Science Round-Up Seconds: Prostate Cancer Special - Are You Going to Die From or With Prostate Cancer? Plus: What Can be Done to Influence This Fate?

Today's SuppVersity article revolves around the question what YOU can do to make sure that the procedure this guy is about to endure is the only thing to be afraid of, when you are going to your check ups ;-)

Let me just get this out there, if you missed an appointment because you were listening to the show live, yesterday, I am sorry. Carl and I actually went "longer than long". What was originally intended to be a one hour show did end being a 125min podcast. That being said, there is little left for the "Seconds" - at least news-wise. So, I decided to kick off today's installment of the traditional SuppVersity Science Round Up Seconds with a quick hit summary of the bottom line of the show. As far as the details are concerned, I would strongly encourage you to download and listen to the podcast. I am not the one to call his own stuff "highly educational", but I guess even those of you who are already well-versed in this issue will find one or another useful bit of information...  

Apropos useful, if you asked me about the one thing you can do to ward off prostate cancer my answer would be "turn to physical culture". Whether you are at risk of developing a form of prostate cancer (PCa) that will have you die or at least suffer from the disease, everybody has in mind, when he thinks about PCa, will not depend on doing A and not doing B. It's, just as so often, a matter of checks and balances. And the things you got to balance are

• 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. (McTiernan. 2008)
  diet,
• exercise,
• sleep, and
• sun exposure

These are the fundamentals and things may in fact be less complicated than many of the numbers I mentioned earlier in the show would suggest. Ok, there is ...

• Don't ignore this post if you are a woman. Most, if not all of the things that help men ward off prostate cancer will also help women to reduce their risk of developing breast and other forms of cancer. A whole foods diet, a reasonable amount of exercise, a lifestlye that tailors to your natural circadian rhythm (learn more) and allows for adequate amounts of quality sleep (7h+ every night) are a MUST for both, women and men who are concerned about developing any form of cancer.
  

  In fact, the way these parameter changed in the course of the last century, is probably the most likely explanation why you may get the impression that developing some sort of cancer is about to become the new normal.
  a 40% risk reduction in advanced PCa for white men consuming a high amount of fruits,
• much to my own surprise no conclusive evidence that veggies are only half as protective as most of us probably thought they would be (think about the heavily advertised effect of DIM in cruciferus vegetables, for example.
• the thing about dairy in whites and meats in black increasing the overall prostate cancer risk by 70% and 80-90% (all meats vs. red meats), respectively
• the "problem" with only whole tomatoes being associated with significant risk reductions and the failure of tomato sauce (likewise pimped as a savior of the average American's prostate in the media) to elicit any effect on the health of your prostate
• an undebatable increase in cancer risk with increasing food consumption (+100% in the third tertile, Rohan. 1995)
• a non-significant association with the risk of developing prostate cancer with high intakes of vegetable oils (+24%; Rohan. 1995)
• a protective effect of saturated fats (-52%; Rohan. 1995) that appears to depend on the population you are analyzing (and I suppose the bias with which you approach the data)
• the protective power of real vitamin A (retinol; -34% for high(er) intakes. Rohan. 1995) and the absence of the latter for carotenes
• etc.

but in the end, all this tapers towards one thing - a dietary prescription that is not much different from the one you read about here at the SuppVersity on an almost daily basis. It is a balanced whole foods diet that is based on a reasonable baseline intake of carbohydrates, proteins and fats. A diet that puts an emphasis on ratios, not total amounts and above all a diet that is able to promote overall health - in mainstream terms, a mixture of the best principles from the two best-established "anti-cancer" diets yielding something you may want to call a Mediterranean, paleo-esque diet.

What's the role of supplements here?

Despite the fact that the word "supplement" already implies that these agents are nothing that's intended to treat, cure and replace, the shiny adds of the multi-billion dollar industry does suggest just that: Don't be fooled. There is probably use in supplements such as

• the usual suspects: lycopene, ginger, pomegrenate, garlic, green tea, curcumin, resveratrol, grape seed extract, milk thistle, DIM,
• methyldonors (choline, betaine, SAM, etc.) and molecules that are important for the optimal function of the methylation cycle (B6, B12, etc.)
• mitochondrially targeted anti-oxidants like CoQ10 --33% reduction in PSA with 100mg in Safarinejedat et al. (2013), 
• "fish oil" and here mostly EPA -- 30% reduction in PSA with 1.2g per day; Safarinejedat. 2013) 
• melatonin (Srinivasan. 2011)
• coffee and coffee polyphenols -- 47% total risk reduction in a recent study by Li et al. (2003); effect was particularly evident in overweight and obese subjects, etc.

but, none of these supplements is a "game changer", let alone able to revert prostate cancer on its own. All that shiny in-vitro data scientists have accumulated for many of the supplements on the above list (and tons of others!) is of little use, as the agents such as resveratrol or curcumin are not going to make it in anywhere similar "petri dish like" concentrations into your blood and right to the tumor to exert their anti-cancerous magic where they are supposed to do it (this is also true for all OTC variants of "enhanced bioavailability" curcumin)... but does that render them useless?

Follow the "Three Simple Rules of Sensible supplementation" (read more)

No, much to the contrary. Most of these "anti-cancer supplements" are either part of the aforementioned diet, already  (e.g. fish, DIM, green tea, ginger, garlic, pomegrenate, tomotoes, watermelon, etc.), or can be part of what Schmitz-Dräger et al. call a "complex diet", when they refer to the overdue "change of paradigm" from single compounds to more complex diets that must be the "starting point of future epdidemiological research" in prostate cancer prevention (Schmitz-Dräger. 2012) - food first, supplements second - and if you chose to supplement, don't lose sight of the "Three Simple Rules of Reasonable Supplementation"

Exercise: Obligatory not facultative!

Contrary supplements, exercise is an obligatory part of the "anti-cancer" lifestyle, of which you should by now realize that it is above all a lifestyle in the most sense. It's not an intervention, a regimen, medication or pill and exercise, in the broadest sense of the word, has to be an integral part and not a doctor prescribed addition to your daily routine. It's not a short term intervention or a quick fix solution and you cannot expect "immediate results". If you start out working out regularly (I suggest to go for at least three and no more than 5 workouts per week), you will be able to reap the fruits of your labor in 10-15 years, when the doctor will stick his finger in your anus and say: "Everything all right Mr Physical Culturist! Absolutely no reason to be worried" (a high fitness level translates to a -64% risk reduction; cf. Olivera. 1996).

You don't want to forget that both exercise and intermittent or alternate day fasting (Varaday. 2008) can help balance the mTOR/AMPK seesaw (read more), and reduce the potential overexpression and overabundance of total and free IGF 1.

Ah, and by the way... whether endurance or resistance training are "optimal" to promote general health and longevity is not a question, simply because both are obligatory. The resistance training to build and maintain muscle mass and the "cardio" training to build (HIIT or HIT) and maintain (LISS) an overall high VO2Max and mitochondrial capacity. That does not mean that you have to run on the treadmill for hours three times a week. But it also precludes going to the gym to sit around "resting" 90% for a "sit your ass flat on the bench and talk with the bros" workout. The latter won't yield a significant glycogen depletion, won't expend significant amounts of energy (-63% risk reduction for 1,000-2,000 kcal being burned during workouts per week; Olivera. 1996), won't increase AMPK (learn more about the "AMPK-mTOR Seesaw"), won't promote autphagy (self-destruction of the cell), won't reduce potentially exuberant IGF-1 levels and won't have beneficial effects on prostate cancer risk.

Don't be scared of your own hormones!

If you pair that with adequate sleep (at least 7h) and light exposure patterns that are both synchronized to your circadian rhythm, there is no reason to be worried about androgens as their effect on prostate cancer is facilitative, not causative (Gershman. 2013), so that even testosterone replacement therapy (TRT) should not pose a problem (Isbarn. 2009).

"Although no controlled studies have been performed to date to document the safety of testosterone therapy in men with prostate cancer, the limited available evidence suggests that such treatment may not pose an undue risk of prostate cancer recurrence or progression" (Morgentaler. 2013)

In fact, case reports and small scale observational studies from Morgentaler et al. and Rhoden et al. clearly suggest that prescribing TRT is not just save even for patients who have just undergone treatment for PCa, it is even more or less warranted, to "reverting iatrogenic hypogonadism and its associated cardiac and metabolic complications" (Aversa. 2012) and can lead to decreases in PSA even in untreated PCa patients (Morgentaler. 2009)

Does estrogen make women better endurance athletes because it increases mitochondrial biogenesis and gears your metabolism towards fatty acid not glucose oxidation? And if that is the case, would men benefit from some more estrogen, as well? Also, what about muscle building, is estrogen your friend or the foe people want it to be (read more)?

Estrogen therapy for prostate cancer? I guess some of you may have thought I was kiddin' when I mentioned that over here in Europe some MDs prefer using synthetic estrogens instead of anti-androgens as a treatment strategy for prostate cancer. As Carl rightly pointed out, this will likewise shut down the production of testosterone and could prevent many of the unwanted side effects on bone and brain. In view of the fact that the progression from benign to highly malignant prostate cancer is usually accompanied by a loss of estrogen beta receptors on the cells (Gabal. 2007), it may yet even serve a more direct purpose, at least in those cancer cells that are still responsive to the estrogen, where the activation of the E2-beta receptor has been associated with a blockade of cancer progression (Hartman. 2012).

