The WHYs behind the Autoimmune Protocol: Nightshades

August 22, 2012 in Categories: by

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Tomatoes, potatoes, eggplants, sweet and hot peppers (but not black pepper), and chili-based spices (including paprika) all come from plants which are members of the nightshade family. Nightshades can be problematic for many people due to their lectin, saponin and/or capsaicin content. They tend to be even more problematic for those with autoimmune disease and of all the foods restricted in the autoimmune protocol, are probably the least likely to be successfully reintroduced, especially tomatoes and chilies.

There are over 2000 plant species in the nightshade family, the vast majority of which are inedible and many are highly poisonous (like deadly nightshade and jimsomweed). Tobacco is also a nightshade, and is known to cause heart, lung, and circulatory problems as well as cancer and other health problems (clearly some of this has to do with the other toxins in tobacco products derived from the processing). Of the edible species in the nightshade family, poisoning can actually occur with excessive consumption and it is possible that the low-level toxic properties of the nightshade vegetables contribute to a variety of health issues as they progress over time 1. So, let’s talk about two (okay, three) key compounds in nightshades that make them such a common food sensitivity and a problematic food for those with autoimmune disease.

Nightshades contain lectins. Actually, all plants (and even animals) contain some lectins, a class of sugar-binding proteins with many biological roles, including protecting plants (especially the seeds of the plant) against predation.Not all lectins are problematic (I have an entire post in the works explaining why the lectins in wheat can be such an issue but the lectins in blueberries aren’t). The lectins which we avoid in the paleo diet are the ones with the ability to increase intestinal permeability (see this post on how lectins do this). These are lectins which resist digestion (typically due to high proline content), are relatively heat-stable (so there are still sufficient quantities to cause an issue after cooking), and have the ability to strongly interact with proteins in the membrane of the cells that line the intestine (and some can even bind to receptors in those membranes and be transported intact across the intestinal barrier). There is huge variability the effect of different dietary lectins, from proinflammatory and promoting a leaky gut on one end of the spectrum to completely harmless and even potentially therapeutic on the other. Until a systematic analysis is performed of all plant lectins and their physiological effects, the foods advocated and restricted on a paleo diet really only represents our best guess based on what is known so far. So, what do we know about nightshade lectins? Tomato lectin is known to enter the blood stream relatively quickly in humans, which suggests that tomato lectin can contribute to the development of a leaky gut 2This information has led me to recommend that tomatoes should be eaten in moderation for most people. People with autoimmune disease are more likely have a leaky gut and have more challenges to healing a leaky gut once it has developed. For these sensitive individuals, tomato lectin should be avoided.

Nightshades contain saponins. The flowers, fruit, and foliage of the nightshade family contain a type of saponin called glycoalkaloids (e.g.the α-solanine and α-chaconine in potato, α-solanine in eggplant, and the α-tomatine in tomato) and contain steroidal drugs (e.g. the stimulating capsaicin in peppers, the tranquilizing nicotine in tobacco)3I explained in detail how saponins can contribute to a leaky gut in this post (also see reference 4). Very importantly for those with autoimmune conditions, saponins, such as α-tomatine, have adjuvant activity. An adjuvant is a chemical that stimulates and exaggerates an immune response. The glycoalkaloid α-tomatine is such a potent adjuvant that it is used in vaccines to ensure that the recipient develops immunity against the virus they are being inoculated against. This is critical in the discussion of autoimmune disease because dietary saponins are believed to rev up the immune response to proteins leaking out of the gut 5. When antibodies are formed against proteins (like gluten) that have amino acid sequences that look very similar to sequences of other normal proteins (like transglutaminase) in the human body, the chances of developing an antibody against one’s self increases. When this happens, the immune system attacks normal healthy proteins/cells in your own body and this is the development of autoimmunity. Beyond these actions of saponins, glycoalkaloids inhibit a key enzyme, acetyl cholinesterase, which is required for nerve impulse conduction. There is also evidence that diets high in potatoes, in particular, result in increased markers of inflammation (this could also be due to the carbohydrate load that potatoes provide and not an effect of the glycoalkaloids themselves). Glycoalkaloid poisoning can occur with excessive consumption of nightshade vegetables, and many researchers have hypothesized that the low level toxic exposure from more moderate consumption of nightshades can contribute to a variety of health conditions 1Another problematic substance is capsaicin, a steroidal stimulant found in chili peppers (it is one of the substances in peppers that give them heat). While a variety of health benefits have been attributed to capsaicin, it is also a potent irritant to a variety of tissues, including skin, eyes and mucous membranes. Very importantly, there is evidence that capsaicin can increase intestinal permeability 6.

