Harnessing metabolic flexibility for optimal health

Photo Cred: Timolina/Freepik

By Kellie Blake, RDN, LD, IFNCP

Flexibility comes in many forms. Whereas psychological flexibility refers to the capacity to direct mental energy to allow for increased resilience in emotional situations, anatomic flexibility encompasses the physical benefits of stretching the body to improve pain, strength, and physical mobility. While both are important, a third type of flexibility, metabolic flexibility, is currently stealing the limelight.

Metabolic flexibility, or the ability of the body to adapt to changes in metabolic demand, has become a mainstream hot topic. My patients seem to be especially curious about fasting and the ketogenic diet, which both take advantage of metabolic flexibility. It’s important for practitioners to understand this concept and how to help patients effectively and safely implement strategies surrounding metabolic flexibility, to allow patients to maintain or regain optimal health and quality of life.

At the core of metabolic flexibility is shifting the body from using glucose for fuel to using fatty acids and ketones for fuel. In my conventional training, I understood glucose to be the optimal fuel source for the brain and body with ketones being inferior or even dangerous. However, as reported in Cell Metabolism, the liver creates up to 300 grams of ketones per day and ketones can provide energy in a variety of situations such as fasting, starvation, during and after exercise, during pregnancy, right after birth, and for those following low carbohydrate diets. Ketones are now known to be the preferred fuel source for the brain and body during fasting and extended periods of exercise and due to their beneficial effect on insulin resistance, can alter the metabolic landscape in conditions like metabolic syndrome, type 2 diabetes, obesity, and heart disease.

For those following the standard American diet with three meals and numerous snacks throughout the day, there is rarely a switch in source outside of strenuous exercise. However, a variety of fasting regimens can encourage metabolic flexibility altering the type of fuel utilized by the body. This in turn may have beneficial effects such as decreased inflammation, weight, and insulin resistance, as well as improved immune system function and cardiovascular health.

While weight loss from fasting does improve many chronic disease parameters, the benefits of fasting are not strictly reliant on weight loss.  As reported in Cell Metabolism, in one clinical trial, men with prediabetes were randomly assigned to early time-restricted feeding (eTRF) where they ate in a six-hour window with dinner before three in the afternoon or a 12-hour feeding window. All participants were provided with a calorie level to maintain their weight. After five weeks, the participants switched to the opposite group. The researchers reported the participants experienced greater improvements in insulin sensitivity, beta cell function, blood pressure, oxidative stress, and appetite when in the eTRF group.

During fasting, as reported in Obesity, the shift away from fat synthesis and storage to the deployment of fatty acids and fatty-acid derived ketones for energy typically occurs between 12 to 36 hours after the start of a fast. This depends on liver glycogen levels before the fast and the level of physical activity while in the fasted state. During this phase of fasting, liver glycogen stores are dwindling and there is an upregulation of fat tissue lipolysis to produce free fatty acids (FFAs) and glycerol. The FFAs enter the circulation and along with ketones created from other cells are sent into highly metabolically active cells to generate adenosine triphosphate. This allows for the preservation of muscle and brain cell function during fasting and prolonged exercise.

Prolonged calorie restriction, which is often recommended for weight loss and other chronic disease states, has been shown to decrease muscle mass. A variety of fasting regimens can actually preserve muscle mass during weight loss. Increased muscle mass is important due to its effect on the resting metabolic rate, insulin resistance, preservation of functional fitness, improved bone health, and decreased risk of falls and injuries during aging. 

Fasting can be a great option because it can be tailored to a patient’s lifestyle increasing adherence. I routinely recommend a 12-hour overnight fast for most of my patients, because it provides an opportunity to rest from digestion, but also offers an easy transition into other types of fasting that can be more beneficial when it comes to flipping the metabolic switch.  Some examples of fasting techniques include:

• Alternate day fasting: no caloric intake for 24 hours and no caloric restriction for the next 24 hours.
• Alternate day modified fasting: consumption of less than 25 percent of caloric requirement alternated with days of no calorie restriction.
• Time-restricted feeding: calorie consumption is limited to a defined period of the day such as six to 10 hours.
• Periodic fasting: fasting for one to two days of the week and eating without restriction for the other days.
• Fasting mimicking diet: a commercial fasting program where 800 to 1,100 calories per day are consumed for five days and then the normal diet is consumed for the rest of the month.

Along with a fasting regimen, I recommend the addition of strength training at least twice per week and increase protein intake recommendations to at least 1.2 grams per kilogram to ensure the preservation of muscle mass.

When it comes to fasting, practitioners should use caution in some instances. Elderly patients, pregnant women, children, and those under chronic emotional stress may not be good candidates for more than an overnight fast. In addition, fasting may interfere with medication use and blood sugar control in those with diabetes and athletes may have impaired performance if fasting is not well-planned.

In addition to fasting, the ketogenic diet and other low carbohydrate diets offer additional options for harnessing the benefits of metabolic flexibility. These diets have become extremely popular related to their positive effects on weight loss and other chronic disease parameters. In one randomized controlled clinical trial reported in Nutrition and Diabetes, participants with type 2 diabetes were randomly assigned to a very low-calorie ketogenic diet (VLCK) or a standard low-calorie diet for four months. The VLCK group experienced greater overall weight loss and reduction in waist circumference and HgbA1c with no safety concerns when compared to the standard low-calorie group.

In general, both the ketogenic and low carbohydrate diets severely restrict carbohydrate intake. The ketogenic diet places more emphasis on fat with moderate protein intake and most low carbohydrate diets focus on increasing protein consumption with moderate fat intake. With both diet types, weight loss can be rapid related to a diuretic effect, but as is the case with fasting, muscle mass seems to be spared.

When it comes to the ketogenic diet, patients can experience some short-term side effects such as nausea, vomiting, headache, fatigue, dizziness, exercise intolerance, and constipation. Typically, symptoms disappear within a few days and ensuring adequate fluid intake helps to mitigate some of these symptoms. Longer term effects can include fatty liver, low protein levels, kidney stones, and deficiencies of certain vitamins and minerals. In addition, when not well-planned, the ketogenic diet can negatively impact the gut microbiome.

Caution should be taken for those with diabetes who are on insulin or oral hypoglycemic agents to prevent hypoglycemia. The ketogenic diet is not to be used for those with pancreatitis, liver failure, and some genetic metabolic disorders.

References

Anton, S. (2018) Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring, Md.). Retrieved from: https://pubmed.ncbi.nlm.nih.gov/29086496/

Bolla, A. (2019) Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes. Nutrients. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/31035514/

Dawson, D. (2020) COVID-19: Psychological flexibility, coping, mental health, and wellbeing in the UK during the pandemic. Journal of contextual behavioral science. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/32834970/

Goday, A. (2016) Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutrition & Diabetes. Retrieved from:  https://pubmed.ncbi.nlm.nih.gov/27643725/

Goodpaster, B. (2017) Metabolic Flexibility in Health and Disease. Cell Metabolism. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/28467922/

Puchalska, P. (2017) Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metabolism. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/28178565/

Sutton, E. (2018) Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metabolism. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/29754952/

Editor’s note: Photo courtesy of Freepik.