The term intermittent fasting is used in a variety of eating settings. In fact, intermittent fasting can be used when describing a prolonged time in which few calories or no calories are consumed. However, its physiological effects on the human body and its metabolic benefits have been the spotlight of 2020. In fact, this global pandemic has been creating a shift in patientâ€™s wellness and self-awareness, therefore a topic of interest in functional medicine practice.
Intermittent fasting (IF) has been a topic of interest since many decades ago. Previously, the dietary approaches to reduce weight involved calorie-restricted diets, with good outcomes. Â A moderate caloric restriction (over 6m periods) allowed the patient to reduce weight, lessen the cardiovascular risk, and improve insulin sensitivity and mitochondrial function. Nevertheless, researchers concluded that this approach was difficult to maintain over a long time, which was when the heads turned to IF.
Variations of IF
|12 hours-fast or longer (typical approach)|
|Alternate day fasting (ADF): the patient avoids consuming calories for one day, and the next day, they eat without restriction.|
|Alternate day modified fasting (ADMF): consists of eating fewer calories for one day (<25% energy needs) and eating without restriction the next day.|
|Time-restricted feeding involves (TRF): restricting food intake to specific time periods of the 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.|
Intermittent fasting benefits
- Improvement of cardiometabolic risk factors: Insulin resistance, dyslipidemia, and reduces inflammatory cytokines.
- Reduce visceral fat mass.
- Promotes weight loss.
- Improvements on lipid profiles.
- Healing thrombophlebitis.
- Healing of dermal ulcers.
- Tolerance for elective surgery.
Metabolism behind IF
To understand how IF can exert these benefits in the human body, we have to refer to basic metabolism and energy biochemistry. In fact, IF has been reported to shift energy metabolism, principally by flipping the preferred substate from glucose from glycogenolysis to fatty-acids and fatty-acid derived ketones. Overall, the main shift is when fat starts being mobilized for energy utilization instead of being synthesized and stored as triglycerides in adipocytes.
To be able to produce this metabolic shift, most patients need to deplete their hepatocyte glycogen storage. This occurs on the third phase of fasting, 12-36, after food intake cessation. Therefore, this action precedes a cascade in which accelerated adipose tissue lipolysis produces increased fatty acids and glycerol.
Adipocytes release their content (triacylglycerol and diacylglycerol) to get metabolized into free-fatty acids, which are then released into the bloodstream. Other cells, like astrocytes, may generate ketones and release them into the bloodstream as well. Furthermore, these components get transported to the hepatocytes and are metabolized to ketones b-hydroxybutyrate (b-OHB) and acetoacetate, which may, in turn, induce mitochondrial biogenesis.
Lastly, ketones are transported to high metabolic activity cells, like muscle and neurons, where they are metabolized to acetyl coenzyme A. Consequently, acetyl coenzyme A is the main substrate for the tricarboxylic acid cycle to generate adenosine triphosphate (ATP). This adapted metabolic â€œshiftâ€ is believed to be a muscle protection mechanism in times of extreme famine or intense physical activity.
Nakura et al. determined that the main action of IFâ€™s metabolic shift on muscle preservation. Their findings suggest that muscle mass stores triglycerides in lipid droplets, and when needed, they get metabolized by b-oxidation. Peroxisome proliferator-activated receptor a (PPAR-a), the transcriptional regulator, induces the expression of genes that mediate fatty acid oxidation in muscle cells and regulates muscle cell mitochondrial biogenesis and glucose metabolism. Other mediators on the metabolic shift induction are the fatty acid translocase CD36, fatty acid-binding protein 3, mitochondrial uncoupling protein 3, PGC-1a, pyruvate kinase dehydrogenase 4, and forkhead box (FOX) O1A.
Intestinal microbiota and IF
The benefits that IF exerts on intestinal microbiota are related to the circadian rhythm and metabolic responses. In fact, glucose load responses tend to slow down during the evening and be faster in the morning. Therefore, a disturbed circadian profile can affect gastrointestinal function, affecting digestion, metabolism, and health.
Studies performed in this matter show that jet lag has in mice and humans is linked to microbial diurnal fluctuation. Besides, these fluctuations can lead to dysbiosis, causing glucose intolerance and enabling â€œobese microbiota.â€
Contributing to this matter, studies report that nighttime eating is associated with reduced sleep duration and quality.
- insulin resistance.
- Increased risk of obesity.
- Cardiovascular disease.
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Despite all of the reported IF benefits, two that stand out the most are reducing inflammation and insulin sensitivity. The molecular and cellular mechanisms involved in IF diabetes reduction and prevention rely upon the insulin receptor’s increased function. Nevertheless, this action guarantees a rapid uptake of glucose in cells like myocytes, hepatocytes, and neurons. Also, it is reported that IF induces cellular stress, which is associated with the protection of B- cells. Lastly, IF’s anti-inflammatory effects are associated with the lack of food ingestion and metabolic processing, and overeating is proinflammatory.-Ana Paola RodrÃguez Arciniega. Master in Clinical Nutrition
Anton, Stephen D., et al. “Flipping the metabolic switch: understanding and applying the health benefits of fasting.”Â ObesityÂ 26.2 (2018): 254-268.
Patterson, Ruth E., et al. “Intermittent fasting and human metabolic health.”Â Journal of the Academy of Nutrition and DieteticsÂ 115.8 (2015): 1203-1212.
Mattson, Mark P., Valter D. Longo, and Michelle Harvie. “Impact of intermittent fasting on health and disease processes.”Â Aging research reviewsÂ 39 (2017): 46-58.
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