by Jason Fung
Counter-Regulatory Hormones
During fasting, insulin falls; in response, other hormones, called counter-regulatory hormones, increase. This name derives from the fact that these hormones run counter, or opposite, to insulin. As insulin goes up, these counter-regulatory hormones go down. When insulin goes down, these hormones go up.
The effect on glucose metabolism is also opposite to one another. Insulin pushes the body toward storage of glucose and body fat, and counter-regulatory hormones push the body toward usage of glucose and body fat. The main counter-regulatory hormones that become elevated from the activation of the sympathetic nervous system include adrenaline and noradrenaline. Other counter-regulatory hormones are cortisol and growth hormone.
THE SYMPATHETIC NERVOUS SYSTEM
The sympathetic nervous system controls the so-called “fight or flight” response. For example, if you suddenly face a hungry lion, your body activates the sympathetic nervous system to prepare your body to fight or to run really, really fast.
Your pupils dilate, your heart rate increases, and your body pushes glucose into the blood for use as a ready source of energy. This is an extreme example; a milder form of sympathetic nervous system activation happens during the early fasting period. The hormones cortisol, adrenaline, and noradrenaline are released into the blood as part of the general activation of the body for action.
Contrary to many people’s expectations, fasting, even for prolonged periods does not cause the body to shut down; instead, it ramps up and gets ready for action because of the energizing effect of the counter-regulatory hormones. Even up to four days of fasting results in an increase in resting energy expenditure (or basal metabolic rate).6 This is the energy used to generate body heat and to fuel the brain, heart, liver, kidneys, and other organs. When measuring the energy used for metabolism, studies show that after four days of fasting the body is using 10 percent more energy than at the beginning of the fasting period. Although most people mistakenly believe that the body shuts down during fasting, the opposite is true. Fasting, at least up to four days, does not seem to make you tired; it gives you more energy.
During fasting, the body is merely switching fuel sources from food to stored food energy, also known as body fat. Imagine we are prehistoric men and women. It’s winter, and food is scarce. We haven’t eaten for four days. If our bodies begin to shut down, then it will be even harder to find food. We fall into a vicious cycle. Every day we don’t eat means that it is much harder to get the energy to hunt or gather. As each day passes, our chance of survival progressively worsens. The human species would not have survived. Fortunately, our bodies are not that stupid.
Instead, our bodies switch fuel sources and pump us full of energy so that we have enough energy to hunt. Basal metabolism, sympathetic tone, and noradrenaline increase to fuel our bodies so that we can hunt. The VO2, a measure of the metabolic rate at rest, increases in conjunction.
GROWTH HORMONE
The other noteworthy counter-regulatory hormone that increases significantly during fasting periods is growth hormone (GH). Studies show that fasting for one day stimulates growth hormone secretion up to two to three times and continues to increase even up to five days of full fasting.7 At first, this seems counterintuitive: Why would we want to increase growth at a time where we are not eating? Growth hormone does exactly what the name implies, telling the tissues of the body to grow bigger and taller. If there are no nutrients available, why grow?
We can find the answer by following our bodies through the entire feeding-fasting cycle. When we eat, glucose and amino acids are absorbed and transported to the liver. Insulin is secreted, telling the body to store the incoming food energy (calories). We are in the fed state. All tissues of the body use glucose, and the excess is stored in the liver as glycogen or as body fat.
Blood glucose and insulin fall several hours after a meal, signaling the start of the fasted state. As described earlier, the body goes through a predictable set of adaptations to fasting or starvation. Liver glycogen is mobilized and broken down to individual glucose for energy. Gluconeogenesis transforms some proteins into glucose. The body begins to shift from glucose metabolism to fat metabolism. During this time growth hormone is increasing, but no proteins are being synthesized because insulin and mTOR levels are low. So little growth is actually happening, despite the high GH levels.
Once you eat, or break the fast, the body goes into the fed state once again. After a long fast, growth hormone is high. Because amino acids are now plentiful after the meal, our bodies rebuild all the necessary proteins to replace those that were broken down. Insulin stimulates protein synthesis. So, now, in the refed state, the body has high insulin, high growth hormone, amino acids, and glucose for energy—all the components it needs to build or rebuild protein. As with autophagy, this process represents renewal, as the body breaks down unnecessary protein preferentially and rebuilds the most necessary ones. Fasting in this sense rejuvenates the lean tissues.
