clinical trial
Aaron Siri is an American lawyer and anti‑vaccine activist. He has become a key figure in contemporary US vaccine‑policy debates, largely through his legal challenges and close ties to health‑policy critics such as Robert F. Kennedy Jr. His following five central claims about vaccines are a mix of selective quoting, misrepresentation of studies, and appeal to legal‑style rhetoric:
- Vaccines cause chronic illness
Siri’s central “smoking‑gun” claim rests on an unpublished Henry Ford Health‑system analysis allegedly showing that vaccinated children have far higher rates of chronic illness than unvaccinated children. Vaccinated children in this dataset had far more health‑care visits than unvaccinated children, so more conditions were diagnosed in them regardless of whether vaccines caused them. This is a textbook example of detection bias, but not evidence of causation. Moreover, the study has not passed peer review; its reported disease prevalences are inconsistent with known epidemiology. It is therefore widely seen as methodologically unsound.
- Vaccines were never properly tested against proper controls
Siri argues that many childhood vaccines have not been tested in inadequately-powered, placebo‑controlled trials. When an effective vaccine exists, medical ethics oppose using placebos in new trials, as that would deny protection to a control group. Moreover, his claim that older vaccines (e.g., tetanus–diphtheria–pertussis) “lack adequate controlled trials” is misleading because earlier trials were designed for different standards and later observational data, post‑licensure surveillance, and large‑scale cohort studies have filled the gaps. In other words, he exploits technical‑sounding language to imply a hiatus of evidence, when in reality the evidence base is broader and more heterogeneous than he portrays.
- The CDC/WHO inflates how many lives vaccines have saved
Siri has attacked the WHO’s estimate that vaccines have saved around 154 million lives, calling it “corruption of science”. The 154‑million figure comes from a modelling exercise [like most “lives‑saved” statements in public health]. It depends on assumptions but is based on vaccine‑coverage and mortality‑trend data, but it is not fabricated. Siri’s rebuttals focus on rhetorically dismissing the exercise as “advertising” rather than engaging its assumptions or proposing alternative, better‑validated models. His claim that this number is “corrupt” thus rests polemic than but not on a coherent technical critique of the underlying epidemiological models.
- Exploiting the 1986 Vaccine Injury Act and “lack of liability”
Siri blames the 1986 National Childhood Vaccine Injury Act for reducing oversight and downplaying risk, arguing that liability protection “corrupts” safety monitoring. Yet the law was designed to protect manufacturers from financially ruinous litigation and to create a dedicated federal compensation program for proven injuries, not to forbid safety monitoring. The US has multiple surveillance systems (VAERS, VSD, CISA) and expert advisory bodies (ACIP, NVAC) that continuously review vaccine safety. Siri’s critique thus conflates legal strategy with scientific oversight, implying that the absence of mass torts proves lax monitoring.
In conclusion, Siri’s vaccine claims are mostly built on:
- one deeply flawed, unpublished observational study,
- selective readings of older vaccine‑trial designs,
- unwarranted dismissal of WHO‑level modelling, and
- a legal framing that conflates liability shields with absence of safety science.
Epidemiologists, infectious‑disease specialists and other experts rightly regard Siri’s arguments as misrepresenting or misapplying biostatistics and failing to meet standards for causal inference. It would be a serious mistake to follow them!
I am sure that many of my readers have no idea what ‘Slinding Cupping Therapy’ is. It is a TCM therapy that, according to the authors of this paper, receives much appreciation for treating plaque psoriasis. This study was designed to test the hypothesis that sliding cupping therapy is non-inferior to narrowband ultraviolet B (NBUVB) therapy in improving disease severity in patients with plaque psoriasis.
This prospective trial recruited 60 patients with plaque psoriasis who were randomized to receive either sliding cupping intervention or NBUVB treatment. The cup was moved 30 times for each skin lesion until the target skin area turned purple. The initial dose (mJ/cm2) of ultraviolet radiation b (UVB) was determined based on sun-reactive skin types I through VI, which ranged from 300 mJ/cm2 to 800 mJ/cm2. Both treatments were performed 3 times per week for 8 weeks. The primary endpoint was the percentage reduction in Psoriasis Area and Severity Index (PASI) score at week 8, with secondary endpoints, including Physician’s Global Assessment (PGA), body surface area, visual analogue scale scores, and quality of life measures.
The total response rates were 69% (18/26) and 79% (19/24) for patients receiving sliding cupping intervention and those receiving NBUVB treatment, respectively, which showed no significant difference (P = .526). The PASI scores, body surface area, and PGA were reduced in patients with plaque psoriasis at W0, W4 and W8 after either sliding cupping intervention or NBUVB treatment (P <.001), and these reductions were not significantly different between the patients receiving sliding cupping intervention and those receiving NBUVB treatment at W0, W4, W8, and W12. At W8, the mean percentage reduction in PASI was 62.4% (95% CI, 54.9–69.8) in the sliding cupping group and 66.9% (95% CI, 59.6–74.2) in the NBUVB group, with no significant difference between groups. The total response rates were 69.23% (18/26) and 79.17% (19/24), respectively (P = .526). Patients receiving sliding cupping intervention and those receiving NBUVB treatment did not show statistically significant differences in these outcomes at W0, W4, W8, and W12 (P >.05).
The authors concluded that the overall results suggest that sliding cupping therapy exhibits statistically similar efficacy and safety profiles as NBUVB treatment, especially at 8 weeks after treatment.
