By Melissa Quick, DO, and David Kiefer, MD, Editor
Dr Quick is a third-year resident in New York at the Beth Israel Residency in Urban Family Medicine.
Dr. Quick reports no financial relationships relevant to this field of study.
Financial Disclosure: Integrative Medicine Alert’s executive editor David Kiefer, MD, peer reviewer J. Adam Rindfleisch, MD, MPhil, AHC Media executive editor Leslie Coplin, and managing editor Neill Kimball report no financial relationships relevant to this field of study.
Worldwide, obesity has nearly doubled in the past 30 years. In 2008, more than 1.4 billion adults were overweight (body mass index [BMI] 25-29.9 kg/m2 ), and of these, 200 million men and 300 million women were obese (BMI > 30 kg/m2 ).1 In the United States, more than one-third of the population was considered obese in 2010.2 A multitude of factors contribute to this epidemic including genetics, inactivity, education, financial limitations, and the globalization of the food industry creating more prepackaged, low-priced, high-energy foods.3
In conjunction with the increasing belt size of the world comes serious health risks that are directly proportional to weight gain. We know that the risk for all-cause mortality increases across the spectrum from overweight to obese.4 Excess weight can also lead to metabolic syndrome — a combination of central obesity, impaired glucose tolerance, hypertension, and dyslipidemia5 — which can lead to an increased risk of developing type 2 diabetes and cardiovascular disease.6 The predominant underlying risk factor for metabolic syndrome is obesity.7 Obesity has also independently been linked to the development of type 2 diabetes, stroke, and some types of cancer (endometrial, breast, and colon).8 As a modifiable risk factor, reducing one’s weight can significantly improve all aspects of metabolic syndrome.9
Research suggests that small reductions in visceral adipose tissue can improve cholesterol, blood pressure, and insulin sensitivity.10 As such, one approach to battling the bulge is to combine weight-loss dietary strategies and exercise with bioactive compounds that may change fat distribution. Enter the increasingly popular "slimming" strategy of dietary supplements, a topic that has been covered in past issues of Integrative Medicine Alert.11-13
Green Coffee Bean Extract
Green coffee bean extract (GCBE) is one dietary supplement that is gaining popularity, specifically for its potential weight-reduction capabilities. Recent endorsement from media star Dr. Oz has helped propel this supplement into the public eye. Dr. Oz recently referred to GCBE as "the green coffee bean that burns fat fast" and has claimed that no exercise or diet is necessary to lose weight.14 Media aside, the question remains: Is GCBE an effective and safe weight loss supplement?
Green (or raw) coffee beans are coffee beans that have not been roasted. Traditionally, GCBE is removed from a green coffee bean, commonly Coffea canephora robusta, using alcohol as a solvent.15 Two major active components in coffee beans are caffeine and chlorogenic acid (CGA). Both have been scrutinized in the media and the scientific community for their potential weight loss capabilities. Although this article primarily will focus on the effects of CGA, as this is the primary component in most formulations of GCBE, it is worth briefly mentioning caffeine’s role in weight loss, as some GCBE formulations contain small amounts of caffeine as well.
Caffeine (1,3,7-trimethylxanthine) is a well-known stimulant that has been linked to weight loss and the reduction of risk of the metabolic syndrome.16 One of the proposed mechanisms of caffeine’s effect on weight loss includes increasing thermogenesis, which consequently enhances lipolysis and lipid metabolism.16 Caffeine has been shown to increase energy expenditure in humans, thereby assisting with weight loss.
