The Metabolic Holy Grail Pt. 2

Adam Plotkin
8 min readFeb 7, 2021

Well if you haven’t read Pt. 1, then you should probably go do that first!

In case I didn’t frame it well enough in Pt. 1 as to why we need metabolic flexibility, let me show you a real world example that should hopefully make things a bit more clear.

Let me ask you: Do you think you are metabolically healthy? Whether you realize it or not, this is a loaded question. You may appear to be healthy on the outside (relatively lean and athletic) but on the inside, you may have done some damage due to the toxic foodstuffs you are ingesting on a day to day basis. Well it turns out that this is the case for about 88% of Americans :(

According to a 2019 study published in the Journal “Metabolic Syndrome and Related Disorders” only 1 in 8 (12%) Americans are considered metabolically healthy (1). This study took data from the National Health and Nutrition Examination Survey from 2009–2016 (n=8,721 adults). The study’s authors defined metabolic health as having ideal levels of 1)blood glucose 2)triglycerides 3) HDL cholesterol 4) blood pressure and 5)waist circumference all without being on medications. All five of these variables are directly associated with a person’s risk for heart disease, diabetes, and stroke (2). Thus, if an individual had just one category out of the ideal range, they were considered metabolically unhealthy. It is quite evident that we are moving in the wrong direction as a country with regards to taking back control of our metabolic health. Therefore, as promised in Pt. 1, I am going to briefly outline some immediate steps we can all take to foster metabolic flexibility and shift us towards optimal metabolic health.

  1. Weight loss. This one seems obvious, but it should be stated nevertheless. By creating a negative energy balance, we force our bodies to learn how to use stored body fat as fuel (3). This is paramount, because as demonstrated in Pt. 1 of this series, obese individuals tend to have a reduced ability to oxidize fats (they have an elevated RQ value and cannot burn dietary fat and body fat for fuel). Thus, think of weight loss as a way to reteach your body how to burn fat for fuel! In fact a reduction in body weight by just 5% can reduce obesity related metabolic disorders (4). Finally along with weight loss may come the loss of visceral fat (fat surrounding the organs) which results in improved fasting glucose, cholsterol:HDL, triglycerides, and diastolic blood pressure (Hmmm…all values that we saw were out of whack in the study mentioned above…interesting; 5)

Now if you haven’t read my other articles yet, I highly suggest you do so, as they outline several strategies to lose weight. However in brief, you should first begin by looking at the ingredients found in the foods you eat on a daily basis. I stick to single/whole foods (1 ingredient) but as you build to that, just be cognizant of the ultra-processed garbage you are putting into your body. Key tip: If your great grandmother would not have recognized it as food…don’t eat it :)

In coming articles I will expound on this idea and other weight loss strategies, but from personal experience, eating whole foods as 90–95% of your diet will change your life and change your metabolic health! For now, if you want guidance on structuring an outstanding weight loss program tailored to you, I highly suggest you check out the RP Strength App.

2. Early time-restricted feeding. If you haven’t read my article on this topic yet, I highly suggest you do so (wow isn’t amazing how everything comes together full circle). I go into extensive detail on this topic in my article, but in short, early time restricted feeding is eating your daily caloric load from between 8am-2 pm (this time frame can be shifted based on your daily schedule, but food should be consumed several hours before you go to sleep). The underlying biochemical mechanisms for this is fascinating and deserves its own article, but by eating earlier in the day you are aligning your eating patterns with your circadian rhythms thereby fostering a harmonious relationship between mind, body, and fuel. I cover this in my other article, but the first of its kind human study on this topic found that individuals on the early time-restricted feeding pattern improved metabolic flexibility and fat oxidation. Individuals also lost more weight than controls due to a reduction in appetite (6).

3. Exercise. Wow shocker. It is well known that regular physical activity improves metabolic flexibility (7). In fact, both aerobic (think long-steady state endurance work) and anaerobic (think high intensity interval training/sprints) increase mitochondrial content and improve glycemic control (8). And we see even better results when we mix aerobic and anaerobic work with resistance training! Just three 30 minute moderate aerobic sessions with one resistance training session is enough to restore basal fat oxidation levels to that of healthy controls (9–12). So really, based on the literature, you can see improvements in your metabolic flexibility by committing to as little as 90 minutes of moderate walking and 30 minutes of slinging some weights around (or bodyweight training)PER WEEK!!!

And I really want to stress this: Exercise is not important because it burns calories. In fact, most people highly highly highly overestimate how many calories they burn when performing an activity. Exercise is actually important because it helps us restore our ability to burn body fat, so when we are fasting (or just not eating) we can tap into our body fat for fuel, rather than rely on carbohydrates!

