Thursday, July 21, 2016

Cordyceps militaris Improves Tolerance to High Intensity Exercise - Effects Take Time and High Dosages (4g/day)

In China, cordyceps is also used in dishes - here: Chicken With Mushroom & Cordyceps Militaris Soup.
Cordyceps is the tribulus of adaptogens... why's that? If you look at the scientific evidence supporting its efficacy the results are similarly ambiguous as they are for tribulus and still, Cordyceps has been among the supplemental topsellers for years - and rarely in the way it is used in classic Chinese Traditional Medicine (TCM) for respiratory and kidney diseases, renal dysfunction, and cardiac dysfunction (Zhu, Halpern, & Jones, 1998b).

The popularity dates back to bogus rumors about Chinese female athletes in the 1990s - god knows what these "world-recordbreaking" athletes took, but cordiceps was almost certainly not the most effective of the PED cocktail.
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Still, in the supplement world rumors and outrageous claims sell and therefore it is not surprising that cordyceps sinensis, the most commonly supplemented species of cordyceps, has been mass-produced and marketed as Cs-4. More recently, scientists have started to develop cheaper and potentially more efficient alternatives such as the synthetically cultivated Cordyceps militaris which may contain a higher concentration of the actually active ingredients (Kim & Yun, 2005).

Figure 1: Time profiles of cordycepin production during submerged culture of Cordyceps militaris (d) and Cordyceps sinensis (s) in a 5-l stirred-tank fermenter. Standard curve was established as a dependence of peak area on the cordycepin concentrations (see inset on the upper right | Kim & Yun, 2005)
As Kim and Yun point out in the introduction to their latest paper, cordyceps has been "escribed as a natural exercise mimetic [that] is thought to improve performance by increasing blood flow, enhancing oxygen utilization, and acting as an antioxidant" (Hirsch. 2016; and there are in fact studies that support beneficial effects of Cordyceps sinensis supplementation on aerobic performance, showing improvements in maximal oxygen consumption (VO2max) and ventilatory threshold (VT). The significance of Cordyceps supplementation on high-intensity performance, on the other hand, is questionable, even if Hirsch et al. rightly argue that the "enhanced oxygen utilization and blood flow, especially to the liver and nonexercising skeletal muscle, may enhance lactate clearance" (Hirsch. 2016) and may thus "allow athletes to maintain a higher intensity of exercise, while the reduction of oxidative stress from high-intensity exercise may delay fatigue (ibid.)
Beware of the "bro-cebo" effect! As Rawdon et al. point out in their 2012 meta-analysis of the placebo effect in nutritional supplement studies on muscular performance point out, cordyceps is on the list of (potential) placebo-ergogenics. This and the fact that the majority of beneficial studies have been conducted by, financed or at least supported by the makers of CS4 and other cordyceps supplements is at least suspicious - in particular in view of the fact that Hirsch et al. (2016) had to resort to a 95% confidence analysis to "prove" the allegedly potent anti-fatigue effects of cordyceps. A statistical trick, others, such as Parcell et al. (2004) didn't use and, consequently, couldn't prove that 3g/day CordyMax Cs-4 tablets would actually increase the endurance performance of twenty-two endurance-trained male cyclists from a local college population.
To date, research on the ergogenic effects of cordyceps is yet "limited and inconclusive" (Hirsch. 2016) as to its benefits to exercise. This is at least partly a result of the significant differences in study design, where dosage (it appears to take several grams) and duration (the longer the better) are only two potentially confounding factors.
"Therefore, the primary purpose of this study was to determine the acute (1-week) effects of a Cordyceps militaris (4 g·d−1) containing mushroom blend on aerobic performance, including oxygen kinetics (VO2max, VT), and time to exhaustion (TTE). A secondary purpose was to explore the ergogenic potential on anaero bic performance (relative peak power [RPP], average power [AvgP], and percent power drop [%drop]). Lastly, an exploratory aim was to evaluate a longer duration (3 weeks) of Cordyceps militaris supplementation" (Hirsch. 2016).
To contribute to the existing evidence, Hirsch et al. recruited 28 trained (16 males; 12 females; trained = defined by an average of five hours per week of structured exercise, had been involved in an exercise program (≥ 3 days/week) for a minimum of one year, adults , between the ages of 18 and 35 years of whom all 28 participated in the acute, yet only 10 subjects in the long(er)-term phase of the study.
Table 1: PeakO2 mushroom blend and placebo ingredient list (Hirsch. 2016).
In a randomized, double-blind, placebo-controlled design, participants were randomly assigned, using Random Allocation Software (Version 1.0.0; Isfahan, Iran), into one of two treatment groups: mushroom (MR) or placebo (PL). Subjects ingested either 1.3 g of a mushroom blend (PeakO2, Compound Solutions, Inc., USA; Table 1) or 1.3 g of maltodextrin (PL) in the form to two capsules, taken orally three times per day (4 g daily) for 1 week (Phase I).
The elderly may benefit more. If you compare studies such as Parcell et al. (2004) in young and trained individuals to those that produced similarly beneficial results as Chen's 2010 experiment in 50-75-year old untrained subjects (+10.5% VO2max, +8.5% increase in ventilatory threshold) , it appears to be reasonable to assume that a lack of training or bad physical conditioning could increase your chances of benefiting of cordyceps supplements. Eventually this is yet speculative.
Capsules were identical in color and taste and packaged in white opaque bottles, randomized and coded by the manufacturer. Participants were randomized using block randomization with codes de-identified from separate white envelopes. Following the 1-week supplementation period, baseline exercise tests were repeated. A sub-set of participants volunteered to complete an additional 2 weeks of supplementation (Phase II), for a total of 3 weeks of supplementation, followed by exercise testing that confirmed what we already knew:
  • in the short run (1 week), there was no significant time × treatment interaction for VO2max (p = 0.364). There was a main effect for time for VO2max (p = 0.011), with significant increases observed in both MR (47.7 ± 9.4 to 49.0 ± 8.6 ml·kg−1·min−1) and PL (46.4 ± 7.9 to 48.9 ± 8.1 ml·kg−1·min−1). In fact, the 95% confidence interval analysis showed a significant increase in VO2max for PL, but not for MR
  • in the long(er) run (3 weeks), however, i.e. after three weeks of supplementation (Phase II), there was a significant time × treatment interaction (p = 0.042). Post-hoc pairwise comparison demonstrated a significant increase in VO2max from pre to post for MR (44.0 ± 10.5 to 48.8 ± 11.2 ml·kg−1·min−1); there was no significant change for placebo (45.0 ± 12.5 to 45.9 ± 9.9 ml·kg−1·min−1). Analysis of 95% CI showed a significant increase in VO2max for MR, but not for PL (Figure 2A).
So what? Well, first of all, benefits were observed only in the long run... by then in only 10 subjects and with error bars (see Figure 2) that raise questions about how beneficial taking 4g of Cordyceps militaris really is for you or everyone else who's interested in its adaptogenic effects.
Figure 2: Phase II changes in performance measures (A) maximal oxygen consumption (VO2max), (B) ventilatory threshold (VT), and (C) time to exhaustion (TTE) presented as 95% confidence intervals (Mean ± (1.96 × SEM) | Hirsch. 2016).
Still, beneficial effects in the long run were also observed for the ventilatory threshold and the time to exhaustion during the standardized exercise test at the end of the supplementation period. Significant improvement in relative peak power and average power which is probably the more important parameter for high intensity athletes, however, were not observed.

