Showing posts with label ultra-endurance. Show all posts
Showing posts with label ultra-endurance. Show all posts

Thursday, December 8, 2016

Potassium-Magnesium Aspartate, an Overlooked Endurance Enhancer? Acute 100% Increase in Time to Full Exhaustion

1952, Italian Fausto Coppi is drenched with water by a fan during the golden years of the Tour. Question: Can the topical application of K & Mg do the same magic? Answer: That's very unlikely, ...
What sounds like a supplement producer was trying to sell his product with a sponsored study is, in fact, the gist of a 1968 study from the Departments of Clinical Physiology and Internal Medicine at the venerable Karolinska Institute in Stockholm, Sweden (Ahlborg. 1968).

The authors' conclusion that "[a]fter administration of potassium-magnesium-aspartate [KMgA] the capacity for prolonged exercise increased about 50 per cent" (Ahlborg. 1968) can thus not be discarded as marketing babble. And, before we decide whether it's too good to be true, I'd suggest we take a closer look at the way the data was generated before we either (a) discard it as outdated or (b) get totally excited for nothing.
Mineral water will contain some K and Mg, too - and it will have other benefits:

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2.5 lbs/8wks of Weight Lost W/ Plain Water

Mineral Water Supercharges 'ur Performance?!
Another ten years before Ahlborg et al. published their study, an effect of potassium and magnesium salts of aspartic acid on muscular fatigability has been demonstrated experimentally in animals by several independent research groups. Back in the 1960s, humans studies had yet only subjectively assessed the effects of KMgA on endurance performance in man. Ahlborg et al. were thus right to consider it... "to be of interest to investigate, whether a positive effect on the capacity for prolonged standardized physical exercise after oral administration of potassium-magnesium-aspartate can be objectively demonstrated" (Ahlberg. 1968).
Table 1: Some anthropometric and other data in the test subjects (Ahlborg. 1968).
The scientists recruited 6 out of a group of 300 military recruits who had been examined at the Military Medical Examination Centre at the Karolinska Institute back in the 1960s. All subjects were subjected to the following routine: On 4 consecutive days, which will be called day 1, 2, 3 and 4, prolonged exercise to exhaustion was performed every day beginning at 1 p.m. The subjects were not fasted.

To get the results they wanted and to make sure the subjects' performance was not thwarted, the scientists required all subjects to record all foods they'd been consuming for the 4 days of the test. This practice was meant to avoid interference with of high carbohydrate intakes of which people back in the day still knew and appreciated that they can "increase the capacity for prolonged exercise markedly" (Ahlborg. 1968).
Does this work for strength training as well? While it may help you up your workouts, a study by Consolazio et al. (1964) found  no measurable beneficial effects on muscle strength. This disappointing result was later confirmed by De Haan, et al. (1985). So, I'd venture the guess that - if KMgA is a thing at all - it's an endurance athletes' thing.
To test each subject against itself while still having averages to compare, the authors had all subjects perform the "W170", a bicycle ergometer ride at a pulse rate of 170 beats/min (duration ~90 minutes until physical exhaustion) on days 1, 2, 3 and four. And here's how the supplementation worked:
"Beginning at 6 p.m. on the day before day 1, 5 tablets were administered every sixth hrs. last 5 tablets were given 1 hr before the prolonged exercise test on day 4, see Fig. 1. All subjects were given placebo tablets before the tests on days 1, 2 and 4. Before day 3 active substance was given. The subjects were told that the tests were aimed at elucidating the influence of a vitamin tablet on maximal performance time. No information was given to the test supervisor (the same nurse on all days) or to the subjects as to when placebo or active substance was administered. The placebo and active tablets were identically looking" (Ahlborg. 1968)
This is admittedly not exactly standard procedure, and one could argue that what we are seeing here is a vitamin placebo effect, but the effect (a) appears to be a bit too large (see data in Figure 1) and you could (b) also argue that the previous two 170Ws may have had a negative effect on the subjects' performance during cycling to exhaustion.
Figure 1: Duration of prolonged exercise (y-axis) in the 6 test subjects after administration (x-axis) of placebo (striped area) and after administration of aspartate (black area) and individual data in the table (Ahlborg. 1968).
As you can see in Figure 1 the effect differed from subject to subject but was (a) highly significant in all of the 6 men and (b) doesn't have a residual effect. The latter suggests that the ~100% increase in time to exhaustion is not the result of K or Mg repletion, but an acute response to the KMgA supplement.
Research overview and supplement suggestion: In order to put the results into perspective I've curso-rily searched subsequent studies on aspartate bound minerals with the following results (in random order): [1] Sign. increased ergogenic effects in with 10 g of potassium-magnesium as-partate over a 24 hr in Wesson et al. (1988) in subjects cycling at 70% VO2Max; [2] no benefits in trained indiv. cycling at lower intensities in Hagan, et al. (1982); [3] no benefits were likewise seen, when the supplement was taken in lower amounts chronically, i.e. 5 weeks, only 2g/day (Consolazio. 1964) and / or when the supplement was controlled against equimolar amounts of "regular" (HCL) Mg + K (Maughan. 1983).
Overall, the research, there-fore, appears to suggest that athletes who perform high-intensity endurance exerci-ses could benefit most from the serial administration of a total of 10g/24h of Mg and K - not necessarily bound to aspartate, for which scien-tists have not conclusively proven benefits when it's taken on its own, either (Trudeau. 2008).
So what's triggering these benefits? As you will know I am not happy if I don't understand the cause-and-effect relationships in any field of research that does not belong to quantum sciences. Unfortunately, I have to admit that, in this particular case, where Heisenberg's uncertainty principle obviously doesn't apply, I still cannot explain exactly what the reason for the surprisingly pronounced ergogenic effects is.