Sliding cupping therapy is a form of cupping in which cups producing mild suction are placed on oiled skin and then moved along the body surface, generating a “reverse massage” that lifts rather than compresses the subcutaneous tissues. The negative pressure is thought to increase local blood flow and lymphatic drainage, reduce perceived muscle tension, and temporarily improve range of motion, though high‑quality clinical evidence for most claimed benefits remains limited.
The treatment is used mainly by massage therapists, physiotherapists, and TCM practitioners in musculoskeletal and sports‑rehab settings, as well as in wellness and spa‑oriented clinics; it is commonly applied to the back, shoulders, neck, limbs, and along fascial lines or acupuncture meridians, often for pain, stiffness, “trigger‑point”‑type tension, and post‑exercise recovery. The popularity of this therapy is best characterised as a niche within broader cupping and fascial‑release practice rather than a mainstream standard treatment.
The new study is a text-book example of how to mislead people with seemingly reliable research. The fact that it was grossly under-powered – and not the effectiveness of the sliding cupping therapy – is obviously the cause of the lack of a difference between the effective therapy (NBUVB) and the sliding quackery.
Let me give you an example: say, we compare antibiotics (A) to homeopathy (H) as treatments for bacterial pneumonia. We treat 10 patientsin each group, and 8 of them recover in group A within a week, while in the H-group the amount is 6 (many patients recover even without an effective treatment). We run statistical tests which tell us that the difference is not significant. Thus we falsely conclude that homeopathy is as effective as antibiotics in the treatment of pneumonia. The 2 treatments were, in fact, not equal but the lack of power of the small study failed to detect the existing difference.
It seems rather obvious to me that a similar thing has happened with the above study. Its authors are to be congratulated for cheating so slyly that neither the editors nor the reviewers of the journal ‘Medicine’ managed to see through their simple litte trick.
Some homeopathy-fans claim that tiny “nanoparticles” survive even in remedies diluted a trillion trillion times (i.e. the process of manufacturing a high-potency homeopathic remedy). They furthermore assume that this phenomenon can explain how homeopathy works. This argument sounds ever so modern and sciency but – unless you are a bit of a dim-wit – it falls apart for several fairly straightforward reasons that almost anyone should be able to grasp.
Too Dilute
Imagine starting with a single drop of medicine and diluting it by adding 99 drops of water, shaking it up, then repeating that hundreds of times. By the 12C stage (about 1 part in 10^24), there’s statistically zero original molecules left – way before most remedies hit 30C or higher. Even if some nanoparticles somehow cling on from the mixing process or glass vials, they’d be so rare (fewer than one per bottle) that they couldn’t reliably affect your body like a real drug.
Breaks the Main Rule
Homeopathy’s main axiom is “like cures like” assumption: a substance that causes a headache in a healthy person should cure headaches when you’re sick. But nanoparticles would just deliver a tiny dose of the ingredient itself, acting like an extremely weak remedy – not following homeopathy’s main axiom. This would turn homeopathy back into normal medicine and miss the basis of its own theory.
Not Based on Materials
Not all homeopathic remedies start with physical ingredients. Some are “imponderables” like “X-ray” (sugar pills exposed to X-ray radiation, then diluted), “vacuum” (made by evacuating air from water), or even “moonlight.” There’s no material at all to leave nanoparticles behind, so this explanation can’t cover those products.
Useless Ingredients
Most homeopathic remedies are based on mother tinctures that have no heath effects, like sepia (ink from cuttlefish), cantharis (Spanish fly blister beetle), or even bits of the Berlin Wall. These aren’t bioactive – they don’t fight infections or reduce pain or do anything else in normal doses. Nanoparticles from such useless junk wouldn’t magically gain healing powers; they’d still do nothing useful for health.
Lack of Convincing Clinical Evidence
As discussed ad nauseam on my blog, there simply is no sound evidence to show that homeopathy works better than a placebo. Any benefits people feel are thus likely from expectation, natural recovery, or doctor attention – and not from nanoparticles. If homeopathy had any real effects to explain, nanoparticles might be worth debating; without them, it’s a dead end.
I do sympathise with the desperation of homeopaths. They feel they must identify a plausible mode of action for their remedies. Their 200 year old struggle to find anything at all is in many ways remarkable. Here are some of the main explanatory ideas homeopaths (or homeopathy-friendly authors) have previously proposed for how homeopathy might work:
- Vital force / life energy – the remedy is said to act on a non-physical “vital force” or life energy that supposedly governs health and disease.
- Water memory – water is claimed to “remember” substances once dissolved in it, even after dilution beyond any remaining molecules, via changes in water structure or hydrogen bonds.
- Electromagnetic signatures – remedies are said to carry subtle electromagnetic patterns or “information” of the original substance, sometimes claimed to be recordable, transmitted electronically, and imprinted on new water.
- Quantum coherence domains – models suggest water forms coherent quantum domains storing drug “information” as electromagnetic frequencies, inspired by Del Giudice and Preparata’s ideas, though lacking solid experimental support.
- Stable water clusters / clathrates – hypotheses that long-lived clusters or cage-like structures (clathrates) in water somehow encode the properties of the starting substance.
- Nanobubbles and interfaces – suggestions that gas nanobubbles or interfaces in the solution store and transmit information about the starting material.
- Hormesis-based explanations – the idea that ultra-low doses act via hormesis (beneficial effects of mild stress or toxins), extended to the extreme dilutions used in homeopathy.
- Resonance with the body – proposals that remedies resonate with biological systems (cells, tissues, or “vital force”) through frequency matching or electric resonance, rather than via chemistry.
- Quantum entanglement / non-locality – claims that patient, practitioner, and remedy become “entangled,” so healing occurs via non-local quantum effects rather than molecules or doses.
