Is Hypoglycemia Obesogenic? Is the GI Totally Worthless? Is Mild, But Chronic Stress Behind the Diabesity Pandemic? Is Leptin Obesogenic? And How Do You Calculate the Energy Requirements of Diabetics?

One of the mistakes researchers and dieters make time and again, using the scale as their only guide

Since I had a couple of interesting, but not earth-shatteringly exciting studies on obesity, body weight gain, the GI, leptin and a couple of other things lying around, I thought I'd compile a brief potpourri for you to get you on par with the helplessness with which researchers are still facing the diabesity pandemic. So don't expect any of the one-size-fits-it-all solutions the scientists still appear to be looking for from any of the following items. What you may find, however, is some inspiration when you read between the lines or follow up on the suggested reads, I mention. And if that's not the case, you can still browse previous articles on fat loss or simply go to the gym and try the fat loss example routine from the SuppVersity "Step By Step Guide for Your Own Workout Routine" or simply go to be early to preserve your circadian rhythm.

• Going "Hypo" time and again will make you fat (McNay. 2012) -- Usually you think of hyogylcemia as a sign of a lack of energy, yet despite the fact that this may well be the case this very lack in energy has recently been shown to exert obesogenic effects in a rodent model.
  
  

  

  Often a picture says more than 1000 words: Normal (left) and repeatedly hypoglycemic rodents after 8 months of weekly insulin injections (McNay. 2012)

  The weekly injections Ewan C McNay and his colleagues administered to their rodents and the subsequent episodes of hypoglycemia lead to profound weight gain in the absence of diabetes, hyperphagia, changes in hypothalamic NPY or POMC mRNA expression and  the other usual suspects that could explain this phenomenon. The one thing that's left is therefore what the researchers call a "multi-faceted deficit in metabolic regulation" (McNay. 2012) - interestingly enough the 69.5% higher body weight at 12 months went hand in hand with the usual laziness (-25% activity) of people whose brains are starving in abundance (e.g. type II diabetics).
  
  What remains to be seen, though, is whether similar effects would occur in response to "regular" non-insulin induced hypoglycemia. In view of the easy with which crash dieters and people with roller-coaster blood glucose levels gain weight, it is yet not unlikely that it is actually the avoidance of (reactive) hypoglycemia and not so so much the prevention of hyperglycemia that makes low GI diets successful for weight maintenance (for weight loss the picture is more complicated, since this will require a energy deficit and that's a game changer).

• Dietary glycemic index and load are not associated with type II diabetes risk in 12,403 Europeans (Sluijs. 2012) -- Apropos GI, scientists from the University Medical Center in Utrecht did not find statistical significant correlations dietary glycemic index and/or glycemic load and the risk to develop type II diabetes in in a subcohort of the European Prospective Investigation into Cancer and Nutrition Study (n = 12,403 participants).
  
  Even when they compared participants in the highest and lowest quantiles, the increase in risk was only 5% and 7% for GI and GL respectively. Since this is by no means the first study that suggests that the still propagated concept of the beneficial health effects "low GI diets" is faulty, I would suggest you rather watch the actual food items, than their respective glycemic indexes if you intend to ward off obesity and diabetes. Potatoes for example may have a high GI (including sweet potatoes, by the way), but their high potassium and overall mineral content, as well as the mere fact that you can hardly eat the same amount of total carbohydrates you can easily annihilate, when you are eating pasta still makes them one of the best sources of starchy carbs you have (learn more in the Potato Manifesto, Part I & II).

• 

  Figure 1: There were no statistically significant difference in terms of weight gain or loss, but the 2-week re-feed had a greater impact on blood glucose and insulin levels in the high GI group (Lagerpusch. 2012)

  There is use for the GI on a bulk or after a diet, but only if you are concerned about insulin sensitivity (Lagerpusch. 2012) -- While the general value of the GI as a means to distinguish good from bad carbohydrate sources is certainly questionable, the recently published results from a study that was conducted at the Institute of Human Nutrition and Food Science, of the -Albrechts University in Kiel, Germany, does suggest that monitoring the GI of your diet and adding additional fiber to reduce the insulin response to your meals can come quite handy, in phases, where you are particularly prone to store body fat. On a bulk, for example, or even more so when you have been dieting and are trying to return to a normal caloric intake.
  
  According to the results Lagerpusch et al. present in the November issue of the British Journal of Nutrition even healthy young men who were subjected to a 3-week diet phase (-50% in caloric intake) and subsequent overfeeding (+50% in caloric intake) the subjects in the high GI study arm had a 135% higher increase in fasting insulin levels during the refeed than those in the low GI group. In view of the fact that the glucose clearance (measured in an oral glucose tolerance test) was identical, it is not only no wonder that the weight gain did not differ either (see figure 1), but also unlikely that we would see significant differences as far as the fat gains are concerned (the latter were unfortunately not measured in the study at hand). At the same time, longer hyper-caloric high GI diets are certainly a risk factor for both insulin resistance and obesity, so that you are probably still at lower risk with 65g instead of 27g of fibre per day and a mean GI of 40 vs. 74.
  
  If you are interested in the influence of different diets on weight gain and health during overfeeding, I suggest you check out the following two SuppVersity posts: "194 Bananas in Three Weeks" and "A Tale of Macro- and Micronutrient Modifications".

• 

  Figure 2: Chronic mild stress leads to an overactivation of the HTPA and subsequen metabolic dysregulations (Takahashi. 2012)

  Further evidence that chronic mild stress is to blame for the obesity pandemic (Takahashi. 2012) -- As researchers from the Tohoku University Graduate School of Medicine in Japan report in the latest issue of the  American Journal of Physiology - Endocrinology & Metabolism, the localized re-setting of the clock genes in the liver, yet not the hypothalamic suprachiasmatic nuculeus (SCN), of BALB/c mice in response to chronic mild stress exposure elevated and phase-shifted serum corticosterone levels (see figure 2).
  
  Takahashi et al. argue that the observed changes are indicative of an overactivation of the HPA axis, which induced disturbances in the rhythmic expressions of core clock genes, e.g. Clock, Npas2, Bmal1, Per1 and Cry1 in the liver and subsequently circadian patterns of glucose and lipid metabolism-related genes such as the proliferator activated receptor (PPAR) family which favor the storage and hamper the oxidation of fatty acids.
  
  If you want to learn more about clock genes and how you can modify them, (re-)read the SuppVersity Circadian Rhythm Series!

• Scientists develop improved formula to calculate the resting energy expenditure of diabetics (Ikeda. 2012) -- While I would hope that you don't belong to the group who would have to use the new and improved formula scientists from the Department of Diabetes and Clinical Nutrition at the Kyoto University in Japan have now proposed, you may have clients or relatives who could benefit from its high predictive validity (78% +/- 103kcal vs. 50% for Harris-Benedict; 38% for Oxford, 42% for Liuand 63% for Ganpule):
  
  
  What you should keep in mind though, is that this equation was tested on Japanese individuals. Since we know from other studies that there are certain metabolic differences between people with different ethnic backgrounds I would remain a "healthy skeptic" as far as the outcomes of this equation are concerned - the same obviously goes for any other equation, e.g. the ones for athletes I provided in part III of the Female Athlete Triad series.

