Elysium's Research Record Reconsidered
[PICTURED: What Car Logo Is This?]
I’m a lawyer, not a molecular biologist, but my spouse is a full professor at a public university, so I do have some familiarity with academic research and its protocols.
I argued last week that Elysium's press release issued in response to ChromaDex's patent infringement suit was jaw-droppingly disingenuous.
But upon reflection, there's another aspect of the press release that deserves attention, too.
I have argued that Elysium dubiously presents itself as some kind of science-driven company guided by scientists doing science -- "dubiously," because the evidence suggests just the contrary, that they are primarily a web marketing company that does not distribute any products developed in-house. (See e.g., Why I Feel Suckered by Elysium Health, Elysium's Goose Is Cooked and Elysium's Unhealthy Business.)
And so I ALSO find it disingenuous when Elysium describes itself, as they did in the press release, as "a life sciences company developing clinically validated health products based on aging research." I just don't think that's what they do. I haven't seen it.
It's TRUE that they have their name on a study, and that study is alleged to be published in a reputable journal -- Nature -- but let's take a close look at their study and see what we can learn.
Although Time magazine said that Elysium's study was "published...in the journal Nature" and others on social media have echoed that inaccurate characterization, Elysium's research article was actually published in npg Aging and Mechanisms of Disease.
"npj" stands for "Nature Partner Journals," which are online-only, open-access journals.
That's like the difference between a Maserati and a Chrysler by Maserati:
Nature has a very high impact factor.
npg Aging and Mechanisms of Disease has no impact factor.
From the npg Aging and Mechanisms of Disease about page:
"npj Aging and Mechanisms of Disease is published in a partnership between Nature Research and Japan Society of Anti-Aging Medicine.”
The co-editors of npj Aging and Mechanisms of Disease are Kazuo Tsubota, Professor and Chairman of the Department of Ophthalmology, Keio University School of Medicine in Tokyo, Japan and Shin-ichiro Imai, Professor in the Department of Developmental Biology at Washington University School of Medicine, who went to MIT to work with and in fact published with -- wait for it -- Leonard Guarente.
Elysium's article includes the three founders of Elysium (Dan Alminana, Guarente and Eric Marcotulli) as authors, as well as the two ChromaDex employees that Elysium hired (Mark Morris and Ryan Dellinger). It was entitled "Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study,” published on November 24, 2017.
But a correction was published on August 20, 2018.
You can find full text of the correction here. It says:
"The original version of the published article contained an incorrect citation for reference 20 “Hubbard, B. P. & Sinclair, D. A. Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric nicotinamide assay. Methods Mol. Biol. 1077, 167–177 (2013).” The citation for reference 20 has been changed to “Cheng, Y. et al. SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury. Apoptosis 21, 905–916 (2016).” The original version of the published article did not list a source for the placebo pills or the investigational product NRPT in the Intervention section of Methods. The last sentence of the Intervention section of Methods now lists the source for the placebo pills and the investigational product NRPT as follows: “The matched placebo pills and the investigational product (NRPT) were provided by Elysium Health (New York, NY).” This has now been corrected in the PDF and HTML versions of the article.” (emphasis added)
Let's start with the changed citation for reference 20. Reference 20 is for this sentence:
"NRPT is a combination of NR and pterostilbene (PT), a naturally occurring analog of the polyphenol resveratrol, which has been found to be a potent SIRT1 activator.” (emphasis added)
The original reference 20 did not contain any mention of pterostilbene, so it was clearly an incorrect citation.
The new reference 20 is a study at the Fourth Military Medical University in Xi'an, China.
Resveratrol has been hotly debated in the scientific literature because David Sinclair reported that it increases SIRT1 activity by direct binding. But several other groups subsequently reported that resveratrol neither activates SIRT1 nor does its effects depend genetically on SIRT1.
Apparently Elysium does not believe that pterostilbene binds to SIRT1, either, because the new reference 20 from the Fourth Military Medical University indicates that pterostilbene changes the expression of SIRT1.
I have actually had a difficult time finding any recent research showing that pterostilbene activates sirtuins -- this study shows just the opposite -- and I was looking because I have to decide whether to add pterostilbene to my Niagen.
But it looks like Elysium has the same problem that I have, because nine months after their study claimed that pterostilbene was "a potent SIRT1 activator," apparently Dr. Guarente had to find a novel theory from the the Fourth Military Medical University in China to support the idea that pterostilbene has anything to do with sirtuins.
That's the best they can do? And Elysium's website still claims it:
Supplied by Elysium
The second correction is also interesting.
Elysium's original paper did not say where the NR and pterostilbene for the study came from. The correction states that the source of the material was Elysium Health in New York City.
I find it HIGHLY unlikely that Elysium Health in New York City made the NR and pterostilbene used in the study.
We know from the litigation that Elysium did not start building its alternate supply chain for Mystery NR until the summer of 2016, at which time they had secured a year's supply of Niagen, so they might reasonably have expected to gain access to Mystery NR within 6-9 months.
But Elysium's study was published in November 2017.
Given that it takes months to years to design, enroll and conduct a clinical study and that Elysium was using ChromaDex ingredients in Basis until summer of 2017, it seems almost certain that the ingredients used in the study that was published in November 2017 were NIAGEN and pteropure provided by ChromaDex, Inc., not Mystery NR provided by Elysium.
If this is the case, then Elysium’s publication in npj Aging and Mechanisms of Disease, which is touted as a Nature paper that attests to the safety of Basis, is actually attesting to the safety of material that Elysium can no longer sell because they refused to pay ChromaDex for materials.
So what if Elysium used an obscure reference and probably fudged the source of the materials in the study?
First, Elysium is still claiming on their website that the pterostilbene in their Basis product activates Sirtuins, but all the King's Nobel Prize Winners and All the King's Men can't seem to marshal much evidence for what their product marketers are saying.
Second, Elysium's human study, which is celebrated with its own page on their website styled on the dropdown menus as "Our Human Study," establishes the safety of Niagen and PteroPure, not of Basis.
Both of these points strengthen my original hypothesis that Elysium is a marketing company, not a science company.