Gluconeogenesis, blood sugar, and protein – we need to stop having the same conversations over and over

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Yup, we’re going to have this conversation again. Protein and Gluconeogenesis. I’m really hoping eventually this misguided, scientifically false, wayyyyyy too often tossed about line of crap goes away. One can hope, right? Hobbits try to stay positive :). I’ve seen it. You’ve seen it. “50–60% of protein become glucose.” “Too much protein spikes blood sugar!” “Too much protein will ruin your kidneys!” Oh, and my all-time favorite… “Keto is MODERATE PROTEIN NOT HIGH PROTEIN!!”

Before we get into the rock-solid and extensive history debunking the protein\blood sugar myth, let’s hit that last one first. They are correct, keto isn’t “high protein.” They are also wrong that the common recommendation of bumping up protein intake 20-30g a day somehow makes the diet “high protein.” Math, I know it is hard for people. Let’s see if we can simplify this a little. What is “high” when talking about macro ratios?
The largest macro amount in calories is the “high” macro. That means means 50% or more of your calories come from that macro. Almost sounds like common sense, doesn’t it?? Showing this should be simple, I hope. Look at calories, not grams. Why? Because the energy values for macros are different – protein is ~4 per gram, fat is ~9, and carbs ~4. Right, fat has more than twice the calories for the same gram intake than the other two. Let’s take an individual with an average of 1600c daily intake. Now, I’m going to subtract the carbs from this because if I don’t, someone will claim my point is invalid because I left out that bowl of broccoli so 4×20 (figuring a 20g carb limitation) is 80c. 1600 – 80 = 1520. With me so far? For their diet to be “high” anything, that means that 760 or more calories (1520 x 50%) need to come from one macro source. Again, calories, not grams. For fats that means any intake of 80g of fat OR eating fats PLUS mobilizing body fat over this number makes it a “high fat” diet. In contrast, Higher than 180g protein would make it a “high protein” diet. Right, upping your protein from 90g to 120g is still a high fat diet.

Moving to the protein\blood sugar\glucose discussion:

Where did this all start? Why did this start? What is the science? A research study in 1915 by Janney calculated that ~3.5 g glucose could be produced for every gram of nitrogen passed in the urine as the result of a beef protein meal. Beef protein is 16% nitrogen so 1 g of nitrogen is excreted for every 6.25 g protein. Theoretically, then, 56% of ingested beef protein, by weight, can be converted to glucose. However, this was only a theoretical calculation. Theoretical means no actual proof. What about some proof? A research paper by Gannon and Nuttall in 1984 point out that shortly after that calculation was reported, a number of researchers showed that the ingestion of protein by subjects with and without diabetes did not result in an increase in blood glucose levels. One of the better-formed studies was done in 1936 by Conn and Newburgh, reporting no effect on blood glucose levels after a meal containing a large amount of protein in the form of lean beef. Fifteen subjects with diabetes and three control subjects were fed breakfasts of glucose, carbohydrate, or protein foods calculated to yield equal amounts of glucose (2 g protein/kg compared to 1 g carbohydrate/kg). The blood glucose response after carbohydrate or glucose was as expected – it went up. However, there was no increase in blood glucose levels after the protein meal even though there was a consistent rise in nitrogen in the urine, indicating protein was being metabolized. This destroyed the theoretical conclusion by Janney. The finding that protein did not raise blood glucose levels seems to have been lost over the years as here we are 100 years later, and people are still referencing the theory of Janney while ignoring the science of Conn and Newburgh. More recently, study by Nuttall in 1989 also showed that glucose concentration does not increase after protein consumption in people with and without diabetes. Nuttall gave nine subjects with mild type 2 diabetes 50 g protein, 50 g glucose, or  combination of 50 g protein and 50 g glucose. He determined the glucose and insulin responses over the next 5 hours. The glucose response to glucose was as expected, but the glucose response to protein remained stable for 2 hours and then began to decline. RIGHT. NO SPIKE! When protein and glucose were combined, the peak response was similar to that of glucose alone. However, during the late postprandial period, the glucose response was reduced by 34%. The insulin responses for protein and glucose were similar, but when combined the insulin response was nearly doubled. The glucose decrease when protein and glucose were combined was attributed to the increased insulin response to the combination. Gannon in 1990 reported on the glucose appearance rate over 8 hours following the ingestion of 50 g protein in the form of very lean beef compared to water in subjects with type 2 diabetes. After water alone, the plasma glucose concentration decreased from 6.7 mmol/l (120 mg/dl) to 5.4 mmol/l (98 mg/dl). After 50 g of protein, the glucose concentration at 1 hour increased by 0.1 mmol/L (3 mg/dl) and then decreased similarly to water. (THREE point increase? That is not a spike. That is not even a speed bump. That’s rolling over a worm and claiming it was a python.) The ingested protein resulted in only ~2 g glucose being produced and released into the circulation. This raises the question if gluconeogenesis from protein occurs, what happens to all the glucose produced as claimed? Several theories have been suggested. The first is that considerably less than the theoretical amount of glucose (50–60%) produced from protein actually is produced and enters the general circulation, and the small amount of glucose released is matched by a corresponding increase in glucose use, if adequate insulin is available. Another theory suggests that the process of gluconeogenesis from protein occurs during a 24-hour period, and the slowly and evenly produced glucose can be disposed of over a long period of time. It is also speculated that the insulin stimulated by dietary protein causes the glucose formed to be rapidly stored as glycogen in the liver and in skeletal muscles. This glucose can then be released when insulin levels are low or glucagon levels are elevated. Glycogen is the stored form of glucose and used for energy – either to the organs that cannot use ketones (such as regions of the brain and liver) or used by the muscles as on-demand fuel. Your muscles will have glycogen, regardless if that glycogen comes from carbs or not). No matter what the reasons, the science shows that eating protein isn’t going to turn all of it (or even half of it) into glucose and knock you out of ketosis.