• 

  If you are interested in ways to modulate your leptin levels that may facilitate weight gain, I suggest you take a look at my second "Carbs Past 6PM Won't Make You Fat" post.

  Leptin induced weight gain? 13% more body fat in 2 weeks, when it hits the wrong part of the brain (Harris. 2012) -- With the mixed results from intervention trials, the enthusiasm around leptin has abated over the past months, the general consensus is yet still that leptin and leptin resistance loom large in the metabolic dysregulation that's at the heart of the diabesity pandemic. Against that background, the results Ruth B.S: Harris presents in her latest paper in the American Journal of Physiology - Endocrinology & Metabolism are unquestionably surprising.
  
  When Harris injected twice the amount of leptin (0.6 µg leptin/day) that had previously been shown to decreased 24 food intake, body fat and lean tissue, when it was injected into the third ventricle of the hindbrain, into the fourth ventricle of her lab rats, the rodents gained an almost incredible amount of 13% body fat within only 2 weeks! And that in the absence of statistically significant change in daily food intake, suggests an "increase in efficiency of energy utilization" (Harris. 2012). Fortunately, further experiments showed that the pro-obesogenic effects of leptin in the 4th ventricle was antagonized when both the 3rd and the 4th ventricle were exposed to leptin. In this scenario the leptin exposure of the 4th ventricle did even protect the lean mass of the rodents from the negative effects the exclusive exposure of the 3rd ventricle had. Overall, the study is yet somewhat chaotic and a clearcut message aside from "look people things are even more complex than we already thought", is probably not going to contribute to a solution of the obesity dilemma in the near future. 

There are, as usual more news on Facebook, some of them, such as the relation between hypothyroidism during pregnancy and the diabetes risk of the offspring later in life, are even related to the topic at hand. And if that's nothing you are interested, you may want to read about ...

• the non-existent effects of coffee consumption before bed on the sleep quality of habitual coffee drinkers (read more),
• the problem with inaccurate vitamin D tests and the absence of a reliable and scientifically sound definition of "vitamin D deficiency" (read more), or
• the strength promoting in-vitro effects of sodium bicarbonate, or in other words, a rather alkaline milieu on muscular force production (read more)

... and if neither of those can satisfy your thirst for more information from the realms of exercise and nutrition sciences, you can still wait for the next serving of facebook news or tomorrow's SuppVersity article :-)


References:

• Harris RB. Leptin-induced increase in body fat content of rats. Am J Physiol Endocrinol Metab. 2012 Dec 4.
• Ikeda K, et al. A new equation to estimate basal energy expenditure of patients with diabetes. Clinical Nutrition. 2012 [article in press] 
• Lagerpusch M, Enderle J, Later W, Eggeling B, Pape D, Müller MJ, Bosy-Westphal A. Impact of glycaemic index and dietary fibre on insulin sensitivity during the refeeding phase of a weight cycle in young healthy men. Br J Nutr. 2012 Nov 28:1-11.
• McNay EC, Teske JA, Kotz CM, Dunn-Meynell A, Levin BE, McCrimmon RJ, Sherwin RS. Long-term, intermittent, insulin-induced hypoglycemia produces obesity without hyperphagia or insulin resistance: a model for weight gain with insulin therapy. Am J Physiol Endocrinol Metab. 2012 Nov 20.
• Sluijs I, Beulens JW, van der Schouw YT, van der A DL, Buckland G, Kuijsten A, Schulze MB, Amiano P, Ardanaz E, Balkau B, Boeing H, Gavrila D, Grote VA, Key TJ, Li K, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Roswall N, Sacerdote C, Sánchez MJ, Sieri S, Slimani N, Spijkerman AM, Tjønneland A, Tumino R, Sharp SJ, Langenberg C, Feskens EJ, Forouhi NG, Riboli E, Wareham NJ; on behalf of the InterAct consortium. Dietary Glycemic Index, Glycemic Load, and Digestible Carbohydrate Intake Are Not Associated with Risk of Type 2 Diabetes in Eight European Countries. J Nutr. 2012 Nov 28.
• Takahashi K, Yamada T, Tsukita S, Kaneko K, Shirai Y, Munakata Y, Ishigaki Y, Imai J, Uno K, Hasegawa Y, Sawada S, Oka Y, Katagiri H. Chronic mild stress alters circadian expressions of molecular clock genes in the liver. Am J Physiol Endocrinol Metab. 2012 Dec 4.

Are You Overtraining? Two Scientifically Proven Methods to Test Yourself - Method 1: Heart Rate Variability Analyses

It may sound like the invention of the heart rate monitor industry, but it's a matter of scientific "fact" that HRV analyses are a great tool to monitor and manage training and recovery.

Overtraining, its existence, consequences and detection is and has always been one of the hottest topics in the fitness community. While some practitioners and trainers claim that it does not even exist, others fear it so much that they constantly undertrain. The result? Stagnation.

In the highly competitive world of the average iron-willed gymrat, it's however pretty rare that the gains ain't coming, 'cause he or she is under-training. I would guesstimate that the exact opposite is the case for at least 75% of the self-proclaimed hard-gainers. Overtraining, undereating and/or  a lack of consistency are the stumbling blocks of 99% of the trainees.

I know that you know all that, ...

... so I'll cut this short and get right to the point. Within the past two weeks I hit upon two interesting papers that describe very different, but - in both cases - effective methods to determine whether you are overtraining, or not. While I originally wanted to tackle both in one article, I had to realize that the day has only 24h for my to write and you to read SuppVersity articles. Therefore, I decided to tackle heart rate variability monitoring today and postpone writing about the other to next week's follow up (stay tuned!).

You can learn more about overtraining at the SuppVersity

Heart Rate Variability

ABEL Test

Overtraining & Undereating

Calculate your Energy Intake!

There Are No Magic Macros!

Reinvent Your Training!

I guess you may have heard about the usefulness of the latter on my buddy Carl Lanore's Super Human Radio, already and are thus familiar with the idea that your heart’s ability to produce fluctuations in the beat-to-beat interval in response to different situations. According to José Morales and his colleagues from the Laboratory of Sport Sciences a the Ramon Llull University in Spain,

Don't turn into the guy on the left, don't overtrain & undereat | learn more

"the use of heart rate variability (HRV) as a training tool has progressively increased and deserves attention as a tool to monitor the possible states of overtraining and recovery after a training process. [...] Several studies suggest that the quantification of HRV can be used as a non-invasive method for assessing autonomic  cardiovascular  control  via  the  impact  of  HRV  on  beat-to-beat  heart  rate  modifications." (Morales. 2013)

The relationship between autonomic modulation and HRV is different during exercise and immediate recovery compared to rest periods. This makes the HRV a viable tool for the non-invasive assessment of the autonomic cardiovascular control and a comparatively objective measure of your training status (Camm. 1996; Seiler. 2007; Bosquet. 2008) .

