Nightshades have a reputation as bad actors in a variety of chronic conditions, such as arthritis, fibromyalgia, and IBS. But what do we really know about how these foods affect our health?

Meet the nightshade (solanaceae) family Tomatoes

Tomatillos

Eggplant

Potatoes

Goji Berries

Tobacco

Peppers (bell peppers, chili peppers, paprika, tamales, tomatillos, pimentos, cayenne, etc) At first glance, the nightshades may look like a random collection of foods that couldn’t possibly be related. However, every nightshade plant produces fruits that all sport that same adorable little green elfish hat. Of the foods above, only tomatoes, eggplants, goji berries and peppers are “fruits” (the potato is a tuber and tobacco is a leaf). The fruits of potato and tobacco plants wear the same telltale hat, but we don’t eat the fruits of those plants.

Glycoalkaloids Glycoalkaloids are natural pesticides produced by nightshade plants. Glycoalkaloids are bitter compounds which are found throughout the plant, but their concentrations are especially high in leaves, flowers, and unripe fruits. They are there to defend plants against bacteria, fungi, viruses, and insects. Cherries, apples, and sugar beets also contain small amounts of glycoalkaloid even though they are not nightshades. Vegetable violence Glycoalkaloids act as invisible hand grenades. They bind strongly to the cholesterol in the cell membranes of predators, and in so doing, they disrupt the structure of those membranes, causing cells to leak or burst open upon contact. Glycoalkaloids are neurotoxins. They block the enzyme cholinesterase. This enzyme is responsible for breaking down acetylcholine, a vital neurotransmitter that carries signals between nerve cells and muscle cells. When this important enzyme is blocked, acetylcholine can accumulate and electrically overstimulate the predator’s muscle cells. This can lead to paralysis, convulsions, respiratory arrest, and death. Military “nerve gases” work exactly the same way. Ok, so glycoalkaloids are clearly nightmarish compounds for the cells of tiny creatures daring to munch upon nightshade plants, but what do we know about their effects on human health?

Nightshade glycoalkaloid health "benefits" Health benefits? From a pesticide? Hmmm . . . Since most people believe plant compounds are good for humans, when scientists conduct experiments with plant extracts, they are more likely to look for health benefits than health risks. Glycoalkaloids are anti-inflammatory. Glycoalkaloids have been shown to reduce inflammation in laboratory animals. This is likely due to the fact that glycoalkaloids are structurally similar to compounds called glucocorticoids, which have well-known anti-inflammatory properties. Familiar examples of glucocorticoids include cortisol (our body’s natural stress hormone), and Prednisone, a commonly-prescribed anti-inflammatory medicine. It should be noted, however, that just because glycoalkaloids or glucocorticoids can reduce inflammation doesn't mean they are always good for you. Prednisone is not something most of us should be taking every day, because it has numerous damaging side effects, and elevated levels of natural cortisol in our bodies weaken our immune system and slow our metabolism. Glycoalkaloids kill bacteria and viruses. It should also not be surprising that glycoalkaloids have been shown in laboratory studies to possess antibiotic and antiviral properties, since this is what nature designed them for. Glycoalkaloids have anti-cancer properties. In laboratory (in vitro) studies, glycoalkaloids can trigger cancer cells to self-destruct. This process is called “apoptosis.” Unfortunately, they can also cause healthy non-cancerous cells to do the same thing. Cancer studies in live animals and humans (in vivo) have not yet been conducted. The problem with so many anti-cancer plant compounds is that they are double-edged swords, killing both cancer cells and healthy cells alike: “The undifferentiating destruction of both cancer and noncancerous cell lines . . . leads to questions of therapeutic uses of glycoalkaloids due to safety considerations. However, it is difficult to translate the results of an in vivo trial in vitro. Therefore, both animal and human experiments are essential to confirm or disprove the in vivo data observed in these studies.” [Milner 2011].

