Caffeine & Cholorogenic Acid - Anti-Obesity Agents from Your Coffee Mug? Human Study Reveals Cortisol Lowering Effects, Mouse Study Confirms Anti-Obesity Effects

Ever since the Vinson study showed that green coffee bean extracts can help overweight women lose weight, green coffee is sexier than roasted one.

Only weeks after Vinson et al. were able to show that "Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 Weeks" (read more), green coffee bean supplements began to swamp the market - a great financial success for the supplement producers, and that despite the fact that follow-up studies that would confirm the amazing effects Vinson et al. report are still lacking. Two recent studies, one from the Queen Margaret University in the UK (Revuelta-Iniesta. 2014), the other from the  Jiangxi Agricultural University in the People's Republic of China (Zheng. 2014) could now shed a little more light on the weight loss effects of green coffee beans and the combination of caffeine and cholorgenic acid (CGA), the allegedly most important active ingredient in unroasted, green coffee beans.
In their 24-week rodent study, Zhang et al. (2014) tried to elucidate the mechanism by which CGA and caffeine regulate lipid metabolism. To this ends, they randomized their forty hairy subjects to diets containing no CGA or caffeine, CGA, caffeine, or CGA + caffeine.

Figure 1: Rel. (vs. control) body weight changes and liver and intraperitoneal adipose tissue weight (Zhang. 2014)

Over the course of the 24-weeks study, the scientists recorded body weight, intraperitoneal adipose tissue (IPAT) weight, and serum biochemical parameters of the rodents, tracked the the activities and mRNA and protein expression of lipid metabolism-related enzymes and analyzed the effects of caffeine, CGA and the combination of the two. What they found was...

1. Figure 2: Effects of chlorogenic acid (CGA) and caffeine on the hepatic protein expression levels of AMP-activated protein kinase (AMPK), adipose TAG lipase (ATGL) and fatty acid synthase (FAS; Zhang. 2014)

   decreases in the body weight and IPAT weight of mice fed the CGA + caffeine diet,
2. significant decreases in the serum and hepatic concentrations of total cholesterol, TAG and leptin of mice fed the CGA + caffeine diet,
3. increases of the activity of carnitine acyltransferase (CAT) and acyl-CoA oxidase (ACO), 
4. decreased levels of fatty acid synthase (FAS) and the respective mRNA levels
5. significantly upregulated mRNA expression levels of AMP-activated protein kinase (AMPK), CAT and ACO
6. pronounced reductions of PPARg2

If we group these findings as follows 3 + 5 and 4+6, we could say that they triggered 1 + 2 by (a) increasing the oxidation of fatty acids (3+5) and (b) decreasing the synthesis and storage of fatty acids (4+6) - an observation that could certainly explain the benefits Vinson et al. observed in their human study.On the other hand, the amount of CGA and caffeine in the rodent diets (0.2 % CGA + 0.03 % caffeine) was quite significant and previous rodent studies on other allegedly promising fat burners were not replicable in human beings either (example: CLA). Against that background it's good to have study #2 by R. Revuelta-Iniesta and E. A. S. Al-Dujaili, who investigated the effects of green coffee (GC), rich in chlorogenic acid, and black coffee (BC) on cardiovascular markers.

New human data with surprising results

The researchers designed a randomised pilot crossover study with healthy subjects who consumed both coffees for 2 weeks.

• The green coffee (GC) used in this project was Ethiopian Harrar 4 (100% Arabica) and the black coffee (BC) was Sainsbury’s Original Blend Cafetitère Coffee.
• The BC was  a blend of Brazilian, Colombian, Mexican, Nicaraguan, Peruvian, and Rwandan beans.

The study participants were asked to have 40 g of GC and BC per day distributed throughout the day into four cups of coffee. Thus, the scientists tried to ensure that high plasma coffee antioxidant concentrations were maintained over a period of time, "allowing effects to take place and the body to develop tolerance to caffeine, which can take 2-3 days." (Revuelta-Iniesta. 2014).

Table 1: Concentration of total polyphenols and antioxidant capacity determined in GC and BC as compared by the three methods of  coffee preparation (Revuelta-Iniesta. 2014).

The GC beans were grounded to powder using an electric coffee grinder. Instructions on how to make the coffee were provided and the Italian cafetière, the French cafetière, or the filter coffee machine was used to prepare the coffee drink.

The researchers measured anthropometry, blood pressure, and arterial elasticity after each intervention and collected urine samples to monitor antioxidant capacity. The free cortisol and cortisone levels you see in Table 2 were obtained from urine and analysed by specific ELISA methods.

Table 2: Comparison of results obtained (mean±SEM) after 14 days of green coffee vs. black coffee intervention (2-week cross over study); F: cortisol; E: cortisone; orange = almost bordeline significant; green = statist. significant inter-group difference (Revuelta-Iniesta. 2014).

In view of the short duration of the study (remember 2 weeks on each coffee), it's not really surprising that we didn't see changes in any of the anthropometric measures. On the other hand, the mere fact that the cortisol/cortisone ratio (indicating 11beta-HSD1 activity) was reduced after GC (from 3.5 +/- 1.9 to 1.7 +/- 1.04, P = 0.002) does not suggest that you will see beneficial effects on body composition in the absence of significant reductions in energy intake. A reduction in glucocorticoid activity can in fact hamper not accelerate weight loss (learn more) and the researchers hypothesis that "GC can play a role in reducing cardiovascular risk factors" (Revuelta-Iniesta. 2014) is a possible, but unconfirmed hypothesis.
References:

• Jaquet, Muriel, et al. "Impact of coffee consumption on the gut microbiota: a human volunteer study." International journal of food microbiology 130.2 (2009): 117-121.
• Revuelta-Iniesta, R., and E. A. S. Al-Dujaili. "Consumption of Green Coffee Reduces Blood Pressure and Body Composition by Influencing 11β-HSD1 Enzyme Activity in Healthy Individuals: A Pilot Crossover Study Using Green and Black Coffee." BioMed Research International 2014 (2014).
• Vinson, Joe A., Bryan R. Burnham, and Mysore V. Nagendran. "Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects." Diabetes, metabolic syndrome and obesity: targets and therapy 5 (2012): 21.
• Zheng, et al. "Chlorogenic acid and caffeine in combination inhibit fat accumulation by regulating hepatic lipid metabolism-related enzymes in mice." British Journal of Nutrition (2014). Ahead of Print.