Do scientific references give credibility to nootropic ingredients?

I am a scientist working on various research projects for over the last 25 years. A critical part of scientific work and writing is the correct use of scientific references.

Let’s look first at what scientific references are: These are the results of colleagues working on a scientific problem that were published in reputable scientific journals. Before these results can be printed, the data and the findings must be evaluated by peers, the peer review, and found credible. Only the peer-reviewed publications in reputable journals are considered scientific paper, and only those should be used as a reference.

Unfortunately, even peer-reviewed publications can be as good as the reviewers. Bad reviewers are likely to pass a mediocre work with questionable data as legit to be published. In recent year, many “scientific” journals popped up that would “peer review” and publish anything as long as the substantial publication fee is paid.

As with any tool, it is essential to know how to use scientific references. References are useful tools to give credibility to one’s own work or statements. If I say that Substance X works and reference a scientific article published earlier in a scientific journal, my claim looks like more substantiated, more credible. However, this is where the danger for the general audience begins.

In the following paragraphs, I will use some examples of improperly referenced scientific papers by experts and explain the reason why these references are misleading.

Let’s use Huperzine A as the first example. Many online “experts,” write that Huperzine A has benefits in fighting Alzheimer’s Disease and works as an antioxidant. To validate their claims, they reference a scientific paper that is seemingly supportive.

The following paper is frequently referenced:

Gao X., Tang X.C. “Huperzine A attenuates mitochondrial dysfunction in beta-amyloid-treated PC12 cells by reducing oxygen free radicals accumulation and improving mitochondrial energy metabolism.”Journal of Neuroscience Research. 2006 May 1;83(6):1048-57.

The title of this paper mentions that mitochondrial dysfunction is “attenuated.” The verbs “dysfunction” and “attenuate” are soft claims scientist use when they are not positively sure that a specific disease (and not a generalizing dysfunction) is blocked (instead of “attenuated”). For example, a title such as “Huperzine A blocks the damage to the respiratory chain in mitochondria by….” would be a much firmer claim but more difficult to substantiate. So this reference already starts with a cautiously formulated “soft” claim.

Now let’s look at the origin of the tissue on which Huperzine A treatment was used. The title clearly spells it out, the PC12 cells. Except for professional neuroscientist and neurosurgeons as we are, most people will not know what “PC12” cells stand for. A quick look at Wikipedia gives us the following insight:

PC12 cells are from RATs (not human) and are of ”..embryological origin with neuroblastic cells means they can easily differentiate into neuron-like cells even though they are not considered adult neurons.” These rat cells are not the brain cells called neurons!

Now, what does it mean when these rat cells are “beta-amyloid-treated”? Beta-amyloids are small parts of proteins and are considered to contribute to Alzheimer’s Disease. This disease kills brain cells called neurons and causes loss of brain function. In the scientific work I used as an example, the scientist exposed rat cells to beta-amyloid to mimic Alzheimer’s disease.

However, veterinarians are pretty sure that rats and mice do not develop Alzheimer’s Disease in nature.

Now the problem with citing this work is more evident. The author of the nootropics blog uses scientific evidence found in rat cells that are not neurons to validate his point that Huperzine A is protective of neurons.

For me as a scientist this approach rises red flags: Hoping (!) that the author of the blog post actually read the scientific paper, how do you suggest that human brain can benefit from something that was used on an animal, a rat, that does not develop Alzheimer’s disease? Using cells from rats and mice is common in science but not to make such sweeping conclusions about human health benefits.

In this section, I have attempted to explain how untrained “experts” can mislead the interested public looking for guidance by referencing scientific papers without actually understanding them.

Trained scientist such as biopharma researchers and other professionals in the business of actually developing drugs for human consumption know that results in rats or mice do not translate well into human treatments. In fact, 99% of all drugs that might work in animals are unsuitable for use in patients as medications. 

How can you make sure whether the information provided by the online experts is trustworthy? First of all, use PUBMED to look for scientific articles about the topic you are interested in. Type in the keyword or the title of the scientific reference and hit the search button!

Here are a few more suggestions:

1.    Make sure that the referenced scientific work is from clinical trials and not from animals. You can check quickly whether a product or substance is in a clinical trial by going to http://www.clinicaltrials.gov. This is an official page maintained by the National Institute of Health and lists all past, current, and future trials and in some cases the outcomes. For example, you will find here that Lion’s Mane has not undergone any clinical trials about brain health. Therefore any claim about human benefits is unsubstantiated.

2.    Make sure that the references are current and not a decade old. In some cases, old references will do, as there might be no existing research on that ingredient, but in general, a well-maintained reference list should cover the current year and the last 4-5 years.

3.    Check if the author of the article actually read the paper and discusses the results of the paper in the context of his writing. Going back to the example above, if the author cites a reference and that reference contains not only positive but also critical comments about the use of Huperzine A, make sure that the author mentions those, too. Otherwise, it is cherry picking.

4.    Validate the credentials of the self-proclaimed experts. Ask what substantiates the personal-trainer-turned-brain-experts claims about his expertise in neuroscience. Did he participate in research, has he/she published any scientific papers that were published, or is she a medical/research professional with proper credentials. Without any substance to validate, anybody can claim anything. Because somebody excels playing the game Flight Simulator does not mean the gamer is an actual pilot. Would you like to fly in an aircraft piloted by this gamer?

5.    Do not take synthetic stimulants, such as racetams, that are sold labeled with terms like “not for human consumption” or for “research use only” and not approved by the FDA. Although the FDA does not get it right all the time, it still prevents many lives from being destroyed by unsuitable drug candidates.

In summary, be your own FDA, do your due diligence and know the limits of your and other real expertise. Don’t listen to the hype, don’t be a neuro-hacker, self-experimenting with potentially toxic drugs to have a more productive or healthier life; you might end up poisoning yourself.

As a wise man said, trusting is good, verifying is better. After all, it’s your life you are gambling with.

Photo by Kendal James on Unsplash