- Information medicine / encoding – framing remedies as carriers of abstract “information” rather than substance, supposedly acting like a software signal on the body’s “hardware.”
Is it not time for homeopaths to accept the only well-proven, plausible explanations as to why their patients feel better after taking their remedies?
- The empathetic therapeutic encounter.
- The natural history of the condition.
- Regression towards the mean.
- Concommittant conventional treatments.
- The placebo effect.
Immunisation and homeopathy are often assumed to be similar; some even claim that the efficacy of the former proves the latter. They both are said to “stimulate the body’s natural defences” and they both allegedly use “tiny does”. Yet they are fundamentally different, not just in their methods, but in their scientific validity and biological mechanisms.
Immunisation (or vaccination) is grounded in the well-understood biological principles of immunology. Simply put, when a pathogen enters the body, the immune system identifies foreign proteins (antigens) and produces antibodies to fight them. Immunization mimics this process without causing the actual disease. By introducing a weakened, inactivated, or recombinant part of a virus or bacteria, the vaccine “trains” the immune system. If the person is later exposed to the real pathogen, their body recognizes it and is capable of launching a rapid defence. This process is quantifiable; doctors can measure “titer levels” in the blood to confirm the presence of antibodies.
Homeopathy operates on two primary axioms:
- The Law of Similars: The belief that a substance that causes symptoms in a healthy person can cure those same symptoms in a sick person.
- The Law of Infinitesimals: The belief that the more a substance is diluted, the more potent it becomes.
Homeopathic remedies are typically diluted to such an extent that not a single molecule of the original substance remains in the final dose. Proponents claim the water “remembers” the substance, a concept known as water memory, which has no empirical support in the scientific community. The confusion between immunisation and homeopathy usually stems from the superficial similarity that both allegedly involve “small doses” to trigger a response. However, the “small dose” in a vaccine is a calculated, detectable amount of biological material designed to trigger a specific cellular reaction. In contrast, the “dose” in homeopathy is non-existent in remedies beyond the C12 potency. While the resopnse to an immunisation is quantifiable, this is not the case with homeopathy.
But the most important difference between immunisation and homeopathy is, of course, this: the former is effective beyond placebo and the latter isn’t.
In short, immunisation is a biological “training manual” for the immune system, backed by centuries of sound evidence and the near-elimination of diseases like polio and smallpox. By contrast, homeopathy is a so-called alternative medicine (SCAM) that relies on implausible assumptions and at best works via a placebo effect.
This landmark study, often called the “Nürnberger Kochsalzversuch”, is historically significant as probably the first recorded instances of a randomized, double-blind, placebo-controlled trial. It was conducted to test a specific claim made by a leading practitioner of the time. By the mid-1830s, homeopathy had gained significant popularity among the upper classes in Nuremberg, then part of the Kingdom of Bavaria (Stolberg, 2006). This success frustrated the city’s medical establishment Thus, in 1834, Friedrich Wilhelm von Hoven, the city’s highest-ranking public health official, published a scathing critique of homeopathy using the pseudonym “E.F. Wahrhold” (Cukaci et al., 2020). Johann Jacob Reuter, a prominent local homeopath, responded by challenging von Hoven to a test which became the now famous Nürnberger Kochsalzversuch. Reuter claimed that even a healthy person would experience “extraordinary sensations” if they ingested a dilution of ordinary table salt (Sodium Chloride, or Natrum Muriaticum, as homeopaths like to call it) (Stolberg, 2006).
The trial was organized by a “Society of Truth-loving Men,” supported by George Löhner, a local newspaper editor who also wrote the final report (Cukaci et al., 2020). To ensure impartiality, they implemented a – for the time revolutionary – study design:
- 100 identical glass vials were prepared.
- 50 were filled with pure distilled snow water (the placebo),
- 50 were filled with a salt dilution prepared exactly as Reuter had instructed (one grain of salt diluted 29 times at a 1:100 ratio.
- The vials were numbered, shuffled, and divided into two lots at random in front of a public audience.
- A sealed list recorded which vial/number contained which substance.
- Neither the distributors/trialists nor the participants knew the contents of the vials.
- The vials were distributed to volunteers.
- They were asked to record any unusual symptoms over the following three weeks.
The results could not have been clearer. Of the participants who reported back (approx. 50–54 individuals), the vast majority experienced no symptoms at all. Moreover, there was no difference between the verum and the control group.
The organizers concluded that, as the “symptoms” were evenly distributed between the salt and water groups, Reuter’s claim was discredited. They attributed any reported symptoms to imagination, self-deception, or preconceived opinion (Stolberg, 2006).
The study has historical importance. It is now celebrated by as a pioneering moment in clinical methodology. It could have established the importance of double-blinding, placebo-controls, and randomisation to eliminate bias. I say “it could have” because, in fact, it did nothing of the sort.
- It took until the 1930s that blinding started appearing in more formal academic settings; and only after 1948 (see below), became blinding accepted widely a “best practice”.
- In 1955, Henry Beecher published his landmark paper claiming that roughly 35% of patients improved on placebo alone. The Kefauver-Harris Amendment of 1962 finally legally mandated that manufacturers prove a drug is “effective” compared to a control, usually a placebo.
- Sir Ronald A. Fisher, a statistician working at an agricultural research station in England, realized that if you test two different fertilizers on two different patches of land, the soil quality might be better in one patch than the other, which would ruin the data. He proposed that only by randomly assigning treatments could you “cancel out” unknown variables (like soil acidity or moisture). His 1925 book, Statistical Methods for Research Workers, provided the mathematical proof that randomization was the only way to eliminate this form of bias.
