Story at-a-glance

• One lifestyle factor that appears to be driving not only obesity but also many chronic disease processes is the fact that we eat too frequently and avoid going without food for very long
• If you eat throughout the day and never skip a meal, your body adapts to burning sugar as its primary fuel, which down-regulates enzymes that utilize and burn stored fat
• Modern science confirms fasting can have a profoundly beneficial influence on your health and longevity, as it improves insulin and leptin sensitivity, triggers autophagy and mitophagy, and allows your body to burn fat for fuel and produce health-promoting ketones
• A recent paper reviews four common types of fasting regimens and the health benefits associated with each. These include classic calorie restriction, time-restricted feeding, intermittent or periodic full or partial fasting, and fasting-mimicking diets
• Benefits of fasting include reversal of insulin resistance and Type 2 diabetes, weight loss and improved body composition, decreased risk for heart disease and cancer, improved cognitive function and increased longevity

Understanding what makes for a healthy diet and lifestyle has never been more important. Shockingly, obesity has now become a greater global health crisis than hunger, and is the leading cause of disability and chronic illness around the world.1,2 On average, the global population is plagued by obesity-related pain and illness during the last 14 years of life, which takes a significant toll on quality of life.3

One lifestyle factor that appears to be driving not only obesity but also many chronic disease processes is the fact that we rarely avoid eating for more than 12 hours. In fact, Dr. Satchin Panda's research shows that 90 percent of us eat across more than 12 hours a day.

Historically, generous amounts of food were not accessible throughout the entire year, let alone 24/7, and evidence strongly shows your body simply isn't designed to run optimally when continuously fed and will radically increase your risk for chronic degenerative disease when you regularly violate this principle.

If you eat throughout the day and never skip a meal, your body adapts to burning sugar as its primary fuel, which down-regulates enzymes that utilize and burn your stored fat. If you struggle to lose weight, this may well be a significant part of the problem — your body has simply lost the metabolic flexibility to burn fat for fuel.

Moreover, research has confirmed that many biological repair and rejuvenation processes take place in the absence of food, and this is another reason why all-day grazing triggers disease. In a nutshell, your body was designed to a) run on fat as its primary fuel, and b) cycle through periods of feast and famine.

Fasting May Be a Key Intervention to Improve Health and Longevity

Fasting — where you abstain from food either for a large part of each day, or a few days each week or month — is one of the oldest dietary interventions in the world, and modern science confirms it can indeed have a profoundly beneficial influence on your health and longevity.

The paper4 "A Time to Fast," published in the November 2018 issue of Science, reviews many of these health benefits, noting that:

"Adjustment of meal size and frequency have emerged as powerful tools to ameliorate and postpone the onset of disease and delay aging, whereas periods of fasting, with or without energy intake, can have profound health benefits.

The underlying physiological processes involve periodic shifts of metabolic fuel sources, promotion of repair mechanisms, and the optimization of energy utilization for cellular and organismal health.

Future research endeavors should be directed to the integration of a balanced nutritious diet with controlled meal size and patterns and periods of fasting to develop better strategies to prevent, postpone and treat the socioeconomical burden of chronic diseases associated with aging …

In general, both prolonged reduction in daily caloric intake and periodic fasting cycles have the power to delay the onset of disease and increase longevity."

How Fasting Benefits Health

While there are many different types of fasting, the key component is the cycling of feeding and fasting. By mimicking the eating habits of our ancestors, you restore your body to a more natural state that allows a whole host of biochemical benefits to occur.5,6,7,8

For example, research9 published in Cell Metabolism concluded that time-restricted eating not only prevented but also reversed obesity and related metabolic dysfunction.

