The Circulating "Food" Supply and The Failed Internal Starvation Hypothesis
There are several recurring themes, mostly from low carb advocates of the "fat burning is best" bent, that keep ... well ... recurring! Perhaps foremost among these is this concept of "internal starvation". From Gary Taubes in Good Calories, Bad Calories:
"For the past century, the conspicuous alternative to the positive-caloric-balance hypothesis has always been, as Pennington, Astwood, and Hilde Bruch suggested, that obesity is caused by a defect in the regulation of fat metabolism. At the risk of repetition, it is important to say this is, by definition, a disorder of fat accumulation, not a disorder of overeating. For whatever reason , the release of fat or its combustion is impeded, or the deposition or synthesis of fat is promoted, as Astwood said, and the result is obesity. That in turn will cause a deficit of calories elsewhere in the body— Astwood’s “internal starvation”— and thus a compensatory hunger and sedentary behavior.
"In this hypothesis , obesity is another variation on the theme of insulin dysfunction and diabetes. In Type 1 diabetes, the cause is a lack of insulin. The result is an inability to use glucose for fuel and to retain fat in the fat tissue, leading to internal starvation, as Astwood put it, excessive hunger, and weight loss. In obesity, the cause is an excess of insulin or an inordinate sensitivity to insulin by the fat cells; the result is an overstock of fuel in the adipose tissue and so, once again, internal starvation. But now the symptoms are weight gain and hunger. In obesity, the weight gain occurs with or without satisfying the hunger; in Type 1 diabetes, the weight loss occurs irrespective of the food consumed.
"This half century of research unequivocally supported the alternative hypothesis of obesity. It established that the relevant energy balance isn’t between the calories we consume and the calories we expend, but between the calories— in the form of free fatty acids, glucose, and glycerol— passing in and out of the fat cells. If more and more fatty acids are fixed in the fat tissue than are released from it, obesity will result. And while this is happening, as Edgar Gordon observed, the energy available to the cells is reduced by the “relative unavailability of fatty acids for fuel.” The consequence will be what Stephen Ranson called semi-cellular starvation and Edwin Astwood, twenty years later, called internal starvation. And as this research had now made clear, the critical molecules determining the balance of storage and mobilization of fatty acids, of lipogenesis and lipolysis, are glucose and insulin— i.e., carbohydrates and the insulin response to those carbohydrates.The less ballyhooed paper (Effects of Diet Composition on Postprandial Energy Availability during Weight Loss Maintenance) to come out of the Ebbeling/Ludwig energy expenditure study, was one putting forth, yet again, a "circulating energy" hypothesis for why carbs and glycemic index alter hunger and eating behavior. I discussed this paper in more depth previously: The Myth of Starving Cells II and NEFA Levels Again
Here are glucose (mg/dL, top), NEFA (mEq/L or mmol, middle), and Energy Available (kcal/L, bottom). I stretched the EA plot a bit vertically for detail, and horizontally to match up the time scale.
What jumped out at me the first time I read this paper was the axis units on EA = kcal/L. With the exception of about 30 minutes -- between 15 and 45 minutes after the ~650 cal meal, the EA remains roughly between 4 kcal/L and 5 kcal/L, or the total energy in 5 liters of blood is between perhaps 20 and 25 kcal. A kcal is a single Calorie. Five -- 5! -- Calorie total swing.
So I got to wondering how these shook out between the energy substrates. I didn't include the ketone plot, because it constitutes only 1-2% of circulating energy anyway, but I used the calculations from the paper to look at the relative EA at several time points. I wanted to get a better feel for which substrate is contributing what. Their factors:
Glucose (mg/dL) * 0.04
FFA (mEq/L) * 2.434
BHB (mmol/L) * 0.437
So again, not all time points were included here, but Total EA remains between 4-5 kcal/L except for the 30 minute spike. While the ratios of circulating substrates were different for the low carb, we see that the least glucose contributes is still over 70% of the Total EA. Immediately after the High GI LF meal, glucose makes up over 90% of the Total EA.
- Normal fasting glucose of 80 mg/dL and fatty acids of 0.4 mmolar, gives a 77% glucose, 23% FFA split of circulating EA of just under 4.2 kcal/L.
- If we increase glucose just 50% to 120 mg/dL, and suppress fatty acids to 25% of baseline at 0.1 mmolar, glucose now becomes 95% of about 5 kcal/L
- To get a 50-50 split of EA between glucose and FFA, one has to go with quite a low glucose of 60 mg/dL and a fairly abnormally high FFA of 1.0 mmolar. In other words, the nature of the calories the cells have access to always favors glucose.
A Few Concluding Comments:
Circulating Calories/Substrates and Carb vs. Fat Burning:
It Appears to be Impossible to Starve Cells of Fat:
Based on the hundreds of glucose and NEFA levels and profiles that I've seen in various studies, coupled with the background physiology, it is fair to say that glucose levels are much more tightly regulated. There is also a pretty definitive minimum (that can be pushed lower in ketosis) for glucose, whereas there does not appear to be a lower danger limit for NEFA. If such exists, it is apparently near impossible to achieve either with diet or drugs. I have seen NEFA suppressed below 0.07 mmolar (using an exogenous agent) with no indication of safety concerns in the experimental protocol. Can you imagine a study allowing people to be given something to drop their blood glucose to 30 mg/dL? This level of NEFA is more like dropping glucose to 10!
Hunger Tracks with NEFA Levels:
The tracking of hunger with EA is most similar to the profile for NEFA such that: low NEFA = low hunger, high NEFA = high hunger. This is in direct opposition with the notion of "starving cells". As I've discussed, non-adipose, aka ectopic, cells receive higher than normal NEFA delivery (often resulting in fat accumulation) when the circulating EA from fatty acids is high as in obesity and diabetes. But this puts the kibosh on the whole insulin → low NEFA → hunger → eating more. Hyperphasia (overeating) has been shown experimentally when glucose levels dip too low, however.