4. Supplementation. This is a topic near and dear to my heart for two reasons. First, it is what my lab and I are studying at the NIH, and two, I just so happen to know the owner of the greatest supplement company in the world, Pinnacle Supplementation. Unfortunately, because our lab has yet to publish a lot of our data, I will have to keep silent on a good amount of info, but I can talk about one interesting supplement: L-carnitine. Without getting too deep into the biochemical weeds, L-carnitine is a biomolecule that helps in the importation of long-chain fatty acids into the mitochondrial matrix for beta-oxidation (the burning of fat for fuel; 13). Current research is demonstrating that obese and diabetic individuals have decreased levels of carnitine and carnitine acetyltransferase that may result in impaired glucose utilization and whole-body glucose tolerance (13–15). Supplementation of L-carnitine in mice has restored levels back to baseline, and studies are currently underway in humans (13). Although Pinnacle Supplementation does not currently have any products with L-carnitine, a little birdie told me that they will be here real soon, so keep an eye out and subscribe to their newsletter.

So when we boil this all down it becomes evident that all of us, despite our external appearances, need some help with improving our metabolic flexibility. This is the ultimate superpower to be able to burn both fat and sugar depending on what we are eating and what we are doing. To start our journey back towards regaining our metabolic health we can begin by first cutting out the processed junk! We can then formulate a well-planned weight loss template and combine that with just a few hours of moderate exercise a week. Finally, we can begin to tweak when we eat our daily caloric load and the supplements we take with our meals.

There is no magic potion or quick fix. Nothing angers me more than people searching for these magical remedies. If your metabolic health is important to you (newsflash: it should be!) then you will need to put in the consistent work to save the sinking ship.

  1. Joana Araújo, Jianwen Cai, and June Stevens.Metabolic Syndrome and Related Disorders.Feb 2019.46–52.
  3. de la Iglesia R, Loria-Kohen V, Zulet MA, Martinez JA, Reglero G, Ramirez de Molina A. Dietary strategies implicated in the prevention and treatment of metabolic syndrome. Int J Mol Sci. 2016;17(11):1–21
  4. DeLany JP, Kelley DE, Hames KC, Jakicic JM, Goodpaster BH. Effect of physical activity on weight loss, energy expenditure, and energy intake during diet induced weight loss. Obesity (Silver Spring). 2014;22(2):363–370.
  5. Gallagher D, Heshka S, Kelley DE, Thornton J, Boxt L, Pi-Sunyer FX, Patricio J, Mancino J, Clark JM; MRI Ancillary Study Group of Look AHEAD Research Group. Changes in adipose tissue depots and metabolic markers following a 1-year diet and exercise intervention in overweight and obese patients with type 2 diabetes. Diabetes Care. 2014;37(12):3325–3332.
  6. Ravussin, E., Beyl, R. A., Poggiogalle, E., Hsia, D. S., & Peterson, C. M. (2019). Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation But Does Not Affect Energy Expenditure in Humans. Obesity (Silver Spring, Md.), 27(8), 1244–1254.
  7. Saltin B, Gollnick PD. Skeletal muscle adaptability: significance for metabolism and performance. In: Peachy L, Adrian R, Geiger S, eds. Handbook of Physiology: section 10: Skeletal Muscle. Bethesda, MD: American Physiological Society; 1983:555–631.
  8. Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 2013;17(2):162–184.
  9. Bajpeyi S, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Hickner RC, Kraus WE, Houmard JA. Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation. J Appl Physiol (1985). 2009 Apr;106(4):1079–85. doi: 10.1152/japplphysiol.91262.2008. Epub 2009 Feb 5. PMID: 19196913; PMCID: PMC2698641
  10. Berggren JR, Boyle KE, Chapman WH, Houmard JA. Skeletal muscle lipid oxidation and obesity: influence of weight loss and exercise. Am J Physiol Endocrinol Metab. 2008 Apr;294(4):E726–32. doi: 10.1152/ajpendo.00354.2007. Epub 2008 Feb 5. PMID: 18252891.
  11. Goodpaster, B. H., & Sparks, L. M. (2017). Metabolic Flexibility in Health and Disease. Cell Metabolism, 25(5), 1027–1036.
  12. Amati F, Dubé JJ, Shay C, Goodpaster BH. Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation. J Appl Physiol (1985). 2008 Sep;105(3):825–31. doi: 10.1152/japplphysiol.90384.2008. Epub 2008 Jul 10. PMID: 18617627; PMCID: PMC2536819.
  13. Noland RC, Koves TR, Seiler SE, Lum H, Lust RM, Ilkayeva O, Stevens RD, Hegardt FG, Muoio DM. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J Biol Chem. 2009;284(34):22840–22852.
  14. Muoio DM, Noland RC, Kovalik J-PP, Seiler SE, Davies MN, DeBalsi KL, Ilkayeva OR, Stevens RD, Kheterpal I, Zhang J, Covington JD, Bajpeyi S, Ravussin E, Kraus W, Koves TR, Mynatt RL. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. Cell Metab. 2012;15(5):764–777.
  15. Xia Y, Li Q, Zhong W, Dong J, Wang Z, Wang C. L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function. Diabetol Metab Syndr. 2011;3(1):31.



Adam Plotkin

Post-Baccalaureate research assistant in the Molecular and Clinical Nutrition Lab at the National Institutes of Health