What appears to be certain (also based on previous studies) is that the 100% increase is not a normal day-to-day performance variation. As Ahlborg et al. point out, the antifatigue effect in previous research in rodents was often interpreted as the result of an ATP and phosphocreatine sparing effect, i.e. a decreased consumption of ATP and phosphocreatine. The authors of the paper at hand, however, believe that it is "more likely that the resynthesis of the energy-rich phosphates ATP and phosphocreatine might be accelerated by potassium-magnesium-aspartate" - quite obviously, the net result will be the same, an increased available amount of energy-rich phosphates in the muscles. This, in turn, was suspected to be due to a glycogen sparing effect of the Mg and K esp. with a focus on aspartate co-administration ('cause Asp is a major source of gluconeogenesis during exercise). Since the latter has been refuted by Trudeau, et al. in 1993, we are thus stuck with hypothesis #2, i.e. a direct effect on the (accelerated) rate of resynthesis of phosphocreatine.

Well, back in the day Ahlborg et al. wrote that "investigations are in progress to evaluate these theories". Unfortunately, the final answer to the question "how does that work" has yet not been found (see box on the right). Increased heart rate, increased lipolysis and glucose oxidation as they have been observed in Wesson et al. who confirmed the benefits on endurance performance in 1988 are probably rather a consequence than the cause of the performance enhancement you may be able to see in the conditions I outlined in the box to the right | Comment!
References:
  • Ahlborg, Björn. Capacity for exercise in man. Forsvarets sjukvardsstyrelse, 1967.
  • Ahlborg, Bjorn, et al. "Human muscle glycogen content and capacity for prolonged exercise after different diets." Forsvarsmedicin 3.Suppl 1 (1967): 85ą89.
  • Ahlborg, Björn, et al. "Muscle glycogen and muscle electrolytes during prolonged physical exercise1." Acta Physiologica Scandinavica 70.2 (1967): 129-142.
  • Ahlborg, Björn, Lars‐Göran Ekelund, and Carl‐Gustaf Nilsson. "Effect of Potassium‐Magnesium‐Aspartate on the Capacity for Prolonged Exercise in Man." Acta Physiologica Scandinavica 74.1‐2 (1968): 238-245.
  • Consolazio, C. Frank, et al. "Effects of aspartic acid salts (Mg and K) on physical performance of men." Journal of applied physiology 19.2 (1964): 257-261.
  • Ekelund, Lars-Göran. "Circulatory and respiratory adaptation during prolonged exercise." Acta physiologica Scandinavica. Supplementum 292 (1967): 1.
  • De Haan, A., J. E. Van Doorn, and H. G. Westra. "Effects of potassium+ magnesium aspartate on muscle metabolism and force development during short intensive static exercise." International journal of sports medicine 6.01 (1985): 44-49.
  • Hagan, R. D., et al. "Absence of effect of potassium-magnesium aspartate on physiologic responses to prolonged work in aerobically trained men." International journal of sports medicine 3.03 (1982): 177-181.
  • Maughan, R. J., and D. J. M. Sadler. "The effects of oral administration of salts of aspartic acid on the metabolic response to prolonged exhausting exercise in man." International journal of sports medicine 4.02 (1983): 119-123.
  • Trudeau, François, and René Murphy. "Effects of potassium-aspartate salt administration on glycogen use in the rat during a swimming stress." Physiology & behavior 54.1 (1993): 7-12.
  • Wesson, Matthew, et al. "Effects of oral administration of aspartic acid salts on the endurance capacity of trained athletes." Research Quarterly for Exercise and Sport 59.3 (1988): 234-239.

Monday, July 13, 2015

Nausea, Leaky-Gut & GI Disturbances - Ginger Ameliorates All | May Be the Perfect Addition to Your Workout Nutrition

You will find dozens of ginger + lemon water recipes on the internet - all of them can pimp your peri-workout drinks and make your tummies "exercise proof".
As a regular here at the SuppVersity you know about the beneficial health effects of ginger. It has potent anti-oxidant and anti-inflammatory effects without the usual side-effects of COX-inhibitors (Mashhadi. 2013), has been shown to have anti-cancer effect on it's own (Kim. 2005), as well as to be a perfect adjunct for conventional cancer therapy (Sontakke. 2003).

Ginger has also been shown to exert cardioprotective effects (Ghayur. 2005; Singletary. 2010), strengthens the immune system (Butt. 2011) and significant beneficial effects on the health of the digestive system - including the make-up of your microbiome (Sutherland. 2009).
One thing that should be in your peri-workout (best post-workout) regimen is creatine 

Creatine Doubles 'Ur GainZ!

Creatine, DHT & Broscience

Creatine Better After Workout

More Creatine PWO Evidence

Creatine Blunts Fat Loss?

