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Showing posts with label acid. Show all posts
Showing posts with label acid. Show all posts

Sunday, March 8, 2015

4g of Conjugated Linoleic Acid Promote CYP17A1 Leydig Cell Testosterone Production and Increase Cardio Mediated Muscle Strength and Endurance Gains

"Thats all the exercise in induced T-response, bro. Now shut up, I got to squat!"
Yes, this is another of those rodent studies of which we simply dont know if the results will eventually translate to humans. In contrast to previous studies on CLA, which dealt with weight loss and produced marvelous results (see "CLA Destroys Body Fat & Increases Endurance!" | read more) which could not be reproduced in human trials.

This very recent paper from Italy deals with CLAs effects on exercise, testosterone, and potential gains in muscle mass and leaves the parameter body fat out of the equation (Barone. 2013).

"Hold on, thats not news, is it?"

When Roy Nelson shot me the link to the pertinent paper by Rosario Barone et al. (2013), the above, i.e. "Hold on, thats not news, is it?" was actually my first thought. After all, I had written about the purported muscle building effects of CLA in the past (see "Review Claims: CLA & Fish Oil Improve "Anabolic" Effects of Exercise - What Does the SuppVersity Sniff Test Say?" | read more). After briefly checking my previous article, I did realize, though: This is news!

The previous article did not discuss the same results. It did however come from the same team of Italian researches and made the claim that CLA & fish oil would be natural anabolics (read it!) - a claim I reviewed and wrote:
"[...] as far as ergogenic and/or anabolic effects are concerned, CLA is unquestionably the more promising fatty acid off the "two" (actually we are talking about four fatty acids, here: DHA + EPA = fish oil and cis-9,trans-11 and trans-10,cis-12 CLA)." (SuppVersity. 2013)
I have to admit, though, that I was thinking of CLAs ability to block the storage of body fat on a bulk, primarily - not so much about its not yet fully, but at least half-way established effects on exercise performance. The testosterone boosting effects, on the other hand, were something I discarded, so that its about time to look at them more closely.

In vitro + in vivo - thats the way Barone et al. did it

In a first attempt to access the effects of CLA on the testicular androgen production, the scientists from the University and Hospital of Palermo conducted a couple of tests in the petri dish. Usually boring stuff, if it were not for geeks like me (and some of you) who always ask the nasty question: "Why".

Figure 1: The same research group published a paper that showed increased testosterone in young men on a resistance training regimen. It is therefore not totally unlikely that the results do translate to human beings; the figure shows the total testosterone before vs. after a workout in ng/dl (Macaluso. 2012)
In this case, we are lucky, because Barone et al. did not focus solely on the amount of steroids the the leydig tumour cells (dont worry that should work with regular cells, as well) were spilling out. They also tested for enzymatic changes and observed that as 17α-hydroxylase/17,20-lyase (CYP17A1), which converts progesterone into androstenedione and has  been demonstrated to have direct downstream effects on the testosterone production (Svechnikov. 2009; Weisser. 2011).

As every SuppVersity reader knows, the cytochrome P450 enzyme cascade is on of the most powerful and overlooked actors in the steroid orchestrate. While CYP17A1, which does effectively increase the production of testosterone pre-cursors and will thus exert an indirect beneficial effect on the testosterone production, other members of the cytochrome family facilitate the conversion and clearance of testosterone.

