An oversimplified version of the idea behind The ROS Theory of Obesity is that a diet high in saturated fat will cause “physiological insulin resistance” in your fat cells and they will fail to store fat. This will make you lean in time. When I first posted The Croissant Diet, my assumption was that trying the diet might elevate your blood sugar after meals and possible even the next morning, but that would be OK because you’d have regained control over your insulin signalling due to ROS generation in the mitochondria.

Based on the feedback from many who have tried the diet, I was clearly wrong about that. There have been some to report higher blood sugar by adding carbs back to a low carb diet, but even more people have reported a DROP in blood glucose levels, both immediately after meals and the next morning.

Not all carbs (or the way they are served) are equal.



~6:30 last night we had Italian. I ate most of a generous serving of gnocchi with a cream-heavy sauce, and a sizable beef meatball.



Besides being delicious this caused no spike at all, if anything overregulating down. #CGM pic.twitter.com/2SmrTLyHxB — Toshi Clark (@maximumcharacte) January 27, 2020

This is true for me too- high starch with high stearic leads to lower FBG, I am beginning to think the reason that I gained fat on zero carb high fat was because I was eating pork rinds, bacon and chicken thighs with skin on- high N-6 PUFA — Emily (@Emily32366118) January 28, 2020

What could be happening here?

Hyperlipid to The Rescue

As usual, an answer could be found in a post by Peter over at Hyperlipid. As usual, it requires some explaining. The post (the second part of it) is about an experiment using “perfused rat pancreas” to study the effects on insulin secretion of several different fats when glucose rises. The pancreas is the organ that releases insulin. “Perfused” means that a solution is pumped through the organ at a steady rate. So you have an isolated rat pancreas, which is being pumped with a buffer solution that contains one of several different fats and a baseline amount of glucose. You suddenly increase the amount of glucose and monitor how much insulin is released by the pancreas. Here’s what happened:

So what’s happening here? (it’s probably easiest to ignore the inset box floating above fractions 0-5). The pancreas’ all have access to a single type of fat. The solid Black Squares are stearic acid (18 carbon length saturated fat), solid triangles are palmitic acid (16 carbon length saturated fat). The open circles are Oleic acid (18 carbon length monounsaturated fat, like in olive oil)., solid circles are linoleic acid (18 carbon length Omega-6 polyunsaturated fat like in soybean oil). Open triangles are Octanoic (8 carbon length saturated like in MCT oil/cocnut oil). The open squares are no fat.

The block of time marked “G 3” is when glucose is held steady at 3 mmol/l. The glucose is suddenly raised to 12.5 mmol/l, “G 12.5”, after fraction 5 and there is a sudden spike in insulin release. Depending on the background fat. As you can see, the longer the carbon chain and the more saturated the fat, the more dramatic the first insulin spike. I’ll let Peter take it from here:

Notice the marked but transient spike in insulin when glucose is raised from 3.0mmol/l to 12.5mmol/l, most obvious in the black squares representing stearic acid as the background FFA (palmitate is the black triangles). After the spike, which I think represents the first phase insulin response, there is a steady climb in insulin, equivalent to the second phase of insulin secretion. … The surge of insulin would hit the liver and interact with the insulin receptor. Two things follow on from this. Most insulin would be metabolised following interaction with its receptor, so insulin would never flood the systemic circulation. Second effect is that insulin/insulin receptor activation would shut down hepatic glucose output while the Glut2 transporters continue to pretty well clear the portal vein of glucose. So a first phase insulin response is designed to protect the systemic circulation from both hyperinsulinaemia and hyperglycaemia. That is its job. Petro Dobromylskyj, https://high-fat-nutrition.blogspot.com/2016/04/dairy-and-diabetes.html

Let’s unpack this. We’ll need to understand what the portal vein is and what the liver’s role in this is. We’ll need to understand the importance of the first-phase insulin response. And what exactly is GLUT2?

The Portal Vein, The Pancreas and The Liver

The portal vein is the highway that connects our digestive organs – the stomach, and intestines – to the pancreas and the liver. As you can see from the illustration, the pancreas – the organ which produces insulin and its counterpart glucagon – sits at the center of the network. The direction of blood flow in all of these veins is from the stomach or intestines past the pancreas and then into the liver.

The digestive system. The portal vein is drawn in blue. The pancreas is the long organ that runs left to right that lies right below the liver. The portal vein takes bloodflow from the stomach and intestines past the pancreas into the liver, where it feeds into the capillary beds of the liver. In this way, the liver gets first access to all nutrients coming out of the digestive system and is influenced by insulin and glucagon produced in the pancreas.

The portal vein feeds into the arterial beds of the liver. Which is to say that the liver gets the first shot at everything coming through the portal vein, which is all of the nutrients extracted by the digestive system. The liver can remove glucose from the portal vein flow or add glucose to it via the action of a glucose transporter called GLUT2. Blood from the portal vein exits the liver through the hepatic veins, which carry the flow to the heart where it is pumped to the rest of the body.

