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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 Peoples 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 which has been retracted in October 2014, though. 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 its 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), its not really surprising that we didnt 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 11?-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.

Even Arnold benefited from ?-hydroxy-isocaproic acid aka HICA - the HICA his body produced and the HICA he got from his diet, whenever he ate cheese and other fermented foods.

You know that I am not the kind of person who likes to tell others what to do. After reading my summary of the contemporary research on ?-hydroxy-isocaproic acid aka HICA, you should yet be able to decide whether its worth a try or not.

If you take a look at the pertinent databases you will realize that there are more patents than papers on ?-hydroxy-isocaproic acid - usually, this is a good indicator we are dealing with another industry scam, but in contrast to the many funky forms of creatine, ?-hydroxy-isocaproic acid does actually have a handful of studies to back up that it does... or I should say "that it could" help you getting big and buffed.
That being said, it may be worth taking a look at what ?-hydroxy-isocaproic acid actually is. Just like HMB which is about to make a comeback in liquid form, these days, HICA is a metabolite of the mTOR and thus protein synthesis triggering branch-chained amino acid leucine. It is also known as "leucic acid" or "DL-2-hydroxy-4-methylvaleric acid" and is formed by ?-hydroxylaction from leucine. Its one of the end-products of leucine metabolism in muscle and connective tissue (Walser. 1978). Its usual concentration in our blood is about 0.2560.02 mmol/L - thats ~100x less than the amount of ?-keto-isocaproic acid (KIC), the corresponding keto acid of leucine of which youll find more than 21 mmol per liter in your blood.

Figure 1: Relative changes in lean mass (%) during 4 weeks of intense soccer training on 1.5g/day HICA (Mero. 2010)

Cheese, wine, soy sauce, etc. - the recently celebrated fermented foods, they all contain HICA, which appears to be the anti-catabolic counterpart to leucine. While the latter is a potent promoter of protein synthesis, the former appears to make sure that the work of its predecessor leucine is not lost.

It is thus no wonder that the promising results of a 2010 study by Mero et al. were recorded during an intensive and thus potentially catabolic training period in soccer athletes. In contrast to the placebo group, where only one individual gained a significant amount of lean mass, while 4 lost muscle, the subjects who had been consuming 1.5g/day of ?-hydroxy-isocaproic acid gained 300g of lean mass, on average, in the course of the 4-week study.

Thats not much and it was not fat free (ca. 150g of fat), but the data in Figure 1 shows that this is a difference between minimal muscle loss and gain... and I guess most athletes would prefer a marginal muscle gain over a marginal loss of lean mass.

HICA, a potent anti-catabolic? I dont think so!

The notion that HICA is, above all, a muscle loss inhibitor appears questionable, if we take a look at the results Charles H. Lang, Hugues Magne, Elizabeth Offord and Denis Breuille presented at a 2013 FASEB meeting. In the abstract to their presentation they cite the results of a rodent study in the course of which the rodents were immobilized for two full weeks. The consequence, an increase in the expression of catabolic hormones and a profound loss of muscle mass was identical in both the HICA and placebo supplemented groups, but in spite of the fact that "?HICA did not alter the immobilization-induced increase in proteasome activity and atrogene expression", the muscle mass had returned to control values only in ?HICA-fed rats after 14 days.
The fast recovery in the HICA group was associated with increased muscle protein synthesis and higher levels of the "protein synthesis pump initiator proteins" S6K1 and 4EBP1 in the previously immobilized muscle. The results Lang et. al. have not yet published in a full paper (at least I couldnt find it) put a huge questionmark behind the long-heralded hypothesis that HICA supplementation would slow muscle loss and puts it in line with its cousin HMB and its precursor leucine as a purported pro-anabolic muscle builder.

Figure 2: Gastrocnemius weight (rel. to control) immediately before and 14-days after the immobilization (Lang. 2013).

The data from the corresponding full paper the authors published a couple of month later in the American Journal of Physiology - Endocrinology and Metabolism you see in Figure 2 are even more impressive, though. According to this rodent data HICA is a more potent muscle (re-)builder than leucine; and, importantly, neither of the two does what the industry keeps promising: prevent muscle catabolism in response to disuse.
Reference:

• Chow K., and Walser M. "Effects of substitution of methionine, leucine, phenylalanine, or valine by their alpha-hydroxy analogs in the diet of rats." J Nutr 1975;105(3):372 8
• Lang, Charles H., et al. "Chronic ?-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy." American Journal of Physiology-Endocrinology and Metabolism 305.3 (2013): E416-E428.
• Mero, Antti A., et al. "Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes." Journal of the International Society of Sports Nutrition 7.1 (2010): 1.
• Walser, Mackenzie. "Therapeutic compositions comprising alpha-hydroxy analogs of essential amino acids and their administration to humans for promotion of protein synthesis and suppression of urea formation." U.S. Patent No. 4,100,160. 11 Jul. 1978.
• Woods M., and Goldman P. "Replacement of L-Phenylalanine and Leucine by a-Hydroxy analogues in the diets of germ-free rats." J Nutr 1979;709:738 43.