Against that background it was sound to expect to observe similar effects in the in-vivo part of the study. The interplay with other enzymes, however, could easily have thwarted the results. Outside of the petri dish the sheer number of variables that could change the outcome of the study makes it more or less impossible to predict the "exact" study outcome and - I want to emphasize this - the latter could well look slightly or completely different from what you see in Figure 2, when you went ahead and tried to support your training efforts with 4g of the patented Tonalin® FFA 80:
Figure 2: Free testosterone and CYP17A1 expression in the supplemented (CLA-) /  unsupplemented (PLA-) mice after 6 weeks of no (SED) or 15-60min (ramp up) of exercise 5x per week (Barone. 2013).
I hope you did notice the important hint I hid in the last sentence above Figure 2, where it says: "Support your training efforts..." If you didnt take a look at Figure 2 ... I guess, its obvious to see that this short insert is of paramount importance: No training, no CLA bonus!
"The protein expression of CYP17A1 was significantly higher in both the trained groups (PLA-TR and CLA-TR) compared to the sedentary groups (PLA-SED and CLA-SED) (P <0.01). Moreover, CLA supplementation induced a further increase in CYP17A1 protein in the CLA-TR group compared to the PLA-TR group (P < 0.01)" (Barone. 2013)
In other words, training alone is a CYP17A1 powered testosterone booster and CLA is an adjuvant, which has no effect in the absence of 6 weeks with five "cardio" sessions/week at an ever-increasing pace and duration (15-60min and 3.2-4.8m/min from week 1-6).
Figure 4: Body weight gain, and force/body weight gain  (in %; top) and distance traveled relative to SED-PLA group (Barone. 2013)
"Wow thats exciting, isnt it?" Actually no - not really. The increase in testosterone alone would hardly be worth the paper this article is probably never going to be printed on. What is at least borderline exciting, though, are the increase in muscle gains, strength and running distance the rodents covered in a standardized test (see Figure 3).

Yeah, I have to admit: The data does look exciting, but that can be said of the previously referenced study by Macaluso, as well. The said human trial (see Figure 1), however, tells us that its probably unrealistic to expect similarly pronounced effects with even more CLA (6g in the Macaluso study from 2012) in men.

Personally, I would save the money, but if you want to try it: Go ahead... and tell us if it works ;-)

I, for my part, am missing anecdotal evidence (You cant tell me that there is no one who has tried that already - so where are the "CLA is king, bro!" posts on the various boards?), the confirmation of this or at least similar effects by other scientists and a Conflict of Interest declaration at the end of a paper that puts such an emphasis on the "®" in  Tonalin® FFA 80.

References:
  • Barone, R, Macaluso F, Catanese P, Marino Gammazza A, Rizzuto L, et al. Endurance Exercise and Conjugated Linoleic Acid (CLA) Supplementation Up-Regulate CYP17A1 and Stimulate Testosterone Biosynthesis.  PLoS ONE 8(11): e79686.
  • Macaluso F, Morici G, Catanese P, Ardizzone NM, Marino Gammazza A, Bonsignore G, Lo Giudice G, Stampone T, Barone R, Farina F, Di Felice V. Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise. J Strength Cond Res. 2012 Jun;26(6):1667-74.
  • Svechnikov K, Spatafora C, Svechnikova I, Tringali C, Söder O. Effects of resveratrol analogs on steroidogenesis and mitochondrial function in rat Leydig cells in vitro. J Appl Toxicol. 2009 Nov;29(8):673-80.
  • Weisser J, Landreh L, Söder O, Svechnikov K. Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells. Mol Cell Endocrinol. 2011 Jul 20;341(1-2):18-24. doi: 10.1016/j.mce.2011.03.008.
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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 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.
There is evidence of beneficial effects of GCA on your gut microbiome (Jaquet. 2009)

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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.
Yes, agents like glycerric acid from licorice increase cortisol levels. Contrary to common believe this will yet not trash your testosterone levels and/or induce weight loss - quite the contrary | learn more
Bottom line: While the rodent study by Zhang et al. appears to support the accuracy of the data Vinson et al. published two years ago, you as a SuppVersity reader should be aware of the fact that the reduction in cortisol / cortisone activity Revuelta-Iniesta and Al-Dujaili observed in their subjects is not necessarily going to facilitate weight loss. As discussed in the corresponding Science Round Up, a normal circadian cortisol rhythm with both spikes and troughs is a prerequisite of optimal fat loss, so that its suppression by green coffee beans or other means is beneficial only for those of us who suffer from chronically elevated cortisol levels.

Overall, we are thus left with a single study the whole "green coffee bean for weight loss"-hype is based on. Well, who cares. For the majority of best-selling supplements we dont even have that ;-)
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.
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