Consumption of Nightshade Plants (Part 3) - by Loren Cordain, Ph.D., Professor
Editor's note: Dr. Cordain latest paper on paleo nutrition discusses the consumption of the nightshade family of plants (potatoes, tomatoes, and chili peppers). This is the final installment in the free weekly edition of The Paleo Diet Update. Parts 1 and 2 of this paper (as well as part 3 beginning June 21) are available for purchase in our web store until July 5, 2010. Afterwards, this paper will be available in its entirety from our web store. Note that the numbering of figures, tables and references in this week's installment reflect the paper in its entirety.
Consumption of Nightshade Plants, Human Health and Autoimmune Disease
Part 3: Chili Peppers
All chili peppers belong to the genus Capsicum (family Solanaceae) and are among the most heavily consumed spices throughout the world57. There are 22 wild species within the Capsicum genus, and five domesticated species58, of which more than 200 or more varieties have been produced depending upon various environmental factors to which the plants are exposed59. Table 6 shows the five domesticated species and lists a few of the more common varieties of chili peppers.
Botanically speaking, the fruit of capsicums are berries. However, the peppers are considered vegetables (e.g. bell peppers) or spices (e.g. cayenne pepper) for culinary purposes, based on factors including fleshiness and intensity of flavor.
Table 6. Some common names for the five domesticated species of the Capsicum genus.
Common name or names Scientific name
Bell pepper, Cayenne pepper, Cherry pepper, Chili pepper, Paprika, Jalapeno pepper, pimento, Serrano pepper Capsicum annuum
Aji, Brown’s Pepper, Peruvian pepper Capsicum baccatum
Habanero chili, Bonnet pepper Capsicum chinense
Tabasco pepper Capsicum frutescens
Rocoto pepper Capsicum pubescens
The sensory "heat" from chili peppers comes from a group of compounds called capsaicinoids. More than 20 capsaicinoids are found in chili peppers, and their concentrations range from 0% by weight to more than 2% by weight60. Daily per capita consumption of capsaicinoids from chili peppers in the U.S. and Europe is ~1.5 mg, whereas in India, Mexico and Thailand it is ~25-200 mg60. Chili peppers are favorite spices throughout the world because of their pungent or "hot" taste and aroma. So, the greater the concentration of capsaicinoids in the chili pepper, the "hotter" it tastes. Table 7 shows the concentrations of total capsaicinoids in a variety of chili peppers and chili pepper containing foods.
Table 7. Concentrations of total capsaicinoids in a variety of chili peppers and chili pepper containing foods (adapted from reference 60).
Pepper/food product Total Capsaicinoid Content (microgram/g)
McCormick ground cayenne pepper 3,588
Habanero pepper, fresh 2,261
Thai pepper, fresh 1333
McCormick original chili seasonings 830
McIlhenny hot habanero sauce 547
Hungarian hot paprika 439
La Costena Chipotle, whole, canned 416
McCormick hot taco seasoning 394
Mezzetta hot chili, canned 306
La Costena jalapeno green whole pickled canned 210
Lawry Choula hot sauce 201
McIlhenny Tabasco original hot sauce 195
McCormick mild taco seasoning 186
Lawry Crystal hot sauce, extra hot 174
La Costena seranno, green whole pickled canned 164
Star Foods pepperoncini canned 82
Serrano, fresh 77
Green jalapeno, fresh 76
Red jalapeno, fresh 46
Safeway hot pepper sauce 45
Mezzetta sliced jalapeno, canned 19
Green, red and yellow bell peppers, fresh 0
Roasted red canned 0
Roasted green canned 0
Whole canned peppers 0
Capsaicinoids seem to have both beneficial and deleterious health effects60, 61. They have long been used in Mayan and Ayurvedic therapeutic remedies62 and more recently have found therapeutic application in pain relief63.
One of the potential shortcomings of chili peppers is their ability to increase intestinal permeability64-69 - and this may be their greatest threat to human health. As far back as 1998 it was suggested that chili peppers - because of their capsaicinoids - "may modulate the absorption of low molecular weight food constituents that are involved in the pathogenesis of food allergy and intolerance" 69. More recently, many scientists now believe that increased intestinal permeability, often times called "leaky gut" represents a universal environmental triggering event for autoimmune diseases14, 15, 44, 45. As stated earlier, when the gut becomes "leaky" it is not a good thing, as the intestinal contents may then have access to the immune system (which in turn becomes activated), thereby causing a chronic low level systemic inflammation known as endotoxemia16 – 18 that may promote cardiovascular disease16, 17 and diseases of insulin resistance18. To date, this chain of physiological events (e.g. consumption of chili peppers increases intestinal permeability which increases low level inflammation, which increases the risk for disease) has not yet been demonstrated in living (in vivo) humans. As always, I believe that anyone suffering from an autoimmune disease should remove suspect foods from the diet for an extended period and then monitor symptoms. If conditions get worse after you re-introduce the food, then this particular food may be problematic for you and should not be part of your lifelong diet.
