In the intricate world of your body's metabolism, the players—carbohydrates, fats, and proteins—dance to the tune of hormones like insulin and glucagon. These hormones are the conductors orchestrating whether your bodies are in a state of building up (anabolic) or breaking down (catabolic). The key to understanding optimal health lies in balancing the insulin-to-glucagon ratio, which dictates your metabolic state and whether you will predominantly store fat (when insulin is high) or actively burn fat as an energy fuel whilst keeping insulin low. Of course you want the latter, at least for most of the time, so let’s find out how this works in practice.
Balancing Act: The Insulin-to-Glucagon Ratio
At the centre of this metabolic ballet are insulin and glucagon. Insulin is like a storage manager, encouraging the body to store nutrients (or energy), while glucagon acts as the counterbalance, pushing the body to use stored nutrients (or energy). Maintaining the right balance between these two hormones is crucial for health.
The Catabolic State
Fasting and adopting a low-carbohydrate diet are powerful tools that swing the body into a catabolic state, where the insulin-to-glucagon ratio is low. In this state, the body shifts its focus from storing nutrients to using them, promoting processes that are beneficial for health. A few of these processes include ketogenesis, autophagy, mitophagy, gluconeogenesis and lipolysis. You want all of these processes to be regularly activated to keep us healthy so let’s take a look at them so that you can understand them a bit more.
Ketogenesis: Making Ketones
When there are few carbohydrates available (and hence insulin levels are low and glucagon levels are raised), the body turns to stored fats for energy, creating molecules called ketones. These ketones become a vital energy source, especially for the brain and other highly metabolically active organs, reducing the need for glucose.
Autophagy & Mitophagy: Cellular Recycling
This low insulin-to-glucagon ratio also triggers processes like autophagy and mitophagy, which are like cellular clean-up crews. They remove damaged or old cellular components, contributing to better overall cell function and longevity. Autophagy is the clean-up or recycling of cells. Mitophagy is the recycling of mitochondria (the little organelles that make your energy).
Gluconeogenesis & Glycogenolysis: Blood Sugar Control
The catabolic state supports processes like gluconeogenesis (making glucose from non-carb sources or fat stores) and glycogenolysis (breaking down stored glycogen). These actions help maintain steady blood sugar levels without needing a constant supply of carbohydrates from food. There is actually only one type of cell in the body that requires glucose as an energy fuel and that is red blood cells which don’t have mitochondria. All the rest can run perfectly, if not optimally, on ketones.
Lipolysis: Breaking Down Fats
Lipolysis, the breakdown of stored body fat into usable energy, is enhanced in a catabolic state. This not only provides extra energy but also helps manage body weight by reducing fat stores.
The Anabolic State
Of course, when you are in an anabolic state things are very different because you are storing energy. Instead, you inhibit or stop ketogenesis and instead fuel your body on glucose from the carbohydrates you are eating. You also inhibit or reduce autophagy and mitophagy, so the recycling of damage or old cells and mitochondria. In addition, you activate glycogenesis and lipogenesis.
Glycogenesis
If the ratio of insulin to glucagon is high you start to make glycogen from glucose and store it in your liver and muscles.
Lipogenesis
You can only store around 1600 calories of glycogen in your body so once these reserves are full and if the inulin to glucagon ration remains high then any excess glucose is converted and stored as fat.
So How Do Carbohydrates, Fat & Protein Impact?
You have probably gathered by now, but I want to spell out for you very clearly, the impact that the different macronutrients have on the ratio of insulin to glucagon and therefore your metabolic health. And it is important to understand this as there are many myths abounding such as 'you must be careful to eat too much protein as it will raise your insulin levels'. So let's look at how different styles of eating and the macronutrient balance affect this.
The SUK Diet
On the SUK Diet (by this I mean the standard UK diet) which is high in carbohydrates and low in fat the insulin to glucagon ration is high at around 4.
A Low Carb Diet
On a low carbohydrate diet (in this case I am talking less than 50g of carbs a day so ketogenic) the insulin to glucagon ratio is around 1.3.
Protein
When protein is added to the SUK diet the insulin to glucagon ration rises to 70! Yikes, yes 20 x higher! But when protein is added to the low carb diet the ratio doesn’t change at all. From this you can see that it is not the protein itself that makes the difference but the combination of carbohydrates and protein that is the problem.
Looking At The Science of Low Carb & Insulin
Here is a study that shows the different effects that the macronutrients have on insulin and you can clearly see the effect of carbs is much greater than either fat or protein.
Tannous dit El Khoury D, Obeid O, Azar ST, Hwalla N. Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males. Ann Nutr Metab. 2006;50(3):260-9. doi: 10.1159/000091684. Epub 2006 Feb 23. PMID: 16508254.
This study shows a control drink (1) which is purely glucose and maltodextrin (very high carb) and what happens when it is given with a variety of different protein drinks (2 - 10 different mixes of amino acids). You can see that depending on the mixture given there are slightly different responses but in all cases there is a fairly big rise in insulin.
Van Loon LJ, Saris WH, Verhagen H, Wagenmakers AJ. Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. Am J Clin Nutr. 2000 Jul;72(1):96-105. doi: 10.1093/ajcn/72.1.96. PMID: 10871567.