Build Your Own Buffered Creatine
Now, it is out of question almost all of these effects would be beneficial to athletes, too. The one I want to focus on, today, though, is directly related to the last-mentioned effect: the beneficial effect on the gut. It is well-known that athletes, in general, and endurance athletes, in particular, are having a hard time keeping their tummy from "leaking" (learn more about the link between exercise and leaky gut). With ginger - that's at least what a recent study from the School of Life Sciences at the Heriot-Watt University in Edinburgh suggests. The scientists went from the observations that
  1. the frequency of upper and lower gastrointestinal disturbance as a function of exercise is reported to be between 30 and 70%
  2. the severity of symptoms ranging from mild stomach discomfort to severe diarrhoea and 
  3. the consumption of beverages either before or during exercise may increase the incidence rate by over 25%
to the hypothesis that spiking said beverages with an agent that has previously been shown to reduce the symptoms of nausea and vomiting could be of great benefit for athletes.
Addendum: Are there pesticides in ginger? Oliver Klettner wants to know if there's a risk that you're intoxicating yourself with ginger. Unfortunately, the data on this subject is scarce. According to an older study in the Journal of Agricultural and Food Chemistry, ginger is yet one of the imported spices that contain relatively little DDT, PCB, Dieldrin, Endrin and BHC residues. The ginger from Nigeria in particular has almost no DDT and BHC, while the products from India contained measurable, but probably uncritical amounts (Sullivan. 1980). Similar and even lower levels were detected more recently by Srivastava et al. (2001) in important ginger powder from India. Data on Chinese ginger, which is what Oliver asked about, in particular, is not available in the literature. What is available, though, is data on commercial ginger powders sold in Germany in the late 1970s. The products of undisclosed origin Boppel (1979) tested contained both lead and cadmium, albeit in low doses (1.9 parts per million and 0.35 ppm). Also, in view of the epidemiological evidence in favor of the health benefits of ginger, it appears rather unlikely that (probably existing) pesticide and heavy-metal residues are a general problem. The average ginger consumer is after all ingesting it with a certain amount of these compounds. If that was a sign. health problem, the health benefits should not exist.
In the present study, this agent was ginger that was added to an isotonic beverage 40 recreational athletes (23 male, 17 female) who had volunteered to participate in the study consumed on one out of three test drinks containing 450 ml of either water or beverage A or beverage B in two 225ml servings before and after their workout:
  • Study Underlines Real World Benefits of 2g/day of Ginger for Type II Diabetics - Effects Almost on Par W/ Metformin | more
    Beverage A contained 7·5% glucose, 10 mM NaCl, citric acid, K sorbate and 62·5 ml of ginger root extract per 1 L.
  • Beverage B was identical to beverage A but the ginger was replaced with 62·5 ml of carrot extract. 
  • The control drink contained nothing but plain water.
During each of the three sessions the volunteers completed a 5 km run around the same course. To minimize unwanted interferences due to the test-drinks or fatigue, the sessions were spaced at least 7 days apart (and the subjects were asked not to change training or lifestyle during the study period).
What's the mechanism behind the exercise induced gastrointestinal disturbances? With exercise it's the reduction in gastrointestinal integrity that's driving the increase in gastrointestinal symptoms. Studies show, the harder you exercise, the more the gut integrity suffers and the more susceptible you become to intestinal disturbances. It's not clear how exactly ginger protects your gut from becoming leaky, but it would appear to be most likely that it's a result of its potent anti-inflammatory effects.
The same 5 item questionnaire that has been successfully used Pfeiffer et al. to probe the effects on nutritional intake on gastrointestinal problems during competitive endurance events in 2012 was used to assess the upper and lower gastrointestinal (GI) symptoms before and after exercise. In said test, the subjects hat to place a mark a 10 cm line to rate the severity / occurrence of symptoms anywhere between 0 (low / never) and 10 (high  / always). 
"Section 1 addressed upper abdominal problems (reflux / heartburn, belching, bloating, stomach cramps/pain, nausea, vomiting); section 2 addressed lower abdominal problems (intestinal/lower abdominal cramps, flatulence, urge to defecate, side ache/stitch, loose stool, diarrhea, intestinal bleeding); and section 3 addressed systemic problems (dizziness, headache, muscle cramp, urge to urinate)" (Pfeiffer. 2012). 
The evaluation of the showed a significnat increase in the incidence of upper GI disturbance (P < 0·05) in response to exercise; stomach problems increased from pre-exercise 1.7 (0.1–6.3) to 2.0 (0.1–8.4) during exercise and nausea increased from pre-exercise 1.1 (0.1–4.5) to 2.0 (01–7.6) during exercise. 
Figure 1: The addition of the ginger root extrac lead to a sign. amelioration of the almost 200% increase of the incidence of gastrointestinal symptoms in the 40 recreational athletes who participated in the study (Ball. 2015).
All other measures of GI disturbance were similar between pre-during and post-exercise and the general consumption of beverages did not exacerbate the GI symptoms during exercise. 

What the ginger containing beverage did, however, was that it reduced the prevalence of stomach problems (4.6 (0.3–6.6)) and nausea (4.5 (0.3–9) decreased significantly (P < 0.05) - an effect that was not observed with either beverage B or water, which were without noticeable effects on stomach problems (5 (0.2–8.2)) and nausea (5 (0.2–7)).  
Bottom line: Overall, the data from the study at hand is the first piece to a puzzle of evidence that could eventually prove the usefulness of ginger as a functional ingredient in pre- and post-workout beverages for endurance athletes - even if it does only ameliorate, not block the dramatic (>100%) increase in gastrointestinal problems.

