Avoiding cholinesterase inhibitors

Many foods and pesticides added to foods contain cholinesterase inhibitors (CIs).  I endeavor to reduce exposure by eating organically grown foods as much as possible, and by avoiding foods which naturally contain cholinesterase inhibitors in their tissues (listed below).  I suspect that this avoidance has helped reduce various issues I associate with cholinergic excess.  I can't say that for sure since I also made other dietary changes at the same time (avoiding processed food, for example), but it's my best working hypothesis and others report improvement on nightshade avoidance as well.  (Good, fairly recent article here.)

According to the best sources I can find (unfortunately dating from the 1980s), these chemicals can build up in your tissues and only slowly be released, so it may take a few weeks before you notice improvement.  You may see some improvement by only avoiding obvious sources of nightshade in your diet.  However, according to Dr. Norman Childers, some people find that symptoms only go away after successfully eliminating even trace amounts.  See the section below on "hidden nightshades" for where these are found. 

Other substances, such as fluoride and choline, may also be of concern for people sensitive to cholinesterase inhibition.  These are explained in greater detail below.

I would be very interested to hear back from people who try this and what results they see.  Please leave comments here.

Cholinesterase inhibiting foods


The following table summarizes the foods I have found listed as containing cholinesterase inhibitors by various sources.  I am most confident of those listed as nightshades (box 1), as those are the best documented.  I endeavor to strictly avoid them, whether overt or hidden, and anything that I know has touched them.

I haven't been able to figure out what source Gloria Gilbère is basing her non-nightshades containing SGA list on (box 2).  I haven't got around to trying any of them myself yet, but may one day (blueberries, okra, artichokes).

The references I can trace for Silverstone (box 3) are old and somewhat ambiguous.  The ones I personally eat frequently and haven't noticed a problem with are in green italics.  The ones I eat small amounts of occasionally and haven't noticed a problem with are in blue italics (though this is far from definitive: in the case of apple I've only tried it once).  The ones I tried and backed off from because my guts didn't seem happy after eating them (though that may be due to factors other than CIs, or just be coincidence) are in red italics.  The rest I haven't tried yet, or in the case of "vegetable marrow", can't find a consistent translation of what it means (some say pumpkin, some say zucchini).  

 Category    Foods Source
 Notes
Nightshades: Family Solanaceae
Potato, tomato, eggplant, peppers*, paprika, pimento, tomatillo, goji berries, garden huckleberry,
 Numerous
Can determine if given plant is nightshade by searching for botanical information and looking at family name
Non-nightshade containing SGA 
 Blueberries, okra, artichokes
Gloria GilbèreI am interested in learning how she determined this and whether anyone else has verified these findings
OtherAsparagus, broccoli, carrot, cabbage, celery, radish, pumpkin, raspberry, vegetable marrow, orange, strawberry, turnip, apple Silverstone 1985, p. 46
I am interested in learning how he determined this and whether anyone else has verified these findings
* Just about everything with "pepper" in the name is nightshade.  The exceptions I know of are black pepper and all the various colors of peppercorns (family Piperaceae), sichuan pepper, and japanese pepper (different parts of the same plant in family Rutaceae).  The ambiguity, as far as I can tell, stems from  Columbus being better at self-promotion than botany.

Hidden nightshades

In addition to obvious sources of nightshade exposure, there are other sources which are less obvious and are often not explicitly included in ingredient lists.  Potato starch, paprika, and peppers are the ones most often hidden this way.  Both Dr. Norman Childers and Gloria Gilbère have written books containing extensive lists of places people have noticed these hidden nightshades:   Arthritis-- Childer's Diet That Stops it, and Invisible Illnesses.  These include:
  • Breads, pastries, and pasta may contain potato starch or potato flour.  In particular, gnocci definitely contain potato.
  • Many bottled sauces, including worchester sauce, contain tomato.
  • Ingredient lists on food containing the phrases "spices," "seasonings,"  or "natural flavors" may contain peppers or paprika (and possibly MSG, which is another reason to avoid foods with these ingredients)
  • Ingredient lists on food, vitamins, and supplements containing the phrases "starch", "food starch" or "modified food starch" may contain potato starch. 
  • Pharmaceutical drugs may contain potato starch, and do not list these as they are considered "inactive" ingredients.  Be particularly careful about generics -- they may contain potato starch even if the name brand versions do not.  It is usually necessary to call the manufacturer to find out about this.
  • Envelope glue may contain potato starch
  • According to Dr. Norman Childers, Vitamin C may be sourced from nightshade plants.  I'm also suspicious of supplements containing lycopene (see below), since tomatoes are the most likely source for it.  If you are taking supplements containing these it might be a good idea to ask the manufacturer where they're sourced from.
I've also noticed potato starch in some instances of baking powder, buttermilk, and probiotics (such as Primadophilus Reuteri).  Sometimes one product will have potato starch in it and another similar product by the same manufacturer wont.  From what I can tell, things labeled "gluten free" are even more likely to contain potato starch than non gluten free variants of the same item.  I always check the labels.  