Health risks of nightshade glycoalkaloids Glycoalkaloids destroy cell membranes. Research has shown that glycoalkaloids can burst open the membranes of red blood cells and mitochondria (our cells’ energy generators). Some scientists have wondered whether glycoalkaloids could be one potential cause for ‘leaky gut’ syndromes due to their ability to poke holes in cells: “Glycoalkaloids, normally available while eating potatoes, embed themselves and disrupt epithelial barrier integrity in a dose-dependent fashion in both cell culture models and in sheets of mammalian intestine. . . . [A]nimals with the genetic predisposition to develop IBD, demonstrated a greater degree of small intestinal epithelial barrier disruption and inflammation when their epithelium was exposed to the potato glycoalkaloids chaconine and solanine.” [Patel 2002] Glycoalkaloids cause birth defects in laboratory animals.

Nightshades and mental health Due to widespread pro-plant food bias, the vast majority of scientific studies of nightshades explore their potential benefits rather than their downsides, so we do not have the studies we wish to have about how these interesting foods actually affect our well-being. However, there have been plenty of documented cases of nightshade toxicity that demonstrate to us how poisonous they can be to our central nervous system—capable of causing severe neuropsychiatric side effects in human beings: "In cases of mild glycoalkaloid poisoning symptoms include headache, vomiting, and diarrhea. Neurological symptoms were also reported, including apathy, restlessness, drowsiness, mental confusion, rambling, incoherence, stupor, hallucinations, dizziness, trembling, and visual disturbances." [Milner 2011] In a group of children who suffered from solanine poisoning as a result of eating potatoes that had been in storage for too long, severe psychiatric side effects were observed: "The largest series of solanine poisoning involved an English day school where 78 schoolboys developed diarrhea and vomiting after eating potatoes stored since the summer term. Symptoms began 7-19 hours after ingestion with vomiting, diarrhea, anorexia, and malaise. Of the 78 boys, 17 were admitted to the hospital. Other symptoms included fever (88%), altered mental status (drowsiness, confusion, delirium) (82%), restlessness (47%), headache (29%), and hallucinations (23%). Three boys were seriously ill with hypotension, tachycardia [rapid heart rate], and stupor out of proportion to fluid and electrolyte imbalance. These boys were discharged 6-11 days after admission, and they had nonspecific symptoms and visual blurring for several weeks after release from the hospital." [Barceloux 2009] Keep in mind that these reactions just happened to be recorded due to their severity. We have no documented information about how everyday consumption of nightshades affects sensitive individuals, only numerous on-line personal accounts of mental health problems such as anxiety, panic, and insomnia that were alleviated by removal of nightshades from the diet. I personally experience profound insomnia and mild panic symptoms when I eat nightshades, which makes sense because glycoalkaloids overstimulate the nervous system. If you experience anxiety or insomnia and are curious to know more about nightshades and the other foods most likely to be contributing to your symptoms, I recommend you read my Psychology Today article “5 Foods Proven to Cause Anxiety and Insomnia.”

Fruits vs vegetables: here we go again! Those of you who are familiar with my philosophy about plant foods know that I believe that when it comes to our health, vegetables are far less trustworthy than edible fruits. Nightshades make this point nicely. [Watch my Ancestral Health Symposium video about vegetables vs. fruits if you are curious about my vegetable philosophy.] As you will see below, even though nightshade fruits contain glycoalkaloids, they either contain lower amounts of these potentially toxic compounds or contain gentler versions of them. Luckily, most of the edible nightshades—eggplant, tomatoes, goji and peppers—are fruits (fruits by definition contain seeds). Tobacco is a nightshade vegetable, but it is typically smoked, not eaten, so the only nightshade vegetable humans consume is the beloved potato.