- The MRC Streptomycin Trial of 1948 finally marked the official birth of the randomized clinical trial (RCT).
But – most importantly in the context of this blog – the trial could have established that highly diluted homeopathic remedies are pure placebos. Sadly, this fact is still being ignored by all homeopaths, most healthcare systems, and far too many consumers across the world.
References
Beecher, H. K. (1955). The Powerful Placebo. Journal of the American Medical Association, 159(17), 1602–1606. https://doi.org/10.1001/jama.1955.02960340022006
Cukaci, C., Freissmuth, M., Mann, C., Marti, J., & Sperl, V. (2020). Against all odds—the persistent popularity of homeopathy. Wiener klinische Wochenschrift, 132(9-10), 232–242. https://doi.org/10.1007/s00508-020-01624-x Cited by: 99
Fisher, R. A. (1925). Statistical Methods for Research Workers. Oliver & Boyd. (Bodmer, 2003; Larson, 2008).
Jamison, J. C. (2016). The Entry of Randomized Assignment into the Social Sciences. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.2739005 Cited by: 29
Stolberg, M. (2006). Inventing the randomized double-blind trial: the Nuremberg salt test of 1835. Journal of the Royal Society of Medicine, 99(12), 642–643. https://doi.org/10.1177/014107680609901216
Large-scale randomized trials have found that multivitamin–multimineral (MVM) supplements and cocoa flavanols may benefit several age-related chronic conditions among older adults, but it remains unclear whether these two supplements directly slow the biological aging process. This prespecified ancillary study evaluated the 2-year effect of a daily MVM (Centrum Silver) and cocoa extract (500 mg cocoa flavanols per day, including 80 mg (−)-epicatechin) on five DNA methylation measures of biological aging (PCHannum, PCHorvath, PCPhenoAge, PCGrimAge and DunedinPACE) among 958 participants (482 women and 476 men) in the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS).
Compared with placebo, daily MVM supplementation modestly reduced the rate of increase of second-generation epigenetic clocks, with a between-group difference in yearly change of −0.113 years (95% confidence interval (CI) −0.205 to −0.020; P = 0.017) for PCGrimAge and −0.214 years (−0.410 to −0.019; P = 0.032) for PCPhenoAge. MVM had a stronger effect on PCGrimAge among those with accelerated biological aging at baseline (−0.236 [−0.380 to −0.091]).
Compared with those with normal or decelerated biological aging (−0.013 [−0.130 to 0.104]; P = 0.018 for interaction). Cocoa extract did not have an effect on the five epigenetic clocks tested. Although the statistically significant but small effects of daily MVM supplementation on slowing biological aging are encouraging, additional studies are needed to determine the clinical relevance of daily MVM supplementation on epigenetic clocks and whether such effects can help explain the beneficial effects of MVM supplementation on aging-related chronic conditions.
Experts who were not involved in the new study urged caution. While the researchers saw an effect with two epigenetic clocks, three other epigenetic clocks included in the study showed no statistically significant change to their speed. “The multivitamin produced small favorable changes in two epigenetic aging markers, but not across all the clocks that were measured,” says José Ordovás, a professor of nutrition and genetics at Tufts University. “That makes the finding interesting, but it is still far from showing that multivitamins broadly slow aging or improve longevity.”
One of the study’s strengths is that the researchers carefully matched the characteristics of people in the vitamin group to those in the placebo group, says Zachary Clayton, an assistant professor of medicine at the University of Colorado Anschutz, who was also not involved with the research. “However, the magnitude of the observed differences was modest, and their clinical significance remains uncertain,” he says. The study doesn’t take a person’s exact diet or physical activity during the two-year period into account, and those factors can’t be ruled out as having an effect on biological aging, he adds.
Still, in nutrition science, randomized clinical trials of this kind are rare. They aren’t generally required to sell supplements like multivitamins, even if the makers claim specific health benefits. Additional trials, the authors note, “are needed to confirm these findings and determine the role of [multivitamins] in extending healthy aging not only among older adults, but also across the lifespan.”
In addition to these criticisms, I would add a few further points:
- Scientists emphasize that “biological age” as measured by DNA methylation is a biomarker, a surrogate endpoint, but not a direct health outcome. It is currently unknown if a 2-month reduction in an epigenetic clock actually translates into a lower risk of disease, disability, or a longer life.
- The 2-year duration of the study is a great achievement for such a trial; yet it still is considered relatively short for assessing biological aging, which is a process that accumulates over decades. Longer-term data is needed to see if these small changes persist or lead to meaningful health differences.
- The fact that those study participants who started “biologically older” saw the most benefit could be a statistical artifact known as “regression to the mean” rather than a true systemic effect of the supplements.
- The study participants were primarily of Caucasian descent and over the age of 60. This limits the ability to generalize the findings to younger populations or diverse ethnic groups.
- Epigenetic alterations are only one of several “hallmarks of aging.” Because the study did not measure other factors like DNA damage, protein stability, or cellular communication, it provides only a very narrow “snapshot” of the aging process.
- The multivitamin might not have “slowed aging” in a general sense, but could have corrected minor, undiagnosed nutrient deficiencies in some participants, which then reflected positively on their biomarkers. If that were true, supplementation of non-deficient volunteers would have no effect.
I have long felt that Cureus is a very strange journal:
- It publishes an incredilby high volume of papers: ~50,000 in 2025.
- An unusual high percentage of these articles are on so-called alternative medicine (SCAM).
- Its article retraction rate seems one dimension higher than the average.
- It charges hefty fees for submissions needing language, formatting, or reference corrections.
