Intermittent Fasting

I get asked a lot about intermittent fasting these days, and for good reason – there is a ton of research being done on this subject, and the science is sure to continue evolving for some time. The first step to getting a grasp on the science behind intermittent fasting is to get familiarized with the lingo. Intermittent fasting refers to any eating plan that requires people to go for 16-48 hours with little or no food, alternating with periods of eating regularly. Time-restricted eating is an eating pattern that restricts someone to eating in a window of eight hours or less each day. A fast-mimicking diet is a low-calorie, ketogenic diet that causes similar metabolic changes to fasting. Most randomized controlled human trials have involved either 60-75% energy restriction (consumption of 500-800 calories) on alternate days or two consecutive days each week. 

Examples of specific intermittent fasting diets include complete fasting every other day (this is known as alternate day fasting) or a 70% calorie restriction every other day.

Before we get into what health outcomes intermittent fasting is and isn’t capable of influencing, we need to review a tiny bit of metabolism.

Stage 1, the fed state, occurs about three hours after we eat. Our blood glucose rises, and insulin is secreted to usher blood glucose into our cells to be used for energy. Lipolysis, the breakdown of fat to release fatty acids for fuel, is inhibited in the fed state because we don’t need any more energy. Once immediate energy needs are met, glucose is fashioned into long chains (glycogen) and stored for later use. The excess energy is stored as fatty acids in the adipose tissue (body fat) if we overeat.

Roughly 18 hours after eating, we enter into stage 2, the post-absorptive (early fasting) state. Now the insulin circulating through the body is significantly reduced. The chains of glycogen stored in our liver and muscle are broken down so that the glucose can be used for energy. When we begin to run low on glycogen, non-carbohydrate substances, including lactate and certain amino acids, are used to produce glucose for energy. Fats are also broken down and used for energy.

After about 36-48 hours of fasting, we enter into stage 3, the fasting state. Now fatty acids and ketones are the primary sources of fuel, and both fat and muscle protein are broken down. Glucagon, a hormone that increases glucose and fatty acids in the bloodstream, is released. Levels of glucocorticoids, a type of steroid that reduces certain parts of the immune system, thereby decreasing inflammation, increase.

If we fast for longer than 48 hours, the breakdown of branched-chain amino acids will stop so that protein and muscle can be spared. The breakdown of fat and release of free fatty acids are the primary source of energy, although the body continues to create glucose via gluconeogenesis from non-carbohydrate sources.

Weight Loss

In studies, alternate-day fasting for two to three weeks has reduced body weight by three percent. More extended periods have shown a higher reduction, of eight percent, along with reduced visceral fat (the dangerous fat that surrounds the organs).

We don’t know if one form of intermittent fasting is better than another for weight loss because they are rarely compared within the same study. Some researchers believe that time-restricted feeding (such as only eating in a six-hour window each day) is not as effective as other variations. However, it seems that time-restricted feeding might be especially beneficial for body composition in athletes.

A few studies have proven that intermittent fasting promotes health benefits beyond those brought about by simple calorie restriction, such as causing a more significant loss of body fat. Still, most research has failed to show a significant difference in weight loss, fat mass, fat-free mass, or visceral and subcutaneous fat loss between people on traditional calorie-restricted diets and those practicing intermittent fasting.

The loss of fat-free mass (mostly muscle) appears to depend on the diet’s overall protein content, whether on an intermittent fasting diet or a standard reduced-calorie diet. Compared to individuals who consume one gram of protein per kilogram of body weight, and who lose 30% of their weight as fat-free mass (mostly muscle), those dieters who eat 1.2 grams of protein per kilogram reduce their weight loss as fat-free mass to 20%. Exercise also helps to prevent muscle loss experienced with weight loss, regardless of the type of diet.

In general, fasting appears to be one option for healthy weight loss, but it isn’t necessarily a superior method. Dropout rates have been as high as 40% in some intermittent fasting studies, raising questions about compliance among medical experts. On the other hand, individuals who adopt intermittent fasting may be less likely to regain the weight they’ve lost than those who lost the weight by following a standard low-calorie diet.  

Diabetes

Even in individuals who do not lose weight, fasting causes insulin sensitivity to rise and circulating insulin levels to fall. Two days a week of intermittent fasting has proven to enhance the reduction of insulin resistance by 25% beyond what would be expected from a standard restricted-calorie weight loss diet, despite comparable reductions in body fat.

In one early study, A1c was decreased more by adding a five-day bout of eating 75% fewer calories every five weeks, compared to doing the same regularly for one day each week for 15 weeks. This effect was independent of weight loss.

In one very promising and very small study, three patients who ate dinner but skipped breakfast and lunch either on alternate days or on any three days a week were said to be able to discontinue their insulin between five and 18 days after initiating the plan.

Even though animal and human trials have proven an increase in insulin sensitivity and demonstrated improved A1c values with intermittent fasting, human trials have not been conclusive. Some researchers have hypothesized that the “feeding window” needs to be early in the day to be beneficial for individuals with diabetes. In fact, in some studies, a feeding window in the late afternoon or evening has worsened insulin response and blood glucose levels after eating.

There is a risk of hypoglycemia in patients on antidiabetic medications, especially insulin and sulfonylureas, and want to try intermittent fasting. With long-term intermittent fasting, individuals need to be careful to consume enough protein on non-fasting days. Some people will need vitamin and mineral supplements, depending on how many days they are fasting and what they are eating on non-fasting days. Anyone with diabetes interested in trying intermittent fasting must receive guidance from healthcare practitioners, as medications may need to be adjusted.

Heart Health

Atherosclerosis is a chronic inflammatory disease that causes plaque to form in arteries, causing stiffening and narrowing of the arteries. C-reactive protein, one measure of inflammation, is decreased among individuals who practice intermittent fasting.

Latter-Day Saints regularly fast as a religious practice. A meta-analysis of two observational studies found that those who routinely fasted were 35% less likely to develop coronary artery disease and 44% less likely to develop type 2 diabetes than those who didn’t fast. Those who regularly fasted also had a lower BMI. Observational studies have shown a lower risk of heart disease and diabetes from as little as one day per month of fasting (practiced over decades). Combining alternate day fasting and a low-fat diet or endurance exercise is especially beneficial for cardiac health.

Intermittent fasting has reduced blood pressure in both animal studies and humans. However, it appears likely that the results are temporary, and blood pressure quickly returns to baseline once someone stops following the intermittent fasting plan.

The reductions in insulin, blood glucose, and fat mass experienced with intermittent fasting benefit the heart, as do the decreases in resting heart rate, homocysteine, total cholesterol, LDL cholesterol, and triglycerides described in some research.

Adverse Effects

In general, about 15% of participants in research studies complain of dizziness, nausea, insomnia, syncope, falls, migraine headache, weakness, or excessive hunger. Individuals with chronic diseases including diabetes, coronary artery disease, unstable angina, heart failure, atrial fibrillation, prior heart attack or stroke, most cancers, chronic obstructive pulmonary disease (COPD), pulmonary embolism, asthma, peripheral vascular thromboembolism, and chronic kidney disease are at a higher risk of experiencing adverse effects.

Pregnant and lactating women, children, adults of advanced age, and older frail adults, as well as people with immunodeficiencies, a history of eating disorders, dementia, or a history of traumatic brain injury or post-concussive syndrome, are at higher risk of adverse events.

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