Introduction

Humans, unlike chimpanzees, have the ability to survive on water for extended periods of time.¹ The primary adaptation is the ability to use ketones from fat metabolism as an alternate fuel for the central nervous system.² The beauty of this adaptation is that during fasting the body prioritizes fat catabolism, the most concentrated caloric energy resource (9 vs 4 kcal for carbohydrates and protein), and thus safeguards catabolism of essential structures (nerves, muscles, organs, etc.) until stored adipose tissue is severely depleted—after fasting several weeks to months, depending on fat stores as well as metabolic, stress, and activity level. However, once this threshold is crossed in unattended fasting, starvation ensues (the body uses essential tissue for fuel, relying on protein as a major fuel source), resulting in death due to organ failure.³

Therapeutic fasting is voluntary, supervised abstinence from all food and drink except water for a specific time. The health promoting benefits are due to the marshalling of our metabolic potential as cellular systems manage internal resources more efficiently. The body thus can restore structure and function in a way analogous to rebooting a computer that has stopped working properly. Unlike a machine, however, the body can adapt dynamically to its internal environment, allowing the body to do what it does best, heal itself.

History

Throughout history, people of various cultures and religions have recognized the value of fasting. Numerous references appear in the Bible, Koran, pagan writings, and writings of the ancient Greeks.^4–6 One of the earliest doctors to use therapeutic fasting in the United States was Isaac Jennings (1788 to 1874). In 1822, Jennings discarded the use of drugs and, through the influence of Presbyterian preacher Sylvester Graham (1794 to 1851), began advocating fasting and other aspects of hygienic treatment (vegetarian diet, pure water, sunshine, clean air, exercise, emotional poise, and rest). This treatment later came to be known as “natural hygiene.”^5–9 Other doctors who followed in the hygienic tradition were James C. Jackson (1811 to 1895), Russell T. Trall (1812 to 1877), William A. Alcott (1798 to 1859), Mary Grove Nichols (1810 to 1884), Thomas L. Nichols (1815 to 1901), Edward H. Dewey (1837 to 1904), George H. Taylor (1821 to 1896), Harriet Austin (1826 to 1891), Charles E. Page (1840 to 1925), Emmett Densmore (1837 to 1911), Helen Densmore (? to 1904), Susanna W. Dodds (1830 to 1915), Felix Oswald (1845 to 1906), Robert Walter (1841 to 1921), John H. Tilden (1851 to 1940), and George S. Weger (1874 to 1935). Most of these physicians graduated as medical doctors (MDs) from eclectic medical schools and published various works on lifestyle, diet, and fasting.^7–14

The hygienic lineage continued into the mid-1900s, mainly due to Herbert M. Shelton, DC, ND (1895 to 1985), who developed a stricter protocol for fasting (water only; no enemas, exercise, or treatments; and complete rest). Shelton began his study of fasting in 1911 by reading the popular writers of his day: Sinclair, Carrington, Hazzard, Haskell, Purinton, Tilden, and MacFadden. He studied under the fasting authorities of his time at MacFadden’s College (Chicago, Ill.), Crane’s Sanatorium (Elmhurst, Ill.), and Crandall’s Health School (York, Penn.).^7,12 (Among the earliest fasting institutions of this time were Lindlahr’s Nature Cure Sanatoriums, including the Jungborn—the last operated by Benedict Lust, the founder of naturopathy in the United States, the MacFadden’s Healthatorium, and the Tilden’s Health School.)⁸ In 1928, he founded a fasting institution and health school that provided services for more than 40 years.⁷

In 1949, Dr, Shelton along with William Esser, ND, DC; Christopher Gian-Cursio, ND, DC; and Gerald Benesh, ND, DC, formed the American Natural Hygiene Society, now called the National Health Association,^7,14 a lay organization dedicated to preserving the tenets of hygiene. In 1978, a professional branch was formed (International Association of Hygienic Physicians [IAHP]) to study and promote therapeutic fasting. Today, the IAHP organizes clinical training and examination, leading to certification in therapeutic fasting.¹⁵

