The Nature Cure

by Andreas Michalsen

  20. Rafael De Cabo, Didac Carmona-Gutierrez, Michel Bernier, Michael N. Hall, and Frank Madeo, “The Search for Antiaging Interventions: From Elixirs to Fasting Regimens,” Cell 157, no. 7 (2014): 1515–26.

  21. Amandine Chaix, Amir Zarrinpar, Phuong Miu, and Satchidananda Panda, “Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges,” Cell Metabolism 20, no. 6 (2014): 991–1005.

  22. Valter D. Longo and Satchidananda Panda, “Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan,” Cell Metabolism 23, no. 6 (2016): 1048–59.

  23. Frank Madeo, Tobias Eisenberg, Federico Pietrocola, and Guido Kroemer, “Spermidine in Health and Disease,” Science 359, no. 6374 (2018).

  24. Carlos López-Otín, Lorenzo Galluzzi, José M. P. Freije, Frank Madeo, and Guido Kroemer, “Metabolic Control of Longevity,” Cell 166, no. 4 (2016): 802–21.

  25. Gerald Huether, Dan Zhou, Sabine Schmidt, Jens Wiltfang, and Eckart Rüther, “Long-term Food Restriction Down-regulates the Density of Serotonin Transporters in the Rat Frontal Cortex,” Biological Psychiatry 41, no. 12 (1997): 1174–80.

  26. L. S. Hermann and M. Iversen, “Death During Therapeutic Starvation,” The Lancet 292, no. 7561 (1968): 217.

  27. A. G. Dulloo and J. P. Montani, “Pathways from Dieting to Weight Regain, to Obesity and to the Metabolic Syndrome: An Overview,” Obesity Reviews 16 (2015): 1–6.

  28. Andreas Michalsen and Chenying Li, “Fasting Therapy for Treating and Preventing Disease—Current State of Evidence,” Forschende Komplementärmedizin / Research in Complementary Medicine 20, no. 6 (2013): 444–53.

  29. Giulia Cesaroni, Francesco Forastiere, Massimo Stafoggia, Zorana J. Andersen, Chiara Badaloni, Rob Beelen, Barbara Caracciolo, Ulf De Faire, Raimund Erbel, Kirsten T. Eriksen, Laura Fratiglioni, Claudia Galassi, Regina Hampel, Margit Heier, Frauke Hennig, Agneta Hilding, Barbara Hoffmann, Danny Houthuijs, Karl-Heinz Jöckel, Michal Korek, Timo Lanki, Karin Leander, Patrik K. E. Magnusson, Enrica Migliore, Caes-Göran Ostenson, Kim Overvad, Nancy L. Pedersen, Juha Pekkanen, Johanna Penell, Göran Pershagen, Andrei Pyko, Ole Raaschou-Nielsen, Andrea Ranzi, Fulvio Ricceri, Veikko Salomaa, Wim Swart, Anu W. Turunen, Paolo Vineis, Gudrun Weinmayr, Kathrin Wolf, Kees De Hoogh, Gerard Hoek, Bert Brunekreef, Annette Peters, and Carlotta Sacerdote, “Long Term Exposure to Ambient Air Pollution and Incidence of Acute Coronary Events: Prospective Cohort Study and Meta-analysis in 11 European Cohorts from the ESCAPE Project,” BMJ, January 21, 2014, accessed January 14, 2019, https://www.bmj.com/content/348/bmj.f7412.

  30. Kristin G. Homme, Janet K. Kern, Boyd E. Haley, David A. Geier, Paul G. King, Lisa K. Sykes, and Mark R. Geier, “New Science Challenges Old Notion That Mercury Dental Amalgam Is Safe,” BioMetals 27, no. 1 (2014): 19–24.

  31. J. S. Lim, H. K. Son, S. K. Park, D. R. Jacobs, and D. H. Lee, “Inverse Associations between Long-term Weight Change and Serum Concentrations of Persistent Organic Pollutants,” International Journal of Obesity 35, no. 5 (2010): 744–47.

  32. Katja Matt, Katharina Burger, Daniel Gebhard, and Jörg Bergemann, “Influence of Calorie Reduction on DNA Repair Capacity of Human Peripheral Blood Mononuclear Cells,” Mechanisms of Ageing and Development 154 (2016): 24–29.

  33. Kristin Prehn, Reiner Jumpertz Von Schwartzenberg, Knut Mai, Ulrike Zeitz, A. Veronica Witte, Dierk Hampel, Anna-Maria Szela, Sonja Fabian, Ulrike Grittner, Joachim Spranger, and Agnes Flöel, “Caloric Restriction in Older Adults—Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function,” Cerebral Cortex 27, no. 3 (March 1, 2017): 1765–78.