Much related to these results is the increasing interest in the usefulness and superiority of intermittent androgen deprivation therapy as an effective alternative to the classic "eradication regimen" with significantly reduced side effects that may yet not be suitable for all patients (Klotz. 2013).

Can your masturbate your way to a healthier prostate?

Apropos side effect. The total eradication of your libido is unfortunately one of the most common side effects of androgen deprivation therapy - I wonder if that happens to the same extent if it's done with estrogen, but I am digressing, ... so back to the libido thing and Carl's absolute favorite, the protective effects of regular ejaculations: 4-7, to be precise is what a  2004 study by Leitzmann et al. found to be associated with a -11% risk reduction in young and a whopping -51% risk reduction in older men (Leitzmann. 2004). We do yet have to be careful, because

1. We all know (at least I hope so) that two parameters that correlate do not necessarily have a causal relationship, as well.
2. The study participants were almost exclusively European Americans and in view of what we have learned from the Hayes study (1999) about the vast differences various dietary factors have on African vs. European Americans, it is not impossible that ejaculations are like grains: beneficial for fair skinned, but carcinogenic for people with dark skin (again no causation implied ;-)
3. We could be dealing with another case of reverse causation, where early symptoms of prostate cancer (like prostate enlargement) cause pain and will have the subjects reduce their ejaculation frequency; luckily the scientists were smart enough to come up with this possible confounding factor as well:
   

   

   A hefty dose of Tongkat Ali is probably not turning you into a bodybuilder, but maybe into a sex machine (read more).

   "We were concerned about the possibility that the observed inverse relationships were due to avoidance of ejaculation among men with early symptoms related to prostate cancer. However, diminished ejaculation frequency as a preclinical consequence of prostate cancer would be expected to be more pronounced among men with advanced prostate cancer than among men with organ-confined prostate cancer, a circumstance that was not supported by our data.
   
   In addition, our findings were essentially unaltered when we excluded cases diagnosed in the early years of follow-up. Hence, our results suggest that reverse causation may have accounted for very little, if any of the observed inverse association between high ejaculation frequency and total and organ-confined prostate cancer risk." (Leitzmann. 2004)

   Thus, pain and subsequent avoidance of sexual intercourse or masturbation does apparently not explain the observed differences.
4. False reporting could be an issue, but within the same cohort of health professionals other studies checked for the accuracy of the reports and found them to be "reasonably accurate" (Leitzmann. 2004). With the questionnaires being totally anonymous, it is thus unlikely that someone lied about his ejaculation frequency.
5. The study did not measure ejaculation frequency during puberty, so that the results are "generalizable to white US men aged 46 years or older" (Leitzmann. 2004), only.

Nevertheless, aside from the Dimitropoulo study from 2009, the negative results of which I discussed on the air (listen to the podcast), there are 9 studies that observed similar beneficial associations (yet not all were significant), 3 studies where no associations were found and 7 studies in which the researchers observed a significant or nonsignificant inverse relationship.

Moreover, we are still at a loss as far as the potential reasons for the touted beneficial effects. Often heard hypothesis usually revolve around

• HPV infections are unlikely the reason for the downsides observed in some of the studies. More recent studies could not find any evidence of previous HPV infections in "the average" prostate cancer patient (May. 2008; Groom. 2012)
  alterations of the composition of prostatic fluid, a decrease of the intraprostatic concentration of xenobiotic compounds and chemical carcinogens, which readily accumulate in prostatic fluid, 
• a reduced development of intraluminal prostatic crystalloids, which have been associated with prostate cancer in some, but not all pathology studies and 
• endogenous effects of the seminal plasma on the local immune responsiveness that may diminish intraprostatic immune surveillance against tumor cells. 

Even the psychological relieve and relaxation that comes with an organism has been implicated as a potential underlying mechanism for the benefits, as the epithelial cell division in the prostate is stimulated by the release of growth factors from adjacent stromal cells that are heavily innervated with α1 adrenergic receptors (summarized based on Leitzmann. 2004)

Against that background I decided (probably much to Carl's dismay, to kick the "masturbate regularly" advice from the initial list of the four pillars of prostate cancer prevention, i.e. diet, exercise, sleep and a reasonable amount of sun exposure. As far as sex and masturbation goes, the jury is simply still out there.

---

So, do we either die from prostate cancer or die with prostate cancer? Those of you who have listened to the show know the answer already. Your chance to die from prostate cancer is 0.018% (CDC data from 2012). So unless you are one of the 188 unlucky guys among 1 million male US citizens, I gather that your chance of dying with "prostate cancer" (i.e. any form of abnormal tissue in your prostate) is probably 10,000x higher (estimated based on data from Zare-Mirzaie. 2012) ... and so is the chance neither you or anyone else will ever notice.

References:

• Aversa A, Francomano D, Lenzi A. Cardiometabolic complications after androgen deprivation therapy in a man with prostate cancer: effects of 3 years intermittent testosterone supplementation. Front Endocrinol (Lausanne). 2012;3:17.
• Barnard RJ, Ngo TH, Leung PS, Aronson WJ, Golding LA. A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro. Prostate. 2003 Aug 1;56(3):201-6.
• Campbell TJ, Tindall DJ, Figg WD. Dihydrotestosterone synthesis from adrenal precursors does not involve testosterone in castration-resistant prostate cancer. Cancer Biol Ther. 2012 Mar;13(5):237-8.
• Dimitropoulou P, Lophatananon A, Easton D, Pocock R, Dearnaley DP, Guy M, Edwards S, O'Brien L, Hall A, Wilkinson R, Eeles R, Muir KR; UK Genetic Prostate Cancer Study Collaborators; British Association of Urological Surgeons Section of Oncology. Sexual activity and prostate cancer risk in men diagnosed at a younger age. BJU Int. 2009 Jan;103(2):178-85.
• Gabal SM, Habib FM, Helmy DO, Ibrahim MF. Expression of estrogen receptor-B ( ER-B ) in bengin and malignant prostatic epithelial cells and its correlation with the clinico-pathological features. J Egypt Natl Canc Inst. 2007 Dec;19(4):239-48.
• Gershman B, Shui IM, Stampfer M, Platz EA, Gann PH, Sesso HL, Dupre N, Giovannucci E, Mucci LA. Prediagnostic Circulating Sex Hormones Are Not Associated with Mortality for Men with Prostate Cancer. Eur Urol. 2013 Jan 11. doi:pii: S0302-2838(13)00006-7.
• Groom HC, Warren AY, Neal DE, Bishop KN. No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses. PLoS One. 2012;7(3):e34221. doi: 10.1371/journal.pone.0034221. Epub 2012 Mar 28.
• Grossmann M, Wittert G. Androgens, diabetes and prostate cancer. Endocr Relat Cancer. 2012 Sep 5;19(5):F47-62.
• Hartman J, Ström A, Gustafsson JÅ. Current concepts and significance of estrogen receptor β in prostate cancer. Steroids. 2012 Oct;77(12):1262-6.
• Hayes RB, Ziegler RG, Gridley G, Swanson C, Greenberg RS, Swanson GM, Schoenberg JB, Silverman DT, Brown LM, Pottern LM, Liff J, Schwartz AG, Fraumeni JF Jr, Hoover RN. Dietary factors and risks for prostate cancer among blacks and whites in the United States. Cancer Epidemiol Biomarkers Prev. 1999 Jan;8(1):25-34.
• Ilic D, Forbes KM, Hassed C. Lycopene for the prevention of prostate cancer. Cochrane Database Syst Rev. 2011 Nov 9;(11):CD008007.
• Isbarn H, Pinthus JH, Marks LS, Montorsi F, Morales A, Morgentaler A, Schulman C. Testosterone and prostate cancer: revisiting old paradigms. Eur Urol. 2009 Jul;56(1):48-56.
• Klotz L. Intermittent versus continuous androgen deprivation therapy in advanced prostate cancer. Curr Urol Rep. 2013 Jun;14(3):159-67.
• Li Q, Kakizaki M, Sugawara Y, Tomata Y, Watanabe T, Nishino Y, Tsuji I. Coffee consumption and the risk of prostate cancer: the Ohsaki Cohort Study. Br J Cancer. 2013 Jun 11;108(11):2381-9.
• May M, Kalisch R, Hoschke B, Juretzek T, Wagenlehner F, Brookman-Amissah S, Spivak I, Braun KP, Bär W, Helke C. [Detection of papillomavirus DNA in the prostate: a virus with underestimated clinical relevance?]. Urologe A. 2008 Jul;47(7):846-52.
• McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008 Mar;8(3):205-11.
• Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009 Feb;55(2):310-20.
• Morgentaler A. Two years of testosterone therapy associated with decline in prostate-specific antigen in a man with untreated prostate cancer. J Sex Med. 2009 Feb;6(2):574-7.
• Morgentaler A. Testosterone therapy in men with prostate cancer: scientific and ethical considerations. J Urol. 2013 Jan;189(1 Suppl):S26-33.
• Oliveria SA, Kohl HW 3rd, Trichopoulos D, Blair SN. The association between cardiorespiratory fitness and prostate cancer. Med Sci Sports Exerc. 1996 Jan;28(1):97-104.
• Rhoden EL, Averbeck MA. Testosterone therapy and prostate carcinoma. Curr Urol Rep. 2009 Nov;10(6):453-9.
• Rohan TE, Howe GR, Burch JD, Jain M. Dietary factors and risk of prostate cancer: a case-control study in Ontario, Canada. Cancer Causes Control. 1995 Mar;6(2):145-54.
• Safarinejad MR, Shafiei N, Safarinejad S. Effects of EPA, γ-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial. Br J Nutr. 2013 Jul;110(1):164-71.
• Schmitz-Dräger BJ, Lümmen G, Bismarck E, Fischer C. Prevention strategies for prostate cancer. Minerva Urol Nefrol. 2012 Dec;64(4):225-31.
• Srinivasan V, Pandi-Perumal SR, Brzezinski A, Bhatnagar KP, Cardinali DP. Melatonin, immune function and cancer. Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):109-23. Review.
• Taksler GB, Cutler DM, Giovannucci E, Smith MR, Keating NL. Ultraviolet index and racial differences in prostate cancer incidence and mortality. Cancer. 2013 Jun 6.
• Torti TC, Matheson GO. Exercise and Prostate Cancer. Sports Medicine. 2004; 34(6):363-369.
• Varady KA, Roohk DJ, McEvoy-Hein BK, Gaylinn BD, Thorner MO, Hellerstein MK. Modified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice. FASEB J. 2008 Jun;22(6):2090-6.
• Waldert M, Schatzl G, Swietek N, Rom M, Klatte T. Sex hormone-binding globulin is an independent predictor of biochemical recurrence after radical prostatectomy. J Urol. 2012 Sep;188(3):792-7.
• Zare-Mirzaie A, Balvayeh P, Imamhadi MA, Lotfi M. The frequency of latent prostate carcinoma in autopsies of over 50 years old males, the Iranian experience. Med J Islam Repub Iran. 2012 May;26(2):73-7.

