Dietary Solanaceous Glycoalkaloids (SGAs) and Anesthesia

Herbal and dietary factors can affect the metabolism and transport of a wide variety of drugs.1 For example, grapefruit has well-known interactions with more than 85 medications, which result in impaired drug metabolism and higher drug concentrations.2 Fasting before anesthesia administration is a common way to avoid pulmonary aspiration, with an added benefit of avoiding the possibility of dietary interactions with anesthetic drugs.3 However, research dating back more than 20 years indicates that meals consumed days before surgery may affect anesthesia.4 Data show that even trace amounts of solanaceous glycoalkaloids (SGAs) found in foods such as tomatoes, potatoes and eggplants can inhibit metabolism of many common anesthetics and muscle relaxants.5 Knowledge of SGAs’ mechanisms of action and their effect on anesthesia is crucial to an anesthesia provider’s practice. 

Glycoalkaloids are nitrogen-containing compounds containing steroids and monosaccharaides.6 They are biologically active secondary metabolites, meaning that they are produced by organisms but not necessary for their growth, development and reproduction.7 SGAs, such as solanine8 and tomatine,9 are glycoalkaloids that are naturally produced in the Solanaceae plant family. Solenaceous vegetables and fruits include Solanum (potato and eggplant), Lycopersicon (tomato), and Capsicum (pepper),10 as well as cherries and beets.8 Though the SGAs in these vegetables and fruits are said to have anticarcinogenic effects,11 high concentrations of SGAs are unsafe for human consumption.12 SGA toxicity leads to inhibition of acetylcholinesterase, the enzyme that normally breaks down acetylcholine.13 Too much acetylcholine affects the parasympathetic nervous system (used for the “rest and digest” function), causing symptoms such as increased secretions, burning in the throat, bronchoconstriction (airway constriction), bradycardia (slow heart rate), vomiting, diarrhea and abdominal cramping.8,14 Severe cases are even associated with muscle spasms, paralysis, confusion, headache, drowsiness, hallucinations, loss of sensation, fever, jaundice, dilated pupils and hypothermia.8,14 While SGA doses of 200 to 400 milligrams for adults and 20 to 40 milligrams for children are necessary for toxic symptoms, it is estimated that commercial potatoes have a solanine concentration of only 0.2 milligrams per gram.8 However, potatoes that have been exposed to light and turned green contain high amounts of solanine, and cooking them does not reduce this amount.15 It is important to keep in mind the role of SGAs in acetylcholine poisoning before consuming SGA-containing foods. 

Not only can SGAs cause parasympathetic nervous system issues when consumed in excess, but they can also affect the pharmacokinetics of anesthetic drugs.4 In fact, this can occur when SGAs are consumed in moderate amounts, days before surgery.4 The effects of preoperative SGA consumption on anesthesia were first discovered in 1998 by researchers and anesthesiologists at the University of Chicago.16 This effect is due to SGAs’ inhibitory effects on acetylcholinesterase and another enzyme, butyrylcholinesterase.17 While acetylcholinesterase maintains healthy nerve and muscle function, butyrylcholinesterase is found in the blood and is responsible for the breakdown of a variety of anesthetic drugs.16 The scientists found SGA-induced enzymatic inhibition, and subsequent reduced metabolism of common anesthetics and muscle relaxants, due to moderate potato consumption days before surgery.5 According to Jonathan Moss, the principal investigator, the study helped explain why dosing models based on weight and height were off by 50 to 100 percent in some patients.16 A study by McGehee et al. used in vitro samples in the laboratory and rabbit models to show that potato SGAs slowed metabolism of mivacurium, which is a muscle relaxant and neuromuscular blocking agent metabolized by butyrylcholinesterase.18 In a more recent review, Krasowski et al. found that SGAs may cause atypical genetic variation in butyrylcholinesterase in humans and influence anesthetic drug metabolism.17 Finally, findings from Bestas et al.’s human study suggested that potatoes eaten the meal before preoperative fasting could prolong the duration of succinylcholine-induced neuromuscular block and delay recovery from anesthesia.19 Evidently, SGAs may interfere with metabolism of anesthetic drugs through enzymatic inhibition. 

It is well known that herbal and dietary factors beyond age, weight, height and sex may affect drug metabolism. Glycoalkaloids from the Solanaceae plant family, which includes potatoes, tomatoes and peppers, can inhibit enzymes in the human body and cause toxicity of certain biological transmitters. Through their enzymatic blockade, SGAs can also interfere with the metabolism of anesthetic drugs and muscle relaxants. Anesthesiology professionals should be sure to consider a patient’s preoperative diet when choosing dosages. However, given a lack of human studies, more research is needed to assess the exact effects of dietary SGAs on anesthesia and necessary dosing adjustments. 

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2. Bailey DG, Dresser G, Arnold JMO. Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? Canadian Medical Association Journal. 2013;185(4):309–316. 

3. American Society of Anesthesiologists Task Force on Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration. Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2017;126(3):376–393. 

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6. Glycoalkaloid. ScienceDirect. Web: Elsevier B.V.; 2020. 

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9. Osman SF. Glycoalkaloids of the Solanaceae. In: Swain T, Kleiman R, eds. The Resource Potential in Phytochemistry. Boston, MA: Springer US; 1980:75–96. 

10. Rubatzky VE, Yamaguchi M. Tomatoes, Peppers, Eggplants, and Other Solanaceous Vegetables. In: Rubatzky VE, Yamaguchi M, eds. World Vegetables: Principles, Production, and Nutritive Values. Boston, MA: Springer US; 1997:532–576. 

11. Friedman M. Chemistry and anticarcinogenic mechanisms of glycoalkaloids produced by eggplants, potatoes, and tomatoes. Journal of Agricultural and Food Chemistry. 2015;63(13):3323–3337. 

12. Kuete V. Health Effects of Alkaloids from African Medicinal Plants. In: Kuete V, ed. Toxicological Survey of African Medicinal Plants: Elsevier; 2014:611–633. 

13. Bushway RJ, Savage SA, Ferguson BS. Inhibition of acetyl cholinesterase by solanaceous glycoalkaloids and alkaloids. American Potato Journal. 1987;64(8):409–413. 

14. Lott EL, Jones EB. Cholinergic Toxicity. StatPearls. Treasure Island, Florida: StatPearls Publishing; June 4, 2019. 

15. Cantwell M. A review of important facts about potato glycoalkaloids. Perishables Handling Newsletter. 1996;87:26–27. 

16. Moss JR. Research Uncovers First Known Link Between Diet and Anesthesia. ASA Annual Meeting,. Web: American Society of Anesthesiologists; October 19, 1998. 

17. Krasowski MD, McGehee DS, Moss J. Natural inhibitors of cholinesterases: Implications for adverse drug reactions. Canadian Journal of Anesthesia. 1997;44(5 Pt 1):525–534. 

18. McGehee Daniel S, Krasowski Matthew D, Fung Dennis L, Wilson B, Gronert Gerald A, Moss J. Cholinesterase Inhibition by Potato Glycoalkaloids Slows Mivacurium Metabolism. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2000;93(2):510–519. 

19. Bestas A, Goksu H, Erhan OL. The effect of preoperative consumption of potatoes on succinylcholine-induced block and recovery from anesthesia. Journal of Clinical Monitoring and Computing. 2013;27(6):609–612.