Intermittent Fasting / Fasting Diet – EXCITING Health Effects

What Is Intermittent Fasting?

Intermittent fasting involves efficient energy production by using fatty acids and ketone bodies instead of glucose. Intermittent fasting first attracted major scientific attention through a 1997 article showing that calorie restriction —reducing food consumption—had remarkable effects on animal aging and lifespan. Researchers proposed that benefits resulted from reduced harmful free radicals.

Intermittent fasting is also called in medical language and social media: intermittent fasting and the fasting diet.

Since then, studies have examined daily or several-days-weekly metabolic switching from liver-derived glucose to fat-cell-derived ketones. Although lifespan effects vary with sex, diet, and genetics, mouse and nonhuman primate studies show positive health effects of calorie restriction.

How Do Cells Respond to Energy Restriction and Fasting Cycles?

As repeated later in this article, fasting produces these metabolic changes: glucose and fatty acids are primary cellular fuels. After meals, glucose supplies energy and fat is stored as triglycerides. During fasting, triglycerides split into fatty acids and glycerol for energy. Many tissues, especially the liver, convert these into ketone bodies, a major fuel particularly for the brain. Blood ketones are low when fed and rise within hours of fasting in humans.

Continuing animal and human research showed benefits derive from reduced free radicals and weight loss not solely .

Intermittent fasting produces responses improving glucose regulation, stress resistance, and reducing inflammation . It activates pathways strengthening defenses against oxidative and metabolic stress and removing or repairing damaged molecules. During feeding, cells undergo tissue-specific growth and plasticity, neural change.

Figure explanation: We think harmful chemicals enter only from outside, but this is not true! Obesity / excess fat is like a factory producing harmful chemicals. Obesity-related cancer, cardiovascular disease, diabetes, and complications relate to excess fat's immune system suppression, chronic inflammation production, microbiome alteration and excessive release of oxygen free radicals . Excess fat can also cause more harmful chemicals to be stored in the body. The striking example is storage of an overlooked carcinogen , dioxinin fatty tissue.

Is a Diet of 3 Meals Plus Snacks Wrong?

Most people eat three meals plus snacks daily, so intermittent fasting does not occur. Preclinical studies in animal models show disease-modifying activity in obesity, diabetes, cardiovascular disease, cancer, and neurodegenerative brain diseases: evidence from animal models indicates that intermittent fasting has effective disease-modifying activity across this wide variety of chronic disorders. 

- Related topic: A more effective new diet aligned with the biological clock

This article reviews animal and human studies showing how intermittent fasting affects health and slows or reverses aging and disease processes.

• First, we examine common regimens and their metabolic and cellular responses.
• Then we discuss preclinical and newer clinical studies testing regimens in healthy people and patients with metabolic disorders.
• Finally, we offer practical implementation information and discuss prolonged fasting, several days to weeks.

What Happens During Intermittent Fasting? (Metabolic Changes)

It initiates use of fat-derived ketones rather than glucose as fuel... Glucose, sugar, and fatty acids are primary cellular energy sources. After meals, glucose fuels cells while fat is stored as triglycerides. During fasting, triglycerides split into fatty acids and glycerol. The liver converts fatty acids into ketone bodies , a major fasting fuel for many tissues, especially the brain. Levels are low when fed, rise within 8 to 12 hours of fasting, and within 24 hours reach 2 to 5 mM.

Commonly studied human regimens include 2 days weekly of 24-hour fasting with time-restricted eating on remaining days, or 1 or more days weekly of 24-hour fasting with markedly reduced calories, for example 500 - 700 calories daily. These are called alternate-day fasting diets. Blood ketones are high on those days.

Calorie restriction improves energy efficiency by using fatty acids and ketones after glucose as fuel.

Ketones are not merely fasting fuel; they are powerful molecules affecting cellular and organ function. They regulate expression and activity of many proteins and molecules influencing health and aging.

Ketones also stimulate brain-derived neurotrophic factor gene expression, with implications for brain health, psychiatric and neurodegenerative disorders. Synthesized from the brain-derived neurotrophic factor gene, this neurotrophin-family growth factor , neurotrophic factor, is a secreted protein found in brain and blood.