Evidence From the Metabolic Ward: 1.6-2.4g/kg Protein Turn Short Term Weight Loss Intervention into a Fat Loss Diet

2x-3x higher than RDA protein intakes work equally well for men and women, to get and stay lean and lose fat and build / maintain muscle.

There are very few principles I believe are set in stone and valid regardless of your age (maybe not for toddlers), your training goals and your nutritional "orientation" (paleo, low carber, low fat eater, or whatever), and among these the "Have at least 30g of quality protein (eggs, meats, dairy, fish, etc.) with every major meal" (this assumes you eat 3meals+ per day) probably is king. It is the recipe to success and I actually don't feel as if it was necessary to convince you of the advantages this high(er) protein intake will have on your physique and - although the medical establishment is still reluctant to admit that - your health, as well. Still, the most recent study from the Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine in Natick, Massachusetts, USA; have much more to offer than "just" some additional evidence to the superiority of high(er) protein diets on a cut.

It's more than high time to revise the RDA

The study was designed to assess the effects of different dietary protein (RDA = 0.8g/kg, 2x RDA = 1.6g/ kg and 3x RDA =2.4g/kg) intake on body composition and postabsorptive and postprandial muscle protein synthesis on a 21-day cut (-30% energy restriction phase; ED). The latter was preceded by a 10-day weight maintenance (WM) period.

To up the calculated energy deficit to 40% the physically active (physical activity 3– 4 d/wk), weight stable ( 2 kg; for a minimum of 2 mo before the study), 39 volunteers [32 men (11 military, 21 civilians) and 7 women (7 civilians)] with a body mass index (BMI) between 22 and 29 kg/m² and a sufficient baseline fitness had to exercise daily:

"You told me to eat more protein and this burger has both meat and cheese!" - This and other mishaps are the rule, not the exception in uncontrolled dietary interventions (learn more). The fact that the study at hand took place in the metabolic ward of the U.S. Department of Agriculture Grand Forks Human Nutrition Research Center really is a HUGE PLUS.

"To isolate the effects of the diet and minimize the potential of an exercise training stimulus, physical activity during WM was prescribed at levels comparable to those reported in prestudy 7-d physical activity records. Volunteers performed low-tomoderate-intensity (40 – 60%Vo2peak) treadmill and cycle ergometry steady-state physical activity sessions daily. Intensity was based on pre-study Vo2peak
measurements obtained during a progressive intensity treadmill test and verified during
familiarization trials using indirect calorimetry (ParvoMedics) and corresponding heart rate. Workloads during steadystate physical activity sessions were adjusted accordingly to
ensure accuracy using the heart rate reserve method and portable heart rate monitors." (Pasiakos. 2013; my emphasis)

The study took place in the metabolic ward (so there was no cheating involved here => HUGE PLUS; cf. ) at the U.S. Department of Agriculture Grand Forks Human Nutrition Research Center. All volunteers were required to abstain from nutritional supplements, alcohol, smoking, and all medications, unless acetaminophen-containing products were provided by the investigator or study physician. Volunteers were also required to be in their assigned rooms with lights out by 11 P.M. (possibly very important; learn why) to ensure adequate and similar levels of sleep.

Don't worry this was not "cardio only"

To maintain prestudy muscular fitness levels, the volunteers also performed resistive-type physical activity 3d/wk. However, "to minimize the potential of an unaccustomed, anabolic stimulus influencing study outcome measures, the intensity and volume of the resistive-type exercise was low" (Pasiakos. 2013):

Table 1: Energy / macronutrient content of the diets (updated on June 21; previously there was a copy + paste error in the table)

"Specifically, volunteers performed one single-joint movement per major muscle group (3 sets of 15 repetitions) using workloads determined during the prestudy period. Frequency, intensity, mode, and volume of resistive-type activities did not change during the 31-d study. Research staff who were blinded from dietary assignment supervised all physical activity sessions for safety and accuracy". (Pasiakos. 2013)

The body weight, was recorded in two day intervals and the body composition was quantified using a  dual-energy X-ray absorptiometry (DXA) during WM (day 9) and ED (day 30). To elicit the underlying mechanisms, the resting metabolic rate, protein synthesis, nitrogen balance and the expression of intracellular signaling proteins were tested, as well.

Figure 1: Change in body composition and protein synthesis (Pasiakos. 2013)

As you can see in figure 1, there was a baseline and dose-dependent effect on the changes it total weight and body composition, respectively.

Body weight during WM was similar between dietary treatment groups and remained stable from d 1 (group mean, 77.5 1 +/-5 kg) through d 10 (77.1 1 +/-5 kg). Overall, volunteers lost 3.2 0 +/- 2 kg during the 21-d ED; 3.5 0 kg for RDA, 2.7 0 kg for 2 -RDA, and 3.3 0 kg for 3 -RDA (P < 0.05). Independent of dietary protein, percentage body fat decreased (P < 0.05) from 19.8 1% during WM to 18.1 1% during ED, and the change in percentage body fat was similar between RDA (1.3 0 +/- 3%), 2 -RDA (1.8 0 +/- 4%), and 3 -RDA (1.9 0 +/- 3%)." (Pasiakos. 2013)

What's worth taking a closer look at, is yet the proportion of total weight loss due to changes in fat mass (FM) and FFM, which differed across dietary protein levels.

• the percentage of total weight loss attributed to reductions in fat mass (FM) was higher (P < 0.05) for 2 -RDA (70.1 7%; 1.9 0 +/- 3 kg) and 3 -RDA (63.6 5%; 1.9 0 +/- 2 kg) than for RDA (41.8 5%; 1.6 0+/-2 kg)
• the percentage of total weight loss due to a loss of fat free mass (FFM) was lower for 2 -RDA (29.8 7%; 0.8 0 +/- 2 kg) and 3 -RDA (36.4 5%; 1.2 0. +/- 3 kg) as compared to RDA (58.2 5%; 2.3 0 +/- 3 kg)
• the fat to lean mass loss ratio was 30% higher in the medium protein intake group, in other words, the increase in protein intake in the 3xRDA group did not protect the lean mass any better than the 1.6g/kg in the 2xRDA group

While the latter change did not reach statistical significance, the trend is clear and I suspect with a higher number of participants, the scientists would have been able to show that the 3x RDA intake is not just worthless, but actually contra-productive, if your goal is stable ongoing fat loss.

No inter-group differences in the majority of signaling proteins

All the changes took place in the absence of statistically significant inter-group differences in the changes in anabolic intracellular signaling and gene expression [ignore the following list if you are no geek ;-], i.e.

• postprandial Akt (Ser 473) phosphorylation was increased 1.4-fold higher (P < 0.05) compared to postabsorptive levels
• postprandial p70 S6K1 (Thr 389), eIF4E Ser (209), and rpS6 (Ser 235/236) phosphorylation status was 16, 1.9, and 15.5-fold higher (P < 0.05), respectively, compared to postabsorptive phosphorylation levels
• phosphorylation status of eEF2 (Thr 56) was lower (P < 0.05) after feeding

The more important general observation was yet that the upregulation of these signals 3 h after consuming a protein-containing meal, demonstrated a main feeding effect for all proteins of interest (P < 0.05). On the other hand, their expression was not influenced by energy status or the level of dietary protein intake (and let's be honest, what would an increase be worth if the data in figure 1 already told us what the real-world implications are?)