Hold on: What exactly is my HRV? Actually it's much less complicated than terms like fourier-transforms and frequency domain suggest. If you say "my heart rate is 60 beats per minute", this is an average you measured over a certain timespan. If you counted every beat for 60s, for example, the iterval between the beats probably was not exactly 1s. One beat may have been "premature", another took a little more than one second to finally come. The HRV is a measure for the variation in the time interval between heartbeats. In other words, if your heart beats 60 times per minute 24/7, your HRV would be zero and you're probably a cyborg ;-)

The HRV responds particularly to heavy loads / intense workouts. The magnitude of the workout-induced stress is thought to be proportional to the activation of the sympathetic arm of the autonomic nervous system and thus the variations in autonomic balance, which can be indirectly assessed using HRV analysis (Seiler. 2007). A significantly lowered HRV days after a heavy workout is thus a signal that your central nervous system is still recovering. It tells you that you'd better insert a light cardio day or spend the time with friends instead of getting back onto the grind for another torturous 5x5 session.

Technology vs. psyche - HRV vs. RESTQ-Sport

Compared to psychological tests like the Recovery Questionnaire for Athletes (RESTQ-Sport), which is frequently used in research to observe the balance between stress and recovery during training processes, the physiological data you evaluate with the HRV method is obviously more objective. It is yet still debated whether it is also reliable and can / should replace or complement the classic psychological testing procedures.

Table 1: Overview of the training weeks of the two groups (Morales. 2013)

For Morales and his colleagues this doubt was among the most important reasons to conduct a study that would integrate both methodologies. To this ends, the researchers recruited 14 male national-standard judo players (age 22.85 years; height 174.08 cm; body mass 76.85 kg) and randomized them to four-weeks of...

• high training load (HTL - 8 sessions per week ➙ short recovery periods)
• moderate training load (MTL - 4 sessions per week ➙ long recovery periods) 

For the detection of the HRV at the beginning of the first and last session in weeks 1 and 4, the researchers used a Polar S810 cardiotachometer which provided the scientists with the following parameters either directly or the corresponding data to calculate them:

Figure 1: A wide spread (green ellipse) of the poincare plot indicates full recovery.

• the mean inter-beat (RR) interval,
• the standard deviation of the inter-beat (RR) interval , 
• the heart rate & its standard deviation
• the square root of the mean squared difference of successive RR intervals, 
• the number of consecutive RRs that differed by more than 5 ms each, and 
• the percentage of consecutive RRs that differed by more than 5 ms each

That sounds extremely complicated, but in the day and age of automated data acquisition and immediate processing (including fourier transformation to get the frequency data, etc.), there are lot of tiny little gadgets and apps that can do all the hard math-work for us.

HRV + RESTQ-SPORT + HTL vs. MTL = reliable training analysis

The next thing they did was to to simply plot pairs of inter-beat intervals, e.g. 1/60 vs. 1/64, 1/64 vs. 1/76, etc. the resulting graph is a so-called poincare plot (see Figure 1) and the spread of the point in this graph can tell you whether you are well-rested (wide ellipse) or overtrained / need rest (narrow ellipse)

Figure 2: Changes in selected HRV variables, left; performance, as well as stress + recovery values in the RESTQ-Sport, right; all differences expressed relative to values at the beginning to study (Morales. 2013)

The data in Figure 2 (left) does yet demonstrate - the poincare plot of the inter-beat variables characterizes the decreased heart rate variability (HRV) quite well.

"The multivariate test indicated that there was an interaction effect between the testing time and group on HRV variables. [...] the HTL group showed lower square root of the mean squared difference for successive RR intervals, very low frequency, high frequency, short-term variability and short-range scaling exponent in the post-test than in the pre-test (p < 0.05). The HTL group showed higher low/high frequency ratio in the post-test than in the pre-test. Finally, there were no differences between the pre-test and post-test in the MTL group." (Morales. 2013)

In other words: While the HTL group showed the expected increase in HRV, the judo players in the MTL group did not experience any significant changes in heart rate variability.

The question that remains - at least until you take a look at the data in Figure 2 (right) - is: Do these abstract figures really tell me that I am overtraining? The answer the comparison to the data from the RESTQ-Sport questionnaire gives us is YES, it does!

Don't be that guy or girl who works his / her ass off for nothing. Learn how to identify and combat the Athlete's Triad | read all articles.

Bottom Line: The accumulating scientific evidence and the ever-increasing number of practitioners (trainers and trainees) who rely on heart rate variability analyses to judge whether or not they are over-training clearly suggest that a heart rate monitor and the appropriate software (usually part of the bundle) would make a valuable addition to any (over-)ambitious athlete's Christmas gift list.

If there is still room for another present on your wishlist, I'd suggest you come back next week for part II of this series, to learn about another, maybe sexier method to find out whether your perception that training 1h-2h with no sweat every day won't have you overtrain (note: not sweating or feeling cold in the gym can be signs of severe or chronic overtraining).

Reference:

• Bosquet, L, et al. "Is heart rate a convenient tool to monitor over-reaching? A systematic review of the literature." British journal of sports medicine 42.9 (2008): 709-714.
• Camm, A. J., et al. "Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology." Circulation 93.5 (1996): 1043-1065.
• Morales, J., Álamo, J. M., García-Massó, X., López, J. L., Serra-Añó, P., & González, L. M. (2013). The Use Of Heart Rate Variability In Monitoring Stress And Recovery In Judo Athletes. Journal of strength and conditioning research/National Strength & Conditioning Association. 
• Seiler, Stephen, Olav Haugen, and Erin Kuffel. "Autonomic recovery after exercise in trained athletes: intensity and duration effects." Medicine and Science in Sports and Exercise 39.8 (2007): 1366.  

Baking Soda For Stressed White Blood Cells: 0.3g/kg NaCO3 90min Before an Anaerobic Workout Protect Your Immune Cells From "Stress" and Oxidative Damage

Image 1: Pure baking soda is not (yet?) a staple of the supplemental arsenal of many athletes. The scientific evidence with regard to its immediate ergogenic effects is ambigious and the mere presence of the word "sodium" in "sodium bicarbonate" scares the hack out of those athletes (bodybuilders and figure competitors) who may benefit most from a few grams of this potent alkalizer.

"Sodium"! This word alone is usually enough to scare bodybuilders and fitness athletes to death. "Sodium!? Isn't that the stuff that makes me look bloated?" The answer is easy: No! While sodium will help you retain enough water in your body to perform in the gym, the amount of sodium you ingest usually has little impact on the amount of water you will be holding, only when you start modulating your sodium intake, your body will react with changes in the renin-andiotensin-aldosterone system and you will be fluctuating "nicely" back and forth from super-bloated to weak and dehydrated... this is yet commonly ignored within the fitness community and thus it is no wonder that most supplement producers are anxious not to include any ingredients in their products that would show up on the label as "sodium" - after all, there are still costumers out there who have not enrolled at the SuppVersity and will thusly run away screaming as soon as they take a closer look on the label of a product they were just about to buy.

It is thusly no wonder that (at least to my knowledge) KreAlkalyn, where NACO3 is the working ingredient of the highly advertised buffering system, is the only product using sodium bicarbonate, or soda ash, as it is also called, as one of its main constituents (more on this topic in the SuppVersity Creatine Special). In medical settings NACO3 was and, in parts, still is still the "drug" of choice to combat acute acidosis. It is thus no wonder that Daniel J. Peart and his colleagues from the University of Hull in the United Kingdom, as well as the Bond University in Queensland, Australia are not the first scientists who speculated that athletes, especially those competing in (primarily) anaerobic sports, could benefit from the alkalizing effects of their grandmothers' secret weapon in the war against fungi and bacteria on her kitchen furnishings (Peart. 2011).