Ginger is also on the list of supps in this SV Classic: "Supplements to Improve & Restore Insulin Sensitivity - Installment #4" | more
What is still missing, though, are (a) long(er) term studies in larger study populations, (b) evidence that the benefits occur in (1) higher-intensity exercise / longer duration exercise (I am thinking along the lines of Ironman training) and (2) anaerobic exercises like resistance training or sprinting which are similar prone to inducing (temporal) gastrointestinal problems and last but not least (c) insights into the mechanism(s) behind the beneficial effect of ginger - effects of which Ball et al. (2015) speculate that they may be, linked to the antagonist effects on serontonergic 5HT receptors, as they have been suggested by Sontakke et al. in a chemotherapy study (2003) | Comment on Facebook!
References:
  • Ball, D., G. Ashley, and H. Stradling. "Exercise-induced gastrointestinal disturbances: potential amelioration with a ginger containing beverage." Proceedings of the Nutrition Society 74.OCE3 (2015): E186.
  • Boppel, B. "[Lead-and cadmium-content of foodstuffs 1. Lead-and Cadmium-content of spices and table salt (author's transl)]." Zeitschrift Fur Lebensmittel-Untersuchung Und-Forschung 160.3 (1975): 299-302.
  • Butt, Masood Sadiq, and M. Tauseef Sultan. "Ginger and its health claims: molecular aspects." Critical reviews in food science and nutrition 51.5 (2011): 383-393.
  • Ghayur, Muhammad Nabeel, and Anwarul Hassan Gilani. "Ginger lowers blood pressure through blockade of voltage-dependent calcium channels." Journal of cardiovascular pharmacology 45.1 (2005): 74-80.
  • Kim, Eok-Cheon, et al. "[6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo." Biochemical and biophysical research communications 335.2 (2005): 300-308.
  • Mashhadi, Nafiseh Shokri, et al. "Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence." International journal of preventive medicine 4.Suppl 1 (2013): S36.
  • Singletary, Keith. "Ginger: An Overview of health benefits." Nutrition Today 45.4 (2010): 171-183.
  • Sontakke, S., V. Thawani, and M. S. Naik. "Ginger as an antiemetic in nausea and vomiting induced by chemotherapy: a randomized, cross-over, double blind study." Indian journal of pharmacology 35.1 (2003): 32-36.
  • Srivastava, L. P., Roli Budhwar, and R. B. Raizada. "Organochlorine pesticide residues in Indian spices." Bulletin of environmental contamination and toxicology 67.6 (2001): 856-862.
  • Sullivan, James H. "Pesticide residues in imported spices. A survey for chlorinated hydrocarbons." Journal of agricultural and food chemistry 28.5 (1980): 1031-1034.

Friday, September 27, 2013

Rats "On" Taurine Can't Ever Get Enough... Exercise of Course! What Were You Thinking About? Mice Cover 50% More Distance W/ HED of 3-4G of Taurine Post Workout

On Taurine? If she was, she could run another marathon 6h later ;-)
Actually, the results a group of researchers report in a recent paper in the Journal of Sports Medicine and Physical Fitness are a bit surprising. After all, taurine is - as you all should know by now - a GABA agonist and should thus rather have had a calming effect on the mice, the scientists used in their experiment. What Yumiko Takahashi, Eiki Urushibata and Hideo Hatta from the Department of Sports Sciences at the University of Tokyo observed when they supplied their lab animals with 0.5 mg/g body weight immediately after they had them run on a treadmill at 25m/min for 90 min was yet quite the opposite of the laziness you would expect after having read about the calming and balancing effects of taurine Mure et al. (2003) observed, when they administered it either alone or in conjunction with caffeine (read pervious SuppVersity article).

Mice on taurine run more, because they can!?

Contrary to the saline-group in which the exhausting bout of exercise lead to a significant decrease in the amount of voluntary wheel running (compared to the non-exercised mice in the control group; p < 0.01), the rodents who had received a human equivalent of 3-4g taurine (that's what a human would have to take) did not exhibit any signs of exercise induced fatigue. On the contrary:
"Significant effects of post-exercise taurine administration on voluntary wheel running during 6 h were found (p < 0.05). The 30-min running distance was significantly higher in the taurine-treated group than in the saline-treated group at 1-1.5 h after treadmill exercise (p < 0.05)." (Takahashi. 2013)
This increase in voluntary endurance training occurred irrespective of similar blood glucose and liver and skeletal muscle glycogen concentrations in both, the supplemented and placebo treated rodents after the treadmill exercise.
Figure 1: Total running distance and running distance per food ingestion (left); liver and muscle glycogen content (right) at different time points before (baseline) immediately after 0 and 3-6h after the forced 90 min run (Takahashi. 2013)
The total food consumption during 6 h of voluntary wheel running was likewise identical, or as the scientists wrote, it "showed no difference between the two groups". This means that the ratio of total running distance to total food consumption was significantly higher in the taurine treated group - a clear advantage for anyone who wants to burn a few additional calories on the treadmill (you should yet always remember that 90% of the weight loss happens in the kitchen, i.e. by dieting, and "training to burn energy", only, is nothing but stupid!)

Now this clearly raises the question "what's going on here?"

SuppVersity Suggested Read: "Taurine Pumps Up Strength & Recovery in Response to Eccentric Curls. NAC Decreases Peformance & Boosts Fat Oxidation!?" | read more
Obviously you and me are not the only ones who are asking themselves this important question. What is it that makes the post-workout so effective? Actually the mere fact that taurine is effective, when it is administered after a workout and not chronic or pre-workout as in the majority of previous studies is already news.

Well, the scientists seem to believe that the effects must be directly mediated by improved post-exercise recovery. With identical blood, liver and skeletal muscle glucose, we do however have to discard the beneficial effects of taurine on glucose metabolism and a potentially faster restoration of muscle glycogen as a potential explanation (click here to learn more about taurine's beneficial effects on glucose metabolism) .

As Takahashi et al. point out, skeletal muscle loses various ions and other solutes including taurine during exercise to compensate for increases in many osmotically active molecules as a result of enhanced energy metabolism (Usher-Smith. 2009). They go on to explain that
"the restoration of [taurine] may no have direct beneficial effects on the contractile properties of skeletal muscle, including the release and uptake of Ca2+ by the sarcoplasmic reticulum in the excitation-contraction coupling process,  prevention of peroxidation of plasma membranes, and recovery from exercise-induced cellular membrane damage." (Takahashi. 2013)
Accordingly, rodents with a knockout of the taurine transporter (which means these rodents could not use the taurine) showed both reduced taurine concentration in skeletal  muscles and tissues and significantly lower endurance capacity (>80%) compared to wild-type mice.

