[Editor's Note: The following article is from a series of comments left by Vogel starting here. Some minor editing has taken place for readability.]
Lifevantage issued a press release today announcing that they had released a research abstract on the Protandim formula sold in Japan (which substitutes piperine for ashwaganda). First, it must be pointed out that this is only a meeting abstract; it is not a full published study and the full study may never be published in its entirety; we’ll have to wait and see to find out. It is not possible to conduct a proper review until and unless the full study is published. That’s why abstracts of this type are considered to be basically worthless.
The company has chosen to continue using the unreliable and inexact TBARS test to measure oxidative stress (why after all this time they have not used more accurate methods remains a mystery). The basic experimental paradigm was a before-and-after comparison of the effects of (1) placebo (2) Protandim without ashwaganda (a 4-ingredient version), and (3) Protandim with piperine substituted for ashwaganda (the Japan version). Oddly (and conspicuously), they did not include (or decided not to report the effects of) the original Protandim formulation. The report does not indicate that the study was randomized or blinded (essential features of a properly designed study).
TBARS in plasma were measured prior to taking the supplements and again after 30 days post-ingestion. The results were as follows:
Placebo (13 subjects): Baseline = 4.70 nmol/mL (uM) / Post-treatment = 6.09 nmol/mL (uM)
PT minus ashwaganda (7 subjects): Baseline = 5.44 / Post-treatment = 7.79
PT minus ashwaganda + piperine (13 subjects): Baseline = 6.31 / post-treatment = 4.90
So what to make of this data. Several things are striking. First, the group sizes are lopsided; there’s no logical reason why the group that received the no-ashwaganda version of PT would include nearly half as many subjects as the other two groups; this is suggestive of either a poor design from the outset or a high subject dropout rate in the no-ashwaganda group). Secondly a group size of 7 is very small (i.e., the study is underpowered).
Moving on, notice that the baseline TBARS values are also badly mismatched. The placebo group had baseline values of 4.7 uM compared with 5.44 and 6.31 uM in the other groups (i.e. relative to placebo the values in those groups were 16% and 34% higher, respectively, at baseline) This is indicative of a poorly designed study since the groups should all have comparable TBARS values at baseline. This alone is enough to negate the study’s findings. Bear in mind also that because the baseline value was low in the placebo group but high in the PT groups, it would be easier to show a TBARS reduction in the latter groups (i.e., they were already low to begin with in the placebo group).
Also remarkable was the fact that TBARS increased in the placebo group (by 30%), whereas logic would dictate that they should have stayed at the same level after 30 days. Similarly, it is also odd that TBARS increased (by 43%) in the group treated with the no-ashwaganda version. The logical inference from this finding would be that without ashwaganda, the concoction increases oxidative stress (a weird and not reassuring finding). The TBARS levels went down (by 22%) in the group that received the piperine (Japan) version of Protandim — but the values were decreased to the same level as the placebo group had at baseline. The logical conclusion then is that if you take the piperine version of Protandim, you can decrease your TBARS to the same levels that you would have had normally without taking anything.
It’s also noteworthy that while the company had previously claimed that the product reduced TBARS by 40% (based on the 2006 study by Nelson et al.), this study using the piperine version showed only a 22% reduction. But where things get really interesting is when we compare these new data with the data from the Nelson study.
Lifevantage had claimed that Protandim prevents age-related increases in TBARS and that the product decreases TBARS to the levels of a “newborn baby”. However, if we look at the TBARS data in the Nelson study we can see that they had baseline values in the range of 1 um (in the youngest subjects, approximately 20 years old) to 3.5 uM (in the oldest subjects, approximately 80 years old). Yet remarkably, in this newly released abstract, the data show that the 3 groups started with TBARS levels higher than that of the oldest subjects in the Nelson study (which is odd because the subjects in the latest study were only 45-69 years old), increased off the charts following ingestion of the placebo or the no ashwaganda version, and were reduced by treatment with the piperine version to levels higher than that of the untreated 80-year old subject in the Nelson study. This really kills their previous marketing story about Protandim eliminating age-related oxidative stress.