Physiology

It has been suggested that humans, like other species, have evolved special biochemical pathways to subsist for long periods without food during periods of food scarcity (climate, injury, illness).¹⁶ While fasting, the body primarily uses fat stores from adipose tissue for energy while recycling nonessential tissue for maintenance of pivotal systems. This streamlining utilizes nonessential protein sources, including digestive and glycolytic enzymes, muscle contractile fibers, and other connective tissue. Research has determined that an average 70-kg man has the fat stores to maintain basic caloric requirements for 2 to 3 months of fasting^17–21 (Tables 37-1 and 37-2). However, as this threshold approaches, the body can no longer effectively or efficiently mobilize fat stores for fuel, and significant protein catabolism again becomes necessary for energy production.¹⁷

TABLE 37-2 Utilization of Energy Reserves

^* These estimates are based on 100% utilization of each fuel.

Data from Shils ME. Modern nutrition in health and disease, 9th ed. Philadelphia: Lea & Febiger, 1998; White A, Handler P, Smith EL. Principles of biochemistry, 6th ed. New York: McGraw-Hill, 1978; Montgomery R, Dryer RL, Conway TW, Spector AA. Biochemistry: a case-oriented approach, 6th ed. St Louis: CV Mosby, 1996; Nutrition reviews’ present knowledge in nutrition, 5th ed. Washington, DC: Nutrition Foundation, 1984:439-453.

During feeding, the conversion of fatty acids to acetyl coenzyme-A (CoA) is regulated by the availability of L-glycerol 3-phosphate (derived from glucose through the glycolytic pathway). As the concentration of acetyl CoA rises, it is resynthesized into triglycerides, with L-glycerol 3-phosphate serving as the accepter to which three acyl CoA groups are attached (through esterification). Conversely, during fasting, there is inadequate glucose to provide the needed glycerol for triglyceride synthesis, resulting in acetyl CoA levels in excess of the oxidative capacity of the Krebs cycle. The excess is then shunted into the synthesis of ketone bodies.²²

Research using respiratory quotient and urinary nitrogen studies has repeatedly shown that triglycerides are the major fuel during fasting.^17–23 Inadequate blood glucose in fasting prompts hydrolysis (lipolysis) of triglycerides within adipocytes, allowing fatty acids and glycerol to leave the cell. The fatty acids are transported in a physical complex with albumin to the liver, muscle, and other tissues. Fatty acid oxidation results in large quantities of ketones secreted into the blood stream, usually noted on urinalysis by day three.²⁴ These ketone bodies (acetoacetic acid, acetone, and β-hydroxybutyric acid) are utilized by the heart and, in fasting, by the brain for energy production.² Because the ketone bodies are acids, their entry into the plasma results in a rise in hydrogen ions. This change is buffered by the conversion of bicarbonate into carbonic acid and then to carbon dioxide, which is exhaled. In extended fasts, the buffering capacity is surpassed and the plasma pH decreases, leading to mild metabolic acidosis with a compensatory increase in respiratory rate with noted electrolyte imbalance.²²

The initial physiologic response to fasting is the liver’s increased release of glucose to maintain adequate blood levels as undigested calories are exhausted in 4 to 8 hours. After only 12 hours, the liver’s glycogen stores become exhausted, and blood glucose is maintained by gluconeogenesis from triglyceride glycerol in fat reserves as well as from glucogenic amino acids and primarily from lactate (Cori) and alanine cycle from muscles.^25,26 Interestingly, muscles contain more glycogen than the liver, but lack the enzyme required to convert glycogen to glucose (D-glucose-6-phosphatase). Through the Cori cycle, stored energy is shuttled as lactate to the liver and then used by body systems as glucose, where as in the feeding state, it would commonly be shuttled back to the muscles¹⁹ (Figure 37-1). As the fast proceeds, the kidneys become progressively more important in the maintenance of blood glucose levels, and eventually, the renal cortex synthesizes more glucose from amino acids than does the liver.¹⁶ Note that glucose is also recycled by the breakdown of blood cells in the liver.^19–21

FIGURE 37-1 Mechanisms of glucose production during fasting.