That the sponsored study (funded by Disruptive Nutrition, Burlington) will still be (ab)used to advertise Cordyceps militaris supplements to athletes competing in high intensity sports has a different reason: at least in the long-run cordiceps or in this study, if we are honest, a blend of several mushrooms (see Table 1) significantly reduced the relative power drop - an often-used measurement of exercise fatigue.
Figure 3: Change in RPP for Phase I (A) and Phase II (B) presented as 95% CI (Mean ± [1.96 × SEM]). ∗indicates a significant improvement, as determined by 95% CI (Hirsch. 2016).
Bottom line: The take home messages of the study at hand are that (a) cordyceps still is the most promising for endurance athletes, (b) it appears warranted to assume that the higher adaptogen content of Cordyceps militars vs. synensis constitutes an ergogenic advantage (future direct comparisons are still necessary) and (c) dosage and duration of supplementation should be high, because short-term effects don't exist and previous studies showed that dosages of only 1g often fail to produce results.

Whether "loading", i.e. initially taking way more cordyceps than the 4g used in the study at hand, is sensible and worth the money, is questionable, and still - as so many things in the world of fitness - common practice | Comment
  • Chen, Steve, et al. "Effect of Cs-4®(Cordyceps sinensis) on exercise performance in healthy older subjects: A double-blind, placebo-controlled trial." The Journal of Alternative and Complementary Medicine 16.5 (2010): 585-590.
  • Hirsch, Katie R., et al. "Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation." Journal of Dietary Supplements (2016): 1-13.
  • Kim, H. O., and J. W. Yun. "A comparative study on the production of exopolysaccharides between two entomopathogenic fungi Cordyceps militaris and Cordyceps sinensis in submerged mycelial cultures." Journal of Applied Microbiology 99.4 (2005): 728-738.
  • Parcell, Allen C., et al. "Cordyceps sinensis (CordyMax Cs-4) supplementation does not improve endurance exercise performance." International journal of sport nutrition and exercise metabolism 14.2 (2004): 236-242.
  • Rawdon, Tarra, et al. "Meta-analysis of the placebo effect in nutritional supplement studies of muscular performance." Kinesiology Review 1.2 (2012): 137-148.