To understand this process of gluconeogenesis and the question of why protein does not affect blood glucose levels, it might be helpful to briefly explain the metabolism of proteins. The amino acids not used for gut fuel (feeding gut bacteria) are metabolized in the intestines and shipped off to the liver for protein synthesis or gluconeogenesis. In the liver, nonessential amino acids are largely deaminated (basically, picked apart), and the nitrogen removed is converted into urea, then passed on to the kidneys for you to pee out. It has been shown that in subjects without and with mild type 2 diabetes, ~50–70% of a 50-g protein meal is accounted for over an 8-hour period by deamination in the liver and intestine and passed out in urine. The essential amino acids pass through the liver into the general circulation, where they may be removed and used for new protein synthesis or, alternatively, for skeletal muscle fuel. Circulating amino acids stimulate insulin and glucagon secretion. The amino acids that stimulate glucagon are different from those that stimulate insulin secretion. Just to keep things confusing, the effect of protein on glucose appearance is influenced by insulin availability. With insulin deficiency (different from insulin RESISTANCE – deficiency means you don’t have enough produced, resistance means you have enough, the cells just aren’t responding to it), the oxidation of branched chain amino acids in muscle and uptake of alanine (the principle glycogenic amino acid) by the liver is ramped up, resulting in increased gluconeogenesis and protein catabolism. The accompanying rise in glucose levels is due to an increased conversion of ingested protein into glucose and to a decreased glucose removal rate. In subjects with diabetes who had insulin withheld for 24 hours, there was a three- to fourfold increase in liver glucose output after protein ingestion. However, in the presence of insulin, alanine uptake by the liver is virtually zero, and hepatic glucose production falls by 85%. Insulin reduces gluconeogenesis in the liver by decreasing the amino acid substrate supply. Insulin also inhibits the degradation of body proteins and lowers the circulating concentration of many amino acids. RIGHT!!! Protein isn’t the devil, neither is insulin. In a nutshell: maybe 50–60% of protein goes through the process of gluconeogenesis in the liver, but virtually none of this glucose enters into the general circulation. Myth. Busted.

Does eating a high-protein diet cause kidney disease?

Despite the widespread belief that protein can influence the development of kidney disease, intake of protein is reported to be similar in patients with or without kidney disease. Nyberg in 1984 investigated protein intake in three groups:

1) patients who had diabetes 30 years or more without kidney disease

2) patients with kidney disease but stable filtration rates

3) patients with progressive kidney disease and declining filtration rates. In all three groups, average protein intake was >80 g/day (~16–17% of daily calories), with no relationship between the amount of protein ingested and the progression of kidney disease, The results of this study were confirmed in duplicate studies by Watts in  1989, Ekberg in 1994, and Jameel 1999. Case closed.


So, bookmark this post if you want, and drag it out when someone starts talking about protein and how bad it is for your blood sugar. Maybe if enough of us do this, the myth will finally die. One can hope…

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1 Comment

  1. […] I preached from the beginning is now slowly getting accepted, I like that. Some of those things are higher protein, watch sugar alcohols, watch out for dairy, not everyone is the same, and yes, you can eat too much […]

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