Cordyceps Crackdown: Hit-or-Miss in Supplements.. Until Now!

We’ve heard about “adaptogens” for decades, but what do they really do? These natural substances are considered to help the body adapt to stress and help to exert a normalizing effect upon bodily processes. They can be considered biological “equalizers”. Sounds great — who doesn’t want to help their body adapt to stress?

Numerous herbs have been presented as adaptogens: Ginseng, Ashwaganda, Licorice Root, Rhodiola, and of course, Cordyceps. Our focus today will be on the mystical and elusive Cordyceps.

Cordyceps is a fungus with a long history of use in medicine. It’s found in the Himalayas around Tibet and Nepal and in small border sections of India and China where the elevation is high enough for its growth. In China and Tibet, it’s traditionally been used as a treatment to improve reproductive function, prevent fatigue, and slow the effects of aging.

In addition, and more along the lines of our readers may be interested in it, Cordyceps have also traditionally been used to help:

• Reduce stress,^[1]
• Increase endurance,^[1-3]
• Promote anabolism and muscle protein synthesis,^[4]
• Improve glucose metabolism and insulin sensitivity^[5,6]
• Boost virility^[7,8]
• Improve general health.^[6,9,10]

Several of the above traditional uses only have data from animal models (such as mice and rat studies) to support such claims, but the latest research on endurance is indeed human-based, prompting the creation of this article.

The medical history of cordyceps

Its use dates all the way back to the 15th century. In an ancient Tibetan medical text, An ocean of Aphrodisiacal Qualities, Zurkhar Nyamnyi Dorje outlines some uses of Cordyceps.^[11] In fact, the fungus’ Latin name comes from both its appearance and origin — cordyceps means “club head,” while sinensis translates to “from China.”

Later on in 1972, cordyceps cultures found in Qinghai province in Central China were isolated by the Chinese Academy of Sciences. There a few different forms of Cordyceps with the most popular one being Cordyceps Sinensis, or “CS”. Further, there were three strains that were first isolated. These strains were called CS-1, CS-2 and CS-3.

Unfortunately, mushrooms don’t play by our rules. These cultures didn’t grow very well in controlled settings,^[12] which resulted in very little reproducible and repeatable research on it, limiting further exploration.

…and then came “CS-4”

Finally, however, the academy isolated the “CS-4” culture of “cordyceps” in 1989.^[13,14] Unlike the previous ones, this one was far more suitable for growing and thus research being performed. Having so much variation and difficulty with this family of fungus already poses some problems, but science dragged forward because the community knew that something was there – it just had to be isolated.

Was this the solution to our cordyceps isolation problem? We thought so, but boy were we wrong…..

What’s it do? Proposed benefits of cordyceps supplementation

As listed above, cordyceps has traditionally been used to improve reproductive function,^[8,15-17] prevent fatigue,^[18] and slow the effects of aging.^[19]

However, more recently there has been some investigation into its ergogenic or performance enhancement potential, as marketed by various companies with celebrity endorsements the past decade or so.

• Decrease fatigue and increase endurance

  

  Cordyceps Benefits: Mice can swim noticeably longer with hot-water fraction cultured cordyceps sinensis.^[1] Why doesn’t this always equate to humans, though, and how can we make it work?? Keep on reading…

  Supplementation with cordyceps has been shown to increase physical endurance and decrease fatigue.^[20] In one double-blind human trial, cordyceps significantly increased oxygen intake during exercise. Not only that, but it was also shown to decrease basal glucose and lactic acid levels. In a separate study, mice given cordyceps increased their swimming endurance from 75 to 90 minutes.^[1]

  In addition, a new cordyceps-based blend named PeakO2 has two clinical studies showing significant endurance increases (in terms of VO2max, VO2peak, lactate, and time to fatigue).^[2,3] Those get covered further in depth later in the cordyceps militaris and PeakO2 sections.

• Decreased stress levels

  In the same first study referenced above, the researchers also noted a change in the weight of the mice’s adrenal glands, spleens, thymus, and thyroids.^[1] This indicated that the cordyceps users experienced less stress.

  Why is this important, besides the obvious benefits? Athletically, less stress means less cortisol, which means less catabolism or muscle wasting and increased fat burn, amongst several other things.^[21] It is extremely difficult to burn fat when cortisol levels are high.

  

  But wait! If cordyceps sinsensis is so great with endurance, why did this study on “CS-4” flop so miserably?!?!^[22] The long answer is coming, but the short answer is… we don’t that was actually cordyceps!!!