The main constituent of GCBE that is responsible for its pharmacological effects is the CGA found in green coffee beans. Other natural sources of CGA include plums,17 apples, and berries.18 CGA — actually a group of acids that are biologically active phenols, the most common of which is called 5-caffeoylquinic acid19 — is found in higher quantities in green coffee beans compared to roasted coffee beans, secondary to the inherent thermal instability of CGA.20 With regard to weight loss, CGA has been shown to modulate glucose metabolism, inhibit fat accumulation, reduce weight in animal models and in humans, and to possibly alter adipokine levels and body fat distribution.21 Other proposed effects include the reduction of postprandial glucose concentrations and reduction of intestinal glucose absorption.22 Additionally, CGA has been reported to selectively inhibit hepatic glucose-6-phosphatase, a rate-limiting step in gluconeogenesis.23
In Vitro and Animal Trials
Several in vitro and animal trials have been performed over the past decade investigating the relationship between GCBE and metabolism. There is evidence that diets high in polyphenols, including CGA, may help to prevent diseases associated with oxidative stress, such as coronary heart disease and some forms of cancer.22 In vitro, CGA exhibits antioxidant properties by scavenging free radicals.24
In 2006, a study showed that a form of GCBE containing CGA combined with caffeine fed to mice for 14 days had an inhibitory effect on fat accumulation and weight gain. Interestingly, however, pure caffeine and CGA independently did not significantly suppress weight gain or visceral fat accumulation in this study. They found that caffeine likely suppresses fat absorption while CGA enhances fat metabolism in the liver and found that the two components functioned synergistically.21
Another animal study performed in 2010 explored the efficacy of CGA vs caffeic acid (another type of phenol and unrelated to caffeine) on induced-obese mice fed a high-fat diet. Both CGA and caffeic acid lowered body weight, visceral fat mass, triglycerides, and cholesterol levels compared to the control group (P < 0.05). In addition, the results suggest that CGA was more effective at body weight reduction and lipid metabolism regulation than caffeic acid (P < 0.05).25
Echoing the previous studies demonstrat-
ing positive effects of CGA, a 2012 study found that coffee extract given to rats with metabolic syndrome improved impairment in glucose tolerance, hypertension, cardiovascular remodeling, and nonalcoholic fatty liver disease without changing abdominal obesity and dyslipidemia.26
At odds with other animal trials is a study published earlier this year that depicts conflicting evidence regarding the benefits of CGA supplementation. This study involved diet-induced obese male mice divided into three dietary groups: normal diet, high-fat diet, and high-fat diet + CGA. The group supplemented with CGA had a higher hepatic lipid content and more hepatic steatosis compared to the high-fat group not given supplementation.27 This suggests CGA is not protective against metabolic syndrome, although no mention was made explicitly pertaining to weight changes associated with the supplement.
Several human clinical trials demonstrate GCBE might offer a modest weight reduction benefit. A three-way, randomized, single-blind, crossover study published in 2003 examined whether the consumption of dietary amounts of CGA in coffee had any effect on plasma concentrations of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) in humans. Nine healthy fasting volunteers consumed 25 g of glucose dissolved in either caffeinated or decaffeinated coffee. The results showed that GIP secretion decreased after both caffeinated and non-caffeinated coffee consumption, but not after consumption of the control beverage (P < 0.005). Additionally, postprandial GLP-1 secretion increased 0-120 minutes (P < 0.01) after decaffeinated coffee consumption compared with the control. These findings confirm the potent biological action of caffeine and suggest that CGA might have an antagonistic effect on glucose transport.19
In 2010, a small, three-way, double-blind, randomized, crossover study was performed with two main objectives: to investigate the effect of coffee supplemented with CGA compared with normal coffee and to evaluate regular supplementation of CGA in overweight and obese subjects.15 CGA was present as 200 mg per 2200 mg of Coffee Slender® , obtained from the beans of Coffea canephora robusta Pierre (Svetol® ; Berkem SA, Gardonne, France).
The first objective was performed with 12 healthy volunteers (BMI < 25 kg/m2 ) who drank either glucose solution (the control), the CGA supplemented coffee (Coffee Slender), Nescafé instant coffee (caffeinated), or Nescafé decaffeinated coffee. Mean glucose plasma concentrations were taken in various minute intervals after the ingestion of the liquid (T = 0, 15, 30, 45, 60, 120). The CGA supplemented coffee group demonstrated a significant reduction in mean plasma glucose concentrations compared to the control group (mean plasma glucose area under the curve [AUC]: glucose control 778 ± 10.2; Coffee Slender 724 ± 8.2, P < 0.05).
The second aspect of this study involved 30 volunteers (BMI 27.5-32 kg/m2 ) divided into two groups: 15 received the CGA supplemented coffee and 15 received normal instant coffee. Each group drank 5 cups of black coffee a day (11 g/day of coffee) for 12 weeks. Weight was monitored (in kg) at the start, week 4, and week 12. There were statistically significant weight reductions for Coffee Slender® vs normal instant coffee drinkers (5.4 ± 0.6 and 1.7 ± 0.9 kg, respectively, P < 0.05). (See Table 1.)
|Table 1: Thom Study Displaying Mean ± SD Body Weight (in kg) for Overweight Volunteers Taking Coffee + CGA vs Coffee over 12 Weeks|
|Group||Start||Week 4||Week 12||Difference( Start–Week 12)||P value|
|Coffee + CGA(Coffee Slender)||85.2 ± 4.5||83.6 ± 4.1||79.8 ± 3.9||5.4 ± 0.6||< 0.05|
|Coffee(Instant Nescafé)||84.3 ± 4.3||83.7 ± 4.1||82.6 ± 4.2||1.7 ± 0.9||Not significant|
The first systematic review and meta-analysis on this subject was performed in 2011, examining only randomized, double-blind, placebo-controlled studies investigating the use of GCBE and the effects on weight loss.22 Out of five eligible trials, three were included in the analysis. The meta-analysis reveals a statistically significant difference in body weight between GCBE and placebo (mean differences [MD], -2.47 kg; 95% confidence interval [CI], -4.23 to -0.72) over one 4-week period and two 12-week periods. Although the three studies in the meta-analysis (including the 2010 study reviewed above) revealed a significant difference in change in body weight between GCBE and placebo, the authors of this study caution that this significance is moderate.