In the U.S. we consume almost 230 pounds of nightshades per person on a yearly basis. These common foods (potatoes, tomatoes, chili peppers, and eggplants) have become such staples in our diets that few people rarely - if ever - consider that they are very recent additions to worldwide human nutrition. In fact, prior to 1492 and Columbus’ "discovery" of the new world, no Europeans, Middle Easterners, Africans or Asians ever had access to these foods, as they are all indigenous to Central and South America. Hence, humanity as a whole has had very little evolutionary experience with foods that contain multiple toxins (saponins and lectins primarily), which cause numerous adverse health effects in humans and animals. For Paleo Dieters my advice would to be to eliminate or drastically reduce potato consumption and for autoimmune and allergy patients to be cautious with the consumption of tomatoes, chili peppers and eggplants.
1. Heiser CB. Nightshades, the Paradoxical Plants. W.H. Freeman and Company, San Francisco, CA, 1969.
2. USDA, Economic Research Service. http://www.ers.usda.gov/
3. Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr. 2002 Jul;76(1):5-56.
4. Leeman M, Ostman E, Björck I. Glycaemic and satiating properties of potato products. Eur J Clin Nutr. 2008 Jan;62(1):87-95.
5. Fernandes G, Velangi A, Wolever TM. Glycemic index of potatoes commonly consumed in North America. J Am Diet Assoc. 2005 Apr;105(4):557-62.
6. Henry CJ, Lightowler HJ, Strik CM, Storey M. Glycaemic index values for commercially available potatoes in Great Britain. Br J Nutr. 2005 Dec;94(6):917-21.
7. Cordain L, Eades MR, Eades MD. Hyperinsulinemic diseases of civilization: more than just Syndrome X. Comp Biochem Physiol A Mol Integr Physiol. 2003 Sep;136(1):95-112.
8. Francis G, Kerem Z, Makkar HP, Becker K. The biological action of saponins in animal systems: a review. Br J Nutr. 2002 Dec;88(6):587-605.
9. Keukens EA, de Vrije T, van den Boom C, de Waard P, Plasman HH, Thiel F, Chupin V, Jongen WM, de Kruijff B.. Molecular basis of glycoalkaloid induced membrane disruption. Biochim Biophys Acta 1995;1240: 216-228.
10. Smith DB, Roddick JG, Jones JL. Potato glycoalkaloids: some unanswered questions. Trends in Food Sci Technol 1996;7:126-131.
11. Patel B, Schutte R, Sporns P, Doyle J, Jewel L, Fedorak RN. Potato glycoalkaloids adversely affect intestinal permeability and aggravate inflammatory bowel disease. Inflamm Bowel Dis. 2002 Sep;8(5):340-6.
12. Iablokov V, Sydora BC, Foshaug R, Meddings J, Driedger D, Churchill T, Fedorak RN. Naturally occurring glycoalkaloids in potatoes aggravate intestinal inflammation in two mouse models of inflammatory bowel disease. Dig Dis Sci. 2010 Mar 3. [Epub ahead of print]
13. Hellenäs KE, Nyman A, Slanina P, Lööf L, Gabrielsson J. Determination of potato glycoalkaloids and their aglycone in blood serum by high-performance liquid chromatography. Application to pharmacokinetic studies in humans. J Chromatogr. 1992 Jan 3;573(1):69-78.
14. Fasano A. Surprises from celiac disease. Sci Am. 2009 Aug;301(2):54-61.
15. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17.
16. Stoll LL, Denning GM, Weintraub NL. Endotoxin, TLR4 signaling and vascular inflammation: potential therapeutic targets in cardiovascular disease. Curr Pharm Des. 2006;12(32):4229-45.
17. Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis. Lancet. 2000 Sep 9;356(9233):930-3.
18. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72.
19. Sweet MJ, Hume DA. Endotoxin signal transduction in macrophages. J Leukoc Biol 1996;60: 8-26.
20. Kallio P, Kolehmainen M, Laaksonen DE, Pulkkinen L, Atalay M, Mykkänen H, Uusitupa M, Poutanen K, Niskanen L. Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome. Am J Clin Nutr. 2008 May;87(5):1497-503.
21. Naruszewicz M, Zapolska-Downar D, Ko?mider A, Nowicka G, Koz?owska-Wojciechowska M, Vikström AS, Törnqvist M. Chronic intake of potato chips in humans increases the production of reactive oxygen radicals by leukocytes and increases plasma C-reactive protein: a pilot study. Am J Clin Nutr. 2009 Mar;89(3):773-7.