Figure 2: Changes in postabsorptive muscle protein synthesis-associated mRNA expression levels during the diet phase (-40% energy intake) of the study (Pasiakos. 2013)

Additionally, the energy deficit increased the mRNA expressions of a couple of other proteins implicated in the intracellular regulation of muscle protein synthesis:

"Transcription of Vps34, a protein involved in amino acid sensing and amino acid-mediated stimulation of mammalian target of rapamycin (mTORC1) signaling, was 1.2-fold higher (P < 0.05), while expression of mTORC1 inhibitors REDD1 and REDD2 were both 1.3-fold higher (P < 0.05) after ED compared to WM. Increasing dietary protein intake increased Vps34 mRNA expression, with 1.2-fold higher levels for 3x-RDA than RDA (P 0.05). MAP4K3, LAT1, and SNAT2 mRNA levels were not influenced by energy and dietary protein manipulations." (Pasiakos. 2013)

In view f the slight advantage of the 3xRDA diet in terms of the stimulation of protein synthesis, you may want to come back to the statistical insignificance of the superiority of the 2xRDA diet to keep indulging the same hilarious amounts of protein that have probably not gotten yourself anywhere near contest shape in the past, well, let's take a look on a couple of other observations, then:

• While the nitrogen balance remained negative (meaning the body was burning more protein than it stored) over the whole trial in the 0.8g/kg group, it returned to baseline (weight maintenance levels) first in the 1.6g/kg (=2x RDA) group (day 17!). This restoration of to pre-diet levels was observed only on day 30 in the high protein group (2.4g/kg) and the that without any significant advantage of the 3xRDA over the 2xRDA intake (if anything it was lower in the high protein group; see figure 3)
• There was no "thermogenic advantage" - or whatever people usually like to call the purported beneficial effect that comes with the ingestion of higher amounts of protein; in fact, the resting metabolic rate was identical for all three groups over the whole 21-day diet period. 
• With a diet that was high in carbohydrates and low in fat (see table 1), the conversion of protein to glucose, was likely relatively limited and the potential downsides of high protein + low carb diets, where most of the protein will be broken down in the liver to supply your body with glucose and any temporary increase in insulin due to fast acting protein sources were not an issue.

In the end, the increase in postprandial protein synthesis in the 3x RDA group is therefore worthless, because it went hand in hand with an increase in wastefulness due to which the absolute protein retention did not differ all that much and the differences in lean mass loss 0.1kg) are clearly insigificant- plus: If you simply do the math, the ratio of fat free to fat mass loss, is still 31% higher in the 2x RDA group.

---

Irrespective of how many supplements you take - you cannot out-supplement a bad diet, laziness and a lack of motivation & determination. Still, especially for the elderly HMB with it's pronounced anti-cababolic effec could help - particularly on a diet (learn more; leucine vs. HMB)

So what's the optimum then? If we reconcile the results of the study at hand, the "optimal" protein intake would thus probably be somewhere between 1.6g/kg and 2.0g/kg an thus in the <200g range for the vast majority of people. If you also consider that this value includes all protein even that from rice, and other "non-quality" protein sources, the study at hand does not confute my previous recommendation to stick to a 1.5g/kg-2.0g/kg (per total body mass) protein intake from quality protein sources, to discount the additional protein you will be getting from "low protein food" (too much counting will only make you neurotic) and to do that irrespective of whether you are bulking and or dieting  .

One thing you may want to keep in mind though, is the fact that the overall calorie deficit of ~40% may still have been a little to high - it was not enough to elicit a significant reduction in the resting metabolic rate, but still enough to induce a loss of at least 30% of lean mass. A lower caloric deficit 20-30%, a little more patience and a focus on hypertrophy-specific weight lifting are thus probably a way more significant difference, than whether you consume 1.6g/kg or 2.4g/kg body weight.

References: 

• Pasiakos SM, Cao JJ, Margolis LM, Sauter ER, Whigham LD, McClung JP, Rood JC, Carbone JW, Combs GF Jr, Young AJ. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013 Jun 5. [Epub ahead of print]

Six Cups Of Coffee (900mg/day): Three Too Much or Just About Right to Speed Up Lipolysis & Fatty Acid Oxidation?

The human equivalent of almost 900mg caffeine per day used in the study at hand did some good, but it also did some harm - read more and decide for yourselves which one you'd consider more important.

It amazes me time and again. Coffee and caffeine in particular are unquestionably the best-researched "supplements", nutraceuticals, drugs, or whatever you want to call. Yet, nevertheless, the number of interesting studies is increasing day by day. Let's see... 2.3+ studies related to caffeine in one way or another were published per day in 2012 and as of now it looks, as if we would easily top that this year. But enough of those stats. Let's get to one of the latest of the 515 hits for this year and take a look at what Eun-Young Choi and Yun-Ok Cho from the Department of Food and Nutrition at the  Duksung Women's University in Seoul has to bring to the table.

What? Another rodent study?

Yeah, I hear you. I would also prefer if the Korean scientists had taken human subjects fed them a standardized diet and gave them water with 0.12 g freeze-dried instant coffee/100 g body weight for 4 weeks, but I hardly doubt the Ethics Committee would have approved of the guys and girls being sacrificed and their organs being harvested at the end of the 4-week period to check, whether or not the combination of coffee supplementation, which was combined with a chronic exercise (treadmills for 30 minutes; 5 d per week, 15° incline, 0.5-0.8 km/h; the dosage was chosen to approximate maximal quantity reportedly consumed by physically active individuals, i.e. 895 mg of caffeine/60 kg/d) regimen in 50% of the animals exerted independent (c) or combined effects on the organ weight liver as well as the liver and muscle glycogen content or not (data see figure 1).

 Figure 1: Effect of acute exercise, training (=chronic exercise) and chronic caffeine intake on heart, spleen, liver and visceral fat weight  (left), serum glucose and liver and muscle glycogen (Choi. 2013)

Luckily, it is quite unlikely that the overall effect of training + supplementation, of which you can see in figure 1 that only the former or a combination of both did have significant effects on heart weight, visceral fat and liver glycogen content, would have been fundamentally different, if the study had been conducted on human beings.

"The heart weights were significantly higher in the two training groups (TC, TCF) than the two control groups (NTC, NTCF). The combined visceral fat masses were significantly lower in the two training groups (TC, TCF) than the two non-training groups (NTC, NTCF). No significant effects on spleen and liver weights were being observed." (Choi. 2013)

As far as the caffeine or rather "simulated coffee consumption" is concerned, however, only the change in liver glycogen was affected. Particularly,

• the chronically trained, caffeine guzzling rodents exhibited the higher liver glycogen levels (measured before acute exercise), while 
• the animals in the non-trained caffeine guzzling group who had been sacrificed immediately after a final short bout of exercise at the end of the fourth week had the lowest liver glycogen concentration 

Overall, "coffee intake decreased liver glycogen levels in the T group, but no significant differences were observed" (Choi. 2013) in the non-trained animals. The muscle glycogen levels, on the other hand, were not significantly effected by caffeine intake. The 4 weeks of training, on the other hand induced a statistically significant increase in muscle glycogen (after rest) in the trained vs. untrained group of rodents - an observation that has previously been made in human studies, where chronic exercise in the presence of adequate carbohydrate nutrition will progressively increase the size of the muscular glycogen stores (supercompensation principle).

Similar to the increase in muscle glycogen during the 4-week training regimen, the observation that all training and/or supplementation regimen increased the amount of free fatty acids (FFA). What may come as a non-necessarily positive surprise to everyone with elevated baseline FFA levels, though is that addition of caffeine to the equation effectively doubled the training induced increase in resting FFA levels in the caffeine + training group. The beneficial effect of training on liver and muscle triglyceride levels, on the other hand, was not significantly impaired. And what many of you will probably deem about as important: caffeine did not affect the muscle, liver and plasma protein levels.

So what did the study find then?

If we summarize the above, the main findings of the study at hand were not exactly revolutionary, but there were some. Worth mentioning are ...

1. 

   Suggested read: "Coffee - The Good, The Bad & The Interesting: 2-4 Cups of Coffee for Adiponectin. Roasted Filtered Coffee & High LDL!? The Optimal Caffeine / Taurine Ratios & the Buzz ". Learn more about the good and bad sides of coffee / caffeine and find out whether taking taurine may buffer the side effects w/out compromising the benefits of exuberant amounts of caffeine, as they have been used in the study at hand? Or will it make things even worse? It certainly won't hurt the liver that's for sure (read more).

   an increase in free fatty acid release and usage during workouts (already well-established), which resulted in slightly more significant reductions in visceral fat, when training and caffeine were combined, 
2. a highly desirable and significant reduction in liver fat in the trained rodents "on coffee" (all day), and a greater reduction in liver trigs in the animals that were only exercised once
3. a more pronounced "in-and-out" of muscle triglycerides in the trained coffee guzzlers with significantly higher levels of muscle triglycerides before and significantly lower muscle triglyceride levels after a workout (probably a mechanism which contributes to the endurance boosting effects of caffeine; Sherman. 1995)
4. a (surprising?) null-result for changes in plasma glucose that should put the "caffeine will give everyone diabetes" fears at rest; you should however remember that the FFA increase can generally become problematic overtime, if there is a concommittant influx of fatty acids from the diet and no fasting / exercise to keep the overall levels in check
5. a significant reduction in glyocogen storage in the liver after a workout, of which I am yet not sure if this was not a result of a reduction in hepatic glycogen depletion due to the increase in fatty acid oxidation (the scientists do state that the training + caffeine group had the highest glycogen levels in the rested state)
6. no effects on muscle glycogen or protein, and no effect on protein levels in other tissues due to caffeine
7. a significant reduction in hematocrit in the coffee group the scientists ascribe to the hampered absorption of dietary iron

The overall image that emerges is thus rather a negative one - allegedly the increased visceral fat loss in nice, but it is not statistically significant compared to training alone (low iron = low oxygen carrying capacity = low performance; plus: low iron also hampers fatty acid oxidation so that even this benefit may be lost over time.