Taurine could also help fatty oxidation; after all, a recent study by Piña-Zentella et al. observed that taurine treatment increased the catalytic activity of cAMP-activated protein kinase A in white adipocyte tissue cells (Piña-Zentella. 2012).
With this kinase being important for the activation of the lipolitic enzyme cascade in both adipocytes and skeletal muscle.
This may not just help you burn off more fat, but also provide you with the fuel you need during prolonged exercise.
Bottom line: While we still do not know for sure, if it is the increase / faster recovery of cellular osmolality or other aspects of skeletal muscle recovery that are promoted by the post-workout ingestion of 3-4g of taurine (that's what a human would take), the real world results in the study at hand appear to suggest that the usage of an amino acid most trainees usually think of as part of a pre-workout formula may make just as much, if not more sense after a workout. This is particularly true, if you are one of the many trainees who can't wait till he or she gets back to the gym.

In conjunction with the recently covered beneficial effects on insulin sensitivity and think of the importance of the latter with respect to the replenishment of glycogen stores, and the triggering of p-Akt and the nutrient-based increase in protein synthesis, it would therefore appear to make sense to get yourself a 250-500g bag of (dirt cheap) bulk taurine and start experimenting with it. As stated before, the effective dose in the study was 3-4g and the insulin sensitizing effects have been observed with dosages in the 6g range (spread evenly across the meals).

Don't go overboard, though, in susceptible individuals the chronic ingestion of high(er) amounts taurine could trigger an increase in anxiety and that despite the fact that it is actually an anxiolytic (=reduces anxiety; cf. Kong. 2006).

References:
  • Kong WX, Chen SW, Li YL, Zhang YJ, Wang R, Min L, Mi X. Effects of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav. 2006 Feb;83(2):271-6.
  • Piña-Zentella G, de la Rosa-Cuevas G, Vázquez-Meza H, Piña E, de Piña MZ. Taurine in adipocytes prevents insulin-mediated H2O2 generation and activates Pka and lipolysis. Amino Acids. 2012 May;42(5):1927-35.
  • Usher-Smith JA, Huang CL, Fraser JA. Control of cell volume in skeletal muscle. Biol Rev Camb Philos Soc. 2009 Feb;84(1):143-59.

Friday, March 9, 2012

Chamois Creme Potential Reason for Elevated Estrogen in Cyclists +Triathletes Have 2x More Testosterone Than Average Men and 71% More Than Active Individuals

Image 1: Norman Stadler 2004 winner of the Ironman Hawaii probably had a hell of a testosterone boost, when this photo was taken (img. Kai Baumgartner. 2004)
Disturbances of the endocrine (=hormonal) milieu are among the hall-mark features of what sport scientists call the "female athlete triad". The unholy trinity of osteoporosis, disordered eating and, as a direct consequence of the aforementioned hormonal imbalances, menstrual disorders. Men, the purportedly "stronger sex", on the other hand are supposedly pretty resistant to exercise-, or, I should say, overtraining-induced hormonal imbalances - bullshit? Well, probably... after all, with insufficient fuel and recovery everyone, man or woman will eventually maneuver him- or herself into a situation where his endocrine system is no longer functioning optimally. A recent study from UCLA does yet show that mother nature must have been aware that a) exercise is part of what the "hunters" (=us men ;-) do and that b) men are in the lucky position not to have carry a child full term - so, as long as they are we are not sick, there is no reason for mother nature to shut our reproductive system down completely.

What's worse? Cycling, or swimming, cycling and running?

To test the hypothesis that "serious leisure time athletes", in this case cyclists (>8h of intense training per week) and triathletes (>5h of intense training per week), are at much greater risk of developing training-related hormonal disturbances than the average "recreational athlete" who performs less than 3.5h of moderate exercise per week, L.Z. Fitzgerald and his colleagues from the School of Nursing at UCLA assessed the body composition, physical activity and hormonal and inflammatory markers of 107 healthy men (age 18-60 years).
Figure 1: Demographic and physical variables of the cyclists (n=46), triathletes (n=16) and recreational athletes (n=45) of which I believe that they me independent (caffeine, age) and dependent (body fat, lean body mass) confounding factors data expressed relative to the statistical average; calculated based on Fitzgerald. 2012
In figure 1, I have compiled a few of the demographic and physiological parameters of the the three study groups of which I believe that they may be confounding factors that may - independent of the type of exercise these men were doing - contribute to differences in the endocrine parameters between the highly active cyclists and triathletes and the moderately active recreational trainees. Of these, the higher age, which is obviously associated with a decline in testosterone levels, and the significantly higher caffeine intake in the cyclists (with 317.3mg/day this is well within the regions where it boosts testosterone, though; cf. Beavan. 2011) are independent, while both the amount of body fat (more = more aromatization = more estrogen and less testosterone), as well as the total lean mass the athletes are carrying around are obviously influenced by the type and amount of exercise they perform.
Figure 2: Estradiol, testosterone, SHBG, luteinizing hormone (LH) and follicle stimulating hormone (FSH) expressed relative to data from a reference cohort I "borrowed" from Brambilla et al. (2009); calculation based on Fitzgerald. 2012
Apropos, as you can see in figure 2 we do once again have one of my favorite (roughly!) bell-shaped dose-response curves (orange line), with the highest exercise load (cyclists - more than 8h of training per week) producing the most unfavorable testosterone to estrogen ratio, a pronounced peak that is associated with the medium to high volume, high intensity approach of the triathletes (>5h) and a slightly above average testosterone to estrogen ratio in the group of recreationally active men.