GLUCOSE REQUIREMENTS AND PROTEIN BREAKDOWN
Under conditions of fasting, the body must maintain sufficient glucose for normal brain functioning. Glucose requirements substantially lower as the liver and muscles switch to fatty acids, and the brain switches to ketones. The body can convert some of the glycerol from fatty acids to glucose, but there is a limit to the amount that can be converted. The rest of the glucose must be delivered by gluconeogenesis, so there is still a small amount of protein breakdown. However, the protein that’s broken down is not specifically muscle cells. The proteins that turn over the most rapidly are the first proteins to be catabolized for glucose, including the skin and intestinal lining. In more than five years of working with patients in his Intensive Dietary Management program (www.IDMprogram.com), which uses therapeutic fasting for weight loss, Dr. Fung has not yet referred a patient for skin removal surgery—even for those patients who have lost more than one hundred pounds. Immune cells also have a high turnover and might be reduced during fasting, which accounts for some of the anti-inflammatory effect seen clinically. Muscle cells, which turn over infrequently, are relatively spared. Overall, protein catabolism drops from approximately 75 grams per day to only 10 to 20 grams per day to preserve protein during prolonged starvation.8
There is a significant difference in protein metabolism between lean and obese subjects. During prolonged fasting, obese subjects burn two to three times less protein compared to lean subjects. This makes perfect sense. If people have more fat to burn, their bodies will use more of it. If there is less fat, the body is forced to rely on protein. This situation holds true not only for humans but also animals. More than one hundred years ago, researchers showed that the proportion of energy derived from protein was lower in animals with more body fat (mammals, geese) than in lean animals (rodents, dogs). If you have more fat, you use it before you use protein. Thus, although obese subjects have more overall protein than leaner subjects, the obese subjects lose it at a slower rate compared to leaner people (see Figure 7.39).
Fig. 7.3: Reduced protein breakdown during fasting with increasing Body Mass Index
During prolonged fasting, a person with a Body Mass Index of 20 (borderline underweight) derives almost 40 percent of energy needs from protein. Compare that to a person with a Body Mass Index of 50 (morbidly obese) who may derive only 5 percent of energy from protein stores (see the figure of reduced protein breakdown). Once again this demonstrates our body’s inherent ability to survive. If we have stores of body fat, we use them. If we don’t have those stores, we don’t.
During prolonged fasting, fat oxidation accounts for approximately 94 percent of energy expenditure in obese subjects, whereas in lean subjects it’s only 78 percent. Protein oxidation accounts for the remainder of the energy because there are almost no carbohydrate stores left in the body after the first twenty-four hours or so. Lean subjects also increase their ketone production much quicker than obese subjects.10
Fig. 7.4: Reduced protein breakdown
during fasting with increasing Body Mass Index
The difference in ketone production during starvation between children, lean adults, and obese adults.
Exactly how much protein you need during fasting depends upon your condition. If you’re obese, fasting is very beneficial, and you will burn much more fat than protein. If you are quite lean, fasting might not be so beneficial because you will burn more protein. Your body is much smarter than you may give it credit for. It can handle itself during both feeding and fasting. Exactly how the body makes this adjustment is currently unknown.
Is this low level of protein breakdown a bad thing? Not necessarily. It is estimated that the obese person contains 50 percent more protein than a lean person.11 All the excess skin, connective tissue holding up the fat cells, blood vessels to supply the extra bulk, and so on is made up of connective tissue. Think about a picture of a survivor of a Japanese prisoner of war camp in World War II. Is there any excess skin on that body? No, all that person’s extra protein has been burned for energy or to maintain more important functions.
More importantly, many age-related diseases are characterized by excessive growth, not just of fat but also protein. Alzheimer’s disease, for example, is characterized by the excessive accumulation of protein in the brain that blocks proper signaling. Cancer is excessive growth of many things, including many types of proteins. If many of the chronic diseases we face today are diseases of “too-much-growth,” then the ability to break down proteins is a very powerful tool for health in the proper setting.
This may be the power of autophagy, the cellular recycling system that powerfully influences health. During fasting, which necessarily includes protein deprivation, the nutrient sensor mTOR is reduced, which stimulates the body to break down old, dysfunctional subcellular parts. Upon refeeding, the body builds new protein to replace the old in a complete renovation cycle. Instead of keeping old parts around, you are making new ones. Replacing old parts with new ones is an antiaging process.
People of many cultures have been drinking tea for thousands of years. It has been used in many Asian cultures for its purported health benefits and as a way of bringing the family together. Tea is a complex brew that contains numerous longevity-promoting compounds. In this chapter, we discuss the history and health benefits of tea, as well as the compounds and mechanisms we believe give tea its health-promoting and longevity properties.
A Brief History
Tea is the second most popular beverage in the world; only water surpasses it. Tea drinking is thought to have originated in China. An estimated 2.5 million tons of tea leaves are produced annually, and approximately 20 percent of that is green tea. The oldest tree in existence, from the Yunnan province of China, is an estimated 3,200 years old.
According to legend, Shen Nong discovered tea in 2700 BC. He was trying to understand the effects of eating various plants, and he tasted more than one hundred plants in a single day. Shen Nong was boiling some water in a pot when some leaves fell in, and he discovered that tea had a bitter taste, but it could make his thoughts quicker and his vision clearer.