Image 2: "Cholesterol is the devil and sodium is his little brother!" Everyone who still believes everything the medical orthodoxy says, please raise your hands!

A note on the dangers of "salt": Firstly, baking soda is "only" ~28% sodium, which means that for every 4 grams you ingest you get roughly 1 g of sodium. Secondly, it is arguable how much of the sodium is effectively taken up and will be floating around in your blood. As T. Lakhanisky points out in his dossier for the Belgian government: "The uptake of sodium, via exposure to sodium carbonate, is much less than the uptake of sodium via food. Therefore, sodium carbonate is not expected to be systemically available in the body." (Lakhanisky. 2002) And thirdly, there is more and more evidence that suggests that the chloride rather than the sodium content of common table salt (NaCl = NatriumChloride) is the root cause of "sodium induced hypertension" in "sodium sensitive" individuals / animal models. Only recently, a study by Schmidlin et al. showed that chloride loading induced hypertension in the stroke-prone spontaneously hypertensive rat despite profound sodium depletion (Schmidlin. 2010). So, if you asked me, rather than pointing at salt as the #2 on the list of greatest evils (obviously cholesterol is still #1, here) the medical orthodoxy would be better advised to address the imbalances between sodium and potassium, which are so characteristic of the western diet, instead of painting yet another black and white picture where sodium is the bad guy and potassium the dangerous mineral that cannot be sold OTC in dosages >80mg.... but hey, this would be the topic for a whole new blogpost and as gross as it may sound, the chance that you get diarrhea from the baking soda is probably 1000x higher than the remote possibility of increases in blood pressure. A 1990 study by Luft et al. even found that the blood pressure of 10 mildly hypertensive and normal subjects decreased by 5mmHg after 7 days in the course of which they drank 3 liters of sodium bicarbonate containing water per day (Luft. 1990)

In their study, Peart et al. had a group of seven recreationally active men (age 22.3 ± 2.9 years,
height 181.6 ± 4.5 cm, body mass 78.1 ± 8.1 kg, and physical activity 4.2 ± 0.6 h/week) "with no history of supplementing their diet with ergogenic agents" perform a 4-min bout of all-out exercise on an air-brake cycle ergometer on three different occasions (spaced exactly 1 week apart). While the first was an acclimatization session the second and third bout were performed after the ingestion of either 0.3g/kg sodium bicarbonate (trial 2) or plain table salt (trial 3) in "low-energy flavored water" 90 minutes prior to exercise.

Figure 1: Blood ph levels after ingestion of placebo or 0.3g/kg sodium bicarbonate (data adapted from Peart. 2011)

As you can see in figure 1, the ingestion of ~23.4g of baking soda produced a rather slight but significant shift towards a more alkaline blood ph level (compared to placebo), which became much more pronounced after the exercise bout (p<0.003). Interestingly, there was yet no significant difference (p>0.26) in exercise performance as measured by average and peak power (means ± SD; average power 292 ± 43 W vs. 291 ± 50 W; peak power 770 ± 218 W vs. 775 ± 211 W; work completed 71 ± 10 kJ vs. 68 ± 10 kJ) between the groups.

Baking soda: A non-ergogenic ergogenic?

The latter observation, i.e. no or statistically non-significant increases in acute exercise performance upon sodium bicarbonate ingestion, stands in line with ~75% of the previous findings, a recent meta-analysis by Carr et al. summarizes as follows:

The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly moderate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5 mmoL/kg/BM (∼0.3 g/kg/BM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of 1.5 mmoL/kg/BM (∼0.5 g/kg/BM) had an unclear effect on performance of 0.0% (±1.3%), [...] Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (±1.1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ±1.2%.

Despite these rather mediocre immediate effects of bicarbonate pre-loading, the main finding of the study at hand hints at hitherto overlooked long(er)-term immune benefits the consumption of sodium bicarbonate might have.

Figure 2: HSP-72 expression in mono- and lymphocytes in response to anaerobic exercise after ingestion of placebo or 0.3g/kg sodium bicarbonate (data adapted from Peart. 2011)

As you can see in figure 2 the stress-induced HSP-72 expression in white blood cells (lymphocytes and monocytes) in response to the HIT exercise was almost completely abolished. Along with the nullification of the already low amount of oxidative stress (cf. T-BARs in figure 3), these results suggest that bicarbonate supplementation has a stress-protective effect on immune cells during anaerobic exercise.

Figure 3: Oxidative stress due to anaerobic exercise as measured by TBAR expression after ingestion of placebo or 0.3g/kg sodium bicarbonate (data adapted from Peart. 2011)

It is yet important to note that the scientists point out that it "is unclear at this stage whether the attenuation was due to a reduced state of acidosis, reduced oxidative stress or a combination of both." Moreover, it is difficult to say which consequences this would have on future bouts of exercise and whether and to which degree athletes would actually benefit - or, if we think of the hormesis hypothesis and the ongoing debate concerning the effects of antioxidants on exercise induced adaptations - maybe even compromise their performance, would yet need further investigations.

We may yet assume that, just as it is the case with antioxidants, the dosage will have to be matched to the individual workload to see optimal results. With people exercising just enough to see any adaptations seeing no and people who do crossfit 2x a day seeing the most beneficial results from (partially) blocking the exercise induced oxidative stress.

Update on Antioxidants & Exercise - Neither Vitamin C Nor E Have ANY Effect on the Response to Intense Exercise.

Image 1: If you add some reactive oxygen species to this mitochondrium, this will trigger beneficial, (mito-)hormetic adaptations, that could be blunted by too many antioxidants.

As a diligent reader of the SuppVersity, you have probably been following my posts on antioxidants and their potentially negative effect on the adaptive (hormetic) response to the exercise induced formation of reactive oxygen specimen. Although, I still believe that the theory may have its merit - especially in metabolically deranged people, where the exercise induced ROS formation would initially have to overcome the low-grade chronic "background" stress - it appears that for healthy people, and "moderately trained young men" on an intense exercise protocol, in particular, the ingestion of reasonable amounts (<1g of vitamin C and <400IU of vitamin E) does not pose a problem. At least this is what the results of two relatively recent studies by scientists from Washington School of Medicine (Higashida. 2011) and researchers from universities in Denmark and France (Yfanti. 2011) would suggest.

The hormetic benefits of inflammation

According to the mitohormesis hypothesis, the beneficial effects of exercise on health, in general, and glucose metabolism, in particular, are at least partly mediated by an increase in reactive oxygen species, which triggers downstream "hormetic" adaptation processes which result in increased oxidative capacity and insulin sensitivity, as well as a reduction in total inflammation (cf. previous posts on the work of S. Schmeisser and M. Ristow from the Department of Human Nutrition at the University of Leipzig. If this theory held true, or let's be more specific, if this theory which is largely based on observations in metabollically derranged, i.e. obese and/or type II diabetic subjects, was applicable to healthy people and athletes, as well, this could mean that the multi-vitamin, the vitamin C pills, the alpha-tocopherol (vitamin E) and all the other little helpers you have been taking religiously to increase your exercise performance would actually have hampered, not promoted your muscle gains, fat loss and whatever else you may have had in mind, when you hit the gym, the road, the field, the court or the green ;-)

Figure 1: Neither the high-dose supplementation protocol in rodents (HED: Human Equivalent Dose for 80kg), nor the moderate dose protocol in humans did block any of the measured beneficial adaptations to exercise in the studies by Higashida (2011) and Yfanti. (2011), respectively.

