If you are on a ketogenic or very low carb (VLC) diet (e.g. with 50-100gr carb/day and/or eating ketone producing MCT oils such as coconut oil), you may have a dilemma of having high Blood Glucose (BG) despite eating LC: If you are keto adapted, that is, your body is using ketones and even though you have sufficient insulin (say >5 microU/ml) your body tries to keep your BG higher than necessary, e.g. above 100-110 mg/dl. That is your BG set-point is always high. If you try to lower the set-point to say 80s, by water Intermittent Fasting (IF), then your body starts to convert your muscles into glucose to keep its high BG set-point. So, you may have a slightly lower BG, but you lose some muscle mass. Having a high set-point has many other problems, e.g. if you eat something with a little bit more carb, say a small fruit, your BG shoots up to 130s and stays there for hours.
This may be due to something called "Physiological Insulin Resistance (PhIR) by Petro Dobromylskyj. He wrote many good articles about it -–thanks Petro--in his blog Hyperlipid. Apparently, PhIR is a normal reaction of the body and quite different from Pathological Insulin Resistance (PaIR). It seems that the main difference between PhIR and PaIR is that insulin is at a normal level in the former and abnormally high in the latter. (PaIR is obviously type2 diabetes.) If I understand correctly, PhIR is kind of IR only in the muscle tissue, that is only the muscles do not react to insulin and NOT use glucose even though it is available. However, if you are eating too much protein, the liver may also be considered IR, because it tries to keep the BG high by converting proteins to glucose, even though BG is already too high, that is, it also may not be responding to insulin. (I think working muscles can use glucose with or without insulin. Would that mean that PhIR does not affect working muscles? If not, then one can reduce his high BG [due to PhIR] by exercising.)
The purpose of this Paleohack question is to understand how this happens to whom and how it can be avoided?
Several things seem to cause PhIR:
“… LC eating rapidly induces [Physiological] insulin resistance. This is a completely and utterly normal physiological response to carbohydrate restriction. Carbohydrate restriction drops insulin levels. Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non esterified fatty acids (NEFA). These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. “…palmitic acid is the primary NEFA released from human adipose tissue during fasting. Think of palmitic as a signal molecule to tell the muscles that inhibition of glucose uptake is needed and to tell the liver that increased gluconeogenesis is required because there is no food coming in. Chris Kresser also supports this view.
Ketone bodies e.g. “Beta hydroxy butyrate. … ketone bodies, one of the hall marks of carbohydrate or total calorie restriction, channel glucose away from muscles, toward brain and add a modest supplementary energy supply to brain tissue too. It's exactly what you expect on an adaptive basis, exactly the same function as palmitic acid performs and clearly the two metabolic pathways are closely linked, though ketones seem to work downstream of the action of palmitic acid.”
Methylglyoxal: “Methylglyoxal is elevated in ketosis, but the bulk is produced by glycolysis… Methylglyoxal is an inhibitor of glycolysis.”
According to Paul Jaminet, the high BG problem is caused by too low carbs in VLC diets and can be avoided by eating some more “safe starches”. According to Dr Ron Rosedale, it is caused by too much protein in the diet. This discussion was taken up also by one Paleohack question, which lists many good links about it. But, I think the best and the most up-to-date link on this discussion is this one, where Dr Rosedale uses color coding to distinguish who said what. It is a good scientific discussion and definitely worth reading to understand many background issues. The amount of protein Dr Rosedale recommends is:
Dr. Rosedale defines his protein recommendation as: “So what’s high [protein]. Certainly above 1 gram [of protein] per kilogram of lean mass is probably high. Most people, I’ll put on 0.7 or 0.75 grams per kilogram of lean body mass. But if I’ve got a diabetic, and I really want to reverse their aging, which means reverse their diabetes, because diabetics is a model of aging, I’ll put them down to 0.5 or 0.6 grams per kilogram of lean body mass per day.” For downloading the full PDF version of this article see: "Protein: The Good, The Bad and The Ugly" http://drrosedale.com/Protein_The_Good_The_Bad_and_The_Ugly.htm
A few other points need to be noted in the above Jaminet-Rosedale (JR) debate in view of several excellent articles recently written by Chris Masterjohn on glycation, glucose synthesis and oxaloacetate :
They generally agree that glycation is important, but ignore methylgloxal, which is higher in VLC and ketogenic diets and 20000 times more glycating than glucose (existence of methylgloxal supports Jaminet’s position) Methylglyoxal is a reactive aldehyde that is very toxic to cells, it can inhibit growth in E. coli at milimolar concentrations. The excessive intake of glucose by a cell is the most important process for the activation of the methylglyoxal pathway. (It is strange that “methylglyoxal is produced by glycolysis… and yet also an inhibitor of glycolysis.” What does it mean?) But, there is also some evidence that methylglyoxal kills some types of cancer cells.
They talk about post prandial blood glucose (PPBG), but ignore PhIR effect on PPBG, which often causes longer PPBG spikes than high glycemic foods (existence of PhIR supports Jaminet’s position).
They do not discuss oxaloacetate (supports Jaminet’s position)
They do not discuss TCA cycle (supports Rosedale’s position)
Although not directly related to the JR debate, apparently, conversion of glucose to fat is not significant in humans.
It should be noted that Dr Rosedale always emphasizes deleterious effects of hormonal changes e.g. of insulin, leptin caused by PPBG spikes, (rather than glycation caused by glucose,) such as mTOR, autophagy etc. He notes that: “However a main point of my argument is that BG levels are only a small part of the story; What higher carb intake does to insulin and leptin is even more important; it raises them promoting insulin and leptin [pathologic] resistance.” " …only measuring blood glucose without knowing what insulin and leptin are doing gives very incomplete and often misleading information when it comes to effects of any intervention such as diet.”
So my question is how can we avoid the high BG caused by PhIR, do we have to keep exercising to reduce BG? Or is high protein the real issue, if yes, then what exactly should be the protein amount. Or should we try to avoid ketosis, but, if you eat MCT oils (e.g. coconut oil) the body produces ketones even at higher carb levels. Also does this happen in other LC diets, such as Atkins and the Optimal Diet of Jan Kwasniewski.