My rule of thumb is to assume the worst of all processed foods -- the majority of them I've checked have either overt nightshade or some sort of ambiguous "starch", "spices", or "flavors."

Other substances inhibiting cholinesterase or of concern to those sensitive to CIs

The following non-food substances either themselves inhibit cholinesterase, or have been implicated as being of particular concern to people who are sensitive to CIs and/or nightshades.  When I want don't know if a given product contains cholineterase inhibitor, I mostly do a google search on the name(s) of unfamiliar ingredient(s) and "cholinesterase inhibitor" to check.
  • Pesticides: Many classes of pesticides, including organophosphates and carbamates, are CIs.  These are used extensively in conventional agriculture to control pests, and are also present in many home and garden pest control products.  According to Dr. Norman Childers, they do not just sit on the outside of the fruits and vegetables they are used on, but are also absorbed into their tissues.  This means that washing, while helpful, only reduces and does not fully remove these residues.  He recommends eating organically grown food as much as possible to minimize exposure.  Be aware that you can also absorb these substances through skin contact and inhalation.  For more info on CI pesticides see http://extoxnet.orst.edu/tibs/cholines.htm
  • Herbicides: Some herbicides, particularly RoundUp, are implicated as inhibiting cholinesterase.  See http://www.naturescountrystore.com/roundup/page7.html for more info.
  • Succinylcholine is used in anesthesia as a muscle relaxant.  It depends on BuChE to break it down and restore muscle function in a timely fashion.  Certain polymorphisms of the BCHE gene, particularly Rs1799807, Rs28933389 and Rs28933390, are known to alter the behavior of this process, and can cause problems such as apnea and/or delayed recovery following use of this drug.  These polymorphisms may also affect CI sensitivity, so if you know or suspect you have CIS you should bring this topic up with your doctor before undergoing anesthesia.  More references on this topic can be provided on request.
  • Fluoride may inhibit cholinesterase.  I have seen this referred to, but have been unable to find a good source to confirm this or give details.  It is referred to in two SNPs of the BCHE gene: Rs28933389 and Rs28933390.  Presumably people with mutations in either of these SNPs are particularly sensitive to cholinesterase inhibition due to fluoride.  I don't know if others with CI sensitivity are also at risk from this, but I filter tap water as much as I can and avoid fluoridated toothpaste as a precaution.  Fluoride is one of those unfortunate topics that's gotten tainted by being associated with people in tin foil hats.  However, I have studied enough chemistry and biochemistry to respect the idea that exposure to fluoride and bromide isn't a good idea.  There are a lot of crucial functions, particularly those related to thyroid function, which are mediated by the iodine receptor.  Fluoride, bromide, and iodine are all halides (in the same column of the periodic table).  My understanding is that all of them are happy to hang out in the iodine receptor (receptor affinities often aren't very specific), but things only work properly when only the occupant is iodine.  
  • Choline is a component of acetylcholine which is included in certain nutritional supplements, vitamins, and energy drinks.  I've encountered anecdotal reports of people associating increased anxiety with times they were taking choline-containing supplements.   Presumably it could do this by altering the rate or amount of acetylcholine synthesis, but I don't understand enough about how that regulation mechanism to know how plausible this would be, or what dosages of choline people were taking when they noticed potential issues.  Chris Masterjohn, who seems to know what he's talking about, says that eating plenty of foods high in choline, such as eggs and liver, is important to protect against fatty liver disease.  I eat lots of eggs and liver, and have never had a problem with it.  So, pending further information, I stay away from supplements containing choline, but consider its presence in real food a plus.
  • Lycopene, which is pretty common to find in supplements, may also be a concern since the most obvious source would be tomatoes.  My one attempt to contact a supplement manufacturer to find out where it was sourced failed.  Pending more information, I just stay away from supplements containing it.  
  • Pyridostigmine Bromide (PB) is a reversible CI (a carbamate) used as treatment for myasthenia gravis and as a prophylactic measure when soldiers are potentially going into a situation where they may encounter nerve gas (which are mostly irreversible CIs).  People who are sensitive to CIs, such as those with variant BCHE and/or PON1 genes, may be more susceptible to PB.  (They're also more susceptible to the nerve gas itself, but that's not very relevant -- everyone avoids that if they can, and is likely dead if they can't.)  This is suspected to be a factor in Gulf War Syndrome.
  • Pyrethroid insecticides and DEET, a common insect repellent, are reported to synergize with CIs.  The original source at http://www.mgfa-mgnet.org/html/insecticide.htm is unfortunately gone now, but happily a version from 2009 was captured by the Internet Wayback Machine.  It says that exposure to these can exacerbate issues of CI exposure and that these  suspected to be factors in Gulf War Syndrome.  Another article at Beyond Pesticides reports that DEET itself inhibits cholinesterase as well.
  • Vitamin A acetate is a synthetic form of vitamin A which is often found in milk, cereals, and vitamin supplements.  Dr. Norman Childers warns that people sensitive to nightshade should avoid this form of vitamin A and opt instead for products containing beta carotene, the version of vitamin A found naturally in food.  I don't understand his basis for making this suggestion, but figure he's been working with nightshade sensitivity for 50 years more than I have, so I'll bow to his greater experience in this area.  Other sources, such as Chris Masterjohn, say that not everyone is good enough at converting beta carotene to vitamin A, that keeping the ratios of vitamins A and D from getting too skewed is important, and that therefore natural sources with a good balance of natural A and D, such as liver, butter, or cod liver oil, is the way to go.
  • Vitamin D: Dr. Childers suggests that those sensitive to nightshade be careful about excessive vitamin D supplementation.  He  suggests instead that they get vitamin D from sunlight (which, of course, is a controversial topic because of skin cancer risk) since the mechanism by which the body produces vitamin D from sunlight runs less risk of developing toxicity.  For more info on his views on this point, read Arthritis-- Childer's Diet That Stops it.  