- Estimates of its profits vary hugely: $3.5M revenue (Growjo), $1.4M (SignalHire), or $25-50M (Cience).
Now RETRACTION WATCH (RW) have reported that Clarivate has removed Cureus from its Master Journal List. The move means Cureus will no longer be indexed in Web of Science or receive an impact factor. Thus, researchers are less likely to submit to the journal.
Clarivate put indexing for the journal on hold last September for concerns about article quality, which the journal has been criticized for in the past. Cureus has retracted about 125 papers since Springer Nature acquired the title in late 2022. Last year, the journal closed six of its academic channels critics described as dressed-up paper mills, and has had to repeatedly retract plagiarized articles, as we’ve previously reported.
In August, Cureus eliminated author suggestions for peer reviewers in an attempt to decrease potential conflicts of interest. The journal has had authorship issues in the past, as RW previously reported. In 2021, a medical resident in New Jersey invited his wife to review his papers without disclosing their relationship, resulting in five retractions. In 2019, another author faked reviewer accounts for two well-known neurosurgeons and was discovered only after a routine editorial audit.
Rebecca Krahenbuhl, a communications manager at Clarivate, told RW a journal is removed from the Master Journals List when it “no longer meets” 24 quality criteria. These criteria include appropriate citations, adequate and effective peer review, and primarily original scholarly content, according to the company’s website. Krahenbuhl also told RW journals are typically on hold for an average of around six weeks, but in cases where publishers “engage” with Clarivate, the company allows journals to remain on hold for longer “to allow time for publishers to conduct their own investigations and take corrective action should they decide to do so.”
Graham Parker-Finger, the publishing director at Cureus, told us the journal was “very disappointed” in Clarivate’s decision and noted the journal would continue “to offer fast, affordable, trusted and quality-assured publishing for the global medical community.”
This study was aimed at determining whether four weeks of Rhodiola rosea (RHO) supplementation improves intermittent exercise performance, post-exercise blood lactate concentrations, and decision-making under fatigue in competitive football players. Twenty-four male competitive football players completed a randomised, double-blind, placebo-controlled 4-week intervention (RHO vs. placebo). Outcomes included Yo-Yo IR2, repeated-sprint ability (RSA), post-RSA blood lactate (0, 3, 5 min), football-specific technical tests (passing and shooting), a video-based decision-making task (reaction time and accuracy), GPS-derived match running metrics, countermovement jump (CMJ), foot tapping (TAP), and haematological markers.
Yo-Yo IR2 performance significantly improved in the RHO group (p = 0.012) and was superior to the placebo group (p = 0.046). For RSA, mean sprint time improved significantly from pre- to post-intervention in the RHO group (p = 0.017), whereas no significant change was observed in the placebo group. Post-intervention, mean sprint time was significantly better in RHO than placebo (p = 0.041), with no between-group difference observed at baseline. Best sprint time showed no between-group difference (p = 0.723). Post-exercise blood lactate concentrations were significantly lower in RHO than placebo at 0, 3, and 5 min (all p < 0.05). Under fatigue, the RHO group demonstrated faster reaction time (p = 0.042) and higher decision accuracy (p = 0.049) than placebo. Additionally, the RHO group showed significant pre- to post-intervention improvements in passing and shooting performance (p < 0.05), with between-group differences observed only for short-pass performance. Match total and high-speed running distances were higher in RHO, accompanied by increases in haemoglobin and haematocrit (p < 0.05).
The authors concluded that four weeks of Rhodiola rosea supplementation enhanced high-intensity intermittent performance and decision-making under fatigue, with findings suggesting improved performance maintenance rather than increased peak sprint capacity.
Rhodiola rosea is a perennial flowering plant that grows in cold, high-altitude regions of Europe and Asia. It allegedly functions as an adaptogen—a natural substance that helps the body “adapt” to stressors. The plant contains bioactive compounds like rosavins and salidrosides. These are thought to modulate the body’s stress response system and increase the efficiency of energy production in the mitochondria. Rhodiola is also believed to prevent the breakdown of neurotransmitters like dopamine and serotonin, helping athletes keep their “head in the game” even when their legs are tired.
As we will soon see the start of the World Cup, some will ask whether professional players can legally use this method to enhance their performance. As of the 2026 WADA Prohibited List (which governs FIFA and the World Cup), Rhodiola rosea is not a banned substance. It is categorized as a dietary supplement or herbal aid. Yet, even though it is legal, elite players should be careful for two reasons:
- Cross-Contamination: Many herbal supplements are manufactured in facilities that also handle banned stimulants. If a “legal” Rhodiola pill is contaminated with a trace amount of a banned substance, the player still faces a ban.
- The “Monitoring Program”: WADA often puts substances on a “Monitoring Program” list before banning them. While Rhodiola isn’t currently there, caffeine (which was once banned) is a reminder that the rules for natural stimulants can shift over time.
So, would I advise World Cup footballers to take Rhodiola rosea?
No – not so much because of the reasons just mentioned, but because the findings of the above-quoted tiny study obviously require independent replication before we can take them seriously.
Debates on researching SCAM frequently hinge on the tension between theoretical plausibility and empirical testing. The central question is this: should interventions that contradict well-established scientific principles nonetheless be subjected to clinical trials? This issue raises fundamental concerns about the allocation of research resources, the epistemology of medical science, and the boundary between scientific openness and credulity.