Under normal feeding conditions, the energy requirement of the mature brain is met almost entirely by glucose. Because the glycogen content of the brain is very low (0.1%), there is essentially no brain glucose reserve. Although the brain converts to oxidation of β-hydroxybutyrate after 4 to 7 days, there is still an obligatory need for approximately 80 g/day of glucose for the brain, red cells, muscles, and other tissues (400 to 600 kcal/day of glucose).^24,27 Approximately 16 g of glucose is synthesized from triglyceride glycerol, with the rest of the glucose requirement (and the other metabolic processes requiring amino acids, such as enzyme turnover) being met by the catabolism of 18 to 24 g/day of protein.

All amino acids are glucogenic (with the exception of leucine, which appears to be a regulator of protein turnover in muscle),²⁸ but alanine plays a prominent role analogous to lactate in the Cori cycle.^25,26 The alanine cycle provides the mechanism for the recycling of a fixed supply of glucose and the effective transportation to the liver of amino acid nitrogen derived from muscle breakdown. Because muscle, unlike the liver, is incapable of synthesizing urea, most of the amino nitrogen from protein breakdown is transferred to pyruvate to form alanine. The alanine enters the blood and is taken up by the liver. The amino groups are removed to form urea, and the resulting pyruvate is converted to glucose. The newly synthesized glucose is secreted into the blood, taken up by the muscle, and catabolized to pyruvate to reseed the alanine cycle.²²

During physical activity and exercise, there are incremental increases in the glucose requirement by the heart and skeletal muscle that require protein catabolism. Although much of the lactate produced by anaerobic metabolism of glucose and glycogen is resynthesized to glucose by the liver via the Cori cycle, the need for glucose is increased, because there is a net loss due to urinary excretion of lactic acid and metabolic inefficiency. Conversely, the energy for resting heart and skeletal muscle is met primarily by oxidation of fatty acids and acetoacetate (ketone). Therefore, during fasting, cannibalized protein reserves are directly related to the degree of physical activity.

Specific physical changes during fasting include decreases in body weight, pulse,^3,18,29 and blood pressure (BP),^3,18,30,31 and a drop in the basal metabolic rate by about 1% per day until stabilizing at about 75% of normal.³¹ Other cardiac adaptations noted on an electrocardiogram present as sinus bradycardia, decreased QRS complex and T-wave amplitude, elongation of the QT interval, and shifts to the right of the QRS and T-wave axes. These changes return to normal with return to food,^3,29,31,32 similar to those animals that have prescribed adaptive mechanisms and hibernation cycles.

Research

Research into fasting has been reported since 1880, with the earliest record of therapeutic fasting in the medical literature appearing in 1910. The earliest research was primarily observational, as physiologic and metabolic changes were recorded while an individual fasted—Tanner (40 days in 1880),³³ Jacques (30 days in 1887 and 40 days in 1888),³⁴ Penny (30 days in 1905),³⁵ and Levanzin (31 days in 1912).¹⁸

In 1923, the classic Fasting and Undernutrition provided in-depth analysis of animal and human physiologic changes and reactions during fasting by Morgulis at the University of Nebraska.³⁰ In 1950, Ancel Keys³ at the University of Minnesota compiled two volumes entitled The Biology of Human Starvation describing the detailed observations of 32 volunteers who fasted for up to 8 months with comparisons to food deprivation observations made during the Second World War. Perhaps the most important observation was that fasting did not cause vitamin or mineral deficiencies. Related starvation research in developing countries noted that those who fasted completely lived longer than those on protein-deficient diets.¹⁶

Since these groundbreaking works, published clinical studies on therapeutic fasting have demonstrated benefit in almost every organ system. The following is a partial list of diseases and conditions that are beneficially influenced by fasting: chemical poisoning, cardiovascular disease and hypertension, diabetes, epilepsy, obesity, pancreatitis, and immune/inflammatory conditions (all expanded upon), as well as asthma, lumbago, depression and psychosomatic diseases, neurogenic bladder, irritable bowel syndrome, dysorexia nervosa (impaired or deranged appetite),³⁶ neurosis and schizophrenia,³⁷ parasites,³⁸ duodenal ulcers,³⁹ uterine fibroids,⁴⁰ varicose ulcers,⁴¹ thrombophlebitis,⁴² eczema,^3,43 and psoriasis.^3,44,45