Another thing Alex Leaf, without even knowing it, reminded me about are the night-sweats and the 4AM wake up call, I know only too well from my own experience with copious amounts of stimulants. They could in fact be brought about by the inability to regenerate liver glycogen fast enough and the subsequent failure of providing your body with glucose from the liver while you sleep. This in turn will have you go hypoglycemic overnight. Your body reacts by spilling out stress hormones that will heat and wake you up...

---

Those three cups are probably as good as it gets, they protect your heart and can ward off cancer (learn more).

Bottom line: In view of the observed downsides, of which I would argue that (5) may actually be the worst for a healthy athlete, the study at hand appears to underline what I have told you before: the consumption of the equivalent of 800-900mg of caffeine per day is clearly counter-indicated even if you don't consume it all at once, and alongside its natural co-factors in coffee (learn more about coffee).

Stick to max. 400mg per day and you are more likely to get the benefits without the sides, about which you have read only a couple of days ago in a SuppVersity article discussing the acute ergogenic effects and accompanying side effects of different doses of caffeine (read more).

References:

• Sherman WM, Leenders N. Fat loading: the next magic bullet? Int J Sport Nutr. 1995 Jun;5 Suppl:S1-12. Review.

Want to Benefit from Plant Sterols? Eat Whole Food or Take Supplements With Meals. Plus: Do You "Benefit" at All?

This is not a joke by a blogger this is how Unilever advocates to use their Flora pro.active product to consumers, who "want to lower your cholesterol and follow a healthy diet and lifestyle."

Pharma companies and supplement producers are notorious for picking foods apart and providing you with concentrated extracts of the "active ingredients".

Aside from the fact that more often then not, the activity of those "active ingredients" is critically dependent on co-factors that are lost during the isolation and extraction processes, scientists from the Division of Gastroenterology-Hepatology at the Department of Internal Medicine of the Maastricht University Medical Center have now been able to show that the mere presence of the bulk in which plant sterols would come in the natural form is critically important to their effects.

Can you achieve a "healthily"(?) low cholesterol level by guzzling tuckloads of low-fat yogurt drinks!?

Based on the negative outcomes of previous studies into the benficial effect of "functional" foods or dietary supplements enriched in plant sterols, D. Keszthelyi had hypothesized  that

"100 mL drink, when consumed before a meal, would empty fast from the stomach and would not sufficiently trigger gallbladder emptying, whereas ingestion with or after the solid meal would enable the necessary physiological changes to aid inhibition of cholesterol absorption" (Keszthelyi. 2013)

To test this hypothesis the researchers recruited a total of 12 healthy male subjects (age, 25 ± 3 years; BMI, 23 ± 2 kg/m²) who reported the scientists' lab on three separate test days with one-week washout between test days.

Does the Paleo diet ruin your cholesterol levels as the conclusion to a recently published thesis would indicate (learn more)?

On each of the days, the participants consumed a Phytosterol (PS) containing yoghurt drink (100 mL, Becel Pro-Activ with PS added as their fatty acid esters (3.2 g, equivalent to 2.0 g PS), either

• 45 min before (test condition A), 

• during (test condition B), or

• 45 min after (test condition C) 

the consumption of a 500 g macaroni meal (Macaroni Bolognese, Henri, Drunen, The Netherlands) at lunch time (I know not the ideal, but for the average Westerner a realistic test meal). T

he sequence of the test days had been determined by a random pre-selection prior to the start of the study. During each test day, gastric emptying of the test drink as well as the effect of the test drink on gallbladder volumes were determined (figure 1, left):

Figure 1: Gastric emptying (left) and gallbladder volume (right) depending on the time of ingestion of a phytosterol containing yogurt drink (Keszthelyi. 2013)

As the results go to show you the ingestion of the functional food before the meal resulted in the fastest gastric emptying. The ingestion with or after a solid meal, on the other hand, caused a significant contraction of the gallbladder.

"Accepting the postulate that concurrent presence of PS with dietary and/or biliary cholesterol in the small intestine is an important mechanism for the LDL cholesterol-lowering action (Ostlung. 2004), a significant stimulus leading to gall- bladder contraction with simultaneous delivery of the PS-containing food format from the stomach into the duodenum is required. It is therefore important to ascertain which stimuli are able to elicit this postprandial response to a sufficient and desirable degree." (Keszthelyi. 2013)

This is actually interesting, because in the end it means that cholesterol clearance, even when it's induced / supported by questionable supplemental phytoestrogens critically depend on fat intake! This in turn would explain why the rodents in the "optimal diabesity diet study" from one of the recent installments of the Short News found elevated cholesterol levels only in the high sugar and high fat + high sugar groups, yet not in the rodents on a high fat diet. One thing to keep in mind, though: The main reason I picked and posted this study is not to pimp the use of phytosterol-spiked imho dys-functional junk food. It's rather to raise your awareness of the importance of the whole nutrient matrix in terms of the effects of the individual agent.

If you want to do something for your blood lipids, you better eat more eggs than overpriced Frankenfood. The eggs will not only improve your cholesterol particle profile, the regular consumption of whole eggs will also increase HDL's ability to carry lipids out of the macrophages. If these accumulate, they will turn the macrophage into pro-atherogenic foam cells (learn more).

In how far the isolation is also behind the previously observed side effects of plant sterols and stanols, which are likewise used in functional foods remains questionable, but it is not unlikely that sides such as

• abortion of pregnancy in animal models (Burckh. 1982)
• reduced sperm concentrations & testis weights
• neg. effects on the vascular system (Boberg. 1991)
• increased intestinal tumor formation (Marttinen. 2013)

are eventually also a consquence of the absence of important co-factors, when the sterols and stanols are removed from their original food matrix and "transplanted" into yogurts, margarines and all sorts of overly expensive and at best useless Frankenfoods.

References:

• Boberg KM, Pettersen KS, Prydz H. Toxicity of sitosterol to human umbilical vein endothelial cells in vitro. Scand J Clin Lab Invest. 1991 Oct;51(6):509-16.
• Burck PJ, Thakkar AL, Zimmerman RE. Antifertility action of a sterol sulphate in the rabbit. J Reprod Fertil. 1982 Sep;66(1):109-12. 
• Keszthelyi D, Knol D, Troost FJ, van Avesaat M, Foltz M, Masclee AA. Time of ingestion relative to meal intake determines gastrointestinal responses to a plant sterol-containing yoghurt drink. Eur J Nutr. 2013 Jun;52(4):1417-20.
• Ostlund RE Jr. Phytosterols and cholesterol metabolism. Curr Opin Lipidol. 2004 Feb;15(1):37-41.

Don't Want to Become Bulky, Just Toned & Strong? A Basic Weight Lifting Routine, Time & Consistency Let's You Achieve Both Without Eating Cotton Balls

Basic weight training to get toned, or hours of cardio in the evening and cotton balls a la pret-a-porter for launch, you got the choice. A choice between health and happiness and chronic fatigue and misery.

The unwarranted fear of getting "bulky" (whatever that may be) is still looming large among the female gym-goers. And since the same goes for the adherence to unnecessary and highly counterproductive hours of "cardio" (*) training in the "fat burning zone" (that is the zone that will burn you out, but not your fat away), I thought it may be nice writing about the results from a recent study that was conducted at the University of Extremadura in Cacare, Spain (Timon. 2013)... If you are now expecting another "revolutionary 2 weeks to your beach body" program, I will yet have to disappoint you. In fact, the only thing that is special about this study is that the thrice a week resistance training regimen the 20 women (age 21-23y) followed was not special, at all. It is rather so conventional that is sounds almost boring and guess what? That's the secret!

*Note: There is nothing to be said against "cardio" training, but if you want to up your cardiovascular capacity you got to challenge your heart, so HIIT for VO2Max increases and nothing but a fast-paced walk on an incline to get some baseline activity into a sedentary day are the tools you should use - no more "training in the zone!"

The scientists had picked their study participants using the following criteria: Healthy physical condition, non-smokers, sedentary or recreationally active (engaging in B20 min of vigorous intensity exercise three or more times per week over the 3 months prior to the study), no use of pharmacologic contraceptives or other medications that might interfere hormone levels, no self-reported endocrine abnormality (diabetes, thyroid or liver disease), self-reported regular menstrual cycles (cycle 25–32 days long) and not to be pregnant. The emphasis on the menstrual regularity actually hints at the real background of the study, which was originally conducted to "evaluate urinary steroid profile across the menstrual cycle phases in healthy women, checking urinary steroid excretion before and after a strength training program" (Timon. 2013); a research question that would obviously also be relevant with respect to what you've read / learned in the SuppVersity Athlete's Triad Series (read more).