Many studies distinguish some benefits from weight loss: improved glucose regulation, blood pressure, heart rate, endurance, and abdominal fat loss.

Intermittent Fasting and Stress Resistance

Unlike people today, ancestors did not eat three large regular meals plus snacks or live sedentarily. They foraged where food was sparsely distributed.

Homo sapiens underwent evolutionary adaptations including thought, imagination, language, and physical changes enabling long-distance pursuit of prey.

How Does Fasting Affect Aging and Health?

Repeated fasting produces lasting adaptive responses providing resistance to later challenges. Cells mount coordinated stress responses including antioxidant defenses, DNA repair, and protein quality control.

Body and brain cells of fasting animals show robust resistance to metabolic, oxidative, ionic, and other potentially harmful insults. Fasting inhibits mTOR, mammalian target of rapamycin, protein synthesis, stimulating autophagy, self-digestion of aged damaged cells, and mitophagy, self-digestion of worn mitochondrial cells. Overeating and sedentary living leave these pathways unused or suppressed.

Until recently, calorie restriction and fasting studies focused on aging and lifespan . After approximately a hundred years of animal research, the general conclusion was that reducing food intake robustly lengthens life.

In an early study, Goodrick and colleagues found starting calorie restriction in young adult mice increased average lifespan by up to % 80.

A University of Wisconsin study showed health and survival benefits, while a National Institute on Aging study found no significant mortality reduction despite improved general health.

Variability in health and lifespan effects may reflect sex, diet, age, and genetic differences.

In humans, fasting diets may improve obesity, insulin resistance, dyslipidemia, hypertension, and chronic inflammation.

Intermittent Fasting Does More Than Reduce Calories

In one study, for 22 days, 16 healthy participants followed fasting regimens and lost % 2.5 of initial weight and % 4 of fat mass. Fasting insulin decreased % 57.

In two other studies, approximately 100 overweight women per study were assigned either 2 days weekly alternate fasting (weekly 2 days of 24-hour fasting) or daily calorie reduction of % 25. Both lost similar weight over 6 months, but weekly 2-day fasting produced greater insulin sensitivity and waist circumference reduction.

What Are Its Physical Effects?

Human and animal studies show improved physical function. Despite similar body weight, fasting mice had better running endurance, balance, and coordination than unrestricted-fed mice. Young men fasting 16 hours daily lost fat while preserving muscle after 2 months of resistance training.

Animal research shows better spatial, associative, and working memory. Fasting and calorie restriction reverse obesity-, diabetes-, and neuroinflammation-related learning and memory impairment.

A trial found improved verbal memory in older adults with short-term calorie restriction. In overweight adults with mild cognitive impairment, 12 months of restriction improved executive and cognitive function.

A recent multicenter randomized trial found that 2 years of daily calorie restriction significantly improved working memory.

Further studies of fasting and cognition in older people are necessary, particularly given the absence of drugs affecting brain aging and neurodegenerative progression.

Preclinical and Human Clinical Studies of Fasting

This section briefly reviews results in animal models and patients with various diseases.

What Are Its Effects on Obesity and Diabetes?

In animals, intermittent feeding improves insulin sensitivity, prevents high-fat diet-induced obesity, and improves diabetic retinopathy, a major current cause of sight loss. Okinawa's indigenous Japanese population typically fasts intermittently, lives long, and has low obesity and diabetes rates.

Okinawans eat low-carbohydrate, energy-restricted but nutrient-rich foods, particularly Okinawan sweet potatoes, vegetables, and legumes.

- Related topic: The 8 shared traits of the world's longest-lived Blue Zone people

A multicenter study showed daily calorie restriction improves many cardiometabolic risks in nonobese people.

A short-term trial in overweight or obese adults found fasting as effective as standard weight-loss diets.

Daily calorie restriction or 4:3 alternate-day fasting, three times weekly for 24 hours, reversed insulin resistance in prediabetes or type 2 diabetes.

However, comparing alternate-day fasting, 24-hour fasting on certain days, daily calorie restriction, and a control diet over 12 months found weight loss in all groups but no insulin sensitivity, lipid, or blood pressure improvement in controls.

What Are Its Cardiovascular Effects?