    Garrett Smith has a more recent article where he says that nightshade plants contain 1,25(OH)D3, which is the form that directly affects calcium homeostasis.  The body usually controls 1,25 (OH)D3 very tightly, and interference with that control loop could account for Dr. Childers' observations of soft tissue calcification in animals that consume nightshade.  Based on what Chris Masterjohn says, heavy vitamin D supplementation also requires enough Vitamin A intake to balance it (see previous bullet point), and enough K2 to properly deal with directing calcium towards the bones and away from soft tissues.  So that too may be part of what led Dr. Childers to be suspicious of D supplementation (the people/animals Dr. Childers observed having problems may have had inadequate intake of Vitamins A/K2, or the wrong kind).  Finally, there may be a difference in outcomes between supplementing with D2 (derived from plants) and D3 (created by animals from sunlight).  Dr. Stasha Gominak says in this youtube video lecture that she has seen bad results with D2 and good results with D3.  She attributes the use of D2 to be a flawed interpretation of old rat studies.  She speculates that rats, being nocturnal grain eaters, may be able to do fine metabolizing D2, which occurs in molds which grow on grain, whereas we can't.  The vitamin D in many supplements, particularly low end ones, and in high-dose prescription formulations, is D2.  

    I avoided supplemental D based on Dr. Childers' advice for a while, but during the fall of 2009, after about a year and a half of avoiding SGA-containing foods, I decided to try vitamin D3 supplementation anyway.  This turned out to have been a good choice for me at that time -- it increased energy and made me much more able to function (likely because I was deficient at that point).  There is a lot of contradictory information on this topic, but the most reasonable sounding take on this that I have found is from the Vitamin D council.  They suggest vitamin D3 supplementation when needed, and regular testing of 25(OH)D levels to keep it in an appropriate range (they suggest 50–80 ng/mL year-round).  I have seen it recommended to test in the fall after solar UVB have dropped below useful levels and in spring before you start getting significant sun exposure.  The idea is to be able to gauge your winter supplementation levels to see if they are resulting in an increase, decrease, or stable vitamin D levels during the winter.  Less supplementation may be required in the summer, since then you may be helped by direct sun exposure (glass blocks UVB so sun through a window doesn't help).  How much vitamin D you get from the sun depends on latitude, time of year, skin pigmentation, how much time spent in the sun, and how much skin is exposed and free of sunscreen (which blocks UVB and hence vitamin D production).  Another thing to keep in mind is that it takes time after sun exposure to reabsorb the converted oils back into your skin.  Dr. Douillard of http://www.lifespa.com suggests waiting about an hour after sun exposure before taking a shower or bath to allow the vitamin D to absorb into your body rather than just being washed off.  

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Please leave comments here if you have relevant experiences to share, or if there are points which require further clarification.  Thanks!
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