Lifting weight increases strength, tones  and leaves the endocrine system intact

The measured changes were yet not so pronounced that you could draw any meaningful conclusions on whether or not a reasonable training regimen like this could skew the menstrual regularity of previously healthy young women. In fact, Timon et al. actually suggest that they could be exploited to increase the benefits from strength training:

The best workout is always the one you can stick to. And the 8% body fat in 10 weeks crossfit workout you read about before does not really fulfill that criterion.

"Focusing on hormonal variations across the menstrual cycle, changes in estradiol and progesterone excretion were observed during the follicular and luteal phases, following a similar pattern both before and after training. [...] Given that there is a high correlation between the blood and the urine steroid profile [...], a large excretion would indicate a rise in ovarian production of estradiol and progesterone during these phases. Based on these hormonal variations across the menstrual cycle, some studies have stated that muscle hypertrophy and strength gain are higher in the luteal phase than in the follicular phase Sakamaki et al. (2012)." (Timon. 2013).

Apropos benefits: What was it about the toning effect? Well, if you take a look at the exercise program, it included neither "toning" exercises nor "cardio" training - just a 10-15 minute warm up with general and specific exercises that was followed by 3x sets of 9-10 repetitions for each of the seven strength exercises:

• 

  Topical fat loss? Thought you may be interested to hear that a 1995 study found that a combination of forskolin, yohimbine and aminophylline (applied 5x/week for 4 weeks) can actually "spot-reduce" body fat. The figure above shows the effect of 10% aminophylline, the most potent of the three agents on thigh circumference in isolation (Greenway. 1995)
  dumbbell lateral deltoid, 

• leg press, 
• hamstring curl, 

• bench press, 

• seated pulley dorsal, 

• dumbbell bicep curl and 

• seated French press

The 2 min recovery time between sets and the 3 min between exercises don't look much like "toning specific" either and the 70–75 % of one repetition maximum (1-RM) are obviously too much to train for strength endurance, of which the average woman's magazine will tell you that it was the way to go to give your muscle that anorexic cover model shape (dunno if you realize that, but that look does not come from muscle, but from sinews and bones, but alas... I don't want to rant).

Figure 1: Body composition, and 1RM strength before and after the 24 training sessions (Timon. 2013)

As the scientist point out, the effects would probably have been more obvious, if the training program had been "accompanied by a specific diet to improve the muscle hypertrophy" (Timon. 2013). But hey, you did not want to build too much muscle anyway, right? And did you lose 1% body fat in the course of the last 2 months without dieting or torturing yourself on the elliptical or stairmaster in your gym? No? That's what I thought. If you did the latter it's in fact more likely you lost much of your power, some muscle and - in the case you accompanied your "toning" exercises with a low calorie diet your menstrual regularity.

---

Learn how to thrive without a scale and program success (read more)

Bottom line: It does not alway have to be a fancy routine to make slow, but significant progress towards improved health and a better physique - and that's true for both women and men. I mean, come on guys 6% more muscle and 6% less fat* in a year with only three workouts per week, no hours of cardio or scary high intensity workouts is better than nothing (*this hilarious calculation assumes that the progress remained constant for a year)!?

Be honest with yourself : Did you achieve that in the past 12 months or were you too busy jumping from one "quick fix solution workout" to the next while constantly scaring the hack out of yourself when you did or didn't see the tongue of the scale moving?

References:

• Greenway FL, Bray GA, Heber D. Topical fat reduction. Obes Res. 1995 Nov;3 Suppl 4:561S-568S. 
• Sakamaki M, Yasuda T, Abe T. Comparison of low-intensity blood flow-restricted training-induced muscular hypertrophy in eumenorrheic women in the follicular phase and luteal phase and age-matched men. Clin Physiol Funct Imaging. 2012 May;32(3):185-91.
• Sowers MR, Crutchfield M, Richards K, Wilkin MK, Furniss A, Jannausch M, Zhang D, Gross M. Sarcopenia is related to physical functioning and leg strength in middle-aged women. J Gerontol A Biol Sci Med Sci. 2005 Apr;60(4):486-90. 
• Timon R, Corvillo M, Brazo J, Robles MC, Maynar M. Strength training effects on urinary steroid profile across the menstrual cycle in healthy women. Eur J Appl Physiol. 2013 Jun;113(6):1469-75.

A Low Fat Advantage For Alternate Day Fasting? While the Improvements in Body Composition Are Virtually Identical, Only the 25% Fat Diet Will Improve Arterial Blood Flow

If I know anything for sure, it is that the reason your midsection does not look like this, but rather like the one of Melissa McCarthy is not a result of the fact that your diet contains 24% instead of 48% fat.

Outrageous, right? What? Well, the title of this post. I mean even the use of the term "low fat advantage" is probably going to piss a couple of people off, these days. So, please low carb crusaders, don't kill the messenger, it was not my idea to put 32 obese subjects (mean age 43y) onto alternative day fasting regimen that provided either 45%  (ADF-HF) or just 25% (ADF-LF) of the energy in form of fat (25% fat) and to observe what happens to their almost 50% fat (46kg of pure fat on 96kg of total body weight) bodies during a 2-week baseline weight maintenance period and an 8-week alternative day fasting weight loss period, in the course of which all foods were provided by the research team at the Department of Kinesiology and Nutrition of the University of Illinois at Chicago (Klempel. 2013).

"Still outrageous, almost blaspheme!",...

... well, so were the results: There were no differences in body weight or body fat loss and as Klempel, Kroeger, Norkeviciute et al. point out "improvements in FMD [brachial artery flow mediated dilation] with ADF [alternate day fasting] may only occur with LF diets and not with HF diets" (Klempel. 2013). Or put simply - as a really obese individual, you would not really have to worry about your carb/fat ratio, if getting lean was all you were concerned about. If you want to improve your heart health, though, it appears prudent to follow a relatively low fat intake - keep in mind 25% is still more than enough to get all the fat you need for your endocrine system to keep functioning.

"Gimme the details on the study protocol!"

So, now that you've got the basic message, let's take a look at how these results actually came about: The subjects had been recruited from the Chicago area based on the following inclusion criteria: Female, age 25–65 years, body mass index between 30 and 39.9 kg m², stable weight for at least three month before the intervention, nondiabetic (this does not mean they were not insulin resistant, but it means their pancreas was not already damaged), no history of cardiovascular disease, sedentary or lightly active for at least 3 months before the beginning of the study, non-smoker, and not taking weight loss, lipid-lowering, or glucose-lowering medications. There were N = 17 an N = 18 subjects in the high and low fat groups respectively (randomized) and the total duration of the study was 8 weeks.

• 

  As usual, there are arguments (though not from fasting studies) on both sides of the divide; studies where people are only given lose instructions and no foods, do yet often produce very questionable results (learn more).

  as mentioned before, all food was provided throughout the 10-week trial to all subjects; the diets were provided as a 3-day rotating menu consisting of typical American foods; participants were requested to eat only the foods provided and to bring back any leftover foods to be weighed and recorded
• moreover, subjects were instructed to keep track of all food items consumed using a ‘Food checklist’, and to report any extra food item consumed using an ‘Extra food log’. If the log indicated that the subject ate extra food items (totaling 450 kcal) on a feed or fast day, that day was labeled as ‘not adherent’.
• hunger, satisfaction and fullness were assessed using a questionnaire with a validated visual analog scale on each fast day; the form was completed in the evening, approximately 5 min before going to bed
• participants had to wear a pedometer each day throughout the 10-week trial, to record the free-living physical activity 
• during the active weight loss pahse (weeks 3-10) subjects consumed 25% of their energy needs on the fast day (24-h period) and 125% of their energy needs on the feed day (24-h period)
• feed/ fast days began at midnight each day
• fast day meals were consumed between 12pm and 2pm

• 

  Most formulas that are used to calculate your energetic requirements are about as "accurate" as the reading from the globe in Anelina,... ah Lara's hand (learn why)

  the same macronutrient composition was used during the weight loss and weight maintenance periods for each group, with...
• ADF-HF (45% fat, 40% carbohydrate and 15% protein),
• ADF-LF (25% fat, 60% carbohydrate and 15% protein)
• the fats in the diets consisted of
• ADF-HF (14% saturated fat, 20% monouns. fat, 11% polyuns. fat and 0% trans fat) and 
• ADFLF (6% saturated fat, 13% monouns. fat, 6% polyuns. fat and, 0% trans fat)
• the energy requirements were calculated at the beginning of the study and at the beginning of the weight loss intervention using the Mifflin–St Jeor equation, using an "activity factor" of 1.2 (=sedentary; learn more about the equation)  

The body weight measurements were taken weekly, and fat as well as fat-free mass (FFM) were reliably assessed by dual-energy X-ray absorptiometry at baseline and week 8, while the waist circumference was simply measured with a tape to the nearest 0.1 cm, midway between the lower costal margin and super iliac crest during a period of expiration.