Potato glycoalkaloids All potatoes are nightshades except for sweet potatoes and yams. Potato plants make two glycoalkaloids: alpha-chaconine and alpha-solanine. These are the most toxic glycoalkaloids found in the edible nightshade family. Alpha-chaconine is actually more potent than alpha-solanine, but solanine has been studied much more thoroughly. There are numerous cases of livestock deaths from eating raw potatoes, potato berries, and potato leaves, but people don't eat these things. However, there are well-documented reports of people getting glycoalkaloid poisoning from potatoes, typically from eating improperly stored, green, or sprouting potatoes. At low doses, humans can experience gastrointestinal symptoms, such as vomiting and diarrhea. At higher doses, much more serious symptoms can occur, including fever, low blood pressure, confusion, and other neurological problems. At very high doses, glycoalkaloids are fatal. Another reason why many people may not be bothered by potatoes is that glycoalkaloids are very poorly absorbed by the gastrointestinal tract, so, if you have a healthy digestive tract, most of the glycoalkaloid won’t make it into your bloodstream. However, if you eat potatoes every day, levels can build up over time and accumulate in the body’s tissues and organs, because it takes many days for them to be cleared. Also, since glycoalkaloids have the ability to burst cells open, they can theoretically cause damage to the cells that line your digestive system as they are passing through (this has been proven in animal studies but there are no human studies, to my knowledge). Due to known toxicity, the FDA limits the glycoalkaloid content in potatoes to a maximum of 200 mg/kg potatoes (91 mg/lb). Human studies show that doses as low as 1 mg glycoalkaloid per kg body weight can be toxic, and that doses as low as 3 mg/kg can be fatal. This means that, if you weigh 150 lbs, doses as low as 68 mg could be toxic, and doses as low as 202 mg could be fatal. Glycoalkaloid levels of a few prepared potato products are available [Milner 2006]: Potato chips, 1 oz bag: 0.36 to 0.88 mg chaconine and 0.29 to 1.4 mg solanine. Total glycoalkaloid concentrations range from 2.7 to 12.4 mg per bag.

Fried potato skins, 4 oz: 4.4 to 13.6 mg chaconine and 2.0 to 9.5 mg solanine. Total glycoalkaloid concentrations range from 6.4 to 23.1 mg per 4 oz serving.

Potato processing 101 The vast majority of glycoalkaloid is in the potato skin, so peeling will remove virtually all of it. Glycoalkaloid levels can be dangerously high in unripe and sprouting potatoes; any greenish areas or “eyes” should be removed or avoided. Glycoalkaloids survive most types of cooking and processing. In fact, deep frying will increase levels if the oil isn’t changed frequently, so fried products such as potato skins and french fries can contain relatively high amounts: “Mechanical damage to potato tissue increases the concentration of glycoalkaloids available for consumption. In addition, frying potatoes at high temperatures does not inactivate but instead serves to preserve and concentrate glycoalkaloids within the potato, leaving them available for ingestion and delivery to the intestine.” [Patel 2002] Boiling—reduces glycoalkaloids by a few percentage points

Microwaving—reduces glycoalkaloids by 15%

Deep frying at 150C (300F)—no effect (McDonald’s uses 340F oil)

Deep frying at 210C (410F)—reduces glycoalkaloid content by 40%

Tomato glycoalkaloids Tomato nightshades include all types of tomatoes: cherry tomatoes, green tomatoes, yellow tomatoes and ripe red tomatoes. Tomatoes produce two glycoalkaloids: alpha-tomatine and dehydrotomatine. The majority is in the form of alpha-tomatine, so we’ll focus on that one here. As tomatoes ripen, alpha-tomatine levels drop dramatically, from about 500 mg/kg in green tomatoes to about 5 mg/kg in ripe red tomatoes, or 2.3 mg/lb. [For those of you keeping score at home—that’s Fruits: 1, Veggies: 0.] Artificially ripened fruits may contain higher amounts than sun-ripened fruits. Tomato glycoalkaloids are about 20 times less toxic than potato glycoalkaloids. (Fruits: 2, Veggies: 0). There are no dosage studies of tomatine in humans, but studies in mice tell us that 500 mg tomatine per 1 kg body weight (or 227 mg per pound) is the median lethal dose (LD50). This doesn’t tell us how much it would take to kill a 150 lb person; it only tells us that it would take 34 grams of tomatine to kill a 150-pound mouse. Since ripe tomatoes contain 5 mg/kg or 2.3 mg/lb of tomatine, it would take nearly 15,000 pounds of tomatoes to kill this Mighty Mouse (probably many fewer pounds if you were to simply hurl them in his general direction from across the room). Since green tomatoes contain 100 times more tomatine, it would only take 150 pounds of green tomatoes to kill the overgrown rodent. We do not understand the effect of low doses of tomatine over time on any type of animal, including humans.

