How to diet fast 1 week

"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).

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.

This is what Photoshop and creativity can tell us about aging men.

It has been a while since weve taken a closer look at the effects of testosterone deficiency and its replacement aka TRT. Basically thats why I decided not to waste the interesting findings from a recently published study in the The Journal of Clinical Endocrinology and Metabolism (Yeap. 2013) in the Facebook News. In combination with the findings Xu et al. report in a paper on the difference in testosterone concentrations in young healthy US versus Chinese men the Yeap study does after all make a decent addition to the 269 of hitherto ~1500 archived SuppVersity articles that deal in one way or another with the famous androgen.

Virile men live longer! Ca. 30% longer, to be precise.

If you take a look at the link between serum testosterone, free testosterone and DHT and the all-cause mortality risk of the 16,451 community-dwelling older men from Perth in Western Australia it should be obvious that the third quartile of all these serum values, is where you want your androgen levels to be, if you intend to live to see your 90th birthday.

Figure 1: Relative reduction in all-cause mortality with total and free testosterone levels, as well as dihydrotestosterone levels in quartile 2,3 & 4 vs. quartile 1 (Yeap. 2013)

To quantify: You want to have your total testosterone levels in the 12.56 – 15.75 nmol/L (362ng/dl - 454ng/dL), your free testosterone levels in the 182.66 – 216.34 pmol/L (5.3-6.2 ng/dL) and your dihydrotestosterone (DHT) levels in the 1.34 – 1.83 nmol/L (DHT; 39-53ng/dL) range if you dont want to miss a couple of years of your life.

And while your androgen levels shouldnt be significantly lower, you also dont want them in the fourth quartile, where the all-cause mortality risk begins to rise again. Unless you dont want to lose the ~30% all-cause mortality of being in the zone, you shouldnt let the rumors about a causal (not corollary) link between testosterone replacement therapy (TRT) and the incidence of prostate cancer upset you. Why, well because ...

"[...] to date, no study or review has definitively shown that androgen replacement therapy is an independent risk factor for development of prostate cancer." (Fisher. 2012) 

The thing you should ask yourself is thus whether you really want to give up on this 30% reduction in all-cause mortality, or the decrease in fatal cardiovascular events, Ramasay et al. list next to the reduction in body fat mass, and insulin resistance among the proven benefits of TRT in their 2012 review of the literature.

Its your decision and therefore you should make sure that its you and not your doctor who takes this decision. If you decide to help your low testosterone levels along, its your doctors job to help and assist you by ordering and interpreting regular hormone and, as Fisher et al. suggest, PSA tests.

Informed decisions, require information, lab values, and reference ranges!

Speaking about "interpreting" hormone panels. One of the problems youll be facing is that nobody can actually tell you what your normal testosterone level should look like. Of course, every med-school graduate will believe that he knew exactly whats good for you, but when its all said eand done, scientists (and doctors) tend to be a bit too egalitarian, when it comes to "normal ranges". So egalitarian, in fact that they simply assume that a lightweight Chinese pencil pusher must have the same testosterone levels as a 6.6 ft tall, 300lbs heavy Caucasian strongman.

Figure 2: Total and bioavailable testosterone levels in US and Chinese young men (Xu. 2013)

Its thus quite refreshing that Xu et al. followed a different path and followed the heavily underused "Equal, but different!"-princple, when they decided to conuct what they claim is the first study to analyze and compare the total (TT), calculated free (FT), and bioavailable testosterone (Bio T) levels of healthy young men (18–29 years) from the Third National Health and Nutrition examination Survey (NHANES III) in the United States (US) to those of men living in a region of China with a similar living standard to the US, i.e., Hong Kong.

By this means, the researchers wanted to find out whether the potentially existing differences in androgen levels in Caucasian vs. Asian young men would warrant a revision / specification of the "normal" range for men from different ethnic backgrounds.

As you can see the results are not exactly easy to interpret (Figure 2) - is this a difference, or not?