In medical research, plausibility refers to the compatibility of a treatment’s purported mechanism of action with established biochemical and physiological knowledge. Treatments such as homeopathy, reiki, bioresonance, etc., etc. are typically judged to be implausible because their mechanisms violate basic physical principles (Ernst, 2010; Offit, 2013). One could argue that conducting randomized clinical trials (RCTs) on such interventions is methodologically and ethically questionable, as the prior probability of efficacy is exceedingly low (Goodman, 1999) and the probability of a positive result obtained with a rigorous trial approaches zero. Framed in Bayesian terms, if a hypothesis begins with a negligible prior probability, even seemingly positive trial outcomes are unlikely to meaningfully change its posterior credibility (Spiegelhalter, 2019).
But insisting that only theoretically plausible hypotheses merit empirical testing risks scientific conservatism. Medical history includes numerous examples – such as the discovery of the antipyretic and antithrombotic effects of aspirin – where therapeutic value was demonstrated before mechanisms were fully understood (Vane, 2000). Advocates of broader testing argue that empirical methods should retain the capacity to surprise theory and that excluding “implausible” ideas a priori risks reinforcing disciplinary dogma (Ioannidis, 2012). This appeal to epistemic humility emphasizes observation as a safeguard against the overreach of theoretical reasoning.
However, defenders of plausibility-based research prioritization contend that such humility must be balanced against the always finite resources for research and the ethical responsibility of researchers. Health research funding is limited, and prioritizing the study of implausible treatments may divert attention from interventions with rational mechanistic foundations and higher expected utility (Sampson, 2005). Additionally, the evidentiary record of clinical trials in SCAM demonstrates a consistent pattern: small, underpowered studies occasionally produce marginally positive results that fail replication, while systematic reviews of rigorous studies yield null or inconclusive conclusions (Shang et al., 2005; Ernst et al., 2011). In such cases, further testing is more likely to perpetuate public misunderstanding than to advance medical knowledge.
So, what is the solution? An epistemologically coherent approach, frequently advocated in evidence-based medicine, is to calibrate evidential standards to plausibility. Highly improbable claims should first demonstrate compelling preclinical signals – biochemical, mechanistic, or reproducible physiological effects – before human trials are considered (Goodman, 1999; Howick, 2011). This proportionality upholds methodological rigor without foreclosing the possibility of genuine empirical discovery. It respects Bayesian reasoning: extraordinary claims require extraordinary evidence.
Science must remain open to the unexpected yet disciplined in method and theory. Medical research is usually at its most productive when it operates between the two extremes—dogmatism that refuses to test unconventional claims, and indiscriminate empiricism that tests everything without theoretical guidance. The prudent path lies in aligning the scope of empirical investigation with scientific plausibility, ensuring openness tempered by rational constraint.
References
- Ernst, E. (2010). “A systematic review of systematic reviews of homeopathy.” British Journal of Clinical Pharmacology, 69(5), 577–582.
- Ernst, E., Pittler, M. H., Wider, B., & Boddy, K. (2011). The Desktop Guide to Complementary and Alternative Medicine. Elsevier.
- Goodman, S. N. (1999). “Toward evidence-based medical statistics. 1: The P value fallacy.” Annals of Internal Medicine, 130(12), 995–1004.
- Howick, J. (2011). The Philosophy of Evidence-Based Medicine. Oxford University Press.
- Ioannidis, J. P. A. (2012). “Scientific inbreeding and same-team replication: Type D personality as an example.” Journal of Psychosomatic Research, 72(6), 408–410.
- Offit, P. A. (2013). Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine. HarperCollins.
- Sampson, W. (2005). “Antiscience trends in the rise of the ‘alternative medicine’ movement.” Annals of the New York Academy of Sciences, 775(1), 188–197.
- Shang, A., et al. (2005). “Are the clinical effects of homeopathy placebo effects? Comparative study of placebo-controlled trials of homeopathy and allopathy.” The Lancet, 366(9487), 726–732.
- Spiegelhalter, D. (2019). The Art of Statistics. Pelican Books.
In recent decades, acupuncture has attracted extensive research spanning an astonishingly wide array of medical conditions, from chronic pain and neurological disorders to infectious diseases and psychiatric ailments. However, the proposed mechanisms of action—ranging from peripheral sensory stimulation to central nervous system modulation—fail to provide a coherent, biologically plausible explanation for efficacy across this disparate spectrum (Zhao et al., 2022; WHO, 2003).
The aim of this post is to examine the breadth of published acupuncture trials, delineate the leading scientific hypotheses for its mode of action, and outline the profound implausibility of these mechanisms universally applying to such varied pathologies, ultimately framing acupuncture as non-specific rather than a specific therapeutic modality (Meissner et al., 2019; Ernst, 2018).
Acupuncture has been subjected to thousands of randomized clinical trials (RCTs) and systematic reviews across virtually every medical specialty. A comprehensive 2022 evidence map published in BMJ Open synthesized 120 systematic reviews, encompassing 1,402 individual RCTs and addressing 77 distinct conditions within 12 broad therapeutic categories (Zhao et al., 2022). These categories include neurological disorders, musculoskeletal conditions, cardiovascular diseases, and beyond, reflecting a research enthusiasm that transcends conventional biomedical boundaries.