Let me say this right away: As long as you have not been following the recommendations of dubious nutritional gurus and self-proclaimed fitness "experts" to take 10g+ of vitamin C and vitamin E supplements in the 3000IU+ range, the little vitamin pills and powders are probably not the reason that your biceps is not growing and your belly is just as fat as it was, when you began training.

Figure 2: Serum vitamin C and vitamin E levels (µmol/L) in 21 subjects before, at the beginning and after 12 weeks of 5x a week strenuous cycling exercise with and without supplemental vitamin C & E (adapted from Yfanti. 2011)

As you can see in figure 2, supplementation with 500mg of vitamin C and 400 IU of vitamin E (more on the protocols used in the studies in figure 1) before and during 12 weeks of strenuous bicycle exercise training with a frequency of 5 sessions per week (HIIT, HIT and stead state, cf. figure 6) did increase the concentration of antioxidants in the blood of the 21 healthy, physically active subjects (age 18-40years) of the Yfanti study, who had not participated in physical exercise more than twice a week before the experiment. Despite higher vitamin C and E plasma levels, and contrary to the research hypothesis of the scientists, who had expected that the anti-oxidant supplementation would blunt the adaptive response to the exercise protocol,

[...] the present study showed that combined supplementation with vitamins C and E before and during 12 weeks of supervised, strenuous bicycle exercise training of a frequency of 5 days/week had no effect on maximal oxygen consumption, maximal power output, workload at lactate threshold, glycogen content, and CS and β-HAD activity in muscle.

In other words, supplementing with "reasonable" amounts of vitamin C and vitamin E had absolutely NO EFFECT (!) on the exercise induced metabolic adaptations or performance increases - that does yet also imply that taking anti-oxidants is of little benefit as long as the minimal dietary requirements are met... and if you still insist to poor money down the literally rat hole, you may be interested to hear that (assuming that the results from Higashida's rat study translate to humans), even 10g of vitamin C and 3000IU of vitamin E a day probably would not really make a difference - as long as you train heavy enough.

Figure 4: Exercise induced changes in GLUT-4 expression (arbitrary units) and 2DG transport (µmol/ml/20min) in rats subjected to 8 weeks of high dose antioxidant supplementation and 6days/week swimming exercise in the last 3 weeks (data adapted fro Higashida. 2011)

Of particular interest in this context is the effect of "mega-dosing" anti-oxidants on the exercise induced increase in insulin sensitivity, which has been reported to be impaired in previous studies (Ristow. 2009). As the data in figure 3 shows, the increase in glucose transporter (GLUT4) expression is slightly greater in the non-supplemented rats, BUT neither this difference nor the difference in measured 2-Deoxy-D-glucose (2DG) transport reach statistical significance.

Figure 5: Exercise induced changes in MDA, SOD and PGC-1α in rats subjected to 8 weeks of high dose antioxidant supplementation and 6days/week swimming exercise in the last 3 weeks (data adapted fro Higashida. 2011)

Moreover, Higashida et al. found no statistically significant differences in the increases of malondialdehyde (MDA), superoxide dismutase (SOD1 & SOD2) or PGC-1α, a marker for the mitochondrial fatty acid oxidation, between the rats in the two groups (cf. figure 5).

Now, I a confused and don't know what to believe

So what does all that tell us? Well, we can now be relatively certain that supplementing with vitamin C and vitamin E is a waste of time and money for most of us. What we still cannot say for sure, though is why the Ristow study from 2009, which even made it to mainstream media news, found detrimental effects of supplementing with 1g of vitamin C and 400IU of vitamin E on the adaptive response to 4 weeks of 5days/week 20min steady state aerobic training + 45 minute circuit training + 20 min warm up + cool down (Ristow. 2009), while the Yfanti study, with 500mg of vitamin C and 400IU of vitamin E did not find any effects of supplementation...

Figure 6: Exercise protocol that was used in the Yfanti study.

...the only reasonable explanation I have is that the protocol in the Ristow study may not have been intense enough. Unfortunately there is no detailed information on what the subjects did in the course of the "circuit training", but if that was your usual sissy type walk from one machine to the next, chances are that the level of ROS that was induced by this "exercise" protocol was so low that it was completely blocked by the supplemental anti-oxidants. The "cycling protocol" in the Yfanti study, on the other hand, is pretty intense. If you look at the schedule in figure 6 you will concede that this is almost the way athletes (and maybe you) train.

All that being said, it appears that all is coming back to what I have been writing (and also saying on SHR) several times before: Controlled oxidation is likely to be beneficial. It's like the fire in the oven that keeps you warm - the one you carefully take care of, in order to prevent your whole house to catch fire... if you are a marathon runner, the latter can happen pretty quickly and you will need (tons of ;-) antioxidants and even that will probably not suffice. If you are the housewife on the treadmill, who walks at 5km/h for 20min two times a week, on the other hand, even a few milligrams of vitamin C and a few units of vitamin E will blunt the little oxidative "damage" that you do and your "efforts" to increase your insulin sensitivity or whatever your intentions may be will be sabotaged by your vitamin supplements.

Men Are Not Always Thinking About Sex. Study Says: There Are At Least 4 "Good" Reasons They Don't - Stress Is #1! Plus: A Proven De-Stress Protocol to Restore Your Libido

If either of these individuals remind you of yourself, you should reduce his stress levels.

Recent research suggest: The good old saying that "Men always think about sex!" is essentially untrue (The "!" indicates that I used the feminist version of this common "wisdom").

If we put faith in the results of a recent European study from the Department of Clinical Psychology at the Instituto Universitário in Lisbon, Portugal, the Department of Psychology at the University of Tromsø in Tromsø, Norway, and the Sexology Unit at the Faculty of Humanities and Social Sciences, University of Zagreb, Croatia, stress is the common denominator that distracts men from their original duty to do what has to be done for the survival of the human race ;-)

Homo coitum quaerens aut evitarens?

It may sound surprising, but unlike sexual function, the sexual desire of the male members of the human race has not been examined as extensively as the one of their female counterparts. When you think about the initially quoted "wisdom", it is actually not that surprising.  Men are are after all believed to be always looking for the next "catch".

The problem cannot be that prevalent, can it? Yes it can! According to recent data from the The National Health and Social Life Survey (NHSLS), the average American's prevalence of “lacking desire for sex” ranged from 14% (for those 18–29 years old) to 17% (for those 50–59 years old). In spite of the fact that the exact figures are debatable, the currently available literature supports the notion that 15-20% of the US men 'don't think about sex at all'. If we take a look at international data the figures don't look better: Depending on the geographic region 13% to 28% of the ~14,000 men aged 40–80 years from 29 countries in the Global Study of Sexual Attitudes and Behaviours said that their sexual desire had been low for at least 2 months Laumann. 2005).

