2. Nightshades—Just Side Effects?


Medical science doesn’t yet fully recognize or understand nightshade sensitivity. With a little logical thinking, we can skip over this gap and still grasp the essence. We’ll be thinking scientifically, and looking through the lens of a pillbox.

Almost everybody takes something at least now and again, some balm or potion from the pharmacy. Whether it’s simply two aspirin, some beta blockers, or immunotherapy wonder drugs, humans have developed an incredibly diverse and sophisticated medical tool kit.

TL;DR All drugs work for some people and not for others, and side effects are part of the bargain. The nightshade family is renowned for high bioactivity. That such a food might elicit side effects should be expected.

Without ever going to pharmacy school, you are also almost certainly aware of two of the most important principles of pharmacology. First, not every drug is going to work for everyone. Second, side effects are real—and a real problem. And not everyone suffers them equally.

So where do we get our drugs, and our ideas for drugs? Acetylsalicylic acid was probably discovered—in the form of willow bark—by some inquisitive healer deep in prehistoric time. Only in 1897 did Bayer turn it into Aspirin. Antibiotics have been copied or inspired by the chemical concoctions of bacteria and fungi. Cancer therapies have come from yew trees and mistletoe.

Most drugs either come from nature, or are informed by nature. When a compound comes from nature, chemists call these natural products.

And nightshades, the Solanacea plant family that has brought us the nightshade vegetables, has delivered far more than French fries and ketchup. Type the name of one branch of the family—Solanum—into the search engine of the Journal of Natural Products and you’ll return nearly 100 articles. Add another branch—Capsicum—and the total results climb to nearly 1000.

Nightshades understand the art of poison. “One of the plant taxa that produce highly toxic compounds is the Solanaceae family,” summarized one academic chemist in a review from 2016. “In this family, in which some of the most poisonous plants can be found, substances and extracts obtained from these plants are also widely used as pesticides.”1

This arsenal also includes chemicals that may be repurposed2 to fight3 inflammation4 and cancer.5 Later in this essay I’ll detail some of the pharmacologic diversity of potatoes, tomatoes, peppers, and more.

Undeniably, the nightshade family is a talented and prolific chemist.

Now let’s talk about when drugs work—and when they don’t work. As we’ve already noted, it’s well understood that not all drugs work for all people. And most drugs also have side effects that affect at least some people, some of the time.

This is the crux of the matter: If nightshades are exciting enough plants to merit prospecting for new drugs, isn’t it then highly probable that they’ll cause a few side effects as well?

This is what working/not working looks like when you plot it out for a drug study, in this case one to treat joint pain.6 The blue lines show improvement of symptoms. The red lines show no improvement, or a worsening of symptoms:

This looks like a very promising remedy, if that’s the only thing you’re looking for. Drug company executives would be thrilled if even half of their drugs promised this much potential against such minimal side effects. But that’s not what concerns us here because it’s the red lines—patients who did fair or worse—that we need to focus on. Most every drug study has them: patients who do worse with the treatment. That’s not an indictment of this particular treatment. It’s just a reality of any treatment: drugs don’t work for everybody, there are often side effects, and some people are more affected by these side effects.

The compound being tested in this trial is anatabine, an alkaloid found in—surprise—the Solanaceae family. It’s present in tobacco, tomatoes, potatoes, peppers, and eggplants. Once sold as a dietary supplement, in the 1990s drug developers got excited by its potential to possibly treat joint pain—and more.

In another study, researchers wanted to test their hypothesis that dietary anatabine might help control thyroid autoimmunity. (Ahead I’ll discuss the intriguing role of tobacco in inflammatory bowel disease and other autoimmune conditions.)

And they were right, because a decent proportion of patients in a small clinical trial did see improvement:

But there were side effects, called ‘adverse effects’ here: dizziness (36%), nausea (8%), and headaches (7%) were the most commonly cited. Of the 84 patients receiving anatabine, seven (8%) withdrew, compared to only one of the 81 patients taking a placebo.7

Again, the point here is not that anatabine is either good or bad.8 The point is that all drugs work for some people and not for others, and that side effects can be significant, and by design affect just a small percentage of people. If we’re going to eat a significant portion of vegetables from a plant family noted for its production of biologically active compounds, it should not surprise us that some people might develop problems.

NEXT: The History of Nightshades as Poisons

  1. “A Review of Bioinsecticidal Activity of Solanaceae Alkaloids” []
  2. “Anti-Inflammatory Spirostanol and Furostanol Saponins from Solanum macaonense []
  3. “Anti-neutrophilic inflammatory steroidal glycosides from Solanum torvum” []
  4. “Anti-inflammatory lignanamides from the roots of Solanum melongena L.” []
  5. “Antioxidant bioactive compounds in tomato fruits at different ripening stages and their effects on normal and cancer cells”; “Anticancer Activity Evaluation of the Solanum Glycoalkaloid Solamargine” []
  6. “Effects of Dietary supplementation with the Solanaceae plant Alkaloid Anatabine on Joint pain and stiffness: Results from an Internet-Based survey study” []
  7. “Anatabine Supplementation Decreases Thyroglobulin Antibodies in Patients With Chronic Lymphocytic Autoimmune (Hashimoto’s) Thyroiditis: A Randomized Controlled Clinical Trial” []
  8. It’s development was short-circuited by a scandal unrelated to its biochemistry, and ultimately, bankruptcy. (retrieved May 10, 2020) []



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