Eggplant glycoalkaloids Centuries ago, the common eggplant was referred to as “mad apple” due to belief that eating it regularly would cause mental illness. Eggplants produce two glycoalkaloids: alpha-solamargine and alpha-solasonine. Solamargine is more potent than solasonine. Whereas potato glycoalkaloids are located mainly in the skin, in eggplants, glycoalkaloids are found primarily within the seeds and flesh; the peel contains negligible amounts. The common eggplant (solanum melongena) contains 10-20 mg/kg (or 4.5 to 9 mg/lb of eggplant). Eggplant glycoalkaloids are considered relatively nontoxic compared to potato glycoalkaloids (Fruits: 3, Veggies: 0). The median lethal dose (LD50) in rodents is 1.75 mg/kg. This means that it would take at least 13 pounds of eggplant to kill a 150 lb monster mouse. [Note to self—when facing a giant rodent in a dark alley, go for the eggplants, not the tomatoes].

Peppers Red and green bell peppers contain less than 10 mg of glycoalkaloid per kg. This is a very small amount, so if you react badly to peppers, you are either very sensitive, or you are responding to other compounds within the peppers, such as the notoriously hot and spicy capsaicinoids. What about goji berries? Your guess is as good as mine . . . I could not locate any scientific information about glycoalkaloids in these foods. Nightshades and nicotine Nightshade foods also contain small amounts of nicotine, especially when unripe. Nicotine is much higher in tobacco leaves, of course. Scientists think that nicotine is a natural plant pesticide, although it is unclear exactly how it works to protect plants from invaders. The amount of nicotine in ripe nightshade foods ranges from 2 to 7 micrograms per kg of food. Nicotine is heat-stable, therefore it is found in prepared foods such as ketchup and French fries. The health effects of these small doses are not known, but some scientists wonder whether the nicotine content of these foods is why some people describe feeling addicted to them. In my opinion, it is more likely that the high carbohydrate content of those foods is responsible for their addictive properties.

Do you have nightshade sensitivity? As with any food sensitivity, the only way to find out is to remove nightshades from your diet for a couple of weeks or so to see if you feel better. There are ZERO scientific articles about nightshade sensitivity, chronic pain, or arthritis in the literature, however, the internet is full of anecdotal reports of people who have found that nightshades aggravate arthritis, fibromyalgia, or other chronic pain syndromes. I am personally very sensitive to nightshades; they cause me a variety of symptoms, most notably heartburn, difficulty concentrating, pounding heart, muscle/nerve/joint pain, and profound insomnia. Everyone is different, so as always, you’ll need to discover for yourself whether these foods may pose problems for your individual chemistry. However, given what we know about nightshade chemicals, common sense tells us that these foods are well worth exploring as potential culprits in pain syndromes, gastrointestinal syndromes, and neurologic/psychiatric symptoms. If you experience anxiety or insomnia and are curious to know more about nightshades and the other foods most likely to be contributing to your symptoms, I recommend you read my Psychology Today article "5 Foods Proven to Cause Anxiety and Insomnia."

Recommended nightshade-free cookbooks The Healing Kitchen is co-authored by the fabulous Sarah Ballantyne (aka PaleoMom) who has an impressive PhD in medical biophysics. This cookbook eliminates nightshades, grains, legumes, nuts, seeds, eggs, and dairy. In addition to delicious recipes, the authors do a beautiful job of explaining the science behind healthy eating, encouraging you to stay positive by focusing on what you CAN eat. The Autoimmune Paleo Cookbook is written by nutritional therapist/cook Mickey Trescott. This beautiful and supportive cookbook includes helpful meal and shopping plans. All recipes are free of nightshades, grains, legumes, nuts, seeds, eggs, and dairy. Quite a few recipes rely on coconut and garlic, so if you have sensitivities to these foods, it may not be the one for you, but otherwise it's a wonderful choice.