The notion of an “exaggerated health claim” is as old as the wellness industry itself, but only in the past few decades have health claims benefited from being periodically shared by the world’s social media “influencers.” The exposure they afford a product is invaluable, amplifying the marketing claims, and occasionally conceiving new ones, to millions of followers and potential customers. Their influence is once again responsible for a concerning fitness trend that lurks on the periphery of popular culture.
In a series of recent online posts, fitness gurus have documented their experiences of using methylene blue—an industrial dye that evolved into a common treatment for the blood disorder methemoglobinemia—claiming the drug improved their cognitive performance and functioned as a “mitochondrial optimizer.” Needless to say that, in a health and wellness industry nearly saturated with pseudoscience, in which baseless claims abound, methylene blue is raising a few skeptical eyebrows.
In this series titled “When Medicine Go Rogue,” I will be exploring products such as methylene blue that are used as legitimate medical treatments, but that have been coopted and misappropriated in the commercial space to sell unreasonable outcomes and false promises.
‘Welcome to the Blueniverse!’
… writes one vendor of methylene blue on their website, claiming their lozenge can “launch you into flow, enhance your memory, recall, productivity, focus, and verbal fluency.” Another retailer claims their 1 percent concentrated solution can “protect your memory,” promote blood and oxygen flow to the brain, and help remedy those times when mitochondria “fails in its function.” As if responding specifically to the broad and numerous claims, the FDA published an article titled “How to Spot Health Fraud,” in which they warned consumers to “be suspicious of products that claim to cure a wide range of unrelated diseases—particularly serious diseases … [because] no product can treat every disease and condition.” 1
Using critical thinking to contextualize the litany of commercial health claims is difficult enough for scientists like me, but it becomes considerably more so when revered athletes and celebrities amplify marketing rhetoric out of financial incentives or sheer ignorance.
For example, personal trainer and fitness influencer Ben Greenfield, who has a combined 650,000 followers on prominent social media platforms, described methylene blue as a “potent cognitive enhancer.” He espoused wide-ranging effects such as enhanced mitochondrial function, neuroprotective effects against brain inflammation, and increased memory and cognitive function: benefits that, fortuitously, precisely echo the manufacturers’ claims. Greenfield is known for promoting myriad supplements and drugs on his website and has numerous affiliate links from which he receives commission. He has investments in several supplement brands and has cofounded a company making branded supplements of his own. He is far from the only influencer promoting methylene blue. Similar endorsements have come from professional runner and influencer Jordan Hasay and U.S. surgeon Cameron Chesnut, alongside respective Facebook and Instagram images of their blue tongues that had been stained by the dye.
Despite being met with mockery and derision when the images appeared online, this issue is more complex than at first glance owing to the clinical literature in support of the drug’s therapeutic effects. So, how did we arrive at this precarious intersection of clinical evidence, commercial hype, and online misinformation?
There Are Two Legitimate (Non-industrial) Uses of Methylene Blue
In medicine, methylene blue (in doses of 1–2 mg/kg) can effectively treat methemoglobinemia2—a condition in which the ability of red blood cells to release oxygen to surrounding tissues of the body has been compromised. Although rare, the condition is potentially fatal,3 but methylene blue, also called methylthionine chloride, is an evidence-based therapy. Because methylene blue will stain most fluids and tissues (see the aforementioned “tongue selfies”), it is also used in microbiology as a staining agent, for example, in the detailed study of animal cell components.4
The clinical benefits of methylene blue are taken out of context and grossly misappropriated.
Since its discovery over 100 years ago, studies have mounted showing clinical benefits of methylene blue. For instance, the commercial claims regarding methylene blue as a “mitochondrial optimizer” may have stemmed from a 2016 study, in which the drug was used to treat mitochondrial dysfunction in premature aging disease.5 Leaping from this study to the commercial claim is an understandable extrapolation, but not a correct one. As a potent “antioxidant,” methylene blue may also treat certain blood flow disorders.6 There is research on possible anti-inflammatory effects in counteracting drug-induced toxicity4 and studies indicating utility in pain relief.7 Finally, the claimed cognitive benefits may derive from a small scale study, in which methylene blue improved performance in a short-term memory task compared to placebo.8
When interpreting the scientific data, context is paramount. Almost every study showing potential benefits of methylene blue has tested the drug in patient populations, specifically as a therapy for methemoglobinemia, neurodegenerative disorders, drug toxicity, and in patients with mitochondrial dysfunction. These benefits do not necessarily extend to otherwise healthy people. So, while methylene blue is well placed as a promising therapy for several diseases and disorders, the benefits for nonpatients are far from clear.