22. Gabor F, Stangl M, Wirth M. Lectin-mediated bioadhesion: binding characteristics of plant lectins on the enterocyte-like cell lines Caco-2, HT-29 and HCT-8. J Control Release. 1998 Nov 13;55(2-3):131-42.
23. Qaddoumi M, Lee VH. Lectins as endocytic ligands: an assessment of lectin binding and uptake to rabbit conjunctival epithelial cells. Pharm Res. 2004 Jul;21(7):1160-6.
24. Pramod SN, Venkatesh YP, Mahesh PA. Potato lectin activates basophils and mast cells of atopic subjects by its interaction with core chitobiose of cell-bound non-specific immunoglobulin E. Clin Exp Immunol. 2007 Jun;148(3):391-401.
25. Johnson IT, Gee JM, Price K, Curl C, Fenwick GR. Influence of saponins on gut permeability and active nutrient transport in vitro. J Nutr. 1986 Nov;116(11):2270-7.
26. Friedman M, Levin CE. Alpha tomatine content in tomato and tomato products determined by HPLC with pulsed amperometric detection. J Agric Food Chem 1995;43:1507-1511.
27. Gee JM, Wortley GM, Johnson It, Price KR, Rutten AA. Houben GF, Penninks, AJ. Effects of saponins and glycoalkaloids on the permeability and viability of mammalian intestinal cells and on the integrity of tissue preparations. Toxicol in Vitro 1996;10:117-128.
28. Kilpatrick DC, Pusztai A, Grant G, Graham C, Ewen SW. Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects. FEBS Lett. 1985 Jun 17;185(2):299-305.
29. Nachbar MS, Oppenheim JD, Thomas JO. Lectins in the U.S. Diet. Isolation and characterization of a lectin from the tomoto (Lycopersicon esculentum). J Biol Chem 1980;2056-2061.
30. Bies C, Lehr CM, Woodley JF. Lectin-mediated drug targeting: history and applications. Adv Drug Deliv Rev. 2004 Mar 3;56(4):425-35.
31. Carreno-Gómez B, Woodley JF, Florence AT. Studies on the uptake of tomato lectin nanoparticles in everted gut sacs. Int J Pharm. 1999 Jun 10;183(1):7-11.
32. Alvarez JR, Torres-Pinedo R. Interactions of soybean lectin, soyasaponins, and glycinin with rabbit jejunal mucosa in vitro. Pediatr Res 1982;16:728-31.
33. Fairweather D, Kaya Z, Shellam GR, Lawson CM, Rose NR. From infection to autoimmunity. J Autoimmun. 2001 May;16(3):175-86.
34. Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol. 2005 Jan-Feb;15(1):17-27.
35. Fairweather D, Rose NR. Women and autoimmune disease. Emerg Infect Dis 2004;10:2005-2011.
36. Mcl Mowat A. Dendritic cells and immune responses to orally administered antigens. Vaccine 2005;23:1797-99.
37. Strobel S, Mowat MA. Oral tolerance and allergic responses to food proteins. Curr Opin Allergy Clin Immunol. 2006 Jun;6(3):207-13.
38. Benko S, Magyarics Z, Szabó A, Rajnavölgyi E. Dendritic cell subtypes as primary targets of vaccines: the emerging role and cross-talk of pattern recognition receptors. Biol Chem. 2008 May;389(5):469-85.
39. Progress in Autoimmune Disease Research. The Autoimmune Disease Coordinating Committee Report to Congress. U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases. Bethesda (MD), 2005. http://www3.niaid.nih.gov/topics/autoimmune/PDF/ADCCFinal.pdf
40. Lee S, Levin MC. Molecular mimicry in neurological disease: what is the evidence? Cell Mol Life Sci. 2008 Apr;65(7-8):1161-75.
41. Blank, M., Barzilai, O. and Shoenfeld, Y. (2007) Molecular mimicry and auto-immunity. Clin. Rev. Allergy Immunol. 32, 111–118.
42. Albert, L. J. and Inman, R. D. (1999) Molecular mimicry and autoimmunity. N. Engl.J. Med. 341, 2068–2074.
43. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006 Jul;7(7):688-93.
44. Arrieta MC, Bistritz L, Meddings JB.Alterations in intestinal permeability. Gut. 2006 Oct;55(10):1512-20.
45. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52.
46. Naisbett B, Woodley J. The potential use of tomato lectin for oral drug delivery: 4. Immunological consequences. Int J Pharm 1995;120:247-254.
