On September 2 R. wrote:
"Can anyone tell me how strong or weak the evidence is in this study?"
Here is the claim: "The first product ever that is designed to Activate your body’s own stem cells. Experience a new level of vitality with improvements to your energy, sleep, reduction in pain, reduction in the appearance of lines and wrinkles and support of faster wound healing, just to name a few of the benefits."
https://lifewave.com/Content/images/home/science/pdf/Published%20Study%20Double-Blind%20Testing%20of%20the%20Lifewave%20X39%20Patch%20to%20Determine%20GHK-Cu%20Production%20Levels.pdf>>>>>>>>>>>>>>>>>>
I found this to be one of the stranger (and more amusing) papers that I have read, and I decided to go into some detail in describing and analyzing it. If you aren’t interested in the details skip to my conclusions. (The answer is that the evidence is very weak.)
The paper is: “Double-Blind Testing of the Lifewave X39 Patch to Determine GHK-Cu Production Levels,” by Connor et al., Internal Medicine Research - Open Journal 6(1):1-3 (2021).
The journal, Internal Medicine Research - Open Journal, is a rapid-publication, open access journal based in India. It is not indexed in Medline. As can be seen from my comments below, it does not appear to include careful peer review.
The first two authors are affiliated with Earth Songs Holistic Research and Consulting, a group that carries out research studies for other investigators:
https://earthsongs.com/Some of these are pseudoscientific, such as research with reiki and other types of energy medicine:
https://earthsongs.com/earth-songs-holistic-research/studies-holistic-research/The members of the research team are described at this page:
https://earthsongs.com/earth-songs-holistic-research/team-holistic-research/The first author, Caitlin Connor, is identified as “Post-Doctoral Fellow, Rewley House, Oxford University, UK,” which implies that this research has some connection with Oxford University. In fact, she “has recently completed a three year post-doctoral health care sciences research training program at University of Oxford, UK,” but there is no evidence that this work was done at or in connection with Oxford (normally a postdoctoral fellow would do research in the lab of an established professor, whose name would then also appear on any paper originating from the research).
The fourth author, Jes Eickhoff, is identified as "Senior Scientist, Biostatistics & Medical Information, University of Wisconsin." He is also listed on the EarthSongs team page. Apparently he provides statistical analysis; otherwise there seems to be no connection of the research to the University of Wisconsin.
The third and fifth authors, David Yue and Amy Chang, are affiliated with "HT-Labs a division of Axis Pharm, San Diego." In trying to find out about HT-Labs, this site:
https://www.buzzfile.com/business/Ht-Labs-858-677-9432gives the following description:
"Ht Laboratories, which also operates under the name Ht Labs, is located in San Diego, California. This organization primarily operates in the Testing Laboratories business / industry within the Engineering, Accounting, Research, and Management Services sector. This organization has been operating for approximately 21 years. Ht Laboratories employs approximately 4 people at this single location."
There is a link to the HT-Labs website, but you need to log in to get to it.
There is a company in San Diego named AxisPharm (no space), but this appears to be a conventional supplier of chemical reagents, and I don't see any reference to Ht Labs there. Searching for Axis Pharm (with a space), I find only a Facebook page for a nutritional supplement company that seems to be based in Egypt.
So it looks like HT-Labs and its parent company are keeping a very low Internet profile.
The final author, Susan Wagner, is listed as Professor, Arizona School of Acupuncture and Oriental Medicine. "Dr." Wagner "completed her Doctorate of Acupuncture & Oriental Medicine while attending American College of Traditional Chinese Medicine at California Institute of Integral Studies" and "is a licensed acupuncturist and herbalist." She is Director of Financial Programs at the school and "has a busy practice in the Tucson area."
https://www.asaom.edu/your-admin-1Unlike HT-Labs and Axis Pharm, LifeWave, marketer of the product (X39 Patch) does have an accessible web site:
https://lifewave.com/with X39 highlighted on the main page.
What is the X39 patch? "Introducing the LifeWave X39 patch. The first product ever that is designed with phototherapy believed to activate your body’s own stem cells. How does X39 accomplish this? Using our proprietary and patented form of phototherapy, X39 elevates the peptide GHK-Cu. This is a naturally occurring peptide in your body that declines significantly with age."
https://lifewave.com/corporphan/store/product/39000.022.009/There is a three minute video, which says that the patch activates stem cells, and uses light to elevate GHK-Cu. One patch is placed anywhere on the body each day. But nowhere does it explain what the patch is, how it works, and how it is related to phototherapy. I will discuss more about how it "works" in connection with the paper.