Neurological applications dominate, with trials targeting stroke sequelae such as hemiplegia and aphasia, vascular dementia symptoms, migraines, tension headaches, and facial nerve palsies like Bell’s palsy (Li et al., 2022; Zhao et al., 2022; WHO, 2003). Musculoskeletal trials are equally prolific, examining low back pain, knee osteoarthritis, fibromyalgia, tennis elbow (lateral epicondylitis), sciatica, shoulder periarthritis, rheumatoid arthritis, and even gouty arthritis (Li et al., 2022; Zhao et al., 2022; Choi et al., 2019; Lam et al., 2020; WHO, 2003). Cardiovascular research has probed essential hypertension, primary hypotension, and pain from thromboangiitis obliterans (Shanghai Medical Clinic, 2025; WHO, 2003). Gynecological and obstetric domains feature prominently, including dysmenorrhea, labor induction, breech presentation correction, pregnancy-related nausea and vomiting, and fertility enhancement (e.g., improved clinical pregnancy rates in IVF protocols) (Zhao et al., 2022; Shanghai Medical Clinic, 2025; Smith et al., 2021; Carr, 2022; WHO, 2003).
Acupuncture trials also extend to psychiatric conditions like generalized anxiety disorder (especially in perimenopause), depression, and other mental disturbances (Zhao et al., 2022; Zhang et al., 2025; WHO, 2003); respiratory issues such as allergic rhinitis and hay fever (Li et al., 2022; Shanghai Medical Clinic, 2025; WHO, 2003); gastrointestinal disorders including acute and chronic gastritis, biliary colic, and postoperative nausea/vomiting (Zhao et al., 2022; Shanghai Medical Clinic, 2025; WHO, 2003); urogenital and nephrological problems like renal colic and radiation-induced leucopenia (often in renal contexts) (Shanghai Medical Clinic, 2025; WHO, 2003); infectious diseases such as acute bacillary dysentery, pertussis (whooping cough), and epidemic hemorrhagic fever (WHO, 2003); pediatric applications, albeit more limited, for post-extubation pain relief and whooping cough (ClinicalTrials.gov, 2013; WHO, 2003); and oncology support for cancer-related fatigue and chemotherapy/radiation side effects (Zhao et al., 2022; Shanghai Medical Clinic, 2025). Additional niches include ear-nose-throat conditions (e.g., rhinitis), eye disorders, connective tissue diseases, metabolic/nutritional imbalances, and skin pathologies (Zhao et al., 2022; WHO, 2003).
This extraordinarily wide spectrum, drawn from seminal analyses like the World Health Organization’s (WHO) 2003 review of controlled clinical trials (WHO, 2003) and Cochrane overviews on pain (Choi et al., 2019; Lee et al., 2011), clearly demonstrates that acupuncture is considered by its proponents to be a ‘cure all’. This begs the question whether such an assumption can be reasonable. The effect sizes are typically modest, and true acupuncture is often no different from sham interventions (e.g., superficial needling at non-acupoints), suggesting limited specific efficacy (Lee et al., 2011).
The scientific literature proposes a constellation of mechanisms to explain how acupuncture might work, integrating peripheral, spinal, supraspinal, and systemic processes. These are often conceptualized through the “Neural Acupuncture Unit” (NAU) model, which posits low-threshold mechanosensitive afferents (Aδ and C fibers) at acupoints converging with brain networks to elicit bidirectional signaling (Zhang et al., 2012).
- Peripheral and Local Mechanisms. Needle manipulation is claimed to induce immediate tissue responses: adenosine triphosphate (ATP) breakdown to adenosine activates A1 receptors, dampening nociceptor firing (Kelly & Suckley, 2016); axonal reflexes release neuropeptides like substance P and calcitonin gene-related peptide (CGRP), modulating local inflammation; and stromal cells exhibit cytoskeleton remodeling, with collagen fibers “wrapping” around needles to propagate mechanical signals (Kelly & Suckley, 2016; Zhang et al., 2012; Li et al., 2025). The characteristic deqi sensation (aching, soreness) correlates with these events, potentially amplifying sensory input (Staud & Price, 2014).
- Spinal Cord Level. Ascending afferents are said to activate the gate control system, presynaptic inhibition, and diffuse noxious inhibitory controls (DNIC), releasing endogenous opioids (β-endorphin, enkephalins, dynorphins), serotonin, norepinephrine, and acetylcholine to suppress nociceptive transmission in the dorsal horn (Kelly & Suckley, 2016; Zhang et al., 2012; Staud & Price, 2014). This underpins analgesia and autonomic regulation, such as reduced sympathetic outflow (Kelly & Suckley, 2016).
- Central Nervous System Modulation. Functional neuroimaging (fMRI, PET) reveals deactivated limbic hyperactivity (amygdala, anterior cingulate), normalized hypothalamic-pituitary-adrenal (HPA) axis activity, and enhanced prefrontal connectivity, particularly in pain, stress, and mood disorders (Kelly & Suckley, 2016; Zhang et al., 2012; Wang et al., 2025). Top-down expectancy modulates descending inhibitory pathways, integrating with reward and mirror neuron systems (Zhang et al., 2012).
- Systemic and Humoral Effects. Acupuncture is also thought to influence immune homeostasis by shifting cytokine profiles (e.g., ↑IL-10, ↓TNF-α, ↓IL-6), autonomic balance (vagal enhancement), and endocrine axes, providing a basis for visceral, metabolic, and inflammatory conditions (Kelly & Suckley, 2016; Li et al., 2025). Recent integrative studies emphasize network pharmacology, where multi-point stimulation perturbs interconnected pathways (Li et al., 2025).
These potential mechanisms have been empirically observed in animal models and/or human imaging studies. They might offer a partial rationale, primarily for analgesia and stress-related syndromes (Kelly & Suckley, 2016; Zhang et al., 2012). The question, however, is whethr they can provide a full explanation for acupuncture’s efficacy in all the above-named conditions.