Another important caveat is the dose. A typical (low) therapeutic dose of methylene blue, used in the clinical setting, is 1–2 mg per kilogram of body weight.9 This equates to about 80–160 mg for an 80 kg (175 lb) adult. Studies in cognitive effects have used an intermediate dose roughly twice this amount (4 mg/kg).8 Yet, commercial iterations of methylene blue typically contain less than 5 mg total, which is thirty times lower than amounts used in published clinical data. There is little-to-no evidence that commercial-grade methylene blue confers any functional benefits. One online review of a methylene blue product, an uncritical anecdote published by a self-confessed “biohacker,” claimed it improved focus, concentration, and creativity. Yet, alongside the small dose of the purported active ingredient were others including nicotine, hemp, and caffeine. Not exactly a controlled study.
Bad Influence
From its humble beginnings as a dye used in the textile industry, methylene blue has been developed into a drug with several clinical applications and is now advocated by online fitness gurus as a magic bullet for health and sports performance. In contemporary health and fitness, it is commonplace for products and services with supporting clinical data to be marketed (and misappropriated) for the commercial sphere, often without convincing evidence. We discussed a similar scenario with respect to intravenous nutrient drips10 in the February issue of this column.
However, lest we forget that, in many instances, influencers are promoting products and brands for financial incentives (i.e., paid sponsorship). Surveys show that approximately 71 percent of an influencer’s income is derived almost exclusively from sponsored online content.11 At the extremes, online sponsorship is absurdly lucrative. The Guardian (UK) reported that Brazilian soccer player Christiano Ronaldo is Instagram’s greatest beneficiary, earning around USD $40 million each year from paid advertising on the platform.12 Although influencers are legally obliged to tag their sponsored posts with a “paid partnership” label, they frequently break the rules with so-called “stealth ads,” prompting written warnings from the Federal Trade Commission.13 This is a worrying trend given that 36 percent of Americans under twenty-five years of age have purchased a product or service because it was recommended by a social media influencer.14 Finally, it is worth noting that antiscience movements are savvy to the tremendous potential of influencer sponsorship: it was recently revealed that several agencies have approached social media personalities offering payments in return for the unscrupulous dissemination of anti-vaccine propaganda.15
With so many financial conflicts of interest, it should come as no surprise that a study of health and exercise advice disseminated on Instagram found that influencers were responsible for spreading predominantly low-quality advice and potentially harmful misinformation.16 In a related finding, influencers with the most followers tended to have fewer educational qualifications.16 Influencers often mean well, but they just as often stumble upon a kernel of truth and use it to prey on the inherent human yearning for simple solutions to complex problems. On social media, good science and sound advice are not only increasingly rare commodities, but they are also rarely simple. Science is complex and messy, and making sense of published data requires a degree of understanding and nuance that social media platforms simply do not allow.
The Risks of Methylene Blue Are Poorly Considered.
Fake news on social media spreads further, faster, and deeper than objective fact.17 Thus, it only requires a small number of recognizable athletes, celebrities, or fitness influencers to endorse a brand for the claims to propagate. In this sense, the widespread use of methylene blue, outside of the clinical environment, may have many nonfinancial costs.
In small, therapeutic doses, the risks of methylene blue are minimal. However, when unshackled from the robust procedures and protocols of clinical practice, the risks of toxicity from inappropriate dosing increase considerably. Even in small doses, methylene blue might reduce exercise capacity because it is used frequently in rodent studies as an inhibitor of nitric oxide (an important blood vessel dilator).18 In high doses, however, methylene blue is outright toxic.19 It is particularly harmful to small children, causing a range of circulatory and respiratory problems.19 There can be drug interactions, specifically with selective serotonin reuptake inhibitors (SSRIs)—the world’s most commonly-prescribed anti-depressant medication—which could result in serious serotonin toxicity20 and even anaphylactic shock.21 It is for these reasons, and many that remain unstated in this short summary, that methylene blue is a controlled (prescription) medicine, belonging to the “Antidotes” class of drugs. It is not FDA-approved. The public can ill-afford more flippant endorsements of methylene blue by non-medical professionals.
Take Home Messages and Ruminations
Methylene blue is the latest in a long line of products and services sold on commercial buzz and often-sponsored influencer endorsements that overlook potential risks. And while there is a strong body of literature on the potential benefits of methylene blue for patient populations, you would be a fool to accept advice from a fitness influencer regarding a controlled drug. The first rule, therefore, is to keep an open mind, but not so open that your brains fall out (Richard Feynman). Nevertheless, we live in the post-truth era, characterized by the death of expertise, in which the loudest voices are the ones inevitably heard, and products such as methylene blue propagate because of the public’s perception that notoriety equals expertise. The second rule, therefore, is that Instagram, Twitter, Facebook, and TikTok followers are not credentials. Increased access to data, which is distinct from knowledge, and the crumbling barriers to discourse that stem for the rapid rise of social media, should have improved our ability to recognize and disseminate good health advice. Instead, just learning to safely navigate social networks has become an enormous resource drain on our critical faculties. It is ultimately worth the trouble, but it is difficult not to wonder how those resources could have been put to better use.
