Inflamed planet: do chemicals explain some pain? (Member Post)

A bit more about detox quackery

I would be interested in detoxing … if I thought it were possible.

At least three times in the last few years I have endured several days of thick smoke in Vancouver. Days of “unhealthy” or “very unhealthy” and sometimes even “hazardous” smoke, with Air Quality Index scores from 150 to 350 that spell unavoidable physiological stress even at the low end. Some prevention is possible (air filters), but treatment? De-toxing what I’ve inhaled? If only!

Unfortunately, we mostly just cannot “detox” much of anything beyond what our organs already do for us (which is quite a bit, but humans can still easily be poisoned). There are only a handful of specific medical treatments for some kinds of poisons, such as anti-venoms or chelation therapy. The massive detox industry is almost pure bullshit, along with basically all popular beliefs about detoxing. For instance, we cannot sweat out toxins,2 or suck them out of our bodies with Epsom salts baths.3

But, like every good scam, detox quackery is based on a seed of truth, and this particular seed is unusually robust and sad: our world is badly polluted, an uncontrolled experiment on a brain-breaking scale. And our food system isn’t exactly pristine either! Trans fats alone are probably worse than several other candidates put together.

I am painfully aware that “it’s the chemicals” is the message many readers will take from this, no matter how much I protest that we really truly do not and cannot know at this time — but we really don’t, and we really can’t.

The major environmental pollutants

Pollutants in the air, water, and food supply are probably most of what people hope to purge when they do a “detox.” People who talk about detoxing are almost never specific about what toxins, exactly, they are talking about. If they knew enough, what should they be talking about? There are four main candidates from the last few decades …

• The persistent organic pollutants (POPs): pesticides, flame retardants, and polychlorinated biphenyls (the notorious PCBs, now banned, but formerly ubiquitous in many a plastic piece of crap). They include well-known dangerous chemicals like DDT and dioxins, along with dozens of more obscure examples. There is a broad scientific consensus that these are hazardous substances, but the practical public health risk varies greatly with the details.4 But there sure are a lot of them, with collectively substantial risk.
• “Forever chemicals,” the per- and poly- fluoroalkyl substances (PFAS), all combine fluorine with carbon-hydrogen (alkyls); they started with Teflon and have since ballooned into an immense family of (I’m not joking) several million distinct chemicals. There are a lot of ways to combine fluorine with alkyls! This is a disturbing POP subcategory that is still defined by scientific uncertainty: only about 10% of PFAs have been studied for health effects as of 2024, and most of those not enough.5 In most cases we know little or nothing about the hazard, and even less about the risk. But we certainly know that they are all around us, not going anywhere, and some widespread harm is plausible.
• Heavy metals, mainly lead! Lead is a useful element that happens to absolutely mess with animal physiology, known for being harmful at literally any dose, no matter how small.6 It might seem like a quaint, old-timey thing that we don’t have to worry about much anymore, but … nope, unfortunately it is still an alarmingly common pollutant, doing plenty of harm. It accounts for (very roughly) half of the known damage from all tracked chemical hazards.7 This hazard and risk are as real and serious as a heart attack … and in fact, weirdly, heart disease is one of the main effects of lead.8 The mechanism? Basically inflammatory. Acute lead poisoning is relatively rare, but it’s fair to guess that long-term exposure to small, accumulating doses is a significant health headwind that makes a small but relentless contribution to inflammaging in a great many of us, and more in an unlucky minority.
• Traffic-related air pollution, and especially diesel exhaust with its sub 100 nanometre “ultrafine” particles, is a well-documented health hazard, that we nevertheless probably continue to underestimate. A good example from some researchers local to me: just breathing diesel exhaust immediately alters brain function! Which is disturbing because that’s not supposed to be possible.9 The result challenges an old assumption that the brain is likely safe from direct pollution damage, thanks to the blood-brain barrier. The authors reckon that the ultrafine particles are either getting in “via the olfactory bulb and/or secondary transmission of inflammation,” circumventing the barrier.10

Cleaning the air

A little ray of light on this dark topic: we can reduce the risks of air pollution significantly. We have the technology! Cleaning indoor air is one of the best bang-for-buck options we have for protecting ourselves from air pollutants.

For instance, I have lovely, smart Corsi-Rosenthal boxes powered by computer fans, a very efficient DIY air filter design which can move a lot of air surprisingly quietly. And with air quality, “clean air delivery rate is all that matters!”

This is my handmade (from a kit) Corsi-Rosenthal box, which uses PC fans for quiet-but-high-volume air movement through the filters. There’s another filter on the other side of the box.

