy persons without elevated cholesterol levels onto long-term statin treatment,” Dr. de Lorgeril and his colleagues said.

First among its major flaws, JUPITER was terminated early and apparently without proper justification according to the study's own protocol prespecifications. Early termination, a practice confined largely to industry-sponsored trials, tends to introduce biases that exaggerate the benefit and minimize the long-term harm of the treatment being assessed, according to the researchers. In this case, it also meant that the study was stopped just as mortality curves between the statin group and the control group had begun to converge, “suggesting that the borderline significant difference between groups may have disappeared” if follow-up had not been prematurely terminated, they wrote.

The main justification for terminating JUPITER was explained as an “unequivocal reduction in cardiovascular mortality” with statin therapy. Yet the JUPITER investigators did not include data on cardiovascular mortality in their published report. Readers would have to infer this result by extrapolating from data on a table. When examined closely, however, that data showed identical cardiovascular mortality between the treatment groups.

“Such a lack of effect on cardiovascular mortality [together] with a strong effect on nonfatal complications strongly suggests a bias in the data set and should have led to the continuation of the trial rather than to its premature ending,” Dr. de Lorgeril and his colleagues asserted.

Second, the ratio of fatal to nonfatal MI was so low as to be “incredible.” In particular, the case-fatality rate in the placebo group was only 8% when it would be expected to be about 50%, “a clinical inconsistency that suggests a major flaw in the study.” Moreover, the case-fatality rate with rosuvastatin was 29%, which implies that the “beneficial” drug actually tripled the case-fatality rate, they noted.

Third, JUPITER failed to explain why a strikingly high number of deaths—19 of 31 deaths in the rosuvastatin group and 25 of 37 deaths in the placebo group—were attributed to cardiovascular causes other than MI or stroke. Proponents of the JUPITER study argued after its publication that this referred to causes “such as aneurysm rupture.”

“Would this mean that in the same period of time there were 6 fatal infarctions and 25 fatal aneurysm ruptures in the placebo group? This is highly unlikely,” Dr. de Lorgeril and his associates said.

JUPITER also failed to report data on sudden cardiac deaths, which is surprising given that this is “the simplest and most reliable diagnosis in cardiology” and that it usually comprises 65%-70% of total cardiac mortality. “The way sudden cardiac death is reported—or not reported—may be a good indicator of the quality of the methods used in a trial,” they noted.

Equally important to these methodological flaws, the JUPITER trial involved several conflicts of interest.

“It was conducted by a sponsor with obvious commercial interests. Nine of 14 authors of the JUPITER article have financial ties to the sponsor. The principal investigator has a personal conflict of interest as a co-holder of the patent for the C-reactive protein test” that figured prominently in the rationale for statin therapy.

In addition, the monitoring board that made the decision to halt the trial early was chaired by an investigator who “has been and still is involved in many other industry-sponsored lipid-lowering trials,” Dr. de Lorgeril and colleagues said (Arch. Intern. Med. 2010;170:1,032-6).

“In conclusion, the results of the JUPITER trial are clinically inconsistent and therefore should not change medical practice or clinical guidelines.” Given that all 12 of the other large cholesterol-lowering trials conducted so far have failed to show any benefit from statins as primary prevention, it appears that “the presumed preventive effects of cholesterol-lowering drugs have been considerably exaggerated,” they said.

In the second study, Dr. Kausik K. Ray of the University of Cambridge (England) and his associates performed a meta-analysis of 11 randomized controlled trials that assessed the effects on all-cause mortality of statins versus a placebo or control therapies on all-cause mortality. They restricted their analysis to data on high-risk patients with no known cardiovascular disease and included previously unpublished data, “to provide the most robust information to date” on statins as primary prevention in this patient group.

The meta-analysis involved 65,229 men and women in predominantly Western populations, with approximately 244,000 person-years of follow-up. There were 2,793 deaths during an average of 4 years of follow-up.

All-cause mortality was not significantly different between patients taking statins and those taking placebo or control therapies. This suggests that “the all-cause mortality reduction of 20% reported in JUPITER is likely to be an extreme and exaggerated finding, as often occurs when trials are stopped early,” Dr. Ray and his colleagues said (Arch. Intern. Med. 2010;170;1024-31).

This meta-analysis shows that statin therapy as primary prevention in high-risk patients is less beneficial than is generally perceived, and it can be inferred to be even less helpful in low-risk patients.

One of Dr. de Lorgeril's associates served as an expert in litigation involving the pharmaceutical industry (not involving rosuvastatin). Dr. Ray and an associate reported financial ties to the majority of companies that market lipid-lowering agents; other associates reported ties to Pfizer Inc., Astra Zeneca, Bristol-Myers Squibb, and Merck & Co.

My Take
Both Critiques Are On-Target
These two critiques offer valuable insights and likely will reignite the long-simmering controversy over the use of statins as primary prevention of cardiovascular events.

Dr. de Lorgeril's critical analysis highlights several anomalies in the JUPITER trial data. In particular, early termination of the study allowed for inflated estimates of benefits, understated harms, allowed the findings to be published earlier (and hence used to advantage in marketing), and reduced the cost of the trial—which all significantly benefited the industry sponsor and a financially invested research team.

Tens of billions of dollars of revenue for the sponsor over the patent life of the drug were at stake in the JUPITER trial, as well as potentially millions of dollars in royalties for the principal investigator. And with three-quarters of statin users taking the drugs for primary prevention, enormous revenues are at stake.

The analysis by de Lorgeril et al. clearly demonstrates why research must be free of incentives to find a particular desired result.

Dr. Ray's report presents what is to date the cleanest and most comprehensive meta-analysis of pharmacological lipid lowering for prevention.

The results make it clear that for primary prevention in the short term, statins' benefits are very small. And in the long term, although sincere advocates on both sides will try to convince us otherwise, we really must admit that we do not know.

LEE A. GREEN, M.D., is in the department of family medicine at the University of Michigan Medical School, Ann Arbor. He reported no financial conflicts of interest. His comments appeared in an editorial (Arch. Intern. Med. 2010:170;1007-8).

From Archives of Internal Medicine

PII: S0300-7073(10)70742-8
doi:10.1016/S0300-7073(10)70742-8

Dr. Judi here: Statin medications have a lot of side effects which have an insidious onset and are hard to tell that the statin is causing them, including muscle pain and memory loss.

Other studies have shown that the best benefit from statins comes from those with high cholesterol and high cardiac c-reactive protein between the ages of 40-60. It is interesting to note that the elderly do not receive benefit from lowering their cholesterol. In fact, those with the lowest cholesterol have higher death rates than those with higher cholesterol. So when your doctor tells you that the statin drugs are the new wonder drug, look at benefits vs. the risks, do some research, and determine what is best for you.

Until we meet again,
Dr. Judi