47. De Aizpurua HJ, Russell-Jones GJ. Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding. J Exp Med 1988;167:440-451.
48. Morrow WJ, Yang YW, Sheikh NA.Immunobiology of the Tomatine adjuvant. Vaccine. 2004 Jun 23;22(19):2380-4.
49. Yang YW, Wu CA, Morrow WJ.The apoptotic and necrotic effects of tomatine adjuvant. Vaccine. 2004 Jun 2;22(17-18):2316-27.
50. Yang YW, Sheikh NA, Morrow WJ.The ultrastructure of tomatine adjuvant. Biomaterials. 2002 Dec;23(23):4677-86.
51. Heal KG, Sheikh NA, Hollingdale MR, Morrow WJ, Taylor-Robinson AW. Potentiation by a novel alkaloid glycoside adjuvant of a protective cytotoxic T cell immune response specific for a preerythrocytic malaria vaccine candidate antigen.Vaccine. 2001 Jul 20;19(30):4153-61.
52. Rajananthanan P, Attard GS, Sheikh NA, Morrow WJ.Novel aggregate structure adjuvants modulate lymphocyte proliferation and Th1 and Th2 cytokine profiles in ovalbumin immunized mice.Vaccine. 1999 Aug 20;18(1-2):140-52.
53. Sheikh NA, Rajananthanan P, Attard GS, Morrow WJ.Generation of antigen specific CD8+ cytotoxic T cells following immunization with soluble protein formulated with novel glycoside adjuvants. Vaccine. 1999 Aug 6;17(23-24):2974-82.
54. Rajananthanan P, Attard GS, Sheikh NA, Morrow WJ.Evaluation of novel aggregate structures as adjuvants: composition, toxicity studies and humoral responses.Vaccine. 1999 Feb 26;17(7-8):715-30.
56. Childers NF. Arthritis - Childer’s Diet to Stop It. Nightshades, Aging and Ill Health, 4th ed. Florida: Horticultural Publications, 1993.
57. Govindarajan VS, Sathyanarayana MN.Capsicum--production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences. Crit Rev Food Sci Nutr. 1991;29(6):435-74.
58. Bosland PW. Chiles: history, cultivation, and uses. In: Charalambous G (Ed.), Spices, Herbs and Edible Fungi (Herbs). Elsevier Science Publishers, Amsterdam, 1994, pp. 347-366.
59. Pruthi JS. Spices and Condiments. In: Chichester EM, Stewart GF (Eds), Academic Press, New York, 1980;p. 13.
60. Kozukue N, Han JS, Kozukue E, Lee SJ, Kim JA, Lee KR, Levin CE, Friedman M. Analysis of eight capsaicinoids in peppers and pepper-containing foods by high-performance liquid chromatography and liquid chromatography-mass spectrometry. J Agric Food Chem. 2005 Nov 16;53(23):9172-81.
61. Surh YJ, Lee SS. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Fd Chem Toxic 1996;34:313-316.
62. Thapa B, Skalko-Basnet N, Takano A, Masuda K, Basnet P. High-performance liquid chromatography analysis of capsaicin content in 16 Capsicum fruits from Nepal. J Med Food 2009;12:908-913.
63. Sasamura T, Kuraishi Y. Peripheral and central actions of capsaicin and VR1 receptor. Jpn J Pharmacol 1999;80:275-280.
64. Isoda H, Han J, Tominaga M, Maekawa T. Effects of capsaicin on human intestinal cell line Caco-2. Cytotechnology. 2001 Jul;36(1-3):155-61.
65. Han J, Isoda H, Maekawa T. Analysis of the mechanism of the tight-junctional permeability increase by capsaicin treatment on the intestinal Caco-2 cells. Cytotechnology. 2002 Nov;40(1-3):93-8.
66. Han JK, Akutsu M, Talorete TP, Maekawa T, Tanaka T, Isoda H. Capsaicin-enhanced Ribosomal Protein P2 Expression in Human Intestinal Caco-2 Cells. Cytotechnology. 2005 Jan;47(1-3):89-96.
67. Komori Y, Aiba T, Nakai C, Sugiyama R, Kawasaki H, Kurosaki Y. Capsaicin-induced increase of intestinal cefazolin absorption in rats. Drug Metab Pharmacokinet. 2007 Dec;22(6):445-9.
68. Tsukura Y, Mori M, Hirotani Y, Ikeda K, Amano F, Kato R, Ijiri Y, Tanaka K. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007 Oct;30(10):1982-6.
69. Jensen-Jarolim E, Gajdzik L, Haberl I, Kraft D, Scheiner O, Graf J. Hot spices influence permeability of human intestinal epithelial monolayers. J Nutr. 1998 Mar;128(3):577-81.