Tea drinking quickly went “viral” and would have broken the Internet had the Internet existed in 2700 BC. Explorers carried the practice of drinking tea throughout the world on the various ancient trade routes. Because unprocessed tea is quite bitter, the origins of the word tea come from tu, which means bitter. In the mid-seventh century, a stroke was removed from the original Chinese character, and the word became cha. Today, virtually all languages worldwide use variations of either tea or cha. The ancient Chinese Min Nan dialect of the Fujian province used the word te, which spread via sea trade and has been translated into all types of languages, from the English word tea to the Maori word tii. The dialects in landlocked regions of China used the word cha and spread tea via the ancient Silk Road; that term led to the Swahili chai and the Russian chay, for example.
Buddhist priests carried the tea-drinking tradition to Korea and Japan, where tea was believed to have many medicinal qualities. In 1211 AD, the Japanese Zen priest Yeisai published the book Kitcha-Yojoki, which translates to Tea and Health Promotion. He wrote about the harvesting and production of tea and its many healthful attributes. Yeisai proclaimed that tea was a “divine remedy and a supreme gift of heaven.” Tea drinking had been restricted to nobility, but it started to spread to the general population. When the Shogun Sanetomo became ill from over-feasting, he summoned Yeisai to offer prayers. The priest supplemented his prayers with tea, and after the shogun recovered, he became a great tea devotee.
Portuguese traders brought tea from China to Europe, and by the 1600s it had spread to England; the English spread their cultural tastes (and their famous stiff upper lip) to much of the rest of the world. England bought so much tea from China that England developed a huge trade deficit because the Chinese didn’t want any English products other than silver.
Arabs introduced opium to China around 400 AD. The English (and other Europeans) later exploited the situation by directing opium trade routes from India to China. The English increased opium trade in China purposely to create a nation of addicts and to help offset their trade deficit. The Chinese government was not happy about the burgeoning opioid crisis and moved to ban the trade. In true gangland, drug-pusher style, the English sent in their big gunships to make sure the opium flowed freely. Thus began the two Opium Wars that eventually won England the port of Hong Kong. As if that were not enough, the English then proceeded to smuggle some trees out of China to set up tea plantations in India, which broke China’s 4,000-year-old monopoly on tea production. That’s the kind of ruthlessness that wins you a global empire.
Early writings about tea focused on its medicinal effects, particularly for digestion, rather than the taste (bitter, kind of metallic). Most modern studies have focused on green tea because of the high concentration of polyphenols and the beneficial effects of a class of compounds called catechins, the most abundant of which is epigallocatechin-3-gallate (EGCG). According to traditional Chinese medicine, tea helps weight control, and current research may only now be catching up to this traditional way of thinking.
What Is Tea?
Tea is the leaf of the plant Camellia sinensis, an evergreen shrub native to Asia. The varieties we consume—white, green, pu-erh, oolong, and black—differ only by the processing. Freshly harvested leaves are steamed, rolled, and dried, which inactivates the enzymes responsible for breaking down the color; the result is the stable green tea leaves you can buy anywhere. The processing also helps preserve the natural polyphenols in the leaves.
White tea is entirely unfermented and is made by harvesting tea leaves before they are fully open, and tiny white hairs still cover the buds; hence the name white tea. Green tea is minimally fermented or not fermented at all. Pu-erh tea is made from a tea base called maocha, and then it’s fermented, aged, and packed into tiny bricks; it has many flavors, including sweet, bitter, floral, mellow, woody, astringent, sour, earthy, watery, or even tasteless. Oolong tea is partially fermented, and full fermentation produces black tea. The polyphenols and catechins in unfermented tea change to theaflavins (although some EGCG metabolizes to theaflavins in the liver), which might have beneficial effects of their own, including antiviral, anticancer, and cholesterol-lowering benefits. People in Europe, North America, and North Africa drink mainly black tea, whereas Asians mostly drink oolong and green tea.
Tea contains more than 4,000 compounds, many of which appear to be beneficial for human health; the different classes of flavonoids are particularly beneficial. Other dietary sources of flavonoids include onions, apples, broccoli, and red wine, which is interesting because many of these foods are believed to be very healthy. An apple a day, for example, is purported to keep the doctor away. Red wine drinking has been associated with increased health and longevity. (Read more about red wine in Chapter 9.) Tea, which contains minerals, antioxidants, and amino acids, is one of the richest sources of phytonutrients available. The nations
of East Asia, such as Japan, are among the largest drinkers of tea in the world. Perhaps not coincidentally, they also enjoy some of the highest life expectancies in the world.1
One cup of tea (2 grams dry tea leaves) provides 150 to 200 milligrams of flavonoids compared to an average daily flavonoid intake of less than 1,000 gm per day. A high intake of dietary flavonoids is associated with a 20 percent lower risk for heart disease.2 Flavonoids may have a beneficial effect on the crucial endothelial cell layer that separates the blood from the artery wall. Any breach of this thin layer will expose the underlying blood vessel wall and trigger an inflammatory reaction that produces atherosclerosis (hardening of the arteries) and may even produce a blood clot, which is the underlying process of heart attacks and ischemic strokes. Depending on where this blockage occurs, this is called different things:
• In the heart, it’s a heart attack.
• In the brain, it’s an ischemic stroke.
• In the legs, it’s peripheral vascular disease.