  34. Kenichi Iwashige, Katsuyasu Kouda, Mitsuo Kouda, Kentaro Horiuchi, Masaaki Takahashi, Akira Nagano, Toshiro Tanaka, and Hiroichi Takeuchi, “Calorie Restricted Diet and Urinary Pentosidine in Patients with Rheumatoid Arthritis,” Journal of Physiological Anthropology and Applied Human Science 23, no. 1 (2004): 19–24.

  35. Dr. Somwail Rasla, Memorial Hospital of Alpert Medical School of Brown University in Providence, Rhode Island, American Heart Association, Scientific Sessions 2016, New Orleans, November 12–16, 2016.

  36. Andreas Michalsen, Martin K. Kuhlmann, Rainer Lüdtke, Marcus Bäcker, Jost Langhorst, and Gustav J. Dobos, “Prolonged Fasting in Patients with Chronic Pain Syndromes Leads to Late Mood-enhancement Not Related to Weight Loss and Fasting-induced Leptin Depletion,” Nutritional Neuroscience 9, no. 5–6 (2006): 195–200.

  37. Alan C. Goldhamer, Douglas J. Lisle, Peter Sultana, Scott V. Anderson, Banoo Parpia, Barry Hughes, and T. Colin Campbell, “Medically Supervised Water-Only Fasting in the Treatment of Borderline Hypertension,” The Journal of Alternative and Complementary Medicine 8, no. 5 (2002): 643–50.

  38. Alan Goldhamer, Douglas Lisle, Banoo Parpia, Scott V. Anderson, and T. Colin Campbell, “Medically Supervised Water-only Fasting in the Treatment of Hypertension,” Journal of Manipulative and Physiological Therapeutics 24, no. 5 (2001): 335–39.

  39. Sarah Steven, Kieren G. Hollingsworth, Ahmad Al-Mrabeh, Leah Avery, Benjamin Aribisala, Muriel Caslake, and Roy Taylor, “Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders,” Diabetes Care 39, no. 5 (2016): 808–15.

  40. Jessica Fuhrmeister, Annika Zota, Tjeerd P. Sijmonsma, Oksana Seibert, Şahika Cıngır, Kathrin Schmidt, Nicola Vallon, Roldan M. De Guia, Katharina Niopek, Mauricio Berriel Diaz, Adriano Maida, Matthias Blüher, Jürgen G. Okun, Stephan Herzig, and Adam J. Rose, “Fasting-induced Liver GADD45β Restrains Hepatic Fatty Acid Uptake and Improves Metabolic Health,” EMBO Molecular Medicine 8, no. 6 (2016): 654–69.

  41. Michael Ristow, “Unraveling the Truth About Antioxidants: Mitohormesis Explains ROS-induced Health Benefits,” Nature Medicine 20, no. 7 (2014): 709–11.

  42. L. Göhler, T. Hahnemann, N. Michael, P. Oehme, H.-D. Steglich, E. Conradi, T. Grune, and W. G. Siems, “Reduction of Plasma Catecholamines in Humans during Clinically Controlled Severe Underfeeding,” Preventive Medicine 30, no. 2 (2000): 95–102.

  43. Chia-Wei Cheng, Gregor B. Adams, Laura Perin, Min Wei, Xiaoying Zhou, Ben S. Lam, Stefano Da Sacco, Mario Mirisola, David I. Quinn, Tanya B. Dorff, John J. Kopchick, and Valter D. Longo, “Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression,” Cell Stem Cell 14, no. 6 (2014): 810–23.

  44. J. S. Bell, J. I. Spencer, R. L. Yates, S. A. Yee, B. M. Jacobs, and G. C. Deluca, “Invited Review: From Nose to Gut—the Role of the Microbiome in Neurological Disease,” Neuropathology and Applied Neurobiology (October 8, 2018).

  45. Lawrence A. David, Corinne F. Maurice, Rachel N. Carmody, David B. Gootenberg, Julie E. Button, Benjamin E. Wolfe, Alisha V. Ling, A. Sloan Devlin, Yug Varma, Michael A. Fischbach, Sudha B. Biddinger, Rachel J. Dutton, and Peter J. Turnbaugh, “Diet Rapidly and Reproducibly Alters the Human Gut Microbiome,” Nature 505, no. 7484 (2014): 559–64.

  46. Xinpu Chen and Sridevi Devaraj, “Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes,” Current Diabetes Reports 18, no. 12 (2018): 129.