Fasting improved many cardiovascular markers in animals and humans: blood pressure, resting heart rate, LDL, HDL cholesterol, triglycerides, glucose, insulin, and insulin resistance.

Improvements generally appear within 2 to 4 weeks of starting alternate-day fasting and deteriorate within weeks of stopping the diet.

What Are Its Effects on Cancer?

Over a century ago, Moreschi and Rous described beneficial effects of fasting and calorie restriction on animal tumors. Numerous subsequent rodent studies showed daily restriction or fasting reduces tumor formation, suppresses growth, and increases chemotherapy and radiotherapy sensitivity.

Fasting is similarly thought to disrupt cancer-cell energy metabolism, inhibit growth, and sensitize cells to clinical treatments.

It may protect against cancer while increasing normal cells' stress resistance.

Several glioblastoma case studies suggest suppressed tumor growth and longer survival.

Ongoing ClinicalTrials.gov studies focus on breast, ovarian, prostate, endometrial, colorectal cancers, and glioblastoma. Whether fasting affects human cancer recurrence (relapse) has not yet been studied.

What Are Its Effects on Neurodegenerative Disorders?

Epidemiological data suggest excess energy intake, especially in middle age, increases stroke, Alzheimer's, and Parkinson's risks. Strong preclinical evidence suggests alternate-day fasting delays onset and progression in animals.

No controlled trial data exist for people at risk of or affected by neurodegenerative disorders.

What Are Its Effects on Asthma, Multiple Sclerosis, and Arthritis?

One study found alternate-day fasting patients had higher ketones on restriction days, lost weight over 2 months, and had fewer asthma symptoms.

Multiple sclerosis is an autoimmune disease involving central nervous system axonal demyelination and neuronal degeneration. Alternate-day fasting and energy restriction in consecutive 3-day cycles reduced autoimmune demyelination and improved functional outcomes in a mouse model.

Reduced inflammation suggests benefits in rheumatoid arthritis, and evidence supports use in arthritis patients.

What Are Its Effects on Surgery and Ischemic Tissue Injury?

Preoperative fasting reduces injury and inflammation and improves outcomes. In animals, 3 days of fasting reduced liver and kidney ischemia-reperfusion injury and trauma before injury.

A randomized multicenter trial showed 2 weeks of preoperative daily restriction improved gastric bypass outcomes, suggesting preoperative fasting may safely and effectively improve surgery results.

Can It Be Applied in Practice? How?

Despite evidence of health benefits and applicability to diseases, barriers hinder widespread adoption by patients and society.

What Are They?

First, three meals plus snacks are deeply ingrained, so patients or doctors rarely accept change. Food abundance and extensive marketing in developed countries are other major obstacles.

Second, many people initially experience hunger, irritability, and reduced concentration from energy restriction. These resolve within 1 month, and patients should know this.

Third, most doctors may lack sufficient knowledge. They can advise gradual transition.

Alternatively, doctors may recommend weekly 1 day during the first month and weekly 2 days during the second, consuming 900 to 1000 calories, using 5: 2 fasting (weekly 2 days of 24-hour fasting). During the third month, weekly 2 days at 750 calories, and in the fourth, weekly 2 days at 500 calories. Gradual restriction can ease adaptation.

A dietitian or nutritionist should ensure nutritional needs and ongoing counseling. As with all lifestyle interventions, doctors must provide adequate information, continuing communication, and support.

Conclusion

Preclinical and clinical studies show benefits for obesity, diabetes, cardiovascular disease, cancer, neurological disorders, and other conditions.

Animal models show lifelong health benefits, while clinical trials involve shorter interventions because people do not continue for years. Whether animal benefits accrue in humans remains undetermined. Trials mainly involve overweight young and middle-aged adults; benefits and safety cannot be generalized to other ages.

Although mechanisms are not fully understood, benefits involve metabolic switching and cellular stress resistance. Some people do not wish to fast. Targeted drugs mimicking effects without major dietary changes have therefore been developed and tested, such as mild metabolic stress agents (2-deoxyglucose, metformin and mitochondrial uncouplers), mitochondrial bioenergetic supplements, ketone esters or nicotinamide riboside, and mTOR inhibitors such as everolimus and sirolimus. Animal studies, however, show these approaches have lower safety and efficacy than intermittent fasting.