The authors also acknowledge that there is a large amount of heterogeneity between the three studies. These studies varied in what information was clearly reported: Specifically, all three of the studies fail to mention technique of randomization; whether allocation was concealed; and if blinding was utilized for the outcome assessor, care provider, or patient. Additionally, the studies differ in number of subjects analyzed and length of time of the study.
The most recent clinical trial on GCBE took place in 2012 and was a randomized, double-blind, placebo-controlled, linear dose, crossover, 22-week study that evaluated the efficacy and safety of GCBE in 16 overweight adults.28 Subjects were randomly assigned a low-dose green coffee extract sequence taken for 6 weeks twice daily, a high-dose green coffee extract sequence taken three times daily, and a placebo sequence taken three times daily.
The results of the 2012 study are much more dramatic for weight loss and BMI than prior clinical studies. For weight, the 2.04 ± 2.20 kg decrease in the high-dose arm was significant (P = 0.003), as was the 1.54 ± 1.74 kg decrease in the low-dose arm (P = 0.005), but the -0.34 ± 1.41 kg change in the placebo arm was not significant (P = 0.355). For BMI, the 0.74 ± 0.80 kg/m2 decrease in the high-dose arm was significant (P = 0.003), as was the 0.58 ± 0.66 kg/m2 decrease in the low-dose arm (P = 0.004), but the -0.12 ± 0.51 kg/m2 change in the placebo arm was not significant (P = 0.384). The authors point out there was no significant change to the participants' diet over the course of the study. (See Table 2.)
|Characteristic||High-dose GCBE||Low-dose GCBE||Placebo|
|Start M ± SD(95% CI)||End M ± SD(95% CI)||P||Start M ± SD(95% CI)||End M ± SD(95% CI)||P||Start M ± SD(95% CI)||End M ± SD(95% CI)||P|
|Weight (kg)||72.86± 8.91||70.82± 8.4||0.002||71.25± 7.3||69.71± 7.3||0.003||72.15± 8.64||72.47± 8.47||0.353|
|BMI (kg/m2 )||26.78± 1.55||26.03±1.63||0.002||26.25± 1.37||25.66± 1.2||0.003||26.55± 1.96||26.67± 1.72||0.384|
|Percent Body Fat||25.94± 5.35||24.75± 5.2||0.001||25.94± 4.99||24.88± 4.99||0.002||25.88± 5.4||25± 5.52||0.014|
According to the Natural Medicines Comprehensive Database, at the time of print, there are 187 products containing GCBE on the market in the United States. GCBE is generally in the form of a pill or as a CGA-enriched green coffee product.
Green coffee beans contain 5-12 g of CGA per 100 g of beans.20 Most formulations of GCBE for weight loss contain 80-200 mg of GCBE daily (generally dosed twice daily and contain approximately 50% CGA). The most recent 2012 clinical study, mentioned above, utilized 700 mg and 1050 mg of GCBE mg in the proprietary form (GCATM) and no adverse effects were reported. In comparison, a regular coffee drinker would ingest approximately 0.5-1 g of CGA daily, presumably less than in GCBE secondary to the thermal degradation of CGA mentioned previously.19,29
In clinical trials, oral consumption of green coffee appears well tolerated. However, it is important to recall that though the studies do not report any adverse events during the research period; this does not correlate with the assumption that GCE intake is a "risk-free" supplement.
The risk of drug interactions when using GCBE are largely theoretical in nature and earn a "D" level of evidence rating, based only on the presumptive pharmacological interactions between molecular compounds, rather than clinical trials or even expert opinion. Many well-known pharmaceutical groups have a "moderate" interaction rating in the Natural Medicines Database, which indicates a patient should "be cautious when combining GCBE with many common medications" such as anticoagulant/antiplatelet drugs, monoamine oxidase inhibitors, lithium, antihypertensive medications, antihyperglycemic medications, and many more.30
In general, caffeine has no significant health risks to consumers, and moderate (< 400 mg/d) caffeine consumption is safe.31 However, high intake of caffeine has been shown to cause headaches, diuresis, gastric distress, nervousness, vomiting, insomnia, anxiety, agitation, ringing in the ears, and arrhythmias.32
Limitations and Cost
There are several limitations to the human studies mentioned above. All of the randomized, controlled studies found on this topic have very small sample sizes. Additionally, the statistical significance determined in the meta-analysis is actually equivocal, because the confidence interval crosses one, thereby negating the significance of these studies as one entity. Also, there is no mention of the mechanism of blinding in these studies, therefore raising the concern of bias affecting the results.