  47. Patrice D. Cani, “Human Gut Microbiome: Hopes, Threats and Promises,” Gut 67, no. 9 (2018): 1716–25.

  48. Cani, “Human Gut Microbiome,” 1716–25.

  49. Marlene Remely, Berit Hippe, Isabella Geretschlaeger, Sonja Stegmayer, Ingrid Hoefinger, and Alexander Haslberger, “Increased Gut Microbiota Diversity and Abundance of Faecalibacterium Prausnitzii and Akkermansia after Fasting: A Pilot Study,” Wiener Klinische Wochenschrift 127, no. 9–10 (2015): 394–98.

  50. TEDx Talks, “Why Fasting Bolsters Brain Power: Mark Mattson at TEDxJohnsHopkinsUniversity,” YouTube, March 18, 2014, accessed January 14, 2019, https://www.youtube.com/watch?v=4UkZAwKoCP8.

  51. TEDx Talks, “Why Fasting Bolsters Brain Power.”

  52. Mark P. Mattson, Keelin Moehl, Nathaniel Ghena, Maggie Schmaed
ick, and Aiwu Cheng, “Intermittent Metabolic Switching, Neuroplasticity and Brain Health,” Nature Reviews Neuroscience 19, no. 2 (2018): 63–80.

  53. Mattson et al., “Intermittent Metabolic Switching,” 63–80.

  54. In Young Choi, Laura Piccio, Patra Childress, Bryan Bollman, Arko Ghosh, Sebastian Brandhorst, Jorge Suarez, Andreas Michalsen, Anne H. Cross, Todd E. Morgan, Min Wei, Friedemann Paul, Markus Bock, and Valter D. Longo, “A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms,” Cell Reports 15, no. 10 (2016): 2136–46.

  55. A. Michalsen, W. Weidenhammer, D. Melchart, J. Langhorst, J. Saha, and G. Dobos, “Kurzzeitiges Therapeutisches Fasten in Der Behandlung Von Chronischen Schmerz-Und Erschöpfungssyndromen—Verträglichkeit Und Nebenwirkungen Mit Und Ohne Begleitende Mineralstoffergänzung,” Complementary Medicine Research 9, no. 4 (2002): 221–27.

  56. Shubhroz Gill and Satchidananda Panda, “A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans That Can Be Modulated for Health Benefits,” Cell Metabolism 22, no. 5 (2015): 789–98.

  57. Hana Kahleova, Lenka Belinova, Hana Malinska, Olena Oliyarnyk, Jaroslava Trnovska, Vojtech Skop, Ludmila Kazdova, Monika Dezortova, Milan Hajek, Andrea Tura, Martin Hill, and Terezie Pelikanova, “Erratum To: Eating Two Larger Meals a Day (Breakfast and Lunch) Is More Effective than Six Smaller Meals in a Reduced-energy Regimen for Patients with Type 2 Diabetes: A Randomised Crossover Study,” Diabetologia 58, no. 1 (2014): 205.

  58. Ameneh Madjd, Moira A. Taylor, Alireza Delavari, Reza Malekzadeh, Ian A. Macdonald, and Hamid R. Farshchi, “Beneficial Effect of High Energy Intake at Lunch Rather than Dinner on Weight Loss in Healthy Obese Women in a Weight-loss Program: A Randomized Clinical Trial,” The American Journal of Clinical Nutrition 104, no. 4 (2016): 982–89.

  59. Mark P. Mattson, “Energy Intake and Exercise as Determinants of Brain Health and Vulnerability to Injury and Disease,” Cell Metabolism 16, no. 6 (2012): 706–22.

  60. Tatiana Moro, Grant Tinsley, Antonino Bianco, Giuseppe Marcolin, Quirico Francesco Pacelli, Giuseppe Battaglia, Antonio Palma, Paulo Gentil, Marco Neri, and Antonio Paoli, “Effects of Eight Weeks of Time-restricted Feeding (16/8) on Basal Metabolism, Maximal Strength, Body Composition, Inflammation, and Cardiovascular Risk Factors in Resistance-trained Males,” Journal of Translational Medicine 14, no. 1 (2016): 290.

  61. Catherine R. Marinac, Sandahl H. Nelson, Caitlin I. Breen, Sheri J. Hartman, Loki Natarajan, John P. Pierce, Shirley W. Flatt, Dorothy D. Sears, and Ruth E. Patterson, “Prolonged Nightly Fasting and Breast Cancer Prognosis,” JAMA Oncology 2, no. 8 (2016): 1049–55.