Unfortunately, the air-cleaning industry is choked with bullshit and misleading claims, and many products are just junk (including some expensive ones). You need a trusted guide. I strongly recommend the “It’s Airborne” blog, by Joey Fox, which does a superb job of filtering out the nonsense. Start with his list of favourite air cleaners. (← Not an affiliate link! I don’t do that. And that’s partly why you pay me for this content — so that I can afford to make recommendations like this without the corruptive force of kickbacks.)

Microplastics … and nanoplastics now, too

Tiny plastic garbage has been much in the news lately: dust-sized particles, microscopic ones, and now we know that there are even nano-scale particles (like diesel’s ultrafine grit). The health effects of this kind of pollution have not yet been studied well enough to know how great the danger is, but there’s plentiful plant and animal evidence so far, and plenty of cause for concern.11 But the surprisingly recent confirmation of ultrafine particles probably increases the exposure and hazard, and therefore the risk.

An important and interesting clue that microplastics might be dangerous is the extreme example of surgical meshes implanted in your body. That is not settled science — but it is definitely possible that some surgical meshes are breaking down and making some people sick. Bombarding skin, lungs, and gut with microplastics surely isn’t as dangerous as a higher dosage right in our flesh, but I doubt that it’s entirely safe either.

(There is more information about surgical implants in the full inflammation guide.)

Nanoplastics are already found in most of our fruits and vegetables.12 This kind of pollution is happening to everyone, everywhere, forever, and still accelerating, and probably cumulative. Even if it’s not a problem in the 2020s, the 2030s may be a different story.

Karimov Denis, Valova Iana, CC BY 4.0, via Wikimedia Commons.

The small green spheres in this image are microplastics particles around and inside a liver cell. They are each about 0.5 μm across — two thousandths of a millimetre. And we know they can get much smaller still. Technically, we don’t yet know if or how harmful this is, but it does seem very what-could-possibly-go-wrong?

Food additives (and other things we aren’t good at digesting)

Talking about food additives risks fanning the flames of detox quackery and chemical paranoia even more than talking about pollutants — but there is another robust seed of truth here too. We have not come unscathed through over a century of industrialization and intense commercialization of the food system. There are some prominent historical examples, and there will probably be more in the future, and for every relatively obvious example there are probably several subtle ones that will never be confirmed.

Some of the things that we put in our mouths that cause systemic inflammation will probably do so through the intermediary of irritable bowel syndrome: our guts are important, so bowel stress and dysfunction leads to more widespread problems. Most of those are probably non-specific responses to mild irritants. They don’t have to be individually “dangerous” to be of concern collectively, and this is partly why we have so much scientific uncertainty about these things — because all the attention and research goes to more sensational dangers.

• Trans fats are the best example of what puts the “junk” in junk food: partially hydrogenated oils powerfully boost cardiovascular disease risk because they exacerbate metabolic syndrome with systemic inflammation. There are many paths to metabolic syndrome, but eating piles of trans fats is taking a highway to heart disease. Although banned in a steadily growing list of countries, they are still widely used around the world… and even where banned they remain in small quantities that can still add up, especially in extremely tempting snack foods. (And junk food is still junky for other reasons, of course.)
• Manufactured citric acid is an old food additive, rather boring and old-school — it has been around for over a century in many different foods,13 so long ago that it was already old when the US FDA got going … and they just gave it a pass and its safety has never really been studied properly. And yet there are specific biological reasons to suspect that it could be mildly toxic to some people.14
• Nonceliac gluten sensitivity is a tricky topic (understatement), but one way or another it is probably an example of struggling to tolerate something we eat — if only we knew exactly what, and how. The major candidates are gluten, FODMAPs, and the amylase-trypsin inhibitors (ATIs). FODMAPs have gotten a reputation for being the real troublemaker in wheat, rather than gluten, but that’s still not clear, and we do know that FODMAPs do not cause an inflammatory reaction — an “intolerance,” not a “sensitivity.”15 But gluten and the ATIs do trigger the immune system (inflammation) in some people. All three factors likely interact in complex ways for different reasons in different people. A practical takeaway from this mess: it is reasonable to be concerned that some people do in fact have allergy-like systemic inflammation triggered by something in wheat. The problem is probably being grossly overstated by many people, but I do think it’s real. I used to roll my eyes at wheat-fear, but I stopped when I learned more.
• Milk is a classic example of one of those things that some of us just aren’t very good at digesting: good old lactose intolerance, notoriously under-diagnosed, is one of so many things that can chip away at us sneakily. Lactose intolerance is not an immune system reaction (although there are also dairy allergies that are), but “it is now [2005] clear that lactose can cause a range of debilitating systemic symptoms, in addition to the well known gut symptoms.”16 At least 50% of people with lactose intolerance report muscle and joint pain.