It should be pointed out that the subjects in this study were described as overweight/obese, and this could have had some impact on baseline TBARS levels (i.e., they might be slightly higher in overweight/obsese vs normal-weight people), but this would have no bearing on most of the design flaws and shoddy data that I described above. Incidentally, I think their angle in enrolling overweight subjects is to support the company’s most recent marketing realignment towards becoming a diet products vendor rather than simply a peddler of fraudulent snake oil wonder cures.
It should also be pointed out that several of the authors of this abstract (Benjamin Miller, Karyn Hamilton, and Christopher Bell) are people we have discussed in the past in connection with meeting abstracts published on Protandim by students at Colorado State University. My guess is that Lifevantage has been compensating these individuals, who are in turn putting students to work generating shoddy scientific propaganda for Lifevantage. This is similar to how we found out that McCord had used U Colorado students on some of the previously published Protandim studies. [Editor's Note: It looks like this organization has admitted to being paid by LifeVantage]
A few other claims from the study abstract and press release warrant further comment. For example, the abstract states:
“Compared with baseline, circulating plasma TBARS were unaffected by placebo or Protandim minus ashwaganda”
How is it possible that they could report that TBARS were “unaffected” in these two groups? TBARS were increased by 30% in the placebo group and by 43% in the group that received the 4-ingredient (no-ashwaganda) version of Protandim. The magnitudes of those increases are far greater than the magnitude of the decrease (22%) reported for the version with piperine added. I can’t imagine any statistical scenario where this would be possible, so it looks like the statistical analysis was fudged or the results misstated. The abstract then went on to conclude the following:
“These preliminary data suggest, in countries where ashwagandha is considered medicinal, piperine may be an acceptable substitute ingredient in the Nrf2 activator, Protandim.”
It’s odd to say the least that they while they suggest that NRF2 activation is the primary mechanism by which Protandim acts, they didn’t bother to assess the effects of the Japan version of Protandim on NRF2. There’s no reason to assume that the in vitro NRF2-activating properties of the Japan version are similar to that of the original formulation. Nor is there any reason to assume that any reductions in TBARS that the product(s) produce are related to NRF2 activation, when the effect can be explained by a simple direct antioxidant/radical scavenging effect independent of NRF2. They have never produced any clinical data showing that Protandim affects NRF2 in people who ingest the product. Now let’s look at what was claimed in the company’s press release, quoting the company’s Chief Science Officer (and supplement scammer extraordinaire) Shawn Talbott:
“In addition, this study demonstrates that both of our formulations of Protandim are potent oxidative stress reducers. This allows us to offer people a powerful Nrf2 activator and oxidative stress reduction product in most jurisdictions."
No it doesn’t demonstrate anything about both formulations. That’s a straight up lie. The study in question did not test “both formulations” of Protandim; the original Protandim formulation was not studied. The lie is even expressed in the abstract’s title:
“Oxidative Stress is Decreased With Short-Term Protandim Use When Piperine is Substituted for Ashwagandha”
Again, the study did not look at “substitution” of piperine for ashwaganda. It looked at “addition” of piperine to a formulation that consisted of 4 ingredients (milk thistle, bacopa, green tea, curcumin), which is not one of the two formulations marketed by the company, and the Japan version of Protandim which contained 5 ingredients (the 4 above + piperine). What the study showed is that 4 of the 5 ingredients in the U.S. version of Protandim do not lower TBARS but that when piperine is added as the fifth ingredient, it does. This would suggest that all of the antioxidant effect of the Japan formulation is dependent on the presence of piperine and nothing else. So a more accurate title for the study would have been:
“Piperine Mediates the Antioxidant Effect of the Japan Formulation of Protandim” or better still...
“The Japan Formulation of Protandim Increases Oxidative Stress in the Absence of Piperine”
Actually, the most interesting title, supported by the data, would be: “Protandim Without Ashwagandha Increases Oxidative Stress by 43% in Overweight Subjects”
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