After focusing more or less exclusively on functional aspects of male sexuality for decades, research does now start to draw and embrace a more versatile image of male and general human sexuality. According to studies by Hyde and Janssen, the black-and-white gender differences which is also at the heard of the saying "men think about sex all day" is in fact non-existent. On the contrary, gender theorists have recently suggested that greater diversity exists within gender than between gender (Hyde. 2005+2007; Janssen. 2008).

Sexual disinterest is stressful!

Faced with the surprisingly high rates of sexual disinterest in men, scientists like Mccarthy et al. have already identified several major relationship problems as potential culprits. In view of what you've learned already, it should be obvious that these problems are not necessarily related to the 'classic' mismatch in sexual interests between a hyperactive male and an (under-)active female partner. On the contrary, the data in Figure 1 makes it plain obvious that for men in their thirties, it would not be unlikely that they are disinterested and their wives or girlfriends dissatisfied.

It goes without saying that problems like these and the mismatch between the perceived and the expected level of sexual desire are stressing - very stressing, according to the data Ana Carvalheira's, Bente Træen's and Aleksandar Štulhofer gathered in inteviews with heterosexual men from Portugal, Croatia, and Norway (Carcalheira. 2013):

Figure 1:Lack of desire and professional stress, two sides of the same coin? Data based on Carcalheira (2013)

In the worst case scenario a man will get caught in a vicious circle of professional stress ⇆ lack of sexual desire ⇆ private stress that is hard to break. Against that background it's only logical that the essence of the recommendations in the bottom line of this article is to get rid of the stress that's keeping you from thinking about sex.

"Stress ⇆ Sexual Disinterest" - it's that easy!

A 2013 study by Talbott et al. suggests that Tongkat Ali, a traditional testosterone and libido booster works mainly be reducing stress levels (learn more)

If you don't believe in the deeper truth of this 'equation', I suggest you go back to an article I wrote earlier this year (see Beyond Testosterone: 200mg/day of Tongkat Ali (Eurycoma Longifolia) for Stress Management & Improved Mood!?" | read more). It deals with a traditional "testosterone booster" and its effects on stressed individuals... you will see: Stress is not only a libido-, it's also a testosterone -killer (no surprise, right?).

It is thus not really surprising that the data from the Carcalheira study tells us that men who feel distressed about their own lack of libido were 2.5x more likely to suffer from anxiety right before sex  and/or have trouble maintaining an erection.

To be stressed or not to be stressed - that's the question!

Just as the cliche would have it, the highly reserved Norwegians were 3x more likely than the red-blooded self-proclaimed Latin lovers from Portugal to suffer from a lack of sexual desire. With a 50% higher risk of losing interest in the other sex, the participants from Croatia end up somewhere in between the 'Latin lovers' and the 'prudish Vikings'.

Table 1: Sociodemographic characteristics, individual variables, and relationship-related characteristics as correlates of a distressing lack of sexual interest among healthy heterosexual men who are not using antidepressants (Carcalheira. 2013)

Aside from their origin there were other sociodemographic characteristics, individual variables, and relationship-related characteristics which were found to be associated with the an increased risk of suffering from a lack of sexual desire. As the data in Table 1 goes to show you, having children, even young ones, was, contrary to what you may have expected, not among these characteristics. In contrast to the self-confidence on erectile function, of course.

What's I personally find quite telling is the high rate of a distressing lack of sexual desire in long-term (5years +) relationships and as a consequence of an indifferent attitude towards the attractiveness of the sexual partner. Interestingly, finding your wife or girlfriend "neither attractive, nor unattractive" is an even greater turn down than thinking of her as a "very unattractive" (see Table 1).

"And that's all stress?"

No, that's not all stress... In the previous paragraph we have already learned about a libido killer that cannot be traced back to stress: The lack of 'adventure', 'novelty' or whatever you may call it - a phenomenon which is probably also the reason that people start looking at their partner as "neither attractive nor unattractive" is another important contributor to sexual disinterested in men. One out of 22 if you will - 22 items on the scientists list of potential causes of a reduced sexual interest:

Table 2: Self-assessed causes of a reduced sexual interest during the past 6 months among heterosexual Portuguese, Croatian, and Norwegian men in percent (Carvalheira. 2013)

I know, not all of them appear logical. Why would masturbating too often be associated with a reduced interest in sex? ⇦ That does not sound right - right? Something similar can be said for the Croatian porn fans (22.5%). In the end, though, it does not change the overall picture: It is stress that's gnawing at our sexual desire, guys.

The Dimou protocol: Diaphragmatic breathing is performed by taking deep diaphragmatic inspirations followed by slow prolonged expirations.  In the second phase of PMR relaxation, patients were guided through successive contractions and relaxations of different large muscle groups in a down-top orientation. The process was complemented by guided imagery involving mental exercises, designed to allow the mind to influence the health and well-being of the body (GI is used with standard medical treatment in people with cancer and other diseases, such as fibromyalgia, as it can help to reduce stress, depression and manage pain). In each step, the patients were encouraged to focus on the difference between tension and relaxation, thus gradually sharpening the perception of the relaxation response.

What So what can be done? By now the question "what can be done" should - at least on the surface level - already have a rhetorical character. It's obvious that you have to de-stress. The only question is: How do you do that? Luckily (for us), P.A. Dimou et al. have just successfully tested an anti-stress program that consisted of progressive muscular relaxation (PMR), diaphragmatic breathing and guided imagery and was topped off with a handful of tips to achieve better time management. The program was designed to optimize sexual health in young men and it worked! It worked like a charm: Over the course of the 8-week stress management program practicing the PMR + diaphragmatic breathing + guided imagery regime twice a day effectively reduced the number of men who were totally or somehow dissatisfied with their sex life decreased from 9 to 4 (-55%; cf. Dimou. 2013). Aside from the intended benefits in sexual satisfaction, the young 60 young men in the active arm of the Dimou study also lost weight (-3% BMI), felt less overall less stressed (-23%; social stress subscale -11%) and achieved +6% higher scores in the general health evaluation.

PMR and guided imagery does not sound like you? Well, I guess simply limiting your mobile phone, email, Facebook and SMS use, making room for the occasional time out with a cup of tea during the working hours, a rigorous 7h+ sleeping regimen and letting go of the 'more is more principle' will work wonders even in the absence of 'meditative' interventions....ah, and don't forget: Don't stress about de-stressing that would ruin all your efforts to find inner peace ;-)

Reference:

• Carvalheira A, Træen B, Štulhofer A. Correlates of Men’s Sexual Interest: A Cross-Cultural Study. J Sex Med. 2013 [accepted manuscript]
• Dimou PA, Bacopoulou F, Darviri C, Chrousos GP. Stress management and sexual health of young adults: a pilot randomised controlled trial. Andrologia2013,xx, 1–10 [accepted manuscript]
• Hyde JS. The gender similarities hypothesis. Am Psychol 2005;60:581–92.
• Hyde JS. New directions in the study of gender similarities and differences. Curr Dir Psychol Sci 2007;16:259–63.
• Janssen E, McBride K, Yarber W, Hill B, Butler S. Factors that influence sexual arousal in men: A focus group study. Arch Sex Behav 2008;37:252–65.
• Laumann EO, Nicolosi A, Glasser DB, Paik A, Gingell C, Moreira E, Wang T; GSSAB Investigators’ Group. Sexual problems among women and men aged 40–80 y: Prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. Int J Impot Res 2005;17:39–57
• Mccarthy B, McDonald D. Sex therapy failures: A crucial, yet ignored, issue. J Sex Marital Ther 2009;35:320–9.