GLUT2 (GLUcose Transporter type 2) is expressed by both the pancreas and the liver. GLUT2 is one of the transporters that can move glucose out of the blood and into the cells WITHOUT being stimulated by insulin. The presence of GLUT2 in the pancreas allows the pancreas to sense glucose coming in through portal flow. GLUT2 has some interesting properties compared to other glucose transporters – it can transport both glucose and fructose, it is capable of transferring large quantities of sugars and it is bidirectional, allowing the liver to export glucose as well as absorb it.

The First-Phase Insulin Response

Let’s look at the perfused rat pancreas again:

When the glucose levels entering the pancreas increases – time period “G 12.5” -the pancreas immediately releases a burst of insulin into the portal vein. Fractions were taken every two minutes during the experiment so fraction 5 is ten minutes in. You can see that the insulin levels peaks in fraction 7, four minutes after glucose rises, and then drops to a significantly lower level than the peak by fraction 9, 8 minutes after the rise in glucose. The times don’t change much if you are eating a starchy meal. Enzymes in your mouth begin converting starch to glucose immediately. The first-phase insulin response happens in the first ten minutes of a meal.

The liver expresses insulin receptors in its capillary beds which bind the insulin coming through the portal vein. The liver’s immediate response to seeing this first blast of insulin is to shut down glucose production. The liver can provide blood glucose by breaking down its stored glycogen in a process know as glycogenolysis or by creating new glucose from glycerol, glucogenic amino acids, pyruvate, lactate and/or some fats in a process known as gluconeogenesis. Either way, the first-phase insulin response tells the liver to stop releasing blood glucose because glucose is coming in from the diet and it’s now time to start storing it as glycogen.

When the liver binds insulin, it rapidly degrades it with an enzyme known as Insulin Degrading Enzyme (IDE). So the first-phase insulin response should be a quick burst of insulin released by the pancreas in response to an increase in glucose in the portal vein. It should shut down glucose production by the liver and trigger the liver to begin rapidly taking up glucose through GLUT2 and storing it as glycogen. The relatively small amount of insulin should be rapidly degraded by the liver and have little effect on systemic insulin.

As you can see, the first-phase insulin response is markedly decreased if the primary fat available to the pancreas is monounsaturated fat (open circles) and it’s almost totally eliminated by linoleic acid (black circles), the polyunsaturated fat found in dietary sources like soybean, safflower and corn oil.

The First-Phase Insulin Response and The Croissant Diet

The liver acts as a sort of metabolic flywheel. It takes incoming glucose, warehouses it as glycogen and then starts to let it back out as blood glucose when needed. The liver can’t store a lot of glycogen – maybe a half lb – and so it acts more like a flywheel than a real energy storage mechanism. But the liver CAN store enough glycogen to absorb the glucose from most meals.

Look at the first tweet from Toshi Clark. The CGM he refers to and the readout he posts is from a Continuous Glucose Monitor. He eats most of a large plate of gnocchi with cream sauce at 6:30 PM (almost on the left hand side of the chart). If anything his blood glucose goes DOWN as a result of this meal due to lowered liver glucose production. Where did the dietary glucose go? Into his liver as glycogen. He clearly has a robust first-phase insulin response. I know from his twitter feed that he’d been eating a diet very high in saturated fat leading up to this plate of gnocchi. Of course we don’t know the total grams of starch from his meal, but a half lb of dry pasta ( most boxes of pasta sold in the US are a pound) only contains 160g of starch, well within the range the liver can store as glycogen. A half lb is a LOT of pasta! (I’m not suggesting he ate that much.)

The other tweets are people reporting lowered fasting blood glucose. As far as I know they were coming from very low carb backgrounds and had their fasting blood glucose lowered due to increasing saturated fat, lowering unsaturated fat and adding back some starch. Most people on a very low carb diet will be glycogen depleted and stay in a more of less constant state of gluconeogenesis to supply the necessary blood glucose. I’m not saying this is a bad thing, and I’m speculating here, but here is my guess as to why The Croissant Diet could lower fasting blood glucose compared to very low carb: by reintroducing some starch in the presence of high saturated fat/absence of PUFA, you re-establish your first phase insulin response. The liver again begins to act as a metabolic flywheel. Gluconeogenesis can be turned off much of the time which results ultimately in lower fasting blood glucose.

I have no proof of this, it’s a guess. It will definitely be an area of future research and speculation.

The Loss of the First Phase Insulin Response is a Bad Thing

Interestingly, loss of the first-phase insulin response is an early warning sign that someone is on the road to Type 2 diabetes. From this review paper:

It is widely thought that diminution of first-phase insulin release is the earliest detectable defect of β-cell function in individuals destined to develop type 2 diabetes Is Reduced First-Phase Insulin Release the Earliest Detectable Abnormality in Individuals Destined to Develop Type 2 Diabetes?

John E. Gerich

Diabetes Feb 2002, 51 (suppl 1) S117-S121; DOI: 10.2337/diabetes.51.2007.S117

This makes sense when you think about it. The first phase insulin response is the thing that tells your liver to stop releasing blood sugar and start absorbing it. If after a meal your liver is happily releasing glucose while glucose is being produced in the portal vein, that sounds like a recipe for high post-meal blood glucose. It seems that the loss of the first-phase insulin response is the first sign that your insulin/glucose system is becoming dysregulated.