They actually make a comment in their conclusion saying that "a mixture of wheat protein hydrolysate, free leucine, phenylalanine, and carbohydrate can be applied as a nutritional supplement to strongly elevate insulin concentrations". Leucine, phenylalanine are amino acids that caused the biggest increase in insulin. Why you would want to do this beats me! But what you can see is that the combination of protein and carbs causes insulin to rise but not protein on its own.
Now I want to draw your attention to diets that are either high carb or low carb but which also include protein to see what happens. So the next study shows the difference in insulin secretion between a 6 week high carb or high fat diet. You can clearly see that the high carb diet increased insulin from baseline (starting point of the diet trial) and a high fat low carb diet reduced insulin.
Hernandez TL, Sutherland JP, Wolfe P, Allian-Sauer M, Capell WH, Talley ND, Wyatt HR, Foster GD, Hill JO, Eckel RH. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. Am J Clin Nutr. 2010 Mar;91(3):578-85. doi: 10.3945/ajcn.2009.27909. Epub 2010 Jan 27. PMID: 20107198; PMCID: PMC3132068.
And another study showing how much lower insulin is on a low carbohydrate diet compared with a control group on a high carbohydrate diet over a 24-hour period.
Guenther Boden, Karin Sargrad, Carol Homko, et al. Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes. Ann Intern Med.2005;142:403-411. [Epub 15 March 2005].doi:10.7326/0003-4819-142-6-200503150-00006
We can see from all this that it is not the protein that makes the difference but rather the consumption of carbohydrates.
The Benefits of a Low Insulin to Glucagon Ratio
Keeping a low insulin-to-glucagon ratio through fasting or a low-carb diet offers numerous health benefits.
Reduced Inflammation
Lowering the insulin-to-glucagon ratio has been linked to decreased inflammation, which supports a healthier immune system and reduces the risk of chronic diseases.
Less Oxidative Stress
High insulin levels can lead to oxidative stress. By promoting a catabolic state, the body can better manage this stress, reducing cell damage and the risk of age-related diseases.
Optimal Power House Function
Mitochondria, the cellular power houses, benefit from a catabolic state. Recycling processes like autophagy and mitophagy keep them in good shape, leading to better energy production and cell function.
More Energy
Shifting towards ketones for energy production results in an increased production (up to 30% higher) of ATP (adenosine triphosphate), the cell's energy currency. This means more fuel for various cellular processes.
Carnitine: The Fat Metabolism Assistant
Carnitine, is an amino acid which is found in red meat with small amounts also made in the body, it plays a vital role in fat metabolism. Think of it as a shuttle that helps transport fat molecules into the power houses (mitochondria) for energy production. Having enough carnitine is crucial for efficient fat use, making it a key player in a low-carb and ketogenic lifestyle.
What To Eat To Optimise Insulin & Glucagon?
There are three key things to remember if you want to optimise the ratio of insulin to glucagon and hence your metabolic health.
Control your intake of carbohydrates.
Eat sufficient protein from high quality sources including red meat.
Top up the rest of your calories from high quality fat (avoiding trans fats and industrially produced vegetable/seed oils.
If you are transitioning onto a low carb diet from a high carb diet you might want to increase your protein intake slowly as your metabolic health improves and your glucose and insulin levels drop.
Finally, If you want to watch a great explanation of all of this then take a look at this video by Ben Bikman as he explains the relevance of protein to insulin and glucagon.
Conclusion
In the complex dance of metabolism, the balance between insulin and glucagon is a key determinant of overall health. Fasting and adopting a low-carb lifestyle are potent strategies to shift the body into a catabolic state, unlocking numerous health benefits. Understanding the importance of carnitine in fat metabolism highlights the significance of choosing high-quality fats and proteins, such as those found in red meat. Your body is a truly remarkable and complex system and understanding a little more about the way it works can really help you to make the best dietary and lifestyle choices to optimise your health and well-being.
References
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Gutniak M, Grill V, Efendić S. Effect of composition of mixed meals--low- versus high-carbohydrate content--on insulin, glucagon, and somatostatin release in healthy humans and in patients with NIDDM. Diabetes Care. 1986 May-Jun;9(3):244-9. doi: 10.2337/diacare.9.3.244. PMID: 2873976.
Oyoun, O. E., & Cahill Jr, G. F. (1968). Metabolic effects of exogenous glucagon-like peptide-1, thyrotropin-releasing hormone, and other gastrointestinal hormones. Diabetes, 17
Tannous dit El Khoury D, Obeid O, Azar ST, Hwalla N. Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males. Ann Nutr Metab. 2006;50(3):260-9. doi: 10.1159/000091684. Epub 2006 Feb 23. PMID: 16508254.
Hernandez TL, Sutherland JP, Wolfe P, Allian-Sauer M, Capell WH, Talley ND, Wyatt HR, Foster GD, Hill JO, Eckel RH. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. Am J Clin Nutr. 2010 Mar;91(3):578-85. doi: 10.3945/ajcn.2009.27909. Epub 2010 Jan 27. PMID: 20107198; PMCID: PMC3132068.
Guenther Boden, Karin Sargrad, Carol Homko, et al. Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes. Ann Intern Med.2005;142:403-411. [Epub 15 March 2005].doi:10.7326/0003-4819-142-6-200503150-00006
van Loon LJ, Saris WH, Verhagen H, Wagenmakers AJ. Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. Am J Clin Nutr. 2000 Jul;72(1):96-105. doi: 10.1093/ajcn/72.1.96. PMID: 10871567.
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