• Elevated cAMP levels

  In a study published in the International Journal of Biochemical Cellular Biology, researchers found the cordyceps is able to elevate cAMP, but in a unique way, via the protein kinase A signal pathway, but not protein kinase C.^[23]

  Typically when people see cAMP elevation they think increased lipolysis and fat loss, yet it actually has other benefits as well. In this case, the researchers noted that cordyceps resulted in increased steroidogenesis via elevation of cAMP and StAR levels.^[16] This brings us to our next benefit:

• Increased testosterone levels in animal models

  …These aren’t “free gains” like a rookie gets using creatine for the first time. Rather, these are “performance gains”…

  In several research studies, albeit using animal models, cordyceps has been shown to increase testosterone production, thus leading to anabolism. This is because cordyceps contain something known as polysaccharides. These are structurally very similar to luteinizing hormone (LH). Thus, when cordyceps are taken, they can mimic LH, which results in the observed increased testosterone levels.^[23] A previously-mentioned paper published in The Journal of Life Sciences tested this hypothesis and found it to be true.^[7] Interestingly, this had also already been established in the earlier 2003 study!^[21]

  Note that nobody is promoting this for increased testosterone levels – it doesn’t seem to have that massive of a response. The reason we mention it is to show that cordyceps is involved in several beneficial biological reactions, not detrimental ones.

As mentioned earlier, cordyceps contains several actives, including some unique polysaccharides, proteins, fatty acids, flavones, 2′-deoxyadenosine, ergosterol, and cordycepin (3′-deoxyadenosine).^[24] According to the aforementioned study, these constituents “include anti-tumour, anti-metastatic, immunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti-ageing, neuroprotective, and renoprotective effects.” Per current research, cordycepin is what seems to be the most active compound inside:

Cordycepin: Potent Immuno-Regulator with unique biological activities

Ironically, despite coming from what’s essentially a fungus, cordycepin has also been shown to have antifungal properties. This was demonstrated by one study that infected mice with C. albicans 64 — the control mice all died, yet 88% of the cordycepin-treated mice survived.^[25]

Cordycepin also upregulates interleukin-10, which is an anti-inflammatory protein in the blood.^[26]

In other processes, the polysaccharide “protects against the free radical-induced neuronal cell toxicity”,^[27] so there may be something going on with neuronal cell protection (cordyceps have often been marketed as nootropics and we expect to see more on this in the future).

Finally, anti-diabetic properties have been discovered while boosting nitric oxide levels,^[28] which may lead further athletic-based research.

But in all honesty, the precise methods in which it works are still not fully understood. This is actually true for nearly all adaptogens – we simply haven’t nailed the mechanisms of action (MOAs) for most of these ingredients, cordyceps included.

All in all, given the wide range of therapeutic properties, the Chinese herbalists seem to have been right about cordyceps, and cordycepin is likely a primary contributor to its benefits.

While there is evidence for its effectiveness via mechanistic studies, animal studies, and even some human ones, there also exist quite a few not so great studies done on cordycep supplementation.

From one of those papers:

Time trial measurements did not differ between groups, nor did they change in response to supplementation. It is concluded that 5 weeks of CordyMax Cs-4 supplementation has no effect on aerobic capacity or endurance exercise performance in endurance-trained male cyclists.^[22]

Another study had similar failings in terms of VO₂ max and ventilatory threshold, although it was performed on elderly participants and there were some metabolic benefits found:^[29]

Significant changes in metabolic or ventilatory threshold were not seen for the subjects in the placebo group after 12 weeks, and there were no changes in V̇O₂ max in either group.^[29]

Up until now most of the research being done on cordyceps has been on Cordyceps Sinensis (CS) (remember CS-1 through CS-4). So how can one study look so good, and the next be a total flop?

The answer is that mother nature has simply fooled us:

That’s not cordyceps you’ve been taking!

It turns out not all “cordyceps” is actually cordyceps!

That “cordyceps sinensis” you may have been purchasing… and the researchers have been using… may not actually be cordyceps sinensis!

For decades, identifying mushroom species was done by visual observation. Over time, researchers created a more scientific approach to identifying mushrooms using DNA sequencing.^[30]

Who put Paecilomyces Hepiali (PH) in my cordyceps field?!

It turns out that the CS-4 we collectively thought was the “easy to grow” cordyceps… was not even cordyceps!! Much of it turned out to be the similar Paecilomyces Hepiali (PH)!

This fungus is part of a different genus called Paecilomyces and is not related to the Cordyceps Genus at all!^[31,32] Yet it looks almost exactly the same, leading researchers to believe it’s just a derivative, at best.^[33] With multiple sources of CS-4 being sold, it is absolutely possible some are actually P. Hepiali, while some others are indeed CS. We simply don’t know.