Reishi Protects Against Cancer & Contains Anti-Androgen; Adrenalin Rejuvenates Brown Fat; Mild Stress Normalizes Cortisol / DHEA Ratio in Elderly; DHEA, Aromatase Inhibitors & BPA vs. Joint & Brain Health; Vitamin E Battles Lymphoma

I am not happy with how the short news on Facebook simply disappear into oblivion.

The SuppVersity figure of the week is "920"! "920" as in "920 published posts" here at the SuppVersity. The reason that's the figure of the week is that I have been thinking about ways to reorganize the archive, but am a bit lost on how to structure things in a better way using blogger. This beast simply isn't made for anything that goes beyond a weekly classic blogpost a la "last week I did this and that, read about..." *yawn*

What's yet even more enervating is that despite having the huge advantage of being easily posted and directly accessible for all of you, the tons of short news items I post on a daily basis on the SuppVersity Facebook Wall simply disappear into the 'Facebook nirvana'. I currently cannot spend any time on those technical / organizational matters, but in the course of 2013 things are going to change.

In the mean time, follow the SuppVersity on Facebook and read the news, right when I post them + use google to find articles you are looking for. You will be laughing, but that's the way I dig through those 920 posts, as well ;-) Simply type whatever you look for and add a "+site:suppversity.blogspot.com" to it.

Chinese fungi are laden with cancer-protective molecules and 5a-reductase (DHT) inhibitors

In view of a recent paper from the Universitat de Valencia (Rios. 2012) it appears that it would actually be hard not to decrease your risk of developing cancer if you include extracts from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata in your supplement regimen. With a total of 81 compounds from Ganoderma lucidum and other species from this genus, as well as 96 compounds isolated from other fungi, principally Poria cocos. It appears that these creatures (fungi are no plants, neither are they animals, but still sort of living beings) could hold the key to hundreds o natural anti-cancer agents.

Ganoderma lucidum better known as Rheishi mushroom may have cancer protective effects, but does not taste so bitter that no sane human being would eat it for a reason (photo by Eric Steinert)

I guess, I don't have to tell you that Chinese Medicine, of course, knew about the powerful anti-inflammatory and anti-proliferative effects of the lanostanes in these fungi, all along. Intuitively and probably by trial and error, the Chinese have found the tetracyclic triterpenoids that are derived from lanosterols in these fungi to be effective in the treatment of various diseases including different types of cancer. As of late the mostly anecdotal effects are backed by more and more research. A preliminary study by Sliva et al. (Sliva. 2002), for example, found that a hot water extract of both spores and the dried fruiting body of G. lucidum inhibited the progression of cancerous growth by reducing the expression of constitutively active growth and inflammation promoting transcription factors AP-1 and NF-κB: 

"The extracts also inhibited the secretion of uPA, thereby suppressing the migration of breast cancer MDA-MB-231 and prostate PC-3 cells. [...] High levels of both uPA and uPAR are associated with advanced tumors and decreased survival time in different malignant human cancers." (Rios. 2012)

These benefits do however come with a downside. At least in vitro, some of the fungi, particularly G. lucidum, obviously exert their effects via anti-androgenic pathways (Liu. 2007). A compound in Reishi that goes by the name ganoderol B, for example, does not just have inhibitory activity against 5α-reductase, but can also bind to the androgen receptor directly (if you will you could say it acts like an anti-anabolic SARM). Now, this was good news in a study that has been conducted by Liu et al., because it inhibited androgen-induced cell growth in an LNCaP cell line while suppressing testosterone-induced regrowth of the ventral prostate in rats. If those effects are however non-selective, you are about to run into problems once the molecules bind to receptors outside the prostate -- epression for example, if they block the androgen effects in the brain, etc.

That reminds me: What did Carl say on Thursday's installment of the SuppVersity Science Round Up? "The good thing about supplements is that they work, the bad thing about them is that they work!" I guess you can basically say the same about Reishi. Good that you as a SuppVersity reader always know about both, the good and the bad sides of supplements!

More short news

With me posting stuff on the fly on facebook, I am actally 'wasting' many of the very short news items, but nevertheless, here are a couple of relatively short news to round things up.

• 

  If you missed Monday's new on the quasi non-existent thermogenic effects of ephedrine, this would be a good time to read that post.

  Stress-induced browning of the fat? Chronic overexpression of noradrenaline (re-)generates wasted brown fat! In a way this is a follow up on the ephedrine post "Fat Burners Don't Work" as well as an addendum to a news on the role of GABA and brown fat in obesity, I just posted on facebook. According to an allegedly old study in the International Jornal of Obesity (Lee. 1986),  the chronic overexpression of noradrenaline as it is observed in humans with a certain form of adrenal tumor known as phaeochromocytoma can actually reactivate the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy.
  
  Lee et al. see this as one of the main contributing factors to the weight loss which is typically seen with phaeochromocytoma. Sounds, logical, since the same stimulus that rejuvenates the Brown fat will also have it burn energy continuously - the overexpression of noradrenaline.
  
  
  Symptoms of overtly high noradrenaline levels include abdominal pain, chest pain, irritability, nervousness, pallor, palpitations, rapid heart rate, severe headache, sweating, hand tremor, high blood pressure, sleeping difficulties, and also weight loss.
  Even patients with Cushing's syndrome (hypercortisolemia) there is an increase in brown fat compared to healthy individuals. That the latter is not as profound is probably due to the ameliorative effect of cortisol on nor-adrenaline. After all, cortisol comes into play, when the stress becomes chronic and the acute nor-adrenaline response to stress, when it was prlonged any further would actually pose a direct threat to your health (just as phaeochromocytoma does, by the way; see red box on the right)
• Repeated moderate stress exposure increases DHEA production and normalizes corticosteriod levels in old apes (Goncharova. 2012). Yep, you are reading right we are not just talking about no rodent studies (although macacs are not exactly very human either ;-), but also about the role of repeated moderate stress in the normalization of aged induced abnormalities in the expression of adrenal hormones.
  

  

  Figure 2: Cortisol/DHEA ratio before and after 2h/day of immobilization stress.

  "In old monkeys the basal DHEAS levels were lower, while the [cortisol]/DHEAS ratio was higher than in young animals. Repeated immobilizations inhibited [cortisol] elevation on day 3, caused no changes in DHEAS reaction, led to increase of basal DHEAS levels and to a reduction of [cortisol]/DHEAS ratio on days 2, 3, 4, 10, 11." (Goncharova. 2012)

  In figure 2 you can see how profound the differences between acute, subchronic (3-day) and chronic responses actually are and that after 10 days of daily stress exposure in the form of daily 2-h immobilization stress actually are. Since I assume you don't want to be bound or enchained (well, maybe you want?), I suppose a viable alternative could be a shorter not too intense workout, although the acute responses to the latter vary with age as well (cf. Lennartsson. 2007).
• Monitor your DHEA levels closely, if you are concerned about joint degeneration According to a study that's about to be published in the next issue of the Journal of Steroid Biochemistry and Molecular Biology, DHEA, or the estradiol your body generates from it via local aromatization, exerts major protective effects against osteoarthritis (Li. 2012).
  