Indeed, intermittent fasting is one of the most effective interventions I've found to reverse insulin resistance, shed excess weight and improve body composition, decrease your risk for heart disease and cancer, protect cognitive function and increase longevity.10 Two core mechanisms responsible for these benefits are:

1. Improved insulin and leptin sensitivity, and improved circulating glucose and lipid levels

2. Triggering your body to more effectively burn fat for fuel, which encourages your liver to create water-soluble fats called ketones that:

• Burn far more efficiently than carbs, thereby creating fewer reactive oxygen species and secondary free radicals that can damage your cellular and mitochondrial cell membranes, proteins and DNA

• Decrease inflammation, as ketones are histone deacetylase (HDAC) inhibitors that radically reduce inflammatory molecules

• Mimic the life span-extending properties of calorie restriction, which includes improved glucose metabolism and reduced inflammation11

• Have a similar structure to branched-chain amino acids, thereby aiding the building of muscle mass and promoting longevity12

Ketone metabolism also increases the negative redox potential of your family of NAD coenzyme redox molecules, which helps control oxidative damage by increasing NADPH and promoting transcription of enzymes of the antioxidant pathways though activation of FOXO3a.13

In a nutshell, ketone metabolism effectively reduces oxidative damage, which translates into improved health and longevity. Both calorie restriction and intermittent fasting also inhibit the mTOR pathway, which has been shown to play an important role in life extension. Note that ketone metabolism, not ketone supplements, has been shown to produce these benefits.

Intermittent Peak Fasting Is a Simple Way to Reap the Benefits of Fasting

What I call "peak fasting" involves fasting for 16 to 18 hours each day and eating all of your meals within the remaining six to eight hours. To make this schedule work, you need to skip either breakfast or dinner.

If you choose to eat dinner, be sure to do so at least three hours before bedtime, to avoid the creation of excessive amounts of damaging free radicals. Avoiding late-night eating is a simple way to protect your mitochondrial function and prevent cellular damage from occurring.

There are also other intermittent fasting plans where you dramatically cut back on your calories for a certain number of days each week, while eating normally during the remainder. The 5-to-2 intermittent fasting plan is one such example. The fasting mimicking diet, developed to match the effects of water-only fasting, is another.

Intermittent Fasting Is Even More Effective Combined With a Cyclical Ketogenic Diet

Recent research also suggests the effects of intermittent fasting are bolstered by combining it with a pulsed ketogenic diet. The ketogenic diet provides many of the same health benefits associated with fasting and intermittent fasting, and when done together, most people will experience significant improvements in their health.

This includes not just weight loss, which is more of an inescapable side effect of the metabolic improvements that occur, but other benefits such as:

• Improved insulin sensitivity14
• Increased muscle mass
• Reduced inflammation
• Reduced risk of cancer and Alzheimer's15
• Increased longevity16

As with fasting, the cyclical pulsing of nutrients will optimize your benefits when on a ketogenic diet. Most people believe continuous keto is the key to success, but mounting evidence suggests this is not the case. This is why the mitochondrial metabolic therapy (MMT) program detailed in my book, "Fat for Fuel," stresses cyclical ketosis. There are at least two significant reasons for the pulsed approach:

• Insulin suppresses hepatic glucogenesis, i.e., the production of glucose by your liver. When insulin is chronically suppressed long-term, your liver starts to compensate for the deficit by making more glucose. As a result, your blood sugar can begin to rise even though you're not eating any carbohydrates.

In this situation, eating carbohydrates will actually lower your blood sugar, as the carbs will activate insulin, which will then suppress your liver's production of glucose. Long-term chronic suppression of insulin is an unhealthy metabolic state that is easily avoidable by cycling in and out of keto.

• As with fasting, many of the metabolic benefits associated with nutritional ketosis occur once your intake of net carbs increases. This is why I stress the importance of increasing your net carb and protein intake at least once or twice a week once you have attained metabolic flexibility. Ideally this is done on days when you do strength training. As a general recommendation, triple the amount of net carbs on these high-carb days.

However, you first need to make sure your body can efficiently burn fat for fuel before you start this pulsing. Keto testing strips can be used to confirm that you're in ketosis, defined as having blood ketones in the over 0.5 t mmol/L. Too many net carbs will effectively prevent ketosis as your body will use any available glucose first, since it's a much faster-burning fuel.

Fasting Boosts Brain Power and Protects Against Neurological Diseases

More and more people are now starting to recognize the health benefits of fasting. The strategy has quickly become popular with Silicon Valley executives, who recognize it as biohacking, opposed to mere dieting.17,18

Geoffrey Woo, CEO of the biohacking company HVMN (pronounced "human"), told The Guardian,19 "Ketones are a super fuel for the brain. So a lot of the subjective benefits to fasting, including mental clarity, are down to the rise in ketones in the system."

Indeed, while many worry that fasting will lead to a deterioration of mental processing and physical functioning, the converse is actually true. As noted by Woo, right around the three-day mark your hunger significantly decreases and mental clarity increases, thanks to rising ketone levels.

In the video above, Mark Mattson, chief of the laboratory of neurosciences at the National Institute on Aging and a professor of neuroscience at Johns Hopkins University, explains this process.

Fasting also has long-term brain benefits that can help ward off neurological diseases and dementia, as the process of autophagy allows your body to break down and recycle beta amyloid protein in your brain believed to contribute to Alzheimer's.

Then, during the refeeding phase, growth hormone increases, boosting the rebuilding of new proteins and cells. Research shows fasting can boost growth hormone by as much as 1,300 percent in women and 2,000 percent in men.20

Fasting also boosts brain-derived neurotrophic factor (BDNF) by 50 to 400 percent, depending on the brain region,21 which activates brain stem cells to convert into new neurons and triggers numerous other chemicals that promote neural health. BDNF also protects your brain cells from changes associated with both Parkinson's and Alzheimer's disease.

Comparison of Four Fasting Strategies

I used to be a strong advocate of multiday water fasting but in researching my next book, "Keto Fast," I realized that this is not the best strategy for most. Compliance is a serious issue with water fasting and very few people will ever agree to go that long without food.

More importantly, I believe that it can actually be dangerous for many. Why? Because when you fast you release fat soluble toxins stored in your fat and unless you have optimized your detox pathways these toxins can contribute to health complications.

I ultimately settled on a partial fast that supplies many of the nutrients that your body needs to support your detox pathways. It involves a base of intermittent fasting for 16 to 18 hours, and once or twice a week you have a 300 to 600 calorie meal loaded with detox supporting nutrients, and then you don't eat anything for 24 hours. So you are only eating one meal in 42 hours.

That said, the featured paper,22 "A Time to Fast," reviews four different types of fasting strategies and the metabolic and cellular responses triggered by each. These include:

Classical calorie restriction, where daily caloric intake is decreased by 15 to 40 percent — Benefits include reduced cancer incidence, life span extension, reduced oxidative damage, enhanced cellular turnover and protein homeostasis, improvement of age-related metabolic disorders such as obesity, insulin resistance, dyslipidemia and hypertension. According to the authors:

"[Calorie restriction] induces profound metabolic and molecular changes in components of the nutrient-sensing and stress-responsive pathways, such as growth hormone, insulin and insulin-like growth factor (IGF) signaling, mechanistic target of rapamycin (mTOR), adenosine 5′-monophosphate-activated protein kinase (AMPK), forkhead box protein O (FOXO), sirtuins, and nuclear factor erythroid 2-related factor 2 (NRF2)."

Time-restricted eating (or what I call "peak fasting"), which limits daily food intake to a narrow window of time, without reducing caloric intake — Animal studies have shown this strategy helps reduce body weight, increase energy expenditure, improve glycemic control, lower insulin levels, decrease hepatic (liver) fat and hyperlipidemia, and lowers inflammation. According to the authors:

"The molecular mechanisms responsible for the effects of altered meal patterns on metabolic health appears to be related, at least in part, to the synchronization between the time of fasting-feeding and the circadian rhythm … A strong relation exists between the circadian clock and metabolism, as they share some common regulators.

Indeed, time-restricted feeding can restore cycling of metabolic regulators, such as … cAMP response element-binding protein (CREB), mTOR, AMPK or the insulin signaling pathway, all of which take part in the life span and health-span benefits of calorie restriction."

Importantly, studies included in this review confirm that in order to optimize benefits from this strategy, you need to eat your meals earlier in the day. When food intake was restricted to late afternoon or evening, at best no benefits were found, and at worst, postprandial glucose levels, beta cell responsiveness, blood pressure and lipid levels worsened.

Intermittent fasting where "no or few calories are consumed for periods of time that range from one to several days, followed by ad libitum [meaning without restriction] feeding on the remaining days" — One example would be alternate-day fasting: a 24-hour water fast followed by 24 hours of normal eating.

This type of intermittent fasting has been shown to boost resistance to stress, "presumably by shifting energy from growth and reproduction to maintenance, recycling and repair in order to increase cellular protection and survival."

In animal research, periodic fasting has been shown to extend life span and protect against obesity, cardiovascular disease, high blood pressure, diabetes and neurological diseases. It also slows tumor growth and sensitizes many cancer cell types to chemotherapy, thereby making them easier to treat, and enhances brain function, improving both performance and behavior.

Partial fasting diets, which "maintain a physiological fasting-like state by reducing caloric intake and modifying diet composition but not necessarily fasting" — As explained by the authors:

"[A fasting-mimicking diet] has low calories and provides for plant-based soups, herbal tea, energy bars, nut-based snacks, and supplements to be gradually implemented in a five-day cycle each month for three months."

Benefits of partial fasting include the maintenance of low circulating concentrations of IGF-1, insulin and glucose, while increasing plasma concentrations of IGF-binding protein 1 and ketone bodies. It's also been shown to have rejuvenating effects, ascribed to an increased number of progenitor stem cells, and improves several disease markers and markers for metabolic function.

In rodents, the diet has been shown to lower cancer incidence and extend health span, but not maximum longevity. It also has antidiabetic effects, regenerating pancreatic beta cells and restoring insulin secretion and glucose homeostasis in mice.

It's also been shown to improve control of multiple sclerosis and other autoimmune diseases through the regulation of the immune system. Interestingly, in very old animals, the fasting-mimicking diet has demonstrated detrimental effects, and may therefore not be advisable for the very old.

Source: Science November 16, 2018; 362(6416): 770-775

Contraindications and Cautionary Advice

While most people would likely benefit from water fasting, there are several absolute contraindications. If any of the following apply to you, you should NOT do extended types of fasting:

• Underweight, defined as having a body mass index (BMI) of 18.5 or less.
• Malnourished (in which case you need to eat healthier, more nutritious food).
• Children should not fast for longer than 24 hours, as they need nutrients for continued growth. If your child needs to lose weight, a far safer and more appropriate approach is to cut out refined sugars and grains. Fasting is risky for children as it cuts out ALL nutrients, including those they need a steady supply of.
• Pregnant and/or breast-feeding women. The mother needs a steady supply of nutrients in order to assure the baby's healthy growth and development, so fasting during pregnancy or while breast-feeding is simply too risky for the child.

I would also caution you to avoid fasting if you struggle with an eating disorder such as anorexia, even if you are not clinically underweight. In addition to that, use caution if you're on medication, as some may need to be taken with food. This includes metformin, aspirin and any other drugs that might cause stomach upset or stomach ulcers. Risks are especially high if you're on diabetic medication.

If you take the same dose of medication but don't eat, you run the risk of having very low blood sugars (hypoglycemia), which can be very dangerous. So, if you're on diabetic drugs, you must adjust your medication before you fast. If your doctor is adverse toward or unfamiliar with fasting, you'd be wise to find one that has some experience in this area so that they can guide you on how to do this safely.