Turning now to the paper itself:
The abstract is strange. Within the abstract, there is a section listing "Materials," which sounds like something in a high school lab report; I've never before seen such a section in the abstract of a scientific paper. It includes things like blood collection tubes, but not the critical element, the X39 patch. The "Method" section only discusses collecting and treating blood samples, not what was done with the X39 patch, and there is nothing about how GHK-Cu was measured.
Continuing to the body of the paper (following the abstract), there are sections titled "Introduction" and "Background," followed by four sections entitled "The Tripeptide," "Non-transdermal Patch," and "Phototherapy," and "Purpose." Normally we would expect to find all of this in a single "Introduction" section. The last two sentences of the "Introduction" describe the subjects and randomization, and thus belong in the "Procedure" section rather than the "Introduction."
The "Introduction" discusses the tripeptide glycyl-histidyl-lysine in complex with copper ions (GHK-Cu) and its possible roles in tissue healing and regulation of numerous genes. Work of Loren Pickart is noted, along with a reference to a paper by Pickart. However, the first reference is not to a journal article but to "DeHaven C (2014) Copper Tripeptide-1. Science of Skincare." This is a 4-page document (pdf can be downloaded) from iS Clinical, a skincare company where DeHaven is Clinical Director:
https://isclinical.com/blog/dr-charlene-dehaven.htmlThe second reference is: Pickart et al. (2014) GHK and DNA: resetting the human genome to health. BioMed Research International 2014:151479
https://www.hindawi.com/journals/bmri/2014/151479/In this paper, effects of the tripeptide on gene expression in cultured cells was measured. 31% of the 13,400 genes were regulated upward or downward. I am not qualified to evaluate this type of experiment, but I am skeptical of these changes being meaningful, especially when so many effects were observed.
For more background, I looked at a Wikipedia article about the tripeptide:
https://en.wikipedia.org/wiki/Copper_peptide_GHK-CuThe Wikipedia article notes "This article needs more medical references for verification or relies too heavily on primary sources." It reviews studies in dermatology and wound healing. There is little about any other application. Most of the references are decades old.
The "Background" section of the paper begins with "The LifeWave X39 patch uses phototherapy to stimulate a rebalancing of the body." It is not explained what "rebalancing" means; achieving "balance" is a vague claim typical of many alternative approaches. It continues, "Based on data from other studies, it was felt that a possible change in the copper tripeptide GHK-Cu might be a factor in the effects of the patch." No citation is given for these other studies (though two references will be cited near the end of the paper), or for anything about what the LifeWave X39 patch is or how it supposedly works. Then there is more discussion of the copper tripeptide in skin healing.
The section "The Tripeptide" describes what GHK-Cu is and notes that it "has never been found to cause an issue in all the research that has been done," which I assume means that it is not toxic and that the increases supposedly brought about by the X39 patch will not be harmful.
The section "Non-transdermal Patch" says: "All X39 patches are sealed to prevent the contact of any of the substances inside to the skin. The sealing of the patches allows for consistent light flow through the patch the entire time the patch is worn. Patches are designed to reflect wavelengths of light in the infrared, near infrared, and visible light bands." When I read this I assumed that it meant that it allows ultraviolet light to penetrate. However, as will be seen later, they seem to be talking about light coming from within the body being reflected back to the body. How can there be "consistent light flow through the patch the entire time the patch is worn" if the patch is exposed to variable amounts of light?
The next section, "Phototherapy," tell us that phototherapy has been used for over 100 years, is safe, and "is a relatively untapped option for healing." It doesn't explain what phototherapy is. Here is one definition: "Phototherapy is a medical treatment in which natural or artificial light is used to improve a health condition. Treatment could involve fluorescent light bulbs, halogen lights, sunlight, or light emitting diodes (LEDs)."
https://www.verywellhealth.com/phototherapy-overview-4177939Thus, as normally understood, phototherapy involves administering some light source. Yet in this paper, there is no mention of any light source. It sounds like the subjects just put a patch on their skin and it lets some of whatever light the person is exposed to get through to the skin (or, as noted, reflects back light emerging from the body). It seems absurd to think that this could produce some specific regulatory effect with widespread health benefits. It is also misleading to describe whatever the patch does (which is probably nothing) as “phototherapy.”
This set of introductory sections concludes with "Purpose," which is to determine if the X39 patch improves production of GHK-Cu.
