In March Clay Jones reported on an unfortunate case of a 55 year-old Spanish woman who died after receiving bee venom acupuncture. This week the Food Standards Agency (FSA) has ordered New Zealand company Nelson Honey & Marketing to stop selling pots of honey laced with bee venom in Britain. Their reason is that the venom has not been demonstrated to be safe for oral consumption.
In short, bee venom is the new snake oil. The term “snake oil” has come to refer generically to fake medicine because actual oil made from snakes was popular in the 19th century, and more recently in Traditional Chinese Medicine, as a patent medicine. Perhaps in a hundred years people will be referring to “bee venom salesmen” the same way we refer to their snake-oil counterparts today.
The use of bee venom and bee products as a medicine is referred to by believers as “apitherapy.” This is a great example of the appeal to nature fallacy – bee venom is sold with the idea that because it is “natural” it is somehow superior as a therapeutic. Marketing of a health halo around anything considered vaguely natural has been so thorough that many people think voluntarily injecting themselves with venom (by definition a “poisonous substance”) is a good idea. Venoms evolved to be efficiently deadly. They are a great example of why being natural does not equate to being benign.
Venoms can be exploited as pharmaceuticals, because they contain potent drugs. Once identified, purified, studied, and tweaked as necessary, and then given in specific doses, they might be useful. Raw venoms, however, tend to be a witches brew of multiple poisonous substances meant to cause harm to the victims that are injected with them. Here is a chemical breakdown:
Bee venom is a mixture of histamine, pheromones (discussed on the pheromone page), enzymes, peptides, amino acids and other acids, with 63 components in total. The main enzymes present are phospholipase A, hyaluronidase, and lecithinase; while the main peptides are mellitin, apamin and peptide 401. Bee venom is cytotoxic (ie. cell-destroying), and has the contradictory effects of inhibiting the nervous system, while stimulating the heart and adrenal glands.
Mellitin, a 26 amino acid peptide, makes up 50% of the dry weight of bee venom, and acts to destroy blood cells by breaking up their membranes. It also lowers blood pressure, causes histamine release, and is the main pain-causing component.
Sounds lovely. I particularly like the part where the venom destroys blood cells by breaking down their membranes. Of course, the body responds to this outright attack by releasing countermeasures. Cortisol is released as an anti-inflammatory, for example. That is often used as the justification for using bee venom, to provoke the body’s response. Plausibility here, however, is extremely thin. The chemical assault is likely to be worse than the response, and this is an awfully crude way to release cortisol in the body. Why not just give corticosteroids in precise doses, bypassing the venom? Any trauma, of course, will provoke a healing or compensatory response, and the alternative guru can always point to markers of healing as the mechanism of any claimed benefit. This logic assumes that the response will somehow be greater than the original trauma, an assumption that does not really make sense or hold up to investigation.
What about the scientific research? Here we find the typical results anyone familiar with alternative pseudoscience should expect. Most studies of bee venom are basic science, meaning they are looking at markers of biological activity in vitro or in animals. This research is all interesting, and entirely unsurprising. As I noted, bee venom evolved to be highly biologically active, and the research finds that it is indeed highly biologically active. There is definitely potential here to isolate useful compounds.
However, basic science studies such as these cannot be used as a basis for clinical claims. The vast majority of interesting effects seen in basic science studies do not translate to useful clinical outcomes. There are many things that can go wrong on the way from the petri dish to the clinic. These include low bioavailability, poor pharmacodynamics or kinetics, short half-life, drug-drug interactions, and excessive toxicity.
Therefore we need clinical studies to see the net effects of using a particular form of a substance in people with the target condition. There are a number of such studies with bee venom, again showing an all-too-familiar pattern. Let’s look at so-called bee-venom acupuncture (BVA) – which conveniently combines two pseudosciences into one treatment.
Acupuncture itself, the sticking of thin needles into alleged acupuncture points, does not work for anything. Proponents, however, have tried to keep this superstition alive by combining with other actual treatments, such as “electroacupuncture.” I used to joke that you could inject morphine into acupoints and call it “pharmacoacupunture.” That is essentially what BVA is, except with snake oil rather than an effective drug.
There are several published reviews of BVA for painful conditions. For musculoskeletal pain the review concludes:
A meta-analysis produced suggestive evidence for the effectiveness of BVA in musculoskeletal pain management. However, primary data were scarce. Future RCTs should assess larger patient samples for longer treatment periods and include appropriate controls.
For post-stroke shoulder pain:
This review provided evidence suggesting that BVA is effective in relieving shoulder pain after stroke. However, further studies are needed to confirm the role of BVA in alleviating post-stroke shoulder pain. Future studies should be conducted with large samples and rigorous study designs.
For rheumatoid arthritis:
There is low-quality evidence, based on one trial, that BVA can significantly reduce pain, morning stiffness, tender joint counts, swollen joint counts and improve the quality of life of patients with RA compared with placebo (normal saline injection) control. However, the number of trials, their quality and the total sample size were too low to draw firm conclusions.
The pattern is the same regardless of indication – there is scant and low grade evidence suggestive of an effect, but we can’t really conclude that it works because of the lack of rigorous data. I suspect there is a reason why this pattern is so ubiquitous when it comes to dubious “alternative” treatments. Proponents figured out that when you do really rigorous studies, they frustratingly tend to be negative. Far better to do a preliminary study with a weak design, that way you can p-hack your way to whatever result you want. This is especially useful when using subjective outcomes, like pain.
Every poorly designed or small study is another headline, promoting the alternative treatment. But we never get across the finish line – we never get to the point that we have reproducible high quality evidence for efficacy.
Further, many of the studies used in these systematic reviews come from China or Chinese researchers. This is a problem because of the demonstrated bias in this research. A 2014 update of prior research found that 99.8% of acupuncture studies from China report positive results. That is clear evidence of a positive bias, and is even suggestive of fraud. There is simply no way to get near 100% positive results from clinical trials, even for an effective treatment, without putting a massive thumb on the scale. Yet this clearly biased research is always included in systematic reviews, with predictable results.
Here is a clear example of such bias, from a BVA study of back pain. The authors begin:
Bee venom acupuncture (BVA) is an effective treatment for chronic low back pain (CLBP) through the pharmacological effects of bee venom and the simultaneous stimulation of acupoints. However, evidence of its efficacy and safety in humans remains unclear.
See the contradiction? BVA is effective, but the evidence is unclear. Then how do you know it is effective? They essentially naively admit in their own write-up of the study that the point of the study was to confirm what they already knew to be true, that BVA works. In this case the research comes from Korea, which has almost as strong a positive bias toward acupuncture as China.
There is a reason for advocating for a relatively high threshold of evidence before accepting a new treatment and integrating it into the practice of medicine. We know have over a century of experience using science to determine which treatments are safe and effective. We can look back over this long experience and reasonably determine where that threshold should be. We can clearly see that when we use a lower threshold, we end up adopting treatments that are likely to not work when the definitive evidence comes in. In short, we cause more harm than good.
Alternative treatments such as acupuncture (with or without bee venom) live below this threshold. They thrive in a world of low quality clinical studies where p-hacking can thrive, and researcher bias reigns. It is unfortunate that this alternative world has so thoroughly infected mainstream medicine, largely sneaking in under the radar by pretending to be scientific. Meanwhile the academics and experts who should be gatekeepers are asleep at the switch.