Issue:
100
Page: 32
Meta-Analysis of Chinese Clinical Trials Suggests Berberine Efficacy in Lowering Blood Lipids
by Heather S. Oliff, PhD
HerbalGram.
2013; American Botanical Council
Reviewed:
Dong H, Zhao Y, Zhao L, Lu F. The effects of berberine on blood lipids: a
systemic review and meta-analysis of randomized controlled trials. Planta Med.
2013;79(6):437-446.
Hyperlipidemia
is characterized by excess cholesterol and triglycerides (known collectively as
lipids) in the blood. Hyperlipidemia increases the risk of stroke and heart
attack. Berberine is an isoquinoline alkaloid isolated from several medicinal
plants* and is used in China to treat hyperlipidemia and type 2 diabetes. The
purpose of this meta-analysis was to evaluate the efficacy and long-term safety
of berberine in the regulation of blood lipids.
The
following electronic databases were searched from their establishment through
April 2012: Medline®, EmbaseTM,
the Cochrane Library, the China Hospital Knowledge Database (CHKD), the Wanfang
database, and various databases of ongoing trials. There were no language
restrictions, but the search was limited to clinical trials. The following
search terms were used: berberine, lipids, human, Huang Lian Su, Xiao
Bo Jian, Xue
Zhi, and Zhi Xue. Huang Lian Su and Xiao Bo Jian are
the names of a single chemical entity of berberine in Chinese. Xue Zhi and Zhi
Xue mean “blood lipids” in
Chinese. Reference lists from articles also were searched. Two independent
reviewers selected articles. The inclusion criteria were (1) trials whose
subjects consumed a berberine monopreparation alone or with other
pharmaceutical agents for ≥ four weeks; (2) randomized
controlled trials (RCTs) with either a parallel or crossover design; (3) trials
in which berberine was used as the active treatment intervention; and (4)
trials in which the data of berberine impact on blood lipid profiles — including
triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol
(LDL), and high-density lipoprotein cholesterol (HDL) — could
be obtained from the study publication. Studies using berberine-containing herbs
or extracts in lieu of berberine as a single chemical entity were excluded.
Study quality was assessed using the Jadad scale. The effects of berberine
intake on blood lipids were calculated as differences between the berberine
group and the non-berberine control group.
Eleven
studies, with a total of 874 patients, met the inclusion criteria and were
incorporated into the meta-analysis. They were published between 2004 and 2012,
and all studies originated in China (four written in English and seven in Chinese).
The primary diagnoses for patients in the studies were type 2 diabetes (four
studies), type 2 diabetes plus hyperlipidemia (one study), impaired glucose
tolerance plus hyperlipidemia (one study), hyperlipidemia (two studies),
hypercholesterolemia (two studies), and polycystic ovarian syndrome plus
insulin resistance (one study). One of two berberine formulations were used for
all of the studies — berberine chloride tablets (10
studies, manufacturer not reported) and berberine chloride liposome capsules
(one study, manufacturer not reported). The dose and duration typically ranged
from 0.9 g to 1.5 g for eight to 16 weeks, with one study using 0.6 g daily and
one study having a duration of 52 weeks. Nine studies were of poor quality
(Jadad score < three), and only two were of high quality.
The
pooled results for the 11 studies show that the berberine groups, compared with
the control groups, had statistically significant reductions of TC (P <
0.00001), TG (P < 0.00001), LDL (P < 0.00001), and HDL (P < 0.001). In
a subgroup analysis, berberine plus the pharmaceutical statin drug simvastatin — compared
with simvastatin alone (two pooled studies) — significantly
improved TC (P=0.02), TG (P 0.02), LDL (P=0.02), but had no effect on HDL. The
individual studies did not report whether the effect size was large enough to
reduce the risk for coronary heart disease (CHD). The pooled data showed a 25
mg/dL reduction in LDL that is statistically significant compared to control.
The authors argue that this level of reduction is clinically meaningful based
on ATPIII (Adult Treatment Panel III) guidelines (i.e., CHD relative risk is
reduced by 30% for every 30 mg/dL reduction in LDL). Pooled adverse effects in
patients taking berberine included mild diarrhea, abdominal distention, bitter
taste, and mild-to-moderate constipation; there was no significant difference
with controls for the incidence of adverse effects. Three studies reduced the
dose during the study due to gastrointestinal discomfort.
The
authors conclude that berberine may be effective in controlling blood lipid
levels. Repeated oral administration of 0.3 g berberine three times per day
decreased the liver enzymes cytochrome P450(CYP)2D6, CYP2C9, and CYP3A4 activities in healthy subjects, and the doses used in three of the included
studies were as great and in seven were higher; therefore, potential herb-drug
interactions should be considered. The safety of berberine needs additional
evaluation. An important limitation of this meta-analysis was that nearly all
of the included data came from studies of relatively poor quality (nine studies
out of 11), which limits the reliability of the conclusions of the
meta-analysis. Also, the authors note that these studies, performed exclusively
on subjects of Chinese ethnicity, might not be applicable to populations of
other ethnic origins.
—Heather S. Oliff,
PhD
*Berberine
is found in the following medicinal plants: the roots of barberry (Berberis spp.,
Berberidaceae), goldthread (Coptis spp., Ranunculaceae), and goldenseal
(Hydrastis canadensis,
Ranunculaceae).
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