Next comes the "Procedure" section. It begins by noting "human research studies ethics board approval," but does not tell what institution this board is associated with (this will be discussed more below). There is a number given, NFFEH 01-16-20-01. Participants were recruited, randomized to treatment or control groups, and baseline blood samples taken. "Additional samples were taken at 24 hours and 7 days of patch placement." It states, "For convenience, participants were asked to use what is a recognized meridian point, GV14 or CV6, for the patch placement." A citation to an acupuncture manual is given. Thus, instead of using a recognized anatomical location, the article refers to a pseudoscientific concept from Chinese medicine, and does not explain to the reader where these locations are.
In fact, GV14 and CV6 are in very different locations. GV14 "is located on the posterior aspect of the body, in the depression below the spinous process of the seventh cervical vertebrae, approximately at the level of the shoulder"
https://www.acupuncturetoday.com/mpacms/at/article.php?id=27591whereas CV6 is near the umbilicus. Did the patients choose which of these two to use? How many chose each point? Were there differences in ambient light exposure for the two points, and does that matter?
In the same paragraph as the placement of the patch, the collection and processing of blood samples is described.
Missing from the Procedure section is any description of the patch and how it supposedly works. It is not stated in this paper whether a single patch was used for the duration of the experiment, or multiple patches. But in preliminary experiments described below, a fresh patch was used each day.
A subsection of "Procedure" is "Analysis of Blood Samples." It says "The blood samples were processed according to the original thesis of Dr. Pickard [sic; should be PIckart]," but there is no citation for this and no description of how GHK-Cu was determined. Another subsection describes statistical procedures.
The Results section is strange. It says, in full: "A sample of convenience of individuals consisted of 60 individuals randomized into two groups (A and B) with an age range of 41-80. Significant results of the LifeWave X39 patch testing are as follows:” Apparently Table 1 is supposed to go here, but it appears instead at the end of the text, after the Discussion. The table does not give any of the actual results; instead, it just gives p values for the differences between treatment and control groups. These are significant for Day 2 to Day 7 in "GHK-Cu concentration (ng/ml)" (p<0.035) and "Total GHK-Cu (ng)" (p<0.03). While the concentration of GHK-Cu in the blood samples might be of importance, it is not clear what is meant by the total amount and why this should be reported. Is it the total in the blood collection tube? This should be approximately the same but would have some variability. Is it the total in the person's body? This would require a measurement of the total amount of blood, which seems unlikely to have been done. Since no raw numbers were reported, the significance of these total values and what information they give beyond concentrations is mysterious.
Next comes the "Discussion." Most of the Discussion (a single paragraph) is devoted to describing an interruption due to COVID as well as subsequent precautions taken to prevent infection in the subjects and study members - something that belongs in the Procedure (if it is necessary to describe at all) rather than the Discussion. The Discussion concludes as follows: "This study confirms that there was a significant change in the levels of GHK-Cu in 7 days in both concentration and total amount. This confirms data from earlier studies [7,8]. The repeated trials data supports promotion of positive benefits to the body through increased production of GHK-Cu by the wearing of the LifeWave X39 non-transdermal photobiomodulation patch." The last sentence is misleading because no "positive benefits to the body" were measured.
Looking up Ref. 7 and 8, we can finally find out more information about the X39 patch. Both of these are cited as "International Journal of Healing and Careing" [sic; the actual word is "Caring"]. This is another journal not indexed by Medline. It is edited by Daniel Benor, a prominent promoter of pseudoscientific approaches such as therapeutic touch and reiki. The volumes and issues are not given, but looking at the web site they can be found. Ref. 7 is:
https://ijhc.org/2020/04/20/lifewave-x39-pilot-demonstrates-light-triggered-changes/(the link is to the abstract, but you can download the entire paper)
Here we find: "The LifeWave patch is non-transdermal. This means that instead of having chemicals imbedded in the patch and intended to be absorbed, nothing contained within the sealed patch enters the body. Instead, this allows the light to flow through the patch without any changes to the contents of the patch throughout the time the patch is worn...The patch uses infrared, light, near infrared light, and visible spectrum light passing through specially processed crystals in solution to send out specific wave lengths that facilitate those changes. The LifeWave patches help to stimulate the body by using that light to create physiological effects...LifeWave patches are placed on specific meridian points to maximize effectiveness." Note that in the paper under discussion (dealing with GHK-Cu), it said "Patches are designed to reflect wavelengths of light in the infrared, near infrared, and visible light bands." So are the crystals actually allowing transmission of selected wavelengths in these bands? Are they supposed to be absorbing some wavelengths and emitting (sending out) different, selected wavelength? It is not clear, nor are we told what these crystals consist of.
