Good Calories, Bad Calories, by Gary Taubes

The difficulty you're having supporting your positions should not serve as an excuse for taking out your frustrations on me and Taubes.

We've been over these two points before.

Mayes and Botham 2004

The consumption of fat-enriched diets may alter the uptake and metabolism of chylomicron remnant cholesterol by the liver. To test this hypothesis, [3H]cholesterol-labelled chylomicron remnants derived from different dietary fats were studied in perfused livers both from rats fed on diets enriched in the corresponding fats and from rats fed on a low-fat diet. Livers from rats fed on each of the fat-enriched diets removed similar amounts (34-40%) of the [3H]cholesterol-labelled remnants added, whereas livers from rats fed on the low-fat diet removed significantly more labelled fish-oil and butter-fat remnants than olive-, maize- or palm-oil remnants. Significantly more remnant [3H]cholesterol was secreted into the perfusate HDL by livers from rats fed on the olive-oil, fish-oil and butter-fat diets when compared with those from rats fed on the low-fat diet or the maize-oil diet. Furthermore, the excretion of remnant [3H]cholesterol via the bile acid was increased by the olive-, maize-, palm- or fish-oil diets, and decreased by the butter-fat diet when compared with the low-fat diet, although the [3H]bile acid excreted remained less on saturated fat diets. This investigation shows that the hepatic uptake and subsequent metabolism of cholesterol from chylomicron remnants is influenced by the type of fat in the diet as well as the fatty acid composition of the particles themselves, and may help to explain some of the hyper- and hypocholesterolaemic effects of saturated and unsaturated fatty acids.

The hepatic metabolism of [1-14C]oleate- and [1,2-3H]cholesterol-dual-labelled chylomