FASTING / DETOX & REJUVENATION
禁食-排毒-嫩肤 JIN SHI / PAIDU & NEN FU

Fasting is not starvation. To fast is to voluntarily abstain from foods for therapeutic or religious purposes. Many religious groups including Muslims, Christians, Jews, Buddhists and Hindus incorporate periods of fasting into their rituals. Muslims fast from dawn until dusk during the month of Ramadan, and Christians, Jews, Buddhists and Hindus traditionally fast on designated days of the week.

Fasting has been practiced for millennia, but only recently studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity in part by reprogramming metabolic and stress resistance pathways. Fasting in humans cleanses the body of toxins and it excites the cells into processes that are not stimulated when a steady stream of fuel from food is present. When fasting, the body does not have its usual access to glucose, forcing the cells to resort to other means and materials to produce energy. As a result, the body begins gluconeogenesis, that is the metabolic process by which organisms produce sugars or glucose for catabolic reactions from non-carbohydrate precursors.

Recent findings suggest that the metabolic switch from glucose to fatty acid‐derived ketones represents an evolutionary conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage with plentiful glucose availability, to mobilization of fat through fatty acid oxidation and fatty acid‐derived ketones in the absence of glucose, which serve to preserve muscle mass and function. In humans intermittent or periodic fasting protects against diabetes, cancers, heart disease and neurodegeneration, and it also helps reduce obesity, hypertension, asthma and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.

Fasting results in ketogenesis, promotes potent changes in metabolic pathways and cellular processes such as stress resistance, lipolysis and autophagy, and can have medical applications that in some cases are as effective as those of approved drugs such as the dampening of seizures and seizure-associated brain damage and the amelioration of rheumatoid arthritis^[1] Depending on body weight and composition, the ketone bodies, free fatty acids and gluconeogenesis allow the majority of human beings to survive 30 or more days in the absence of any food and allow certain species to survive for over 5 months without food. Note the king penguins.^[2]

Reduction in caloric intake without malnutrition, has consistently been found to produce reductions in body weight and extend healthy life span across a variety of species^[3] Studies conducted in overweight humans indicate that short‐term─6 months─ of caloric restriction (CR) can significantly improve several cardiovascular risk factors, insulin‐sensitivity, and mitochondrial function^[4] Findings also show that the vast majority of humans have significant difficulty sustaining daily CR for long periods of time^[5] In contrast to traditional caloric restriction paradigms, Intermittent Fasting (IF) is a dietary approach that requires fasting for varying periods of time, typically for 12 hours or longer.^[6] Intermittent fasting isn’t just a weight loss strategy or a trick bodybuilders use to lose fat quickly while maintaining lean muscle mass. It is at its best a healthy lifestyle informed by human evolution and the study of metabolism. It asks the human body to be much more efficient and self-protective than it is accustomed to being in modern times. There are many things that happen when fasting that either do not happen when in constant fed state, or that happens very slowly in the background of glucose metabolism.

TERMS USED TO DESCRIBE DIFFERENT TYPES OF EATING PATTERNS

Caloric restriction (CR)	This eating pattern involves a continuous reduction in caloric intake without malnutrition.
Intermittent Fasting (IF)	This eating pattern involves fasting for varying periods of time, typically for 12 h or longer.
Time‐restricted feeding (TRF)	This eating pattern involves restricting food intake to specific time periods of the day, typically between 8 and 12 h each day.
Alternate‐day fasting (ADF)	This eating pattern involves consuming no calories on fasting days and alternating fasting days with a day of unrestricted food intake, or a “feast” day.
Alternate‐day modified fasting (ADMF)	This eating pattern involves consuming less than 25% of baseline energy needs on “fasting” days, alternated with a day of unrestricted food intake, or a “feast” day.
Periodic fasting (PF)	This eating pattern consists of fasting only 1‐2 d/wk and consuming food ad libitum on 5‐6 d/wk.

 

 

 

MECHANISM OF FASTING

In most mammals, the liver serves as the main reservoir of glucose, which is stored in the form of glycogen. The metabolic switch typically occurs in the third phase of fasting when glycogen stores in hepatocytes are depleted and accelerated adipose tissue lipolysis produces increased fatty acids and glycerol. In humans this metabolic switch usually occurs between 12 and 36 hours after cessation of food intake depending on the liver glycogen content at the beginning of the fast, and on the amount of the individual’s energy expenditure or physical activity during the fast.^[7]

In a well-fed state, the individual cell in the body is in ‘growth’ mode. The insulin signaling and mTOR pathways that tell cells to grow, divide, and synthesize proteins, are active. The mammalian target of rapamycin (mTOR) wants to have plentiful nutrients around, especially carbohydrates and proteins. When active, mTOR tells the cell not to engage in autophagy, or cellular self-eating, which is a recycling and cleanup process that rids the body of damaged and misfolded proteins. The well-fed cell is not efficient and does not recycle its components – for it is occupied in growing and dividing.

In a well-fed state, cells and their components are highly acetylated. This means that various molecules in cells, including the packaging proteins called histones that wrap around DNA within the core of the cells, are closely surrounded by acetyl groups on their amino acid lysine residues. The well-fed cell has many genes, including those turned-on associated with cellular survival and proliferation. This is because acetylation tends to loosen the packaging proteins that normally keep DNA wrapped up and lets packaging DNA be read for protein production.

While cells turn-on cellular growth and proliferation genes during feeding states, they turn-off other genes, which include genes related to fat metabolism, stress resistance and damage repair, that when fasting, in the absence of glucose and proteins, the fatty acids released by the liver into the blood metabolize into ketone bodies that turn these genes back on, leading to lowered inflammation and stress resistance in the brain.

Stored fat is used by the liver to produce ketone bodies. Ketones serve as an alternative energy source for the cells of the heart, skeletal muscle, and brain, when glucose is not readily available. In a feeding state, the brain uses up the majority of the glucose available when the body is in the resting state. When fasting, ketones generated by the liver replace glucose as fuel for the brain as well as other organs. This ketone usage by the brain is one of the reasons that fasting is often claimed to promote mental clarity and positive mood; ketones produce less inflammatory products as they are being metabolized than does glucose, and they initiate production of brain-derived neurotrophic factor BDNF.

With regards to adaptive responses of the brain to limited food availability during human evolution is BDNF. Studies have shown that strenuous exercise and intermittent fasting,  mutually exclusive (not together), increase BDNF expression in several regions of the brain. BDNF signaling in the brain may also mediate behavioral and metabolic responses to fasting and exercise including regulation of appetite, activity levels, peripheral glucose metabolism and autonomic control of the cardiovascular and gastrointestinal systems. Ketones have been shown to reduce cellular damage and cell death in neurons and reduce inflammation in other cell types. ^[8][9]

The human body has a well-preserved starvation program that kicks the cells into a different state when food, particularly glucose, is not present. During fasting and physical activity, the AMPK signaling pathway is activated. AMPK or 5′ AMP-activated protein kinase is the brake to mTOR’s gas pedal. AMPK signals the cell to go into self-protective mode, activating autophagy and fat breakdown. AMPK inhibits mTOR.

At the same time, while fasting the levels of an organic molecule called NAD+ begin to rise because the dietary proteins and sugars that normally convert NAD+ to NADH through the Krebs cycle are not present. Resveratrol promotes longevity by activating proteins called sirtuins. For sirtuins to function, they require the coenzyme NAD+. NAD+, a coenzyme whose precursor is Vitamin B3, activates the sirtuins SIRT1 and SIRT3. These sirtuins are proteins that remove the acetyl groups we talked about above from histones that wrap around DNA within the core of the cells and other proteins. NAD+ is vital for youthful cell function including DNA repair. In this process, the sirtuins silence genes related to cell proliferation and activate proteins involved in creating new mitochondria ─the power-generating factories of cells─ and cleaning up reactive oxygen species.^[9]

WHAT HAPPENS DURING A FAST

If a high carbohydrate or high protein meal is consumed, insulin will spike, and it will take about 8 to 10 hours to start to decrease. If only a small meal was consumed the insulin will decrease a lot quicker. Fasting starts at the moment one stops eating.

At 12 hours from the last meal, production of growth hormone is initiated. Growth hormone helps burn fat, build muscle, and slow aging. After the 12 hour fast the increase of growth hormone is about 1300% and the body enters the metabolic state called ketosis.^{[10] [11]} Ghrelin, the hunger hormone, also promotes growth hormone secretion. Growth hormone helps preserve lean muscle mass and reduces fat tissue accumulation, particularly as we age. It also appears to play a role in mammalian longevity and can promote wound healing and cardiovascular health.^[12]

At 13 to 15 hours the body senses that outside source of fuel has stopped, and it goes to fat reserves to use as energy as opposed to sugar. It begins to burn fat. Gluconeogenesis begins. Gluconeogenesis is the metabolic process by which organisms produce glucose for catabolic reactions from non-carbohydrate precursors. Ketones begin to increase.

At 16 to 17 hours autophagy begins. Lowered insulin levels put a brake on the insulin and mTOR signaling pathways, activating autophagy. Autophagy is the body’s way of cleaning out damaged cells, in order to generate newer, healthier ones.^[13] “Auto” means self and “phagy” eat. So, the literal meaning of autophagy is “self-eating.” Autophagy continues on up to 72 hours. Gluconeogenesis continues, ketones continue to increase.

At 18 hours to 23 hours, the body has switched to fat-burning mode and is generating significant ketones.^[14] It is now possible to measure blood ketone levels above baseline values. Under normal conditions, the concentration of ketones in plasma ranges between 0.05 and 0.1 mM (nanometers). When fasting or restricting carbohydrates in the diet, this concentration can reach 5-7 mM. As the level of ketones in the bloodstream rises, they act as signaling molecules, similar to hormones, telling the body to ramp up stress-relieving pathways that reduce inflammation and repair damaged DNA.

At 24 to 35 hours magic happens and continues. A process called autophagy begins when the body is substantially depleted of glucose stores and the insulin levels have dropped. Three major organs start to repair. Large intestinal stem cells start to regenerate (leaky gut, candida, etc. are all influenced); the body starts to create more of the protein BDNF in the brain, fertilizer for the brain, this protein finds neurons and dendrites in the brain that are degenerating and cause memory loss, influence Alzheimer’s, lack of focus, depression, anxiety; CRP C-Reactive Protein levels begin to decrease because inflammation begins to lessen.  CRP is a protein made by the liver. It is sent into the bloodstream in response to inflammation. Inflammation is the body’s way of protecting tissues if injured or have an infection. It can cause pain, redness, and swelling in the injured or affected area. Gluconeogenesis continues, ketone production continues. Until feeding restarts, all of these changes continue to happen.^[15]

At 36 to 48 hours Gluconeogenesis continues and ketone production accelerates and signals Gamma aminobutyric acid production (GABA), which is a naturally occurring amino acid that works as a neurotransmitter in the brain. Neurotransmitters function as chemical messengers. GABA is considered an inhibitory neurotransmitter because it blocks, or inhibits, certain brain signals and decreases activity in the nervous system. GABA relieves anxiety, improves mood, reduces symptoms of PMS, and treats ADHD. It also promotes lean muscle growth, burning fat, stabilizing blood pressure, and relieving pain. ^[15]

At 39 to 54 hours, insulin has dropped to its lowest level point since fasting begun and the body is becoming increasingly insulin-sensitive.^[16] Lowered insulin levels can reduce inflammation, make the body more insulin sensitive and/or less insulin resistant, which is especially good in a high risk of developing diabetes or to protect from chronic diseases of aging including cancer.

By 72 hours, the body is breaking down old immune cells and generating new ones and stem cell production accelerates and healing continues.^[17]

Prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations. IGF-1, or insulin-like growth factor 1, looks a lot like insulin and has growth-promoting effects on almost every cell in the body. IGF-1 activates signaling pathways including the PI3K-Akt pathway that promotes cell survival and growth. PKA activates the mTOR pathway  and too much caffeine during a fast may promote activation of PKA.

Pressing the brakes on IGF-1 and PKA through nutrient restriction and fasting can turn down cellular survival pathways and lead to breakdown and recycling of old cells and proteins. Studies in mice have shown that prolonged fasting ─greater than 48 hours, by reducing IGF-1 and PKA, leads to stress resistance, self-renewal and regeneration of hematopoietic or blood cell stem cells. Through this same mechanism, prolonged fasting for 72 hours has been shown to preserve healthy white blood cell or lymphocyte counts in patients undergoing chemotherapy.

SOME DETOX SYMPTOMS DURING A FAST

Rash	Headaches
Eczema	Fainting
Acne	Fever
Weakness	Diarrhea
Nausea	Muscle aches
Dizziness	Bad breath
Fatigue	Stuffy nose
Hot flashes	Runny nose
Bronchitis	Irregular heartbeat
Asthma	Menstrual irregularities

 

REFEEDING

The last and important stage of fasting is the refeeding stage. It is imperative to break the fast with a nutritious meal that will further improve the function of cells and tissues that went through cleanup while in the fasting state. A ketogenic state of living is necessary to reap the benefits of fasting. Ketogenic state does not mean ketogenic diet in its entirety, but a modified version of it is recommended. The modified ketogenic diet will be plant based with non-starchy vegetables, fermented foods, i.e. kimchi, natto, pickled items, low-glycemic fruits, i.e. berries family, pomegranate, kiwi. The ideal diet  includes some animal products, i.e. low-mercury fish as in Salmon, Mackerel, Anchovies, Sardines, and Herring; lamb, and Healthy monounsaturated fats, such as nuts, seeds, olive oil, coconut oil. The meats in the diet are not the center of the meal, but a side of it; the vegetables are the center. In the Intermittent Fast (IF), the ketogenic state refers to a 12 hour nightly fast and a 3 hour fast before bedtime. Making IF and ketogenic state dieting a lifestyle will ensure lasting rewards and longevity.

HOW TO BREAK THE INTERMITTENT FAST (IF)

How to break the fast can be just as important as how one fasts.

First. Break the IF with a small low carbohydrate snack such as bone broth.

Second. Have the first meal an hour or two after the broth snack.

Third. Resist the urge to “reward” yourself with big meals or junk foods. The gastrointestinal system is not ready for that. Plus, why work so hard to keep insulin low if you are just going to spike it when you are done? Stick to the usual, healthy, plant base and high quality complex-carb-protein-fat balanced fare.

Fourth. Resist the urge to increase your calorie intake to “make up” for the fast. If anything, the first 12 hours should have fewer calories than the usual eating pattern, slowly returning to a healthier normal over the next 24 hours.

In terms of the re-feeding period and foods to ingest after an extended water only fasting, detailed care is crucial for the success of the fasting experience. In fasting centers, a common recommendation is that the faster take half the time of the fast to ease back into eating. So, if the fast lasted 7 days, another 3-4 days should be taken to ease into refeeding. A conservative approach to re-introducing food and activity is in the best interest of all water only fasters at any age.

Upon refeeding, the food ingested stimulate release into the blood of the Incretin hormone, a glucagon-like peptide 1 (GLP1) from enteroendocrine cells in the gut. GLP1 enhances clearance of glucose from the blood by stimulating insulin release from the pancreas and increasing the insulin sensitivity of cells. GLP1 crosses the blood–brain barrier and can act directly on neurons to promote synaptic plasticity, enhance cognition and bolster cellular stress resistance.^[18]

STEPS TO BREAK THE PROLONGED WATER ONLY FAST

Depending on the length of the water only fast, repeat Day 1 on half the number of days the fast lasted, before starting on Day 2.

On day 1

First. 15 to 30 minutes after the morning water, drink 4, 6, or 8 oz. freshly extracted orange juice with pulp or fresh kiwi juice ─this generally promotes peristalsis. If this does not occur within the next 60 to120 minutes later, take 1 tablespoon olive oil followed by sipping 1 cup of boiled water. Repeat this once a day until your first bowel movement.

Second. When there is desire to eat next, drink 6 to 8 oz. bone broth. 

Third.  Next feeding 4 to 6 oz. green juice with kale, cucumber, celery, lemon, ginger, and apple.

Fourth. Repeat second or third.

Drink plenty of water in between, and have a good night’s sleep. If sleep is hard to come-by, rub the soles of your feet with olive oil, or any oil right before sleep. 

On day 2

First. Repeat day 1.

Second. Repeat day 1.

Third. At lunch time eat a pureed soup of either potato, sweet potato, pumpkin, cauliflower, or any pureed soup you know how to make, and may be accompanied with steamed broccoli, or spinach, or beets, or your preferred green or other color vegetable.

Fourth. Afternoon snack drink 6 to 8 oz. bone broth or green juice.

Fifth. For dinner have grilled salmon with steamed vegetables.

Drink plenty of water throughout the day, and have a good night’s sleep. If sleep is hard to come-by, rub the soles of your feet with olive oil, or any oil right before sleep. Take magnesium glycinate and potassium glycinate or citrate approximately 1 hour before bed. 

On day 3 and After

Change your lifestyle to eating a modified ketogenic diet with vegetables as the main course, or a Mediterranean diet.

WHAT TO AVOID AT REFEEDING AFTER WATER-ONLY FASTING

Commonly made mistakes after fasting are: eating too much too soon, and moving too much too soon. Food and physical activity needs to be gradually introduced after a period of water only fasting. A long fast shall be successfully broken with a succession of diluted and full strength vegetable juices, melons and other fresh fruits, and cooked vegetables, sweet potatoes, and grains such as rice, oatmeal, oats and barley; wheat such as cuscus, and popcorn. Avoid simple sugars and processed/packaged foods. Each individual should learn what works best for them. The physical activity should be slow and gradual. The refeeding part of fasting and mindful physical activity after the fast are the most significant parts of a healthy longevity program.

HOW TO AVOID REACTIVE WEIGHT GAIN AFTER WATER ONLY FASTING

Given the elimination of all calories during a fast, and a natural starvation response that is enhanced at and during the initial refeeding, there can be significant reactive weight gain after a fast if healthy lifestyle habits are not maintained in the form of low caloric density, low sodium, and plant-based eating until the body settles into its new clean, svelte and healthy state. There is a kind of an internal recognition system that the body has to match its caloric intake to its caloric output. If food intake is restrictive of calories but burning a lot of calories in physical activity, the body will slow down resting metabolism to hold on to future calories more forcefully, and weight gain on less and less food intake will ensue. The key is to rest as much during the refeeding time as it were during the fast.

Since there are no calories coming in during a water only fast, increasing physical activity during a fast is not only potentially dangerous, but can promote excessive reactive weight gain after the fast. Therefore, maintaining as much rest as possible is recommended during the fast, followed by a diet without added oil, refined sugar, animal products, or salt.

REINTRODUCING ACTIVITY AFTER A WATER ONLY FAST

Physical activity should be slowly and gradually introduced after a fast. Equal rest observed during an extensive fasting period should be continuously implemented during the initial half the amount of time the fasting period lasted. i.e. If the fast lasted 30 days, 15 days of continuous rest should be observed after refeeding started. Once the 15 days are up it is in your best interest to ease back gently into an ongoing physical activity starting with a 5 minute walk or stationary biking a few times a day. Doing too much too soon can cause undue physiological stress to the body, and even potentially provoke some unforeseen damage and disability.

