Optygen research marches – err, crawls on!


2022 was a good year for Cordyceps research! Recent science is finally exposing details of how human bodies and cells recognize, respond to, and utilize adaptogen compounds to improve overall health. First of all, the published research on Cordyceps militaris – one of the two types of Cordyceps in Optygen – has exploded, with good, applicable science cred demonstrating impacts to immune support and GI health. Second, new research on Cordyceps sinensis – which is similar to the Cs-4 Paecilomyces hepiali Cordyceps extract, the other type of Cordyceps in Optygen – has also demonstrated new endurance effects, including boosting aerobic performance while lowering heart rate.

These findings support what First Endurance has known since we started producing Optygen back in 2002: adaptogens like Cordyceps take time and stressful endeavors to manifest their bounty. Research is finally catching up. 

The path to discovery isn’t always resistance-free, though, and in this case, the resistance was often coming from inside the house. In 1993, wide publicity of Chinese athletes benefiting immensely from Cordyceps led to an explosion of Cordyceps use for exercise performance. In response, modern researchers churned out what us researchers call "quick and dirty" studies riddled with flaws that reduced the ability to give Cordyceps a fair look (Steinkraus 1994). Common deficiencies among these studies included low subject numbers, durations that were too short for adaptogens to take effect, and exercise that wasn’t stressful enough. There wasn’t anything nefarious going on; the researchers were simply unfamiliar with even basic concepts of adaptogens. As a result, these studies didn’t assess the totality of evidence that objective researchers rely on for deductions. (See Table for only one of many reasons why these pooh-pooh-able studies are bad – in this case, subject numbers too low to find any differences.)

80% of studies with more than 24 total subjects find significant changes from Cordyceps, but only 21% of studies with less than 24 subjects found significant effects of Cordyceps. Null hypothesis is that there is no difference between placebo and active groups. The highly significant P value shows that short-term studies are not the right way to gauge efficacy of Cordyceps for exercise, which has been the modus operandi of adaptogens for modern exercise performance studies.

Despite the limited findings of those limited studies, science clearly shows adaptogens work when taken for a long enough time during very stressful conditions. We care because the one-two punch of two types of Cordyceps in Optygen keeps getting stronger support from the latest research for why you care: Cordyceps helps dedicated athletes perform better while supporting better overall health.

Now, for the research updates. We’ll take a look at two impact areas: performance and general health (immune and gut). To begin with, let’s take a look at the update we all admittedly care about most: exercise performance!

Update 1: Exercise Performance

Here’s the headline:

“...supplementation with Cordyceps sinensis improves the aerobic performance of amateur marathoners.”

And here are the details: 30 amateur marathoners in Brazil took placebo or 2000mg of Cordyceps sinensis for 12 weeks, which ties for the longest duration of study reported for Cordyceps and endurance exercise (Savioli 2022). Before we get to the detailed results, two housekeeping items on how the study relates to Optygen.

First, C. sinensis is a material similar to the Cs-4 Paecilomyces hepiali in Optygen, which is one of the strains found in traditional caterpillar-based Cordyceps. (But despite the occasional caterpillar/crawling pun, we use only cultured Cordyceps – no caterpillars are harmed, harvested, or involved in the making of Optygen. More on that later.)

Second, the daily dose used in the study is equal to the Cordyceps dose during the loading phase for Optygen, and the Optygen dose is half after that; but remember, Optygen has active Rhodiola and other nutrients, and we use concentrated extracts, not just herbal powder – all of which increases the effectiveness, making the study results relevant to Optygen.

And now, the results of the study. By eight weeks, Cordyceps showed lowered heart rate for the same amount of effort, and by 12 weeks, aerobic performance was significantly better than placebo – results similar to other C. sinensis studies (Chen 2010; Thongsawang 2021; Zhu 2004). The Savioli marathon study was randomized, double-blind, placebo-controlled, and used more subjects than most other Cordyceps and exercise studies (meaning more power to find significant results and less of the self-limiting strawman risk). Bravo, homen e mulheres!



Update 2: Immune & GI Support

If you’re not into scientific literature, you may not realize that cordycepin and nucleotide analogues have garnered the most attention as bioactive agents in Cordyceps research. You may also not realize that those aren’t the predominant parts of Cordyceps extracts. That distinction belongs to polysaccharides – long, complicated carbohydrate chains with beneficial structural and biological activities. Their chemistry is difficult to decipher, but science marches on, and recent research reveals new secrets.

This brings us to our second latest research update, which is tied to the other half of Cordyceps in Optygen, Cordycep militaris extract, itself another one of the strains normally found in traditional caterpillar-based Cordyceps. Performance-first readers will be happy to learn that C. militaris has been shown to improve exercise performance (Dudgeon 2018; Hirsch 2017). But it’s also done so much more in recent studies focusing on different biomarkers, due in part to polysaccharides.

Several new reviews on C. militaris have shown that the polysaccharides in Cordyceps extracts have powerful signaling properties to support immune and GI tract health (Das 2021; Miao 2022; Yuan 2022; Zheng 2022). This echoes earlier findings (Jung 2019; Kang 2015). Those polysaccharides are not just useless fiber, they are bioactive agents with the following activities, to name only a few (Das 2021; Miao 2022; Yuan 2022; Sah 2022; Zheng 2022).

  1. Antioxidant effects
  2. Production of immune system signaller cytokines
  3. Support of immune system foot soldiers: Dectin-1, macrophage activation, NK cell activation, MAPK & tyrosine kinase binding/triggering
  4. Gut microbiome prebiotic changes that upregulate multiple genes and proteins related to lipid absorption & metabolism
  5. Suppression of inflammatory signallers: eotaxins COX2, IL-4, IL-5, IL-13, IL-18, IFN-gamma, Smad2/3protein phosphorylation, TGF-beta1 & IgE levels
  6. Mediation of inflammatory pathways by activating toll-like receptors
  7. Upregulation of heme oxygenase, liver vascular regeneration, Nrf2, signal regulatory protein alpha1, stromal cell-derived factor-1alpha & VEGF

Because structure = function, there is no way that Cordyceps extracts cannot do these activities. Still, many older human studies of adaptogens in general – and Cordyceps in particular – have “missed the boat” by not choosing to measure biomarkers that are affected by Cordyceps. This recent wave of research is correcting that oversight. 

The overall net effect of the above list is health-promoting. If one mechanism doesn’t work, then others will, and they don’t all necessarily need to “click” at the same time. For example, the microbiome mechanisms alone take time to remodel gut bacteria, which accounts for the several weeks of adaptation period before the full effects of Optygen can be felt or measured, at least in that sphere of action.


All this gobbledegook and name dropping means, essentially, that Cordyceps has multiple ways of working to change your body to resist stress depending on the severity of the stress levels activating degradative processes and inhibiting helpful processes like cell/tissue repair and metabolism. It’s just finally being documented effectively in research.

Each of these ways-of-working impacts your signaling network to shape a masterpiece sculpture out of bare rock, edging you closer to homeostasis – or, simply, the state of being healthy. Recent science is exposing details of how human bodies and cells recognize, respond to, and utilize adaptogen compounds to improve overall health. Human clinical studies have a long way to go to reach this level of confidence – but, as the above shows, they’re getting there. When they arrive, we’ll be waiting, and we’ll let you know.


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February 16, 2023 — Luke Bucci

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