Metabolic Flexibility

Written by Dr. Ryan Kneessi, ND

The mechanisms this protocol supports

After a meal, insulin helps move glucose into cells, and between meals the body should shift toward using stored fat. AMPK is the cell’s energy sensor, and it helps coordinate this switch along with mitochondrial function.

Nutrient sensing pathways such as insulin signaling, AMPK and mTOR also influence how cells age, and they respond strongly to diet, movement and sleep. Gut bacteria play a role too, and Akkermansia muciniphila is a bacterium being studied for its connection to the gut lining and metabolic health.

Research has linked reduced metabolic flexibility with insulin resistance, type 2 diabetes and obesity. You can read more in my articles on glycemic control and AMPK.

What is in the protocol

The exact products and directions are listed in the Fullscript plan, and here is what each one is commonly used to support.

Metabolic Synergy from Designs for Health is a multivitamin and mineral formula with nutrients that support healthy glucose metabolism. Berberine with InSea2 combines berberine, which activates AMPK in laboratory research, with a seaweed polyphenol extract that was linked in a small trial with a lower insulin response after a carbohydrate meal. ProOmega from Nordic Naturals provides the omega-3 fats EPA and DHA, which support cell membrane health and a balanced inflammatory response.

Liquid D3/K2 provides vitamin D and vitamin K2, which support immune, metabolic and bone health and work together in calcium metabolism. ABC from InfiniWell combines the beneficial bacterium Akkermansia muciniphila with a prebiotic fiber and a peptide complex, and it is commonly used to support the gut lining and a healthy metabolic environment in the gut.

Related protocols you may find helpful include Longevity Foundation.

How to use it thoughtfully

Please talk with your provider before starting, especially if you take medications, are pregnant or nursing, or have a health condition. This page does not list amounts, so follow the label or the specific guidance your provider gives you. When you can, add one product at a time so it is easier to notice how you feel. Sleep, nourishing food, daily movement and stress care are the foundation, and supplements are meant to build on them.

Berberine can interact with many medications, including diabetes medications, and it is not appropriate during pregnancy. Vitamin K can interact with blood thinners such as warfarin, so check with your prescriber first.

What the research shows

This protocol has not been tested as a whole in a clinical trial, so the studies below cover its main ingredients.

Berberine has the most blood sugar research. In a 2008 pilot study by Yin and colleagues, 36 adults with newly found type 2 diabetes took berberine or metformin (500 mg three times a day) for three months, and HbA1c fell from 9.5% to 7.5% with berberine, similar to metformin. In a second group of 48 adults, HbA1c fell from 8.1% to 7.3%. About a third had stomach side effects. These were small, short studies, and berberine can interact with medicines.

The seaweed extract was tested by Paradis and colleagues in 2011. In a crossover trial with 23 adults, 500 mg of brown seaweed taken 30 minutes before 50 grams of bread carbohydrate lowered the insulin response by 12.1% compared with placebo, but did not significantly change blood sugar. This was a single-dose study.

Frequently asked questions

Sources

• Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 2012. PMID: 22436748. https://pmc.ncbi.nlm.nih.gov/articles/PMC5726489/
• Depommier C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 2019. PMID: 31263284. https://pmc.ncbi.nlm.nih.gov/articles/PMC6699990/
• Goodpaster BH, Sparks LM. Metabolic Flexibility in Health and Disease. Cell Metab 2017. PMID: 28467922. https://pmc.ncbi.nlm.nih.gov/articles/PMC5513193/
• Lee YS, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006. PMID: 16873688. https://pubmed.ncbi.nlm.nih.gov/16873688/
• Paradis ME, Couture P, Lamarche B. A randomised crossover placebo-controlled trial investigating the effect of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) on postchallenge plasma glucose and insulin levels in men and women. Appl Physiol Nutr Metab 2011. PMID: 22087795. https://pubmed.ncbi.nlm.nih.gov/22087795/

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