No synthesis of these mechanisms plausibly accounts for acupuncture’s claimed benefits across unrelated conditions, exposing a core scientific paradox. Musculoskeletal pain might align with local adenosine/opioid effects and spinal gating (Kelly & Suckley, 2016), but how do these explain microbial clearance in bacillary dysentery, hypertensive vascular remodeling, or synaptic imbalances in major depression? (Meissner et al., 2019; Ernst, 2018). Gynecological infertility involves ovarian endocrinology, distant from needle-evoked sensory cues; infectious pertussis implicates Bordetella immunity, not HPA modulation (WHO, 2003; Meissner et al., 2019). This biological implausibility echoes homeopathy critiques: a single intervention cannot verifiably target such heterogeneous pathophysiologies without invoking non-specific forces (Fabrizio et al., 2010).
Trial data reinforce these doubts: meta-analyses consistently show that verum acupuncture is hardly different from sham acupuncture, and sham elicit up to 80% of verum’s effects (Kelly & Suckley, 2016; Meissner et al., 2019; Fabrizio et al., 2010; Kaptchuk et al., 2013). Such considerations implicate patient and therapist expectations, therapeutic ritual, and patient-practitioner alliance as the true mechanism behing the observed outcomes (Meissner et al., 2019; Kaptchuk et al., 2013). Neuroimaging effects often mirror expectancy manipulations in non-needling studies, suggesting top-down confounds (Fabrizio et al., 2010). Lab phenomena (e.g., adenosine release) occur but yield trivial clinical effects, dwarfed by psychosocial amplification (Fabrizio et al., 2010).
Acupuncture’s elaborate ritual maximizes contextual healing, outperforming inert pills but lacking disease-modifying specificity (Meissner et al., 2019; Ernst, 2018). Paradoxes abound—positive preclinical signals evaporate in blinded RCTs; cultural bias inflates Asian trial positives; poor sham penetration and blinding failures perpetuate illusions (Fabrizio et al., 2010; Ernst, 2018). For non-pain conditions, evidence thins further, with publication bias and flexible outcome reporting inflating apparent successes (Fabrizio et al., 2010).
Acupuncture carries risks including minor issues like bleeding, needle site pain, vegetative reactions (e.g., dizziness or nausea), and symptom aggravation, alongside rarer serious events such as pneumothorax, infections, or organ injury. Overall, at least one adverse event in 9.31% of patients undergoing a treatment series or 7.57% of treatments, with half of these being mild local reactions. Serious adverse events seem to be uncommon. Reliable prevalence figures do not exist because there is no adequate surveillance system in place (Ernst 2006).
Acupuncture’s trial proliferation signals cultural and patient-driven demand rather than mechanistic or evidential triumph. Its broad therapeutic claims by far overreach evidence (Staud & Price, 2014). Rigorous advancement would require objective biomarkers (e.g., cytokine assays, EEG), dose-response optimization, adaptive sham designs, and large pragmatic trials stratifying contextual from specific effects (Zhang et al., 2012; Fabrizio et al., 2010). Until compelling evidence exists, acupuncture remains a testament to human suggestibility’s power, but not a biomedical panacea.
References
- Carr, D. (2022). Acupuncture as Treatment for Female Infertility. Medical Acupuncture, 34(1), 12-21.
- Choi, D., et al. (2019). Cochrane reviews on acupuncture therapy for pain: a snapshot of the current evidence. Systematic Reviews, 8, 231.
- ClinicalTrials.gov. (2013). Pediatric Laser Acupuncture and Renal Biopsy (NCT01879826).
- Ernst, E. (2006). Acupuncture–a critical analysis. J Intern Med, 259(2):125-37.
- Ernst, E. (2018). Acupuncture Research: The Problem. Pain Medicine, 19(6), 1287-1288.
- Fabrizio, P., et al. (2010). Paradoxes in Acupuncture Research: Strategies for Moving Forward. Explore (NY), 6(4), 231-239.
- Kaptchuk, T. J., et al. (2013). Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, or Placebo Needle in Irritable Bowel Syndrome. PLoS ONE, 8(7), e67485.
- Kelly, R., & Suckley, S. (2016). Mechanisms of acupuncture. European Journal of Integrative Medicine, 20, 1-11.
- Lam, M., et al. (2020). Acupuncture and Chronic Musculoskeletal Pain. Medical Acupuncture, 32(6), 357-366.
- Lee, M. S., et al. (2011). Acupuncture for pain: an overview of Cochrane reviews. Chinese Journal of Integrative Medicine, 17(3), 187-189.
- Li, T., et al. (2022). Evidence on acupuncture therapies is underused in clinical practice. Frontiers in Medicine.
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- Meissner, K., et al. (2019). Acupuncture for the Treatment of Pain – A Mega-Placebo? Frontiers in Neuroscience, 13, 1119.
- Shanghai Medical Clinic. (2025). WHO Approved Acupuncture List of Conditions.
- Smith, C. A., et al. (2021). An Overview of Systematic Reviews of Acupuncture for Respiratory Diseases. Frontiers in Public Health.
- Staud, R., & Price, D. D. (2014). Acupuncture therapy: mechanism of action, efficacy, and safety. International Review of Neurobiology, 111, 171-189.
- Wang, L., et al. (2025). Possible antidepressant mechanism of acupuncture. Frontiers in Neuroscience, 19, 1512073.
- WHO. (2003). Acupuncture: Review and Analysis of Reports on Controlled Clinical Trials.
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- Zhang, Y., et al. (2025). Patient-reported outcome tools of acupuncture clinical trials. Journal of Pain Research.
- Zhao, C., et al. (2022). Evidence mapping and overview of systematic reviews of the effects of acupuncture therapies. BMJ Open, 12(6), e056803.