Of all the foods restricted on the paleo diet autoimmune protocol, nightshades are the least likely to be reintroduced successfully. In fact, many people are sensitive to nightshades independent of illness or autoimmune issues.In my own experiences, two meals (on two consecutive days) containing a small amount of tomatoes nearly two months ago resulted in a massive lichen planus flare (it was also timed with some stressful life events, which I’m sure didn’t help). Two meals of tomatoes set me back months in my recovery. I am only in the last week or two starting to see some improvement to the new lesions that formed nearly overnight. While frustrating, I try and focus on the positive: I now know that tomatoes are not good for me. And avoiding them is worth it.

1 Childers N.F., and Margoles M.S. “An Apparent Relation of Nightshades (Solanaceae) to Arthritis” Journal of Neurological and Orthopedic Medical Surgery (1993) 12:227-231

2 Carreno-Gómez B et al. “Studies on the uptake of tomato lectin nanoparticles in everted gut sacs.” Int J Pharm. 1999 Jun 10;183(1):7-11.

3 Gee JM, et al “Effects of saponins and glycoalkaloids on the permeability and viability of mammalian intestinal cells and on the integrity of tissue preparations in vitro.” Toxicol In Vitro. 1996 Apr;10(2):117-28.

4 Francis G et al.“The biological action of saponins in animal systems: a review.” Br J Nutr. 2002 Dec;88(6):587-605.


6 Jensen-Jarolim E et al. “Hot spices influence permeability of human intestinal epithelial monolayers.” J Nutr. 1998 Mar;128(3):577-81.


I have recently been thought to have an autoimmune issue which has caused a flare in acne and boils on my body. When I changed my diet to take out all sugar, processed foods, nightshades, gluten, and taking curcumminoids, along with a nice hot bath several times a week and antibacterial soaps, my skin clears, I have less GI problems, and my overall mental health as well seems more stable. I have not stuck with that diet recently and all of my symptoms have returned. Additionally, I have noticed a decrease in memory ability and my language has suffered recently as well-quite noticeably in verbal expression. I had done some online research of acetyl cholinesterase awhile back in relation to the development of Alzheimer’s, so this post is very relevant to me, especially with a familial history of Alzheimer’s. Food for thought….thanks for the info. I’m currently gaining strength to get back on the diet; the boils alone are so painful and not worth eating certain foods. Initially, my autoimmune response, I concluded was from taking antibiotics for several years, contributing to leaky gut which has now caused an autoimmune response. I’m tempted to go back to the antibiotics because it takes a few weeks to get my body back in good health after eating badly for a few days, but I know it’s not the true answer and will only subside my symptoms and in turn, potentially make my leaky gut worse in the long run.

I’m so sorry that you’re having such awful symptoms, but that’s pretty incredible that you’ve been able to find relief through your dietary changes, as well as the hot baths. I’m glad you found the post helpful. If you do decide that the antibiotics have become necessary, Sarah has a great post on recovering from anitbiotics. -Kiersten

When you say that tobacco causes “heart, lung and circulatory problems as well as cancer” are you talking about eating it?
About the nightshades… I LOVE spicy foods. Red, yellow, orange peppers, jalapeños, etc. Potatoes are like their own food group in my mind. What are the chances that if I enjoy eating them so much (and I don’t really enjoy eating at all) that they are bad for me? I have no noticible reaction.

It is impossible to say whether nightshades are bad for you personally. However, if you have an autoimmune condition or joint pain, it may be worth removing them from your diet for at least 30 days and then retesting them. Sometimes we don’t notice that we are reacting to something until we remove it and add it back in. -Kiersten

My son is three and a half years old and has autism. Recently we took gluten and dairy out of our son’s diet but I was shocked to discover that nightshades are as bad for you. My son has a leaky gut and digestion problems as we can tell by his nappy. My son is a fussy eater but he wasn’t to begin with. I’ am aware that fussy eating due to autism is mostly down to sensory and reflux problems that begins early on. He will only eat his lunch/dinner if it has tomato pasta sauce on it. The brand he likes only has 6% tomato puree and 14% tomatoes, then herbs and sugar etc. I thought that the sugar would be bad for him but now because of your posts I can see that it is the tomato that is the problem. Do you think that eating this amount of tomato for about 2 odd years could be the reasons to my son’s problems and any ideas how I can replace the tomato taste he likes but with a heathier alternative? He has reflux problems so prefers to eat with a sauce base.

It’s impossible for me to say whether or not the tomato sauce is the cause, and likely there isn’t just one cause, but a combination of things. But nightshades definitely do pose issues for a lot of people (as does sugar). Sarah has a recipe for nightshade free bolognese sauce on page 226 of The Paleo Approach Cookbook. -Kiersten

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