If you cherish your manhood, man up and don't use chamois cream

A closer analysis of the individual hormone levels does yet reveal a pretty awkward phenomenon: In spite of having the lowest luteinizing hormone levels of all three groups (-56% below "my" reference, i.e. Brambilla. 2009) and an exorbitant amount of estrogen (+113% more than "my" reference) they also have the highest amount of testosterone in their blood. And while I am usually smart-assing scientists for following mainstream paradigms and not following up interesting / surprising results, this is one of the rare cases, where I really have to take my hat off to Mr. Fitzgerald and his colleagues, because I would never have thought of the somewhat shocking explanation the guys came up with:
Some cyclists apply chamois cream to their perineum area to help prevent chafing and bacterial infections related to bicycle saddle sores. The various commercial creams contain a variety of ingredients including lubricants, polymers, oils (jojoba, lanolin, mineral, olive, peppermint, rosewood, soybean, tea tree, St John’s wort), vitamins (A, C, D, E), and alcohols. Additionally, some of these creams contain parabens which are anti-microbial preservatives, but also weak estrogen agonists (Frederiksenet. 2011). In vitro studies demonstrate that parabens bind to estrogen receptors and initiate estrogenic cellular path-ways (Darbre. 2004).
And in fact, a follow up questionnaire confirmed the scientists' suspicion. While only 10% of the triathletes, who obviously cycle as well, used paraben-containing chamois cream roughly 50% of the cyclists applied them regularly to their best parts - with shocking side-effects:
Among the cyclists, there was a significant dose-dependent increase in estradiol levels with increasing years of chamois cream use for men using the cream for more than 4 years (p = 0.03) with notable effect size (partial n² =0.12).
If we briefly discard the high estrogen levels in the cyclists and take an objective look at what conventional wisdom tells us about the detrimental effects of high intensity endurance exercise in general and the arduous combination of swimming, cycling and running, also known as triathlon, this study does still provide enough evidence to cause another of our broscientific myths to totter...

...high intensity endurance exercise does not per se reduce testosterone levels!

Image 2: I wonder if there is a "don't use if you don't want to castrate yourself" warning anywhere on this tub of chamois crème.
At least in the study at hand, both triathlon training and cycling even at doses of >1h per day was associated with statistically significantly higher testosterone levels, statistically identical cortisol levels (cyclists: 309µg/dL; triathletes: 292µg/dL; recreational athletes: 376µg/dL) and - as if that was not beneficial enough - significantly reduced baseline interleukin 6 levels (-50% in cyclists; -74% in triathletes)... if future controlled studies are able to confirm these preliminary results, this would not only confirm the initial hypothesis that the male hormonal milieu is much more resilient than its female counterpart, it would also put a huge question mark beyond the underlying hypothalamic adaptation processes and the dose-response relationship - after all, these results to not contradict previous findings by Hackney et al., who did even coin a special term for the ultra-endurance exercise induced downregulation of the reproductive system: the "exercise hypogonadal male condition" (Hackney. 2008).

Saturday, November 5, 2011

Astragalus membranaceus: Purported Telomerase Activator Increases Exercise Capacity by +56%, Fights Cancer and May Be a Healthy Adjunct to Chemotherapy and Vaccines

Image 1: Astragalus membranaceus, one of the 50 fundamental herbs in traditional Chinese medicine (TCM). A purported telomerase activator that contains potent antioxidants.
There is hardly one month passing without some media reports about a group of scientists who supposedly found the royal route to health and longevity. With all those potentially life-extending drugs, herbals and nutritional supplements that have thus surfaced in the course of the last decades, it is actually almost surprising that we still die like flies, isn't it? Well, one possibility would obviously be that the scientifically-backed wonder-potions you can buy in the snake-oil shops all over the Internet do not work at all - impossible? I don't think so. Consequently, I was and still am very skeptical about the dubious claims about the "life-extending" effects of a patented Astragalus membranaceus (also Astragalus propinquus) extract - and that despite or, I should say, because of its "scientifically proven" effect on telomerase length in 114 older (63 +/-12 years) subjects. After all, the respective study was not only by the owner of the company which holds the patent for T-65(R), a (I quote) ">95% pure single chemical entity isolated from a proprietary extract of the dried root of Astragalus membranaceus" (Harley. 2011), but the authors (guess what all somehow involved in the sale of the product) also use several more or less clever tricks to polish their results. While they have to admit that
Two independent measures of median or mean telomere length (by FlowFISH and qPCR) showed no consistent change with time on PattonProtocol-1 (data not shown).
they cleverly handpicked 7 out of 13 tested subjects in which the percentage of nuclei with short telomeres had declined at 12-18 months compared to baseline. Now, while this decline may be statistically significant (p<0.05, according to the scientists), I wonder what happened to the other 6 subjects... and even if you were among those lucky 7, this does by no means indicate that that will actually prolong your life.

Who wants to live forever, anyway...

That I did nevertheless dig a little deeper into the research on astragalus had two reasons. One was that I wanted to find any other data on its potential effects on telomerase length - and more importantly its practical outcome in rodents or even my "favorite" subject of medical research, the roundworm Caenorhabditis elegans, or "C. elegans" (do I have to say that there are no such studies?). The other reason was that astragalus membranaceus has been used in Traditional Chinese Medicine for centuries. So, even if it would not make you live forever there obviously had to be some benefits to this flowering plant from the family of Fabaceae. And as it turned out, Chinese researchers have been performing numerous studies into its antioxidant, anti-diabetic, anti-hypertensive, and immunomodulatory activity within the last decades, of which a very recent one could be of particular interest for fitness enthusiasts and even professional athletes.

... isn't performance the only thing that counts?

Image 2: While this is not the exact model that has been used in the study, this is what "exercise" looks like if you are one of those poor lab rats... well, not so much different from what a whole host of trainers still suggest their clients should do to lose weight... but I am digressing, here ;-)
If you look at the sales-ranks of various dietary supplements, it is quite obvious that (potential) long-term effects on health and longevity usually stand second to immediate benefits like increased energy, well being, weight loss or exercise performance. "If you don't feel it, it doesn't work!" is the mantra of many fitness enthusiasts; a montra on which the manufacturers of purported fat-burners and pre-workouts, 99% of which are only caffeine, geranamine and yohimbine loaden stimulants, monetize big time. And as long as those cheap stims keep the sales of their products up, the producers obviously would be stupid if they changed their formulas and included more expensive "adaptogens" - chances are the customers would not be willing to pay the price, anyway. Accordingly, you won't find references to studies like the one Deng and Hu recently published in the Academic Journals on any of the labels of the currently available mainstream supplements (Deng. 2011).