Notes
1. Research C for DE and. How to Spot Health Fraud. FDA. Published online November 3, 2018. Accessed April 14, 2022. https://www.fda.gov/drugs/bioterrorism-and-drug-preparedness/how-spot-health-fraud.
2. Clifton J, Leikin JB. Methylene blue. Am J Ther. 2003;10(4):289-291. doi:10.1097/00045391-200307000-00009.
3. Ludlow JT, Wilkerson RG, Nappe TM. Methemoglobinemia. In: StatPearls. StatPearls Publishing; 2022. Accessed April 13, 2022. http://www.ncbi.nlm.nih.gov/books/NBK537317/.
4. Nedu ME, Tertis M, Cristea C, Georgescu AV. Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications. Diagnostics. 2020;10(4):223. doi:10.3390/diagnostics10040223.
5. Xiong ZM, Choi JY, Wang K, et al. Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria. Aging Cell. 2016;15(2):279-290. doi:10.1111/acel.12434.
6. Salaris SC, Babbs CF, Voorhees WD. Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury. Biochem Pharmacol. 1991;42(3):499-506. doi:10.1016/0006-2952(91)90311-r.
7. Lee SW, Han HC. Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism. Front Neurosci. 2021;15:663650. doi:10.3389/fnins.2021.663650.
8. Rodriguez P, Zhou W, Barrett DW, et al. Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain. Radiology. 2016;281(2):516-526. doi:10.1148/radiol.2016152893.
9. Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012;96(1):32-45. doi:10.1016/j.pneurobio.2011.10.007.
10. Tiller N. Intravenous Nutrient Drips: An Expensive Solution to A Nonexistent Problem | Skeptical Inquirer. Published February 21, 2022. Accessed April 14, 2022. /exclusive/intravenous-nutrient-drips-an-expensive-solution-to-a-nonexistent-problem/.
11. Study: 71% of social influencers’ income is almost exclusively from sponsored content. Marketing Dive. Accessed April 14, 2022. https://www.marketingdive.com/news/study-71-of-social-influencers-income-is-almost-exclusively-from-sponsor/448110/.
12. Sweney M. Cristiano Ronaldo shoots to top of Instagram rich list. The Guardian. Published June 30, 2021. Accessed April 14, 2022. https://www.theguardian.com/technology/2021/jun/30/cristiano-ronaldo-shoots-to-top-of-instagram-rich-list.
13. Morran C. Report: Instagram Influencers Continue To Ignore Warnings About Stealth Ads. Consumer Reports. Accessed April 14, 2022. https://www.consumerreports.org/consumerist/report-instagram-influencers-continue-to-ignore-warnings-about-stealth-ads/.
14. 1/5th of American Consumers Have Made a Purchase Based on an Influencer. CivicScience. Published January 16, 2019. Accessed April 14, 2022. https://civicscience.com/1-5th-of-american-consumers-have-made-a-purchase-based-on-an-influencer/.
15. The YouTubers who blew the whistle on an anti-vax plot. BBC News. Published July 24, 2021. Accessed April 13, 2022. https://www.bbc.com/news/blogs-trending-57928647.
16. Marocolo M, Meireles A, de Souza HLR, et al. Is Social Media Spreading Misinformation on Exercise and Health in Brazil? Int J Environ Res Public Health. 2021;18(22):11914. doi:10.3390/ijerph182211914.
17. Vosoughi S, Roy D, Aral S. The spread of true and false news online. Science. 2018;359(6380):1146-1151. doi:10.1126/science.aap9559.
18. Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol. 1993;45(2):367-374. doi:10.1016/0006-2952(93)90072-5.
19. Ginimuge PR, Jyothi SD. Methylene Blue: Revisited. J Anaesthesiol Clin Pharmacol. 2010;26(4):517-520.
20. Gillman PK. Methylene blue implicated in potentially fatal serotonin toxicity. Anaesthesia. 2006;61(10):1013-1014. doi:10.1111/j.1365-2044.2006.04808.x.
21. Dewachter P, Mouton-Faivre C, Tréchot P, Lleu JC, Mertes PM. Severe anaphylactic shock with methylene blue instillation. Anesth Analg. 2005;101(1):149-150, table of contents. doi:10.1213/01.ANE.0000153497.60047.80.