A Canadian brand of “cyclamate,” the least potent of the common artificial sweeteners, and the one I like the best. I use a half packet in my coffee every day. I have wondered about its effect on my digestion, but also failed to confirm anything, despite a major effort.

• Olestra/Olean is an artificial fat (sucrose polyester) that infamously causes one of the most cringe-inducing symptoms of them all: anal leakage! But that’s just the tip of the iceberg of intestinal outrage.17 It’s likely that it has systemic health effects through the intermediary of IBS. And it’s still around in related forms! The sucrose esters are mostly dead as the basis for branded fat-replacement products, but they are still widely used as a food additive in smaller and less obvious ways.
• Artificial sweeteners are perpetually controversial, their safety endlessly ambiguous. Despite all of the research and media attention, most of that has focused on carcinogenicity, and the remainder has been about hormonal/metabolic effects (e.g. do artificial sugars make us insulin-resistant). A lot of those concerns are probably over-heated, classic examples of fear-mongering about chemicals. But what about the effect of artificial sweeteners on gut health? Which might actually drive inflammaging? Scientific crickets! A 2016 review declared that we know essentially nothing, and yet there are perfectly good where-there’s-smoke-there’s-fire reasons for the research.18 This is the more plausible way that artificial sweeteners could be a problem, and yet it’s the hazard that has not been studied.

•

This post, big as it is, it just an excerpt from some major updates to a much longer guide to low-grade inflammation and inflammaging.

Last summer I added food additives to the guide, but it was pretty basic, really just a list of possibilities. This summer I returned to really beef it up … then gave the same treatment to pollutants … then added a bunch more about allergies, and added mammalian meat allergy as a really interesting example … and then got lost for a while in the surgical mesh debate and updated that section too … then mold! And then there was a wave miscellaneous improvements and edits through the whole article.

Several hours of work!

But it’s never done. What should still be added? What have I strangely overlooked? I look forward to smacking my forehead as your suggestions roll in.

Notes

1. Pain: the final medical frontier. These are the voyages of the starship Salamander. Its five-year mission: to explore strange new aches; to seek out new ideas and hypotheses; to boldly go where no pain nerd has gone before!
2. Imbeault P, Ravanelli N, Chevrier J. Can POPs be substantially popped out through sweat? Environ Int. 2018 Feb;111:131–132. PubMed 29197670 ❐
3. Epsom salt in your bath is cheap and harmless and it makes the water feel “silkier,” but it’s unlikely that it has a therapeutic effect on aches and pains. It definitely doesn’t “detox” anything. Magnesium supplementation might be helpful for some people with deficiency and chronic pain, but it probably can't soak through the skin. The soothing heat of a nice bath is probably the main source of health benefits. The case for the healing powers of Epsom salt is mostly made by people selling the stuff, or recommending it as casually and imprecisely as an old wives’ tale. See Does Epsom Salt Work? The science and mythology of Epsom salt bathing for recovery from muscle pain, soreness, or injury.
4. An important basic idea about poisons is the distinction between hazard and risk. "Hazard" is the harm that a substance would cause if you took a shower in it — how inherently nasty is it — while "risk" is the chance that you'll ever actually be exposed to enough of it to get hurt. Another way to put it: it’s the difference between how dangerous something is in theory (hazard) versus practice (risk).
5. Shirke AV, Radke EG, Lin C, et al. Expanded Systematic Evidence Map for Hundreds of Per- and Polyfluoroalkyl Substances (PFAS) and Comprehensive PFAS Human Health Dashboard. Environ Health Perspect. 2024 Feb;132(2):26001. PubMed 38319881 ❐ PainSci Bibliography 49865 ❐

   This paper is a “systematic evidence map,” a kind of scientific review, of evidence about the health effects of per- and polyfluoroalkyl substances (PFAS), AKA the “forever chemicals.”

   They looked for epidemiological and mammalian bioassay evidence that could inform human health hazard identification for 345 PFAS previously flagged by the US EPA for potential toxicity, mainly identified by in vitro toxicity — in other words, PFAs that can murder cells in a petri dish. Despite the large number of candidates studied here, there are still plenty of other PFAs to assess!

   They trolled through more than 13,000 studies were identified from scientific databases, whittling the list down to mammalian bioassay and epidemiological studies for just 41 PFAs, only about 10% of the 345 they were looking for data on.

   “No epidemiological and/or mammalian bioassay evidence were identified for most of the PFAS included in our search.”