If we take another look at the data in Figure 2 and compare the relative differences between the total testosterone levels of young US vs. Chinese men to those that made a significant difference, in the previously discussed study by Yeap et al. (see Figure 1), we will have to concede that the xisting differences can hardly be significant. They are after all a magnitude smaller than the quartiles in the Yeap study.
That being said, there are at least three additional reason that speak against establishing specific testosterone cut-off values for different ethnic groups based on the Xu study:

1. The Xu study is not representative of "all" Chinese young men: The Xu study compares US citizens in the US to Chinese citizens in China. Who tells us that the values they obtained for young Hong Kongers are valid for 2nd generation Chinese immigrants to the US, as well? Environmental conditions, dietary factors, etc. all that could just as well be the reason for the measured differences as ethnicity-specific genetic differences.
2. The Xu study, or rather the NHANES data is not representative of a specific ethnicity: By analogy to (1), the Xu study, which uses data from NHANES III to gauge the average testosterone levels of male US citizens, relies on data from Asian, African American, Native American, Hispanic and Caucasian US citizens. How on earth would you establish ethnicity specific normal values based on that?
3. Using the Yeap study as a reference to determine "optimal levels" is unwarranted: With old men as study participants, the significance of the optimal total testosterone levels from the Yeap study (12.56 –15.75 mmol/L ≡ 362- 454ng/dL) is about as questionable as the assumption that older men are actually supposed to have significantly lower testosterone levels.

And even if you wouldnt agree that these objections are valid, there would be a simple, yet effective solution to end this discussion once and for all: Measure (or calculate) the free testosterone levels!

If you do that, i.e. compare free instead of total testosterone levels, you will find that the purported ethnic differences disappear. And this is true not solely for the comparison of the data from Chinese and US men Xu et al. analyzed, but also for the existing differences between Mexican-American, non-Hispanic black and non-Hispanic white men in the NHANES study by Rohrmann et al. (2007). Specific reference ranges for Asian, Caucasian, African American, Hispanics, ... are thus probably unwarranted (not sure about Aliens, though ;-).
References: 

• Ramasamy, R., Fisher, E. S., & Schlegel, P. N. (2012). Testosterone replacement and prostate cancer. Indian journal of urology: IJU: journal of the Urological Society of India, 28(2), 123.
• Yeap, B. B., Alfonso, H., Chubb, S. P., Handelsman, D. J., Hankey, G. J., Almeida, O. P., ... & Flicker, L. (2013). In Older Men an Optimal Plasma Testosterone Is Associated With Reduced All-Cause Mortality and Higher Dihydrotestosterone With Reduced Ischemic Heart Disease Mortality, While Estradiol Levels Do Not Predict Mortality. 
• Perry III, H. M., Miller, D. K., Patrick, P., & Morley, J. E. (2000). Testosterone and leptin in older African-American men: relationship to age, strength, function, and season. Metabolism, 49(8), 1085-1091. 
• Rodriguez, A., Muller, D. C., Metter, E. J., Maggio, M., Harman, S. M., Blackman, M. R., & Andres, R. (2007). Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. Journal of Clinical Endocrinology & Metabolism, 92(9), 3568-3572.
• Rohrmann, S., Nelson, W. G., Rifai, N., Brown, T. R., Dobs, A., Kanarek, N., ... & Platz, E. A. (2007). Serum estrogen, but not testosterone, levels differ between black and white men in a nationally representative sample of Americans. Journal of Clinical Endocrinology & Metabolism, 92(7), 2519-2525.
• Traish, A. M., Miner, M. M., Morgentaler, A., & Zitzmann, M. (2011). Testosterone deficiency. The American journal of medicine, 124(7), 578-587. 
• Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999). A critical evaluation of simple methods for the estimation of free testosterone in serum. Journal of Clinical Endocrinology & Metabolism, 84(10), 3666-3672.
• Xu, L., Au Yeung, S. L., Kavikondala, S., Leung, G. M., & Schooling, C. M. (2014). Testosterone concentrations in young healthy us versus Chinese men. American Journal of Human Biology, 26(1), 99-102.