"Ok, that's enough, what about the results"

Wow... now, that you know all the important and less important details about the methods, it's about time to eventually look at the actual outcomes of the study:

Figure 1: Changes in body composition (left) and adipokine levels (right) from week 0-8 (Klempel. 2013)

It does not take a rocket scientists to see that the inter-group differences were marginal and statistically non-significant. What's also interesting, is the fact that the weight of the high fat diet group decreased significantly more during the baseline weight maintenance period (2.1±0.4 kg vs. 1.7±0.4 kg). Funnily, this was a period in which all subjects followed the same low(er) fat diets consuming what the scientists calculated would be their maintenance intake (note; this does tell you something about how much those guys usually ate and "why they were fat" to begin with - the girls ate too much).

Low fat and satiety, how does this go together?

What is quite astonishing - and this goes against everything you'll hear on the Internet about the downsides of "low fat" and the benefits of "high fat diets" - is that the subjects in the low fat group, were slightly less hungry (25 vs. 24), experienced a significantly larger increase in satifsaction (+26 vs. +1) and fullness (+20 vs. -17) and did not decrease their daily activity level to the same extent the high fat dieters did (-157 vs. -644).

Looking at the absolute levels, not the differences from baseline, the image is yet less clear. In absolute terms, the satisfaction and fullness levels, of which the scientists point out that it "started out low in the LF group, but gradually increased over 10 weeks" (Klempel. 2013).

Still, it were the participants in the low fat group who saw greater improvements in adiponectin (51±7% vs. 43±7%), a less pronounced drop in leptin (30±3% vs. 32±5%) and a minimally greater improvement in resistin (27±4% vs 23±5%; cf. figure 1) levels, none of which was found to correlate with fat mass loss and can thus expected to be diet and not fat loss specific. Furthermore, it is, as the scientists point out, well possible that it is at least partly due to these changes in adipokine expression that the low fat group saw improvements, the high fat group further deterioration in brachial artery flow mediated dilation:

Insulin is a natural NO booster: You may remember having read about it on the SuppVersity Facebook wall. Insulin has a direct effect on the NO induced widening of the arteries - as long as the cells in the arterial wall, are not already insulin resistant, that is (cf. Rajapakse. 2013). Since intermittent / alternate day fasting will help restore this insulin sensitivity, the increase in FMD could well be "insulin-dependent", as well.

The role that leptin and resistin have in mediating FMD most likely involves changes in the production of NO. More specifically, leptin and resistin blunt the production of NO, which likely occurs through the stimulation of reactive oxygen species that scavenge NO and impair endothelial NO synthase function. As concentrations of these adipokines were reduced in the present trial, we would assume that there would be less leptin and resistin in the circulation to inhibit NO. This would lead to a higher production of NO, resulting in an enhancement in endothelium-dependent vasodilation. The reason why these decreases in leptin and resistin did not contribute to increases in FMD is unclear. However, it is possible that greater decreases in leptin (450%) would be necessary to improve FMD." (Klempel. 2013)

As mentioned before, the other differences are actually not worth discussing and if it was not for the statistically significant improvement in the flow-mediated dilation of the brachial-artery (+2.1%), which was absent in the high fat group (-1.8% reduction in FMD, you would be hard pressed to find arguments in favor of any of the diets.

---

The evidence for or against low vs. high fat diets is far from being conclusive. I guess that's also why the "war" between the proponents of one or the other way of eating is fought with with no holds barred.  There is still much to be learned and many results, such as the non-fattening effects of low fat diets on a caloric surplus go against the unique and all-across the board, one size fits it all benefits of low carbing (learn more)

So what's the verdict then and are there implications for true intermittent fasting? Well, first of all the differences are not large enough to warrant the scientists' implicit assertion that "only" the low fat alternative fast was beneficial. On the other hand, the results of the study at hand clearly disprove the current Internet paradigm that a higher fat and lower carbohydrate intake would yield more pronounced fat loss and greater satiety not only, but especially, when the diet involves long phases of "not eating" aka fasting.

That being said, it is not warranted to draw any reliable conclusions wrt to a "lean gains" type of intermittent fasting in athletic individuals based on the study at hand. In my humble opinion, there is yet no good reason that would speak in favor of going low carb either. This is particularly true if you are adding a reasonable workout routine that goes beyond doing a one-rep max effort per day to exponentiation the results of the diet. In that case, you are better off providing your muscles and liver with glucose directly than having the latter produce it from protein (first) and fat (second), which is what will necessarily happen unless you are eating so little protein that you actually make it into full ketosis.

References:

• Klempel MC, Kroeger CM, Norkeviciute E, Goslawski M, Phillips SA, Varady KA. Benefit of a low-fat over high-fat diet on vascular health during alternate day fasting. Nutr Diabetes. 2013 May 27;3:e71.
• Rajapakse NW, Chong AL, Zhang WZ, Kaye DM. Insulin-mediated activation of the L-arginine nitric oxide pathway in man, and its impairment in diabetes. PLoS One. 2013 May 2;8(5):e61840.

Yerba Mate, Yohimbine & Yucca - Potent Fat or Unhealthy Money Burners? Tea Catechins Were Yesterday, Saponins Are the Future! GMO Rice "Safe for Human Consumption"?

Are you living in one of the hotspots of diabesity and laziness? Check out the map in the bottom right of my little collage and find out what the CDC data from 2008 can tell you about the regional differences in the US. Which are the top (=healthy & active; violet) and which the flop (=diabetic and sedentary; blue) counties in the US?

58%, that's not just the SuppVersity Figure of the Week it is also statistical testimony to the superiority of lifestyle interventions over drugs. Why? Well it is the rate by which even the CDC admits the diabetes risk of the average US citizen would drop, if he or she lost 5-7% of body weight (I know, I would likewise prefer a body fat number) and increased their "exercise" level to 150min of brisk walking (or more intense exercise) per week.

I know this is nothing new to you, but we all know one of these people who are subservient to "authorities" and like to get their (often oversimplyfied) advice right from the feds. So I suggest you just email the introduction to this article along with the picture on the right to this person... in 99% of the cases it won't help, but who knows, maybe he or she asks you if you can help!?

I am pretty sure that a diligent student of the SuppVersity as you are will have no problem whatsoever with getting him / her set up for a healthier and consequently longer life - right?

The SuppVersity short news for calender week 24 | read all previous installments

A-Z Supplement Review - "Y" as in Yerba Mate, Yohimbine & Yucca (Godfrey. 2013) -- If you have been following the SuppVersity Facebook News for more than just the past 3 weeks, you will have heard about the "A-Z Supplement Review" series, the British Journal of Sports Medicine has been running for years, now. Meanwhile they have arrived at "Y" (for thematic reasons they did not stick to the A-Z sequence with every article in the past, though); and in this issue S.J. Stear, RJ Godfrey and MW Laupheimer have compiled mini-reviews on the usefulness of yerba mate, yohimbine and yucca, respectively.

"In sport, yohimbine is perceived to reduce body fat and mobilise lipid, as well as to enhance endurance. Accordingly, it is often used in bodybuilding and other aesthetic sports, and in sports where there is a significant aerobic component. However, despite these claims, research findings actually refute any ergogenic benefit for sport (Ostojic. 2006; Herda. 2008) In addition, [...] adverse effects have been established."

I know, I know the highly questionable fat loss in the Ostjic study would speak a different language, but it has never been replicated in another trial. In fact, a previous study in 43 men using dosages of 41(!) mg/day did not observe any effects on body composition (Sax. 1991). And a more recent review by Climolai et al. states "There is no conclusive evidence for this drug to be of benefit in bodybuilding, exercise tolerance, physical performance, or desirable alterations of body mass." (Climolai. 2011)

Did you know that mate has about the same amount of caffeine than coffee? 150ml = 75mg; according to Stear for coffee that's what you get from ~250ml with most roasts... I have my doubts about that, and would rather believe that the content is about identical (usually the caffeine content of coffee is said to be 55-85mg/100ml). Still, being rich in chlorogenic acid and caffeic acid mate could probably serve as a replacement for regular coffee, for those who don't like the taste of coffee.

Don't despair, we do still have two other supplements in the review, so let's see... what about yerba maté? Being made of dried leaves of the Ilex paraguariensis tree this tea has been widely consumed in South America for centuries. Maté tee contains numerous active phytochemicals of which chlorogenic acid and the xantines caffeine and obromine are the most abundant ones. It does yet also contain alkaloids (caffeic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid), flavonoids (quercetin, kaempferol and rutin), amino acids, minerals (phosphorus, iron and calcium) and vitamins (C, B₁ and B₂).