6. WHO.int [Internet]. World Health Organization. Lead poisoning; 2023 Aug 11 [cited 24 Aug 14]. PainSci Bibliography 49870 ❐
7. WHO.int [Internet]. World Health Organization. The public health impact of chemicals: knowns and unknowns; 2021 [cited 24 Aug 14]. PainSci Bibliography 49871 ❐
8. Chowdhury R, Ramond A, O'Keeffe LM, et al. Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2018 Aug;362:k3310. PubMed 30158148 ❐ PainSci Bibliography 49868 ❐
9. Gawryluk JR, Palombo DJ, Curran J, Parker A, Carlsten C. Brief diesel exhaust exposure acutely impairs functional brain connectivity in humans: a randomized controlled crossover study. Environ Health. 2023 Jan;22(1):7. PubMed 36641507 ❐ PainSci Bibliography 49863 ❐

   Some interesting details and disclaimers:

   The precise functional impact of the changes seen in fMRI are unknown but are likely modest given the small magnitude of change, as expected with such limited exposure. That said, real-world exposures are often more persistent, particularly in regions of the world for which levels such as those we use are not uncommon. It is hypothesized that chronic exposure is effectively a series of short-term exposures (only one of which our participants were exposed to) that ultimately leads to accumulated deficits through a stress on allostatic load, but whether or not this applies to pollution in the neurocognitive realm, while hypothesized, requires further study. That being said, our results are consistent with a study of chronic air pollution exposure in Germans.

10. Gawryluk et al. elaborate a little, citing Oberdörster et al.’s animal research: “More precise mechanisms have been elusive to date, though a link to neuroinflammation (difficult to measure directly in the intact human), potentially secondary to particle migration via the olfactory bulb as seen in animal models, seems likely.”
11. Blackburn K, Green D. The potential effects of microplastics on human health: What is known and what is unknown. Ambio. 2022 Mar;51(3):518–530. PubMed 34185251 ❐ PainSci Bibliography 49860 ❐ Note that this study specifically calls out inflammation (“provoking immune responses”):

    “Whilst definitive evidence linking microplastic consumption to human health is currently lacking, results from correlative studies in people exposed to high concentrations of microplastics, model animal and cell culture experiments, suggest that effects of microplastics could include provoking immune and stress responses and inducing reproductive and developmental toxicity.”

12. Lazăr NN, Călmuc M, Milea ȘA, Georgescu PL, Iticescu C. Micro and nano plastics in fruits and vegetables: A review. Heliyon. 2024 Mar;10(6):e28291. PubMed 38545146 ❐ PainSci Bibliography 49864 ❐
13. Sodas, juices, powdered beverages, candies, frozen foods, some dairy products, and most canned produce. Here's a weird one: cheap ice.
14. Sweis IE, Cressey BC. Potential role of the common food additive manufactured citric acid in eliciting significant inflammatory reactions contributing to serious disease states: A series of four case reports. Toxicol Rep. 2018;5:808–812. PubMed 30128297 ❐ PainSci Bibliography 52323 ❐

    Citric acid is a natural substance in fruits and vegetables, but manufactured citric acid (MCA), a ubiquitous food additive. MCA is made from the fungus Aspergillus niger, which is a known cause of allergies. MCA is “generally recognized as safe” by the FDA despite a complete lack of safety research. This paper present four cases of patients with symptoms of systemic inflammation following ingestion of MCA (most likely related to the fungus used to produce it, and not the citric acid itself). They suspect that the MCA was harming these patients. Their observations do not constitute evidence of a risk, but further study may be warranted.

15. Verbeke: >“FODMAPs trigger gastrointestinal symptoms in subjects who are hypersensitive to luminal distention owing to osmotic effects, attracting water to the intestinal lumen, and bacterial fermentation, resulting in (excessive) gas production. As such, the immune system is not involved in symptom generation, and the symptoms should be classified as food intolerance rather than food sensitivity. Although intolerance to fructans and other FODMAPs may contribute to NCGS, they may only explain gastrointestinal symptoms and not the extraintestinal symptoms observed in NCGS patients, such as neurologic dysfunction, psychological disturbances, fibromyalgia, and skin rash. Therefore, it is unlikely that they are the sole cause of NCGS.”
16. Matthews SB, Waud JP, Roberts AG, Campbell AK. Systemic lactose intolerance: a new perspective on an old problem. Postgrad Med J. 2005 Mar;81(953):167–73. PubMed 15749792 ❐ PainSci Bibliography 49866 ❐
17. Kelly SM, Shorthouse M, Cotterell JC, et al. A 3-month, double-blind, controlled trial of feeding with sucrose polyester in human volunteers. Br J Nutr. 1998 Jul;80(1):41–9. PubMed 9797642 ❐
18. Spencer M, Gupta A, Dam LV, et al. Artificial Sweeteners: A Systematic Review and Primer for Gastroenterologists. J Neurogastroenterol Motil. 2016 Apr;22(2):168–80. PubMed 26932837 ❐ PainSci Bibliography 51289 ❐ “The 2 main areas on which there is data to suggest that artificial sweeteners affect the GI tract include motility and the gut microbiome.