In what they themselves claim is one of the few studies (to my mind the first to be published in an international journal) investigating the effects of Astragalus membranaceus polysaccharides (AMP) on exercise performance, the scientists from the Kunming University in China orally administered 50, 100 or 200mg/kg of previously extracted pure astragalus polysaccharides to 6-8 week old male Sprague-Dawley rats for 30 successive days. In the course of the last week of the experimental period the rats, who had been fed ad-libitum for the whole study period, were accustomed to running on a treadmill for 15-20min at 15-30 m/min (=0.9-1.8km/h), so that they would be able to perform an exercise test that consisted of running on a 10° incline (30m/min, ~75%VO2Max) until exhaustion on day 30.
Figure 1: Running time to exhaustion (in s, left) in rats who received either saline control or astragalus membranaceus polysaccharides at a dosage of 50, 100 or 200mg /kg per day and the extrapolated dose-response relationship (data calculated based on Deng. 2011)
As the data in figure 1 shows, the supplemental regimen, which had no effects on the body weight of the then 12-week old rats, significantly improved the running endurance of the laboratory animals. Interestingly, the extrapolation of the dose-dependency suggests that dosages above 300mg/kg (human equivalent ~50mg/kg) will probably not yield much better results than the 200mg/kg maximal dose that was used in the study (human equivalent ~35mg/kg).
Figure 2: Effects of astragalus supplementation on anti-oxidant enzymes after exhaustive endurance training in rats; values expressed relative to unsupplemented control (data calculated based on Deng. 2011)
The post-exercise glutathione peroxidase (GSH-Px) activity exhibits a similarly logarithmic dose-response relation (cf. figure 2). The decreases in malondyaldehyde (MDA), as well as the increase in superoxide dismutase (SOD), on the other hand appear to be almost linear. And, lastly, the lower increase in catalase (CAT) in the high dose astragalus group could be a consequence of the fact that, with GPH-Px and CAT both being responsible for the catalyzation of hydrogen peroxide to water, there simply was no need for additional cat activity, when the GPH-Px activity already increased by >100%.

If (the big if ;-) those results could be confirmed in human trials, the +56% increase in exercise endurance in the 200mg/kg (i.e. 35mg/kg for humans) of astragalus could in fact be the "next big thing" in terms of natural ergogenics. For the time being, it is yet only another item on the list of purported benefits, I am now going to conclude on another anon more health related note.

Beyond exercise performance: Cancer protection and immuno-modulation

While I initially voiced some doubts with regard to the purported longevity effects of astragalus, its relatively well-established anti-carcinogenic effects could well help many of us to substantially prolong our lives. After all, numerous studies have established the anti-cancerous activity of various natural constitutents of astragalus. Among the cancer cell lines that were tested were  
If you look a the publication dates and authors, you will notice that despite its longstanding tradition within TCM scientists have only lately begun to realize that we could have overlooked a vital contribution in the ongoing battle against cancer - and what's more, the studies are mostly done by TCM practitioners at the School of Chinese Medicine, who certainly ain't under suspicion to be interested in monetizing on a new drug. After all, natural medicine is not patentable.

From the petri dish to the bedside: APS improved quality of life in cancer patients.

Image 3: Astragalus has already proven its usefulness as an adjunct to the toxic cocktail cancer patients receive as part of their chemotherapy
In a first trial (Guo. 2011), the intravenous administration of astragalus polysaccharides (APS) at 250mg/day in connection with chemotherapy for 7 days lead to statistically significant improvements in the overall quality of life of advanced non-small-cell lung cancer patients. Personally, I find it most remarkable that it reduced the chemotherapy induced fatigue by >50% (as measured by a standardized Quality Of Life questionnaire). The objective response rate to chemotherapy was higher, as well: 42.64% (29/68) in the APS supplemented patients vs. 36.76% (25/68) in the control arm of the study, but these effects did not reach statistical significance (P = 0.483, indicating that chances are about 43% that this was just "conincidence").

In view of the immune-weakening effects of chemotherapy, it may also be important that astragalus has established anti-viral effects. It has been tested as an adjunct to interferon alpha-2b in anti-herpes therapy (Zhang. 1998) and against (chronic) hepatitis B infections (Wu. 2001; Dang. 2009) - the effects are yet rather mediocre and may be mediated by the same general immune-stimulatory effects of the herb (Block. 2003; Jiang. 2010). In this context, it is particularly noteworthy that a paper on herbal medicinces for viral myocarditis published in the reputable Cocraine Database of Systematic Reviews that ...
[..a]stragalus membranaceus (either as an injection or granules) showed significant positive effects in symptom improvement, normalisation of electrocardiogram results, CPK levels, and cardiac function.
And with the current vaccination-hysteria, we may soon see the practical realization of a proposal that has been made by Lin et al. in a recent paper on the effects of Astragalus polysaccharides (APS) on foot-and-mouth disease in swine (Lin. 2010), i.e. the addition of APS as an immuno-modulator for various vaccines (I guess it would certainly be better than mercury, don't you think ;-).

Conclusion: A promising herb... without a future?