This study (Ref. 7) notes approval "from National Foundation for Energy Healing number NFFEH 8-28-18-07," which explains the number in the paper under discussion. However, I cannot find any link for National Foundation for Energy Healing. It says that "The participant was asked to wear the patch 8-12 hours each day. The participant removed the patch at night and a fresh patch was applied each morning prior to 8 am. The patch was worn for a minimum of 1 hour before the additional data measures were taken. Patches were worn for a total of 7 days." Note that in the paper under discussion, no such details were given. The data showed "improvement in blood pressure, 17 statistically significant amino acid changes over the 7 days, significant improvement in anti-inflammatory response, improvement in sleep levels, reduction in blood pressure, improvement in short term memory, improvement in reported feelings of vitality." However, the sample size was small (15) and there were no controls.
Ref. 8 is:
https://ijhc.org/2020/04/20/changes-in-tripeptides-produced-by-thelifewave-x39-patch/This paper gives another "explanation" for how the patch works: "All X39 patches are sealed so that none of the substances in the patch actually penetrate the skin. This allows for consistent patch promotion of the electrodermal skin response in the infrared, near infrared, and visible light spectrums throughout the time the patch is worn. Electrodermal activity (EDA) is the property of the human body that causes continuous variation in the electrical characteristics of the skin. Patches are designed to reflect wavelengths of light in the infrared, near infrared, and visible light bands. The patches act as a transducer and transmitter, like a router on a computer network, or one of the old crystal radio sets. They receive signals from the body, strengthen them, send them back, and then the body receives them." So now, instead of transmitting light from outside, it sounds like the patches are receiving light from the skin, which are then "strengthened" and sent back! Can this really be called "phototherapy"? It also notes that "Specific meridian points were chosen to maintain consistency and improve comparability between studies. They were also chosen for ease of access and description in the future." As in the main paper under discussion, these were the CV6 and GV14.
It was amusing to see that the paper (Ref. 8) was published with what appears to be an editorial comment left in: "The blood samples were processed according to the original thesis of Dr. Pickard(Pickart& Thaler, 1973) AGAIN WHICH Pickart?]." It looks like the authors were requested to provide a citation for the Pickart paper, and after doing so the comment was left in place. (Note also that "Pickart" is misspelled.) There are also many spaces missing between words, and an entire line of text repeated: "BD Vacutainer Safety Loc Blood Collection sets were used with Pre-attached holder sized 21GX0.75 or BD Vacutainer Safety Loc Blood Collection sets were used with Pre-attached holder sized 21GX0.75 or 23GX0.75 and placed in lavender top tubes."
The paper (Ref. 8) reports a significant increase in the GHK level after 24 hours of the patch, and a significant increase in the GHK-Cu level after 7 days. However, these are reported only as changes from baseline; absolute values are not reported, nor are changes that were not significant reported. So it is difficult to see if there is any pattern or whether these were just random fluctuations, and one cannot judge if these might be clinically significant. Again, the sample size was small (10) and there were no controls.
Returning to the original paper under discussion, it ends with a two sentence “Conclusion” section: “This study explored the changes in amounts of GHK-Cu present in the blood as a result of wearing the LifeWave X39 patch 8-12 hours per day for 1 week. A significant increase in GHK-Cu concentration in the blood of the active group was seen in the p-value for comparing changes from Day 2 to Day 7 between Group A vs. Group B in GHK-Cu Concentration (ng/ml) at p<0.035 and in Total GHK-Cu (ng) at p<0.03 (Table 1).” As noted, Table 1 appears at this point rather than in the Results section.
My assessment:
1. Important experimental details are missing. What the X39 patch is and how it is supposed to work are not explained. One needs to go to other papers (Ref. 7-8) to find out more about the patch. The paper also does not explain how the measurements of GHK-Cu were made.
2. In looking at Ref. 7-8, the explanations for how the patch “works” are pseudoscientific and contradictory. It seems improbable that the patch can actually produce any physiological effect.
3. The experimental data are not given, only p values that are significant, so there is no way to judge whether changes appear to be meaningful.
4. The paper is very poorly written and edited.
5. The patch is incorrectly described as “phototherapy.”
6. The paper is published in a rapid-publication, non-Medline indexed journal.
7. Although there seems to be some connection of the tripeptide to wound healing, connections to other benefits (such as “a new level of vitality with improvements to your energy, sleep, reduction in pain” mentioned in the promotional material quoted at the start of the post) seem to be based only a small uncontrolled study (Ref. 7).