That certainly sounds promising, unfortunately the evidence on its ergogenic effects is not conclusive and while it has been shown to be hypocholesterolaemic, hepatoprotective, a central nervous system stimulant, diuretic, antioxidant, of benefit to the cardiovascular system, and associated with both the prevention and increased risk of some types of cancers (Heck. 2007), Stear is right that the high amount of active ingredients will also increase the risk of unwanted side effects - or as my friend Carl likes to say: "The good thins is that yerba maté works, the bad thing, on the other hand, is that it works [and thus has effects and side effects]" ;-)

A major problem about yucca, the last item on the list is probably that there is no such thing as a specific yucca plant. The term "yucca" refers to a whole series of 40–50 medicinally potent plant species that generally thrive in arid parts of southwestern USA and Mexico. As Laupheimer points out:

While yucca is actually one of the few supplements I have not yet covered on the SuppVersity, you may want to read up on the leptin sensitizing effects of yerba maté in a previous article (read more)

"The yucca extract is widely used as an animal feed additive to increase growth rate, improve feed conversion efficiency and to ease joint pains in horses and dogs. Yucca has also been shown to have antioxidant, anticancer, antidiabetic, antimicrobial and hypocholesterolaemic properties. [...] Yucca saponins are precursors to cortisone. Yuccaols and resveratrol, which are mainly found in the yucca bark, are known to have a variety of actions, including inhibitors of the nuclear transcription factor κB (NFκB) and thus anti-inflammatory, antioxidant and free radical scavengers In addition, resveratrol has been shown to have an influence on muscle fibres, strength and possible ergogenic effects."

As usual there is yet insufficient evidence to formulate scientifically warranted dose recommendations and  evidence of ergogenic benefit in sports performance is missing.

---

Bottom line: From the three "Y"s in the latest installment of the Supplement Review, maté is probably the one with the best scientific support for it's ergogenic effects. If nothing else, the high caffeine content alone would classify the South American tea as a performance booster. The most promising agent may in fact be the yucca extracts, but it is certainly premature to recommend taking respective supplements.

And what about yohimbine? It's if anything useful during a fast on a very hard diet + exercise regimen to further the release of fatty acids from the "stubborn fat areas", where alpha- instead of beta receptors are the main mediators of FFA release. If you want still want to try it, make sure you use the clean HCL version - with the extracts you have no idea what it is you are actually getting.

~ ~ ~ ~ ~ ~

Catechins are so yesterday, tea saponins are the future (Yu. 2013) - You will be aware that we have long ascribed the beneficial health effects of green, black, white and other teas to the catechins (e.g. EGCG, ECG, etc.) they contain. A recent study from the University of Wollongong in China does now suggest that we may have been missing an important part of the natural (not proprietary ;-) anti-obesity blend in the Camellia sinensis (that's the scientific name of the "tea plant") brews we have been making for centuries.

Figure 1: The restored leptin sensitivity is probably the reason why the rodents did not overeat and thus returned to and maintained a relatively normal body weight (Yu. 2013)

Tea saponins! This is a term by which the researchers refer to a whole class of triterpenes that are present in different concentrations in various types of tea. These molecules are natural antagonist of the NF-kB signaling and have anti-inflammatory potential.

No wonder Yu et al. suspected that they could be used to treat diet induced obesity. To validate this hypothesis they fed a group of mice a high fat diet for 40days. At the end of that period all rats were obese, inflamed, insulin and leptin resistant. Another 21 days and thus 21x 10mg servings of 96% pure tea saponins from Aladdin Chemistry Co. Ltd, China, later 50% of the mice were not exactly lean, but had achieved a new, lower maintenance weight (see figure 1).

Based on the data they have, the scientists concluded that these benefits were brought about by the rostoatin of brain leptin sensitivity that went hand in hand in with increases in insulin sensitivity... hold on insulin sensitivity? Yeah that's right and you are not mistaken, both, leptin and insulin were in the news today, before. In the face book news, to be precise: "There is no such thing as 'leptin resistance'" (read more)

---

Wrong! Fat does not ameliorate, but potentiate the insulin response to carbs (learn more)

Bottom line: If we take the decreased inflammation, the ameliorated weight gain, the increased expression of POMC neurons low levels of which which have previously implicated in human weight gain (learn more), and the other beneficial effects Yan et al. observed in the study hand  and combine that with the previously mentioned hypothesis by Nazarians-Armavil, Menchella and Belsha.

The message is thus quite clear: Tea saponins are a potent insulin resensitizer. Once they have done their job, and your body is able to "hear" the most important signal in the metabolic concert again, the rest will fall into place.

~ ~ ~ ~ ~ ~

GMO rice safe for rat consumption Chinese scientists say (Yuan. 2013) - While I am not sure whether there are any hidden ties of the Genetically Modified Organisms Breeding Major Projects of P.R. China grant to the usually suspects from the West, it appears unlikely that Monsanto & Co were involved in the latest study from the Laboratory of Food Safety at the College of Food Science and Nutritional Engineering of the China Agricultural University in Beijing.

Figure 2: The short-term safety is accompanied by an unexpected weight gain in the male rodents that starts at weight 6, and does (lucky for the sponsors) not reach significance before the study was terminated (Yuan. 2013)

Now, it still goes without saying that the Chinese government will have a vested interest in developing a GMO variant of their bread-and-butter food item that produces the gram-positive spore-Bt toxin they would otherwise have to apply to the crop to protect it on it's own. It is therefore good news (for the Chinese) that none of the dozen parameters the scientists monitored (microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, intestinal immunity + all the standard measures you can think of) did not show any effect of the chronic ingestion of the BT/GMO rice.

What is yet hidden in the supplemental material that came with the study is the weight development of the rodents. In the course of the hilariously short study (I suspect the researchers wanted to make sure they would not observe anything similar to the tumors that brought their French colleagues right into the headlines of the mainstream media outlets; cf. gofl-ball sized tumors due to GMO corn), there was an unexpected and though not yet statistically significant difference in the weight development of the male rodents in the GMO rice group, who began gaining weight at an increased rate 12 weeks into the study.

---

Bottom line: If you conduct a rodents study and don't chose a study duration that would allow for long-term effects to surface (it should be obvious that this does not apply to a 90-day study period), you can hardly argue that the product you are testing is "safe" for human consumption - well unless we are talking about short-term consumption.

Aside from being able to assess the effects the GMO rice has on cancer rates (remember cancer takes time to grow) and all-cause mortality, even the sudden disconnect in body weight development in the male animals after 6 weeks would - at least in my humble opinion - warrant further studies, before you can unleash the genetically modified beast on your people, but I guess the Chinese official think "wtf. we have enough workers for our economy to flourish and if they die early, we don't have to pay their pensions"...

That's it for this week,...

... and the one thing that's still left to do is to wish all of you an active and happy weekend. Ah..., right. For those of you who still have some time to kill before whatever activity will start, here are a couple of SuppVersity Facebook News, you may want to read before finally starting into the "active part" of the weekend:

• 

  Many of the underlying causes of "self-inflicted hypthyrodism" will also hamper your performance in the gym and elsewhere. Now, what's particularly nasty, is the fact that for many gymrats performance or "looking" good naked, respectively the strive for any or both of the two are the (over-)motivational roots of the misery (read more)

  A new whey (all puns intended) to treat cystic fibrosis (CF) - Researchers from the Macdonald Campus of McGill University in Canada have found that pressurized whey protein hydrolysate could be a cheap and effective way to ameliorate cystic fibrosis | read more
• Are only phospholipid pound "omega 3s" good omega 3s? Paper puts another emphasis on the superiority of phospholipid bound DHA & EPA (as in food) over triglyceride bound DHA & EPA (as in fish oil caps), when it comes to the touted health benefits of high(er) omega 3 intakes | read more
• "No extra-shoes necessary" that's the message a recent study that investigated whether people who overpronate would need special (expensive) running equipment | read more
• Oldie but goldie: If reverse T3 is protein sparing at all, it has no direct effect and works only by blocking the receptor | read more

Alright, now you are good to go. So log out and come back in ~12h for more Facebook news and ~24h for the Sunday's SuppVersity article, of which I believe it will revolve around fasting - alternate day fasting and macronutrient composition... hah, now I got you hooked, right?

References:

• Cimolai N, Cimolai T. Yohimbine use for physical enhancement and its potential toxicity. J Diet Suppl. 2011 Dec;8(4):346-54.
• Godfrey RJ, Laupheimer MW, Stear SJ, Burke LM, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 45. Br J Sports Med. 2013 Jul;47(10):659-60.
• Heck CI, de Mejia EG. Yerba Mate Tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J Food Sci. 2007 Nov;72(9):R138-51. Review. 
• Herda TJ, Ryan ED, Stout JR, Cramer JT. Effects of a supplement designed to increase ATP levels on muscle strength, power output, and endurance. J Int Soc Sports Nutr. 2008 Jan 29;5:3.
• Ostojic SM. Yohimbine: the effects on body composition and exercise performance in soccer players. Res Sports Med 2006;14:289–99.
• Nazarians-Armavil A, Menchella JA, Belsham DD. Cellular insulin resistance disrupts leptin-mediated control of neuronal signaling and transcription. Mol Endocrinol. 2013 Jun;27(6):990-1003. 
• Sax L. Yohimbine does not affect fat distribution in men. Int J Obes. 1991 Sep;15(9):561-5.
• Yu Y, Wu Y, Szabo A, Wu Z, Wang H, Li D, Huang XF. Teasaponin reduces inflammation and central leptin resistance in diet-induced obese male mice. Endocrinology. 2013 Jun 10. [Epub ahead of print]
• Yuan Y, Xu W, He X, Liu H, Cao S, Qi X, Huang K, Luo Y. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement. Sci Rep. 2013 Jun 11;3:1962.