After this period, activity can be extended several minutes a day to build up to about 30-45 minutes a day for the remaining 15 days, and then resume exercising normally. Being conservative in eating and exercise choices after water only fasting will enhance all of the benefits achieved during the fasting period.

INDIVIDUALS WHO SHOULD NOT FAST

Unsupervised Fasting for long periods may be life threatening.

People with Type II diabetes must either be thoroughly informed before undertaking a fast on their own, or should only fast under supervision, because it can lead to dangerous dips and spikes in blood sugar. Fasting is helpful for the condition of diabetes, for it can reset the metabolism to a perfect balance of Yin & Yang and essentially cure it, followed by a well done ketogenic state with the Bredesen Protocol and lifestyle.

People who should not fast at all include pregnant women or those breastfeeding, anyone with a chronic disease, individuals with eating disorders, people who are underweight, individuals with a heart condition, people with Type I diabetes, those with unexplained or uncontrolled chronic headache, the elderly, and children.

Glossary

AMPK: a protein and cellular energy sensor that is activated in response to stresses that deplete supplies of cellular ATP (the cell’s energy currency) such as low glucose, hypoxia and exposure to toxins. It activates autophagy. AMPK is considered to be a major therapeutic target for the treatment of metabolic diseases including type 2 diabetes and obesity.

Autophagy: a process by which components inside of cells (including proteins) are degraded and recycled. Autophagy can protect brain cells against accumulation of “bad” proteins that cause neurodegeneration.

Gene: basic physical and functional unit of heredity. Genes are made up of DNA and some genes act as instructions to make molecules called proteins.

Glucose: simple sugar with the molecular formula C₆H₁₂O₆. Glucose is the most abundant monosaccharide, a subcategory of carbohydrates.

Insulin: a hormone made by the pancreas that helps glucose in the blood enter cells in muscles, fat, and liver, where it is used for energy (according to the National Institute of Diabetes and Digestive and Kidney Diseases).

Ketone bodies / Ketones: organic compounds produced by the liver and used as an energy source when glucose is not readily available.

Ketogenesis: biochemical process through which organisms produce ketone bodies through breakdown of fatty acids and ketogenic amino acids. This process supplies energy under circumstances such as fasting or caloric restriction to certain organs, particularly the brain, heart and skeletal muscle

Lipolysis: the breakdown of fats and other lipids by hydrolysis to release fatty acids.

mTOR: a protein, originally discovered in yeast, that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. As a central controller of cell growth, TOR plays a key role in development and aging and has been implicated in disorders such as cancer, cardiovascular disease, obesity, and diabetes.

NAD+: nicotinamide adenine dinucleotide, a cosubstrate (an activating substance) for other enzymes such as the sirtuins. Cellular NAD+ concentrations decrease during aging and increase NAD+ concentrations, for example through supplementation, and may promote longevity.

Sirtuins: anti-aging genes and proteins that require NAD to function. SIRT1 activates the production of new mitochondria ─the cell’s power-generating organs, and cleanup of damaging reactive oxygen species.

 

NUTRITION

LONGEVITY

______________________________________________________________________________________________________________________________________________REFERENCES
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[12] Natalucci et al. (2005) Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern.
[13] Priya Khorana, PhD, in nutrition education from Columbia University. https://www.healthline.com/health-news/calorie-restrictive-diets-benefits#1
[14] Anton et al. (2018) Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. https://onlinelibrary.wiley.com/doi/full/10.1002/oby.22065
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[16] Klein et al. (1993) Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men.
[17] Cheng et al., 2014. Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression.
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-Above Article Written by Dr. Osorio, Gloria DAOM, L.Ac. 2010 (Revised 2020).