Image 4: If all the info got you interested, Carl Lanore from Super Human Radio has recently sourced a bulk powdered version of astragalus. The bulk source is probably the only way not to run out of money before you notice any effects ;-)
Despite the accumulating evidence for the many health benefits that could be derived from the administration of crude extracts or isolated fractions of astragalus, chances that it will make it from Carl Lenore's Super Human Radio shop to the mass market are low ... or I should say non-existent, as long as the latter is still controlled by BigPharma and their right-hand men and women in the bureaucracy. After all, Astragalus membranaceus is not only non-patentable, it also does not appear to have any side-effects, the pharma companies could monetize on ;-) So regardless of whether future studies will validate or maybe falsify the hopes many naturopaths and TCM practitioners are pinning on this herb, MDs who follow the official guidelines, which state that the...
evidence for using astragalus for any health condition is limited. High-quality clinical trials (studies in people) are generally lacking (NCCAM. 2010),
will probably never prescribe it to their patients... unless, well unless some genius of a molecular biologist in one of the pharma-companies applies a few minor melcular tweaks to some of the active ingredients of astragalus, so that his company can file a patent application that goes beyond the extraction technique that has been patented for Harley's (questionable) T-65(R).

Wednesday, October 19, 2011

CoQ10 for Ultra-Endurance Athletes: 150mg of Ubiquinone Reduce Stress & Inflammation and Stabilize Cell Membranes in 52.4 Mile Torture from 640m to 3,393m!

Image 1: Susan Kokesh, blogger and the Crazy Running Mum at the Sierra Nevada ultra-endurance run a 52.4 miles "double marathon"
  in September 2010; I probably would not even have survived this torture - respect!
As a health conscious physcial culturist, you are probably aware that the vitaminesque nutrient CoQ10, which, due to its ubiquitous presence in all living beings, is also known as ubiqinone, plays a fundamental role in cellular bioenergetics. It is a necessary cofactor in the mitochondrial electron transport chain (i.e. your cell's way of "breathing", its respiratory chain) and is therefore essential for the production of ATP, the fundamental energy unit your cells are operating on. In that, CoQ10 works as a mobile redox agent that shuttles electrons and, interestingly, also protons (those little blue and red balls from Bohr's atom model ;-) in the electron transport chain. Within the health and fitness community, it is however better known for its antioxidant value, as in its reduced form, ubiquinol, it is a potent lipophilic (which means that it does not combine with fats) antioxidant, which is able to recycle and regenerate other antioxidants, such as vitamin E and vitamin C (Ernster. 1995). Moreover, CoQ10 participates in cell signaling and gene expression and has been used as a dietary supplement (among others) for the treatment of neurodegenerative diseases and statin-induced myopathies.

In view of its pluripotent influence on mammalian metabolism (on a side note: the "-10" in CoQ10 indicates the length of the isoprenoid sidechain that is attached to the common benzoquinone ring structure; the latter is unique and can be found in humans and a few other mammals only), it should thus not surprise you that Chavier Díaz-Castro and his collegues from the University of Granada report that the intake of 150mg of the natural version of CoQ10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone; natural = has trans configuration), profoundly modulated "the undesirable effects of the evoked oxidative stress and inflammation signaling during high-intensity" (Díaz-Castro. 2011).
Illustration 1: Supplementational protocol used in the study; CoQ10 was administered as 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone in powder form in 30mg capsules.
As you can see in illustration 1, the 20 highly trained male amateur athletes (all had run The Sierra Nevada ultra-endurance race in the previous 2 years), who participated in the study were not given the whole dose of 150mg of CoQ10 at once, but followed what I would like to call a "loading protocol" in the two days before the event. The placebo group received an identically looking product containing beer yeast, cellulose,
acacia, silica stearic acid, magnesium stearate, cellulose gum, and maltodextrin.

The total distance of The Sierra Nevada run is >50km. It is considered one of the hardest trials worldwide, mainly because the run, in the course of which the participants "climb" from 640m to a final altitude of  3,393m is almost on a continuous incline! A 5.5 hour torture, for which the CoQ10 supplemented athletes needed on average ~25min less than the subjects in the placebo group. In this study, the exercise performance was yet of negligible importance. What the scientists were really interested were the markers of oxidative damage and inflammation and as the following data shows, those were markedly influenced by the ingestion of this rather "mediocre" (compared to what you see some "health-gurus" advocate) amount of CoQ10.
Figure 1: Effects of CoQ10 supplementation of total bilirubin, triglycerides and urinary creatinine in 20 ultra-endurance runners (data calculated based on Díaz-Castro. 2011)
As you can see in figure 1, CoQ10 induced a significant reduction in urinary creatinine even before the race started (figure 1, left column). Moreover, there were significant differences in the bilirubin (indicates heme catabolism), triglycerides and (again) creatinine (indicates net protein catabolism):
Intense physical exercise resulted in an increase in net protein catabolism and an increase in
creatinine excretion in the PG after the physical test (p < 0.001); however, the urinary levels of creatinine were lower (p < 0.05 before and p < 0.001 after the physical test) in the CoQ10 treated group. Other interesting result was that although there was an increase in urinary creatinine in the CG, it was lower than in PG (38.77 ± 10.20 vs. 88.23 ± 11.21, p < 0.05). We also observed a decrease in the bilirubin concentrations in the CG after the run (p < 0.001) with lower values compared to PG group.
There were also significant differences in the inflammatory response, with (statistically significant, p<0.05) lower values of interleukin 6 (IL-6; -32%) and TNF-alpha (-23%) before the start of the race, and -22% lower TNF-alpha values after the "torture". Moreover, the basal hydroper-oxide content in the erythrocyte membranes, the scientists measured as an indicator of the degree of oxidative stress were lower before and after the exercise test, as the scientists call it.

Taken together, these results suggest that the addition of a small dose of CoQ10 to your supplemental regimen could induce unexpectedly profound cell-stabilizing benefits, of which it would yet be interesting to see how those translate into performance benefits, health and longevity, in the long run.