  
  An additional note of caution with respect to the abuse of aromatase inhibitors, natural or not. Since they have the potential to reduce the expression of estrogen at the neuronal level in the brain they can precipitate  Alzheimer's dementia. While estrogen appears to decrease the MMP-3 & 13 expression in the cartilage reasearch by Merlo et al. suggests that it will increase others, namely namely MMP-2 and MMP-9  in the brain and thus facilitate the clearance of the ameloid beta plague that's rendering the brains of AD patients more and more dysfunctional (Merlo. 2012). You see, it's no chance that pre-menopausal women are protected from Alzheimer's yet more susceptible to multiple sclerosis (MS). After all, high MMPs 7 & 9 have only been observed in kids with MS, as well (Unsal. 2012).
  In their experiments on a rabbit model of osteoarthritis the scientists from the Zheejiang University in China tried to nail down the beneficial effects of DHEA on chrondocites and cartilage to estrogen by co-administering DHEA with the aromatase inhibitor letrozole, and/or the estrogen receptor inhibitor fulvestrant and observed that the
  

  "[e]xpression of MMP-3 and MMP-13 increased in both DHEA-treated chondrocytes and cartilage in the presence of letrozole and/or fulvestrant, while the expression of TIMP-1 and collagen type II (Col-II) decreased." (Li. 2012)

  With the former metalloproteinases (MMPs) being proteolytic enzymes, which break down cartilage and the latter, i.e. the tissue inhibitors of metalloproteinases (TIMPs), acting as their antagonists, it appears clear why both patients on testosterone replacement therapy who use too high of a dose of aromatase inhibitors and athletes who abuse respective products on cycle or during PCT often suffer from severe cartilage degeneration - I mean, combine the endogenous cartilage destruction due to high MMPs and low TIMP levels with the wear and tear of weight lifting... what good could come out of that?
  
  Note: A very similar effect has been reported for bisphenol A by Wang et al. in 2010, already (Wang. 2010). No wonder, after all BPA decreases the local expression of aromatization in joints and cartilage so that less estrogen will be floating around to keep the MMP levels in check and TIMP up (Watanabe. 2012).
• Alpha tocopherol to prevent lymphoma Regular vitamin E, i.e. the alpha-version of the tocopherols is no longer the star at the supplement sky it has once been hailed to be. A recent study by Renu Sharma Manjula Vinaya that's been published ahead of print in the journal Molecular Biology Reports shows however that this does not mean that it's outdated and useless (ask Ray Peat about it ;-).
  
  

  

  Figure 3: Lifespan (top) and ascite volume (=water accumulation in the abdominal area) of lymphoma carrying mice treated with what would be in human terms ~325, 650 and 975 IU/day of an alpha tocopherol only supplement  (Sharma. 2012)

  In order to test the hypothesis that the ROS scavenging abilities of vitamin E should help with cancer prevention (as a student of the SuppVersity you know that respective data from epidemiological studies are equivocal, some suggesting the exact opposite; read more), the researchers initially induced the growth of lymphomas in 10-15 week old male mice and subsequently treated them with either 1.5 mg (50 mg/kg bw), 3 mg (100 mg/kg bw) or 4.5 mg (150 mg/kg bw) of alpha-tocopherol for 14 days.
  
  As the data in figure 1 goes to show you, the treatment increased the lifespan of the rodents by 25% and reduced the ascite fluid volme (see image in figure 1) by ~46%. This was accompanied by reductions in protein carbonylation and increases in the "master anti-oxidant" GSH, as well as several other markers showing that vitamin E exerted profound anti-inflammatory effects in this rodent model of lymphoma.
  
  At least in my humble opinion that does not change the fact that your best sources of vitamin E are natural and that's smart to stay away from alpha-tocopherol only supplements and prefer a whole spectrum tocopherol + tocotrienol supplement. Remember: More is not better, when the one thing that counts are the ratios (read more about vitamin E)!
  

That's it for this week's installment of On Short Notice. As mentioned in the introduction, there are more and even shorter news on the SuppVersity Facebook Wall, which usually gets updated 3+ times per day with I would guess 9-12 items total - depending on whether it's a slow news day or not and the time I have to skim studies and popular science mags and repost summaries and links of and to the latter. Let's see what did we have today, already? Ah, yeah: "Review concludes: Just being patented makes Kinesio® no better than conventional taping" (more), "Interesting stupid science finds that GABA directly mediates energy expenditure." (more), or maybe you are interested in "If rapamycin blocks seizures in model of epilepsy. Is mTOR to blame for both?" (more)?

References:

• Goncharova ND, Vengerin AA, Chigarova OA. Repeated Moderate Stress Stimulates the Production of Dehydroepiandrosterone Sulfate (DHEAS) and Reduces Corticosteroid Imbalance in Old Macaca Mulatta.  Bulletin of Experimental Biology and Medicine Volume 153, Number 5 (2012), 750-753. 
• Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. Int J Obes. 1986;10(3):219-27. 
• Lennartsson AK, Kushnir MM, Bergquist J, Jonsdottir IH. DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biol Psychol. 2012 May;90(2):143-9.  
• Li WJ, Tang LP, Xiong Y, Zhou XD, Wu LD. The chondroprotective effects of dehydroepiandrosterone probably exerted by its conversion to estradiol. J Steroid Biochem Mol Biol. 2012 Oct 18. 
• Liu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007 Jul 15;15(14):4966-72. 
• Merlo S, Sortino MA. Estrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid degradation. Mol Cell Neurosci. 2012 Apr;49(4):423-9.
• Ríos JL, Andújar I, Recio MC, Giner RM. Lanostanoids from Fungi: A Group of Potential Anticancer Compounds. J Nat Prod. 2012 Oct 23.
• Sharma R, Vinayak M. α-Tocopherol prevents lymphoma by improving antioxidant defence system of mice. Mol Biol Rep. 2012 Oct 14.
• Sliva, D.; Labarrere, C.; Slivova, V.; Sedlak, M.; Lloyd, F. P., Jr.; Ho, N. W. Biochem. Biophys. Res. Commun. 2002, 298, 603– 612.
• Unsal Y, Kıvılcım G, Ayşegül A, Arzu A, Esra G, Ercan D, Ayşe S. Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple sclerosis. Pediatr Neurol. 2012 Sep;47(3):171-6.
• Wang KC, Lin YF, Qin CH, Chen TL, Chen CH. Bisphenol-A interferes with estradiol-mediated protection in osteoarthritic chondrocytes. Toxicol Lett. 2010 Oct 5;198(2):127-33. 
• Watanabe M, Ohno S, Nakajin S. Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines. Toxicol Lett. 2012 Apr 5;210(1):95-9.