We must recall that "dietary supplements" are a relatively new category and are regulated by the FDA as a "food" rather than a drug. Under the Dietary Supplement Health and Education Act, a manufacturer of a supplement takes responsibility for determining that the dietary supplements it manufactures or distributes is safe; thus, the FDA does not need to approve a supplement before it is placed on the market. Interestingly, it is illegal for a manufacturer to market a dietary supplement product as a treatment or cure for a disease, so one will never see a label for GCBE to cure overweight or obesity.33
Since the dietary supplement industry is not regulated in the same way as the pharmaceutical industry, products often contain multiple constituents that are not clearly advertised. An unknowing consumer could easily purchase a form of GCBE unaware that caffeine or other herbal components are present.
Furthermore, only two formulations of GCBE on the market (GCATM and Svetol® ) were used in all known published clinical trials.30 Thus, it is recommended to only use GCBE that contain these formulations, as human studies have not been performed with other formulations and safety cannot be determined.
There are additional studied benefits from CGA worth mentioning, specifically the purported effects CGA has on lowering blood pressure. Regular coffee consumption has been linked to increased blood pressure, likely secondary to the effects of caffeine. However, research with CGA has shown spontaneously hypertensive rats given GCBE to have a reduction blood pressure after a single dose.34 A human study performed in 2005 suggested that daily use of CGA has a blood pressure-lowering effect in patients with mild hypertension, particularly with higher doses of GCBE leading to greater systolic blood pressure reductions.35
A final consideration is the price of this supplement. A recent Amazon.com search finds multiple brands of GCBE costing between $12 (60 capsules) and $30 (90 capsules).
Certainly the potential benefit of a dietary supplement to reduce weight and thereby reduce the health risks associated with overweight and obesity is tremendous. CGA, the main active pharmacological ingredient in most formulations of GCBE, has been shown to modulate glucose metabolism, inhibit fat accumulation, reduce weight in animal models and in humans, and to possibly alter adipokine levels and body fat distribution. The trend of the reviewed animal studies demonstrates that CGA tends to be most effective lowering body weight, decreasing fat accumulation when working synergistically with either caffeine or caffeic acid. Initial evidence from small, randomized, clinical trials indicates that GCBE promotes weight loss compared to control groups in trial times ranging from 4 to 22 weeks. Additionally, it appears that overall, GCBE is a relatively safe supplement with no adverse effects reported in past clinical studies.
Should we recommend GCBE to our overweight and obese patients? Traditional weight loss methods (dieting, self-monitoring, stimulus control, nutritional counseling, physical activity, etc.) can be related to patient motivation and even then, may
not be entirely effective. Is GCBE an "easy way" to lose weight? That is unlikely, and, in the current
state of the medical literature about GCBE, it is difficult to say for sure.
One must always weigh, no pun intended, the risks and benefits of any intervention. For example, bariatric surgery is often considered in adults (BMI ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with significant obesity-related comorbidities) who have not achieved weight loss with dietary or other interventions.36 Though preliminary research shows much promise with this intervention, one must recall the great risks inherent to a surgical procedure, including the risk of death. Comparatively, the risks associated with a dietary supplement such as GCBE are likely significantly lower than an invasive surgery.
As health care providers, it is our role to educate our patients about the health risks of overweight and obesity. We must be their advocate and encourage safe and effective mechanisms to reduce weight. It is important to emphasize to patients that even modest weight reduction (5-10%) can have significant health benefits.36
Thus, in summary, based on the current evidence surrounding GCBE and weight loss, it seems that overall this is a safe and possibly effective supplement. While an effective dosage for GCBE for use as a weight loss supplement is not established, study doses with no reported adverse effects range from 200 mg twice daily to 700 mg once daily. Exceeding this amount has unknown effects at this time. Ultimately, it is prudent to proceed cautiously when discussing GCBE as a weight loss option with patients, and to not detract from other efforts to implement a healthy diet and lifestyle. Further research with increased sample sizes and longer study durations is paramount to advancing our knowledge about the efficacy and safety of this dietary supplement.