  62. Alessio Nencioni, Irene Caffa, Salvatore Cortellino, and Valter D. Longo, “Fasting and Cancer: Molecular Mechanisms and Clinical Application,” Nature Reviews Cancer 18, no. 11 (2018): 707–19.

  63. Hermann Hesse, Siddhartha. An Indian Poem: A New Translation by Susan Bernofsky (New York: The Modern Library, 2008), 54.

  CHAPTER FIVE: THE KEY TO HEALTH

  1. “Diet, Nutrition and the Prevention of Chronic Diseases,” World Health Organization, October 06, 2014, accessed January 14, 2019, https://www.who.int/dietphysicalactivity/publications/trs916/en/.

  2. Cristin E. Kearns, Laura A. Schmidt, and Stanton A. Glantz, “Sugar Industry and Coronary Heart Disease Research,” JAMA Internal Medicine 176, no. 11 (2016): 1680.

  3. Daniel G. Aaron and Michael B. Siegel, “Sponsorship of National Health Organizations by Two Major Soda Companies,” American Journal of Preventive Medicine 52, no. 1 (2017): 20–30.

  4. Michael Greger and Gene Stone, How Not to Die: Discover the Foods Scientifically Proven to Prevent and Reverse Disease (New York: Flatiron Books, 2015).

  5. Neal D. Barnard, Dreena Burton, and Marilu Henner, The Cheese Trap: How Breaking a Surprising Addiction Will Help You Lose Weight, Gain Energy, and Get Healthy (New York: Grand Central Life & Style, 2017).

  6. Greger and Stone, How Not to Die.

  7. Lewis C. Cantley, “Cancer, Metabolism, Fructose, Artificial Sweeteners, and Going Cold Turkey on Sugar,” BMC Biology 12, no. 1 (2014): 8.

  8. “National Center for Health Statistics,” Centers for Disease Control and Prevention, May 03, 2017, accessed January 14, 2019, https://www.cdc.gov/nchs/fastats/obesity-overweight.htm.

  9. Dean Ornish, Jue Lin, June M. Chan, Elissa Epel, Colleen Kemp, Gerdi Weidner, Ruth Marlin, Steven J. Frenda, Mark Jesus M Magbanua, Jennifer Daubenmier, Ivette Estay, Nancy K. Hills, Nita Chainani-Wu, Peter R. Carroll, and Elizabeth H. Blackburn, “Effect of Comprehensive Lifestyle Changes on Telomerase Activity and Telomere Length in Men with Biopsy-proven Low-risk Prostate Cancer: 5-year Follow-up of a Descriptive Pilot Study,” The Lancet Oncology 14, no. 11 (2013): 1112–20.

  10. Dean Ornish, “Intensive Lifestyle Changes for Reversal of Coronary Heart Disease,” JAMA 280, no. 23 (1998): 2001–07.

  11. Ornish et al., “Effect of Comprehensive Lifestyle Changes on Telomerase Activity and Telomere Length in Men with Biopsy-proven Low-risk Prostate Cancer.”

  12. Michel de Lorgeril, Patricia Salen, Jean-Louis Martin, Isabelle Monjaud, Jacques Delaye, and Nicole Mamelle, “Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction,” Circulation 99, no. 6 (1999): 779–85.

  13. Delfin Rodriguez-Leyva, Wendy Weighell, Andrea L. Edel, Renee Lavallee, Elena Dibrov, Reinhold Pinneker, Thane G. Maddaford, Bram Ramjiawan, Michel Aliani, Randolph Guzman, and Grant N. Pierce, “Potent Antihypertensive Action of Dietary Flaxseed in Hypertensive Patients,” Hypertension 62, no. 6 (2013): 1081–89.

  14. Michael Pollan, In Defense of Food: An Eater’s Manifesto (London: Penguin Books, 2009).

  15. Pollan, In Defense of Food.

  16. Pollan, In Defense of Food.

  17. Thomas M. Campbell and T. Colin Campbell, The China Study: Revised and Expanded Edition (Dallas: BenBella Books, 2016).

  18. Kayo Kurotani, Shamima Akter, Ikuko Kashino, Atsushi Goto, Tetsuya Mizoue, Mitsuhiko Noda, Shizuka Sasazuki, Norie Sawada, and Shoichiro Tsugane, “Quality of Diet and Mortality among Japanese Men and Women: Japan Public Health Center Based Prospective Study,” BMJ 352 (March 2016): i1209.

  19. Dan Buettner, The Blue Zones: Lessons for Living Longer from the People Who’ve Lived the Longest (Washington, D.C.: National Geographic, 2008).