The 2006 Wei paper mentioned above states in its abstract,

As to Paecilomyces hepiali, it was proved to be a distinct species outside Cordyceps sinensis and its anamorph.^[31]

As basic evidence, just go to Google Images and search for “Paecilomyces Hepiali” to see the confusion — you’ll find yourself looking at images of CS-4 Cordyceps, which was grown from the mycelial strain Paecilomyces hepiali!^[29] Nobody without DNA sequencing technology seems to know the difference between these two!

But for more concrete evidence, a 2015 paper published in Mycology: An International Journal on Fungal Biology titled “Cordyceps industry in China” exposed the truth, stating,

Although P. hepiali was isolated from Chinese cordyceps, it should be regarded as an independent cordyceps fungus other than associated fungus of Chinese cordyceps based on its phylogenetic lineage.^[14]

Funny enough, the original study from the Chinese Academy of Sciences that isolated “CS-4” was even titled “Research on Paecilomyces Hepiali”,^[13] leaving us to wonder how it started getting marketed as “cordyceps” in the first place…..

The final nail in the P. Hepiali / CS-4 coffin came recently in 2015, with a paper titled “Neotypification of Paecilomyces hepiali (Hypocreales)”,^[34] that once and for all isolated and established its true genetic code.

In short, just because it’s associated with or grows along with cordyceps doesn’t mean that it is cordyceps! But for 23 years, we were all collectively fooled, all to be saved by modern technology.

So now what?

With supplement raw materials manufacturers historically relying upon visual inspection (and that’s if we’re lucky they bothered to look), we’ll never truly know what’s been in some of those older “cordyceps supplements”. They could very well have been Paecilomyces Hepiali instead. And while PH may have some benefits (such as anti-tumor properties^[33]), from what we can see, they don’t seem to extend to athletics and neuroprotection, the target for many cordyceps consumers.

So if it didn’t work for you, or it didn’t work in the study, you may now have a reason: misidentified raw materials, and possibly even flat-out deception.

Could this be the cause for the difference in athletic performance study results and spotty consumer feedback? We can’t make guarantees, but we believe so. At this point, as athletes, we currently can’t trust much of anything labeled “cordyceps sinensis”, and definitely not “CS-4”.

Realize once again that this doesn’t make CS-4 bad, it’s just not guaranteed to be pure cordyceps, and we don’t see it having the athletic prowess it was hoped to have.

There’s a way around it though: skip cordyceps sinensis altogether:

Recently a new form cordyceps has entered the market: Cordyceps Militaris (CM), and it has left quite a mark, without the confusion of mistaken identity.

Several research papers have historically reported that CM products contain higher levels of active ingredients than CS products. In a comparative study of the protective effects against oxidative damage, Militaris-based extracts were found to have higher antioxidant efficiency, higher contents of bioactive ingredients cordycepin and adenosine, higher polyphenolic contents, and higher flavonoid contents than CS extracts.^[35]

Cordyceps militaris: more potent than cordyceps sinensis

Kim (2005) also found higher concentrations of exopolysaccharides and cordycepin in CM than in CS in submerged mycelial cultures.^[12] In that study, cordyceps militaris had over twice the max cordycepin potency, which we believe to be one of the primary constituents as discussed above.

Cordyceps Militaris is also easier to grow in a cultured setting, allowing us to skip much of the trial-and-error we’ve had with Sinensis. But if we grow it in a lab, will that lead to diminished active ingredient yields? Doesn’t look like it: Li (2001) reported strong anti-oxidation activity in Cordyceps and that the activity in cultured mycelium was equal or greater to that in the natural form.^[36]

So now it’s time to take this better-and-easier form of cordyceps to trial — with endurance athletes:

Introducing PeakO2 by Compound Solutions: The Cordyceps Militaris Blend that works

In 2016, we finally got some legitimate evidence on trained athletes:

“Chronic, 3 week supplementation of a mushroom blend at 4 grams per day may improve VO2 max, increase Time to Exhaustion and augment Peak Power during high-intensity aerobic exercise.

A blend containing Cordyceps militaris may be an effective method for enhancing aerobic performance and delaying fatigue by improving oxygen kinetics. This could have positive implications for maintaining and improving training volume, especially in endurance athletes.”^[2]

This combination of mushrooms is now created and sold under the trademarked name PeakO2 by Compound Solutions, and we believe this cordyceps militaris blend is the “Next Big Thing” that cordyceps consumers have really been looking for all these years.

In the above study, there was a significant increase in time to exhaustion. The researchers had subjects peddle at full speed for as long as they could, until they’d fall below a set resistance point. They then cut resistance out, let the subjects get speed back up, and then reintroduce the resistance again.

