Metabolic Flexibility as a Marker of Health

Julia Malkowski, ND, DC | June 22, 2021

     5 Signs That You're Metabolically Flexible

  • You have stable blood sugar levels.
  • You have excellent satiety between meals.
  • You don’t get the 'hangries' (hungry + angry)
  • You can extend your overnight fast.
  • You have the ability to exercise in a fasted state for 2+ hours.

In the quest for health, patients seek fad diets, pricey products and even trendy teas. What if one of the best endeavors for health is simply to eat as usual one day, and not to eat the next? The ability to adapt seamlessly to these changes in metabolic demand is defined as Metabolic Flexibility. Considerations with regards to Metabolic Flexibility include leptin, adiponectin, Metabolic Inflexibility and the ketogenic diet (keto/KD).

Leptin is a key hormone involved in the regulation of body composition, weight and energy homeostasis. Leptin, synthesized primarily in adipocytes, influences the hypothalamus directly via LEPRb-expressing neurons. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body fat. Adiponectin is the most abundant adipokine. The effects of adiponectin include blood glucose regulation, insulin sensitivity, fatty-acid oxidation, improved energy homeostasis and anti-inflammatory influences. When in balance, leptin and adiponectin work synergistically. High leptin to adiponectin (LAR) ratios in serum have been associated with obesity, type II diabetes, insulin resistance, inflammation, and cardiovascular disease. Recent evidence indicates that a high LAR is more clinically sensitive for risks of metabolic syndrome than either adipokine alone.

Metabolic Inflexibility is potentially a marker of poor health. Metabolic Inflexibility is the inability to switch from carbohydrate utilization to the absence of carbohydrates/fat burning as characterized by fatigue, headaches, irritability, severe cravings, etc. These individuals are accustomed to consistent carbohydrate consumption, typical of a modern western diet, and unaccustomed to the absence of carbs. The human body may have utilized fats as the primary source of fuel prior to the widespread implementation of agriculture and flour mills. To assist into fat burning a ketogenic diet is often employed. 

A keto diet primarily entails feeding the body fat as its source of fuel. Proponents of the diet emphasize healthy fats, like grass-fed meats, eggs, avocado and macadamia, as well as low carbohydrate vegetables, while avoiding grains and processed foods. The keto diet may be appropriate to address abdominal adiposity associated with modern western diets. Much debate has arisen with regards to the length one should remain on the keto diet. Some advise that indefinite keto diets are safe, while others maintain only short term, or intermittent adherence is best. Recent evidence has shown that long term keto diets contribute to gastrointestinal (GI) dysbiosis. Keto GI dysbiosis is characterized by excess inflammatory bacteria such as Proteobacteria and Escherichia spp., and decreased beneficial Clostridia Class and Faecalibacterium prausnitzii. A dreadful lack of soluble fiber on the keto diet is a primary cause for GI dysbiosis. Intermittent keto or “diet cycling”, even with low simple carbs, may be a means to minimize this specific proinflammatory dysbiosis.

Considerations with regards to Metabolic Flexibility include leptin, adiponectin, Metabolic Inflexibility and the ketogenic (keto) diet. Those undergoing a strict, sustained keto diet may benefit from GI microbiome evaluations and appropriate interventions. Perhaps one of the best indicators of health is Metabolic Flexibility, which may be evident with an ability to skip meals and snacks without a sense of distress.



Goodpaster BH, Sparks LM. Metabolic Flexibility in Health and Disease. Cell Metab. 2017 May 2;25(5):1027-1036. doi: 10.1016/j.cmet.2017.04.015. PMID: 28467922; PMCID: PMC5513193.

Wang ZV, Scherer PE. Adiponectin, the past two decades. J Mol Cell Biol. 2016 Apr;8(2):93-100. doi: 10.1093/jmcb/mjw011. Epub 2016 Mar 18. PMID: 26993047; PMCID: PMC4816148.

Wheless JW. History of the ketogenic diet. Epilepsia. 2008 Nov;49 Suppl 8:3-5. doi: 10.1111/j.1528-1167.2008.01821.x. PMID: 19049574.

Zhou Y, Rui L. Leptin signaling and leptin resistance. Front Med. 2013 Jun;7(2):207-22. doi: 10.1007/s11684-013-0263-5. Epub 2013 Apr 12. PMID: 23580174; PMCID: PMC4069066.

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