  20. Ancel Benjamin Keys, Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease (Cambridge, MA: Harvard University Press, 1980).

  21. Walter C. Willett, P. J. Skerrett, Edward L. Giovannucci, and Maureen Callahan, Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating (New York: Simon & Schuster Source, 2001).

  22. R. Estruch, E. Ros, J. Salas-Salvadó, M.-I. Covas, D. Corella, F. Arós, et al., “Primary Prevention of Cardiovascular Disease with a Mediterranean Diet,” New England Journal of Medicine 368 (2013): 1279–90.

  23. Christa B. Hauswirth, Martin R. L. Scheeder, and Jürg H. Beer, “High ω-3 Fatty Acid Content in Alpine Cheese,” Circulation 109, no. 1 (2004): 103–07.

  24. Greger and Stone, How Not to Die.

  25. Hans Konrad Biesalski, Stephan C. Bischoff, Matthias Pirlich and Arved Weimann, Ernährungsmedizin: Nach dem Curriculum Ernährungsmedizin der Bundesärztekammer (Stuttgart: Georg Thieme Verlag, 2018).

  26. Dagfinn Aune, Nana Keum, Edward Giovannucci, Lars T. Fadnes, Paolo Boffetta, Darren C. Greenwood, Serena Tonstad, Lars J. Vatten, Elio Riboli, and Teresa Norat, “Whole Grain Consumption and Risk of Cardiovascular Disease, Cancer, and All Cause and Cause Specific Mortality: Systematic Review and Dose-response Meta-analysis of Prospective Studies,” BMJ (2016): i2716.

  27. The Editors of Encyclopaedia Britannica, “John Harvey Kellogg,” Encyclopaedia Britannica, December 10, 2018, accessed January 14, 2019, https://www.britannica.com/biography/John-Harvey-Kellogg.


  28. Gary Taubes, Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health (New York: Anchor, 2008).

  29. Tobias Hoch, Silke Kreitz, Simone Gaffling, Monika Pischetsrieder, and Andreas Hess, “Fat/Carbohydrate Ratio but Not Energy Density Determines Snack Food Intake and Activates Brain Reward Areas,” Scientific Reports 5, no. 1 (2015).

  30. Lewis C. Cantley, “Seeking out the Sweet Spot in Cancer Therapeutics: An Interview with Lewis Cantley,” Disease Models & Mechanisms 9, no. 9 (2016): 911–16.

  31. John Yudkin, Pure, White, and Deadly: How Sugar Is Killing Us and What We Can Do to Stop It (New York: Penguin Books, 2013).

  32. Robert H. Lustig, Fat Chance: Beating the Odds against Sugar, Processed Food, Obesity, and Disease (New York: Plume, 2014).

  33. Costas A. Lyssiotis and Lewis C. Cantley. “F Stands for Fructose and Fat,” Nature 502, no. 7470 (2013): 181–82.

  34. T. Jensen, M. F. Abdelmalek, S. Sullivan, K. J. Nadeau, M. Green, C. Roncal, T. Nakagawa, M. Kuwabara, Y. Sato, D. H. Kang, D. R. Tolan, L. G. Sanchez-Lozada, H. R. Rosen, M. A. Lanaspa, A. M. Diehl, and R. J. Johnson, “Fructose and Sugar: A Major Mediator of Non-alcoholic Fatty Liver Disease,” Current Neurology and Neuroscience Reports, May 2018, accessed January 14, 2019, https://www.ncbi.nlm.nih.gov/pubmed/29408694.

  35. Allison M. Meyers, Devry Mourra, and Jeff A. Beeler, “High Fructose Corn Syrup Induces Metabolic Dysregulation and Altered Dopamine Signaling in the Absence of Obesity,” PLoS One 12, no. 12 (2017).

  36. Martin Raithel, Michael Weidenhiller, Alexander Fritz-Karl Hagel, Urban Hetterich, Markus Friedrich Neurath, and Peter Christopher Konturek, “The Malabsorption of Commonly Occurring Mono and Disaccharides,” Deutsches Aerzteblatt Online, 2013.

  37. Fernando Elijovich, Myron H. Weinberger, Cheryl A. M. Anderson, Lawrence J. Appel, Michael Bursztyn, Nancy R. Cook, Richard A. Dart, Christopher H. Newton-Cheh, Frank M. Sacks, and Cheryl L. Laffer, “Salt Sensitivity of Blood Pressure,” Hypertension 68, no. 3 (2016): e7–e46.