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

References:

• 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.

Cordyceps Sinensis - Another Supplemental Non-Starter: Human Data Shows No Increase in Testosterone, No Strength Gains, No Improvements in Body Composition.

Image 1: As it turns out it's not necessary you start eating parasites (img nepaliproducts.com)

In view of the public attention adaptogens have gotten, ever since everyone is self-diagnosing him- / herself with "Central Fatigue Syndrom", I assume you will be aware that the parasitic fungus, Cordyceps sinensis (CS) that is found on larvae of Lepidoptera, and has been used for centuries in traditional Chines medicine as a tonic, has lately been marketed as powerful modulator of the hypothalamus-thyroid-pituitary axis (HTPA). Extracts from cordyceps have in fact been shown to have various biological and pharmacological actions on the liver, the kideys, the endocrine and the vascular system. It appears to stimulate erythropeoiesis (production of red blood cells) and haemopoiesis (formation of blood cellular compounds), and it exhibits immunomodulatory and anti-tumor activities.

Within the health and fitness community Cordyceps sinensis has yet been touted as "natural HCG" (human chorionic gonadotropin), because, just like the latter, it stimulates the release of luteinizing hormone and thus testosterone secretion in rodent models (mice and rat; cf. Huang. 2001; HSU. 2003; Huang. 2004). Not long ago, scientists have identified cordycepin as the active ingredient in the parasite extract - an ingredient, which, according to Pan et al., does not only stimulate steriodogenesis, but also exhibits anti-cancer effects by inducing apoptosis in MA-10 mouse Leydig tumor cells (Pan. 2011).

Illustration 1: Training protocol the subjects in the study performed  3x à week for a total of 8 weeks.

With its endocrine and haematopoietic effects, cordyceps looks like the perfect substitute for what you may call the "Tour de France performance package", i.e. the combination of testosterone (e.g. Landis) and erythropoietin (e.g. Riis). Consequently, one should expect that an 8-week (3 training sessions per week)randomized double-blind place-controlled study with sixteen previously not resistance-trained young volunteers (male, age: 19-25; BMI: 24kg/m²; body fat: 14.65%), like the one performed by Hsu et al. at the Graduate Institute of Sports Science at the National Taiwan Sports University, should show at least some measurable effects on strength and muscle gains and/or body composition of the subjects.

Figure 1: Muscle strength as maesured by 1RM after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

Figure 1, however, shows no greater strength improvements in the Cordyceps sinensis (6 caps à 400mg of an extract containing 0.33% soluble protein, 5.81% sugars, 5.92µmol/g adenosine derivatives (5.92 µmol/g), 1.23µmol/g cordycepin and 8.81 µmol/g ergosterol) supplemented strength trainees (CS) compared to the subjects in the placebo group (PL). And even the +7% greater increase in 1RM strength on seated rows does not reach statistical significance.

Figure 2: Changes in body composition after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

Similarly, the cordyceps supplement had no measurable beneficial effects on the accrual of lean or the loss of fat mass in the course of the 8-week strength training protocol (cf. figure 2). Although statistically non-significant, the subjects who received the CS supplement did in fact lose some lean mass and gain some fat mass... certainly not what you would have expected from the purchase of a "testosterone boosting adaptogen"!?

Figure 3: Testosterone levels after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

A pros pos "testosterone boosting", as the data in figure 3 clearly shows, there was a "boost", but the latter was identical between groups and - as the body composition data in figure 2 shows - the placebo group, whose baseline testosterone levels were 7% lower than those of the subjects in the CS group, took greater advantage from this probably exercise-induced and in view of the diurnal fluctuations of serum testosterone statistically non-significant increase.

Figure 4: Changes in serum levels of BUN, Creatinine, ALT and AST after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

It would be unfair though to say that the ingestion of 2.4g of Cordyceps sinensis was totally pointless. After all there was a non-negligable decrease in the purported "liver values" ALT and AST. Now, as a diligent reader of the SuppVersity you are among the few chosen ones who outsmart 99% of the general practitioners and know that the enzymes ALanine Transaminase (ALT) and ASpartate Transaminase (AST) are by no means "liver values", i.e. liver-specific. In fact, their elevation in hard training athletes is completely normal and an indicator of muscular, not hepatic, damage, as both, ALT and ALT, are expressed in skeletal muscle, as well (Petterrson. 2007). This does not change that - once again - beneficial effects that have repeatedly been observed in rodent studies did not translate to humans, but it could explain why Quinc, senior member on the Mind and Muscle Forum and a true believer in the potency of cordyceps maintains:

I can't say I have noticed any 1RM gains, but I have noticed a quicker recovery time between sets and more endurance. (Quinc. 2011)

In view of the beneficial effects on the amino acid transferase enzymes, it may well be that the scientists just measured the wrong parameters. If their subjects had participated in the Tour de France, it could well be that the CS group had survived a few kilometers more, before they had had to be picked up by one of the team vehicles ;-)

Luteineizing Hormone Boosting Fungus Cordyceps Sinensis is A Powerful Ergogenic: 1.79-fold Increase in Exercise Endurance in Rodents

Figure 1: Cordyceps sinensis
(photo NW Botanicals)

Would you have suspected that the parasitic relationship between the fungus and the larva of the ghost moth would turn out to be a powerful ergogenic? No? Well, what if I told you that this very "relationship" is the resource of which the commonly known fungus Cordyceps sinensis is derived? Ok, I see you know this one... A very recent study (Kumar. 2011) which was published in the Journal of Ethnopharmacology confirmed earlier study results that have attracted supplement companies to this inconspicuous, yet highly ergogenic fungus from the order of the Hypocreales.

The Indian scientists investigated the effect of 200 mg/kg of air-dried cordiceps powder (human equivalent approx. 33mg/kg) to rats for 15 days. The 24 rats were randomized to one out of four groups: control (C), CS supplemented without exercise (CSS), exercise (E, swimming exercise 1h/day without load) and CS supplemented along with exercise (CSS + E) groups. On day 16 all rats were subjected to a exhaustive swimming protocol, in order to differentiate effects of supplementation / training on exercise performance. The results were quite impressive:

Both CS supplementation and supplementation concurrent with exercise improved exercise endurance by 1.79- (P < 0.05) and 2.9-fold (P < 0.01) respectively as compared to placebo rats. CS supplementation concurrent with exercise also increased the swimming endurance by 1.32-fold (P < 0.05) over the exercise group.

What is yet even more interesting, is the data related to the underlying mechanism(s) of these performance improvements:

To study the molecular mechanism of the observed effect, we measured the expression levels of endurance responsive skeletal muscle metabolic regulators AMPK, PGC-1α and PPAR-δ as well as endurance promoting and antioxidant genes like MCT1, MCT4, GLUT4, VEGF, NRF-2, SOD1 and TRX in red gastrocnemius muscle.

Taken together this molecular changes, which took place in trained and untrained animals, are responsible for an upregulation of skeletal muscle metabolism, angiogenesis, better glucose and lactate uptake, as well as adaptations in the anti-oxidant response to exhaustive exercise.

Figure 2: Chemical structure of Cordycepin, the purported
working ingredient in Cordyceps sinensis (Wikipedia)

Combine these results with the recently confirmed (Leu. 2011) stimulatory effect of cordycepin (fig. 2) on Leyding Cells and, via luteinizing hormone, testosterone production and you have a perfect natural ergogenic.