The goal in this type of study is to peddle all-out 100% for three minutes, which is impossible. However, when we say “significant increase in time”, we mean that they added over a minute to the time before resistance was cut.

Think about this: How many non-hormonal supplements have given such noticeable/trackable impact in just seven days? This isn’t a study done at some no-name university. It’s UNC, and it’s a randomized, double-blind, placebo controlled design.

Follow-up study: Lower Dose, Still Significant Endurance Benefits

While the above study was fantastic, the fitness community still wanted more proof, in the form of a follow-up study. In addition, 4g/day is quite a bit. It was postulated that a lower dose of PeakO2 taken for a longer period of time could still elicit significant endurance benefits.

Dudgeon, et al took to the task in 2018 in a study that had two trials:^[3]

1. Low-Dose (2g/day) over 28 days vs. Placebo
2. High-Dose (12g/day) for 7 days vs. Placebo

After four weeks of supplementation, the low-dose group yielded the following:

• significant increase in time to fatigue,
• significant increase in VO_2peak, and
• significant decrease in blood lactate levels

Meanwhile, the high-dose group also showed significant decreases in submaximal heart rate, an effect I have long noted on my heart rate monitor here at PricePlow. The high-dose group also had improved Peak Power Output, which may lend to a “mega-dosing” strategy a week before a competition. Note that these effects were more pronounced in individuals with less aerobic fitness.

How does cordyceps militaris work?

As mentioned above, adaptogens aren’t fully understood. The data is strong and there are more studies in progress to better understand. Although there are theories, there’s no proof yet. We’re confident that cordycepin, described above, is a key player.

Mike McCandless, founder of Scivation, stated,

I’m blown away how effective PeakO2 is. I think it’s the most effective supplement since creatine. Combined with BCAAs, it’s a beautiful combo.

— Mike McCandless, Scivation

What does all of this mean? As more studies come out, Cordyceps Militaris may prove to be a breakout supplement for the latter half of the 2010s. Cordyceps Sinensis just has too many question marks and identification problems.

So if you’ve tried cordyceps and didn’t notice much, or cannot get repeatable results from bottle to bottle, our recommendation is to find a PeakO2-based formula, dose it at 2-4g per day as used in the studies above, and judge for yourself.

Given the sinensis and CS-4 identification problems, we’re sticking to cordyceps militaris for the time being, and PeakO2 is the one ingredient blend from a trusted raw materials supplier that has actual research performed on it.

Note, however, that PeakO2 is a blend that’s led by cordyceps militaris, but has other beneficial mushroom constituents as well, which could definitely play a part in the success of those studies. How much those other ingredients contribute to PeakO2’s early success versus just cordyceps militaris is impossible to determine. Ultimately, we’re interested in the end results and benefits, and if it takes a mushroom blend to make it work best for athletes, then so be it.

Since writing this article, several PeakO2-based supplements have come out, many with great success. But the Xtend brand was first to do it, and their Xtend Elite BCAA supplement included even more beneficial endurance ingredients, including Beta Alanine and Citrulline Malate. This is an amino acid supplement that you typically drink during your workout. It’s dosed at 2g/scoop, so over the course of a month, you can replicate Dudgeon’s 2018 study (and then some, thanks to the added ingredients).

To replicate Hirsch’s study at UNC, two servings per day are to be used, but that will of course affect your budget twice as hard.

As with all other Xtend products, it contains 7g branched chain amino acids that will help keep muscle tissue in an anti-catabolic state and prevent them from breaking down, likely helping to increase endurance and recovery as well.

How to take it

Our recommended dosing protocol is to use it pre-workout, or if using an intra-workout supplement, to use it throughout your workout.

Update: See also PrimaForce Peak O2

If you want to try PeakO2 all on its own, PrimaForce now has a standalone version of this cordyceps / mushroom extract from Compound Solutions!

PrimaForce Peak O₂ is a standalone supplement that simply contains 120g of the extract – enough for sixty 2g servings!

You can then add this to your own favorite BCAA supplement, pre workout supplement, energy drink, etc.

We tried it raw and can guarantee that it won’t taste too good all alone in water, but we know how some of you are!! It’s worth at least dipping your finger in to try the “earthy” taste. What we’ve discovered is that sweeter drinks mask it best.

So… will it make my athlete’s foot flare up? To this point, no significant side effects have been noticed. It’s a fully intact mushroom, no weird isolations.

Quite the opposite, in fact

When exploring the research looking for side effects of cordyceps, it’s actually more common to see cordyceps used as a conjunctive therapy alongside aggressive medical treatments to help prevent side effects of those treatments!

That’s out of the scope of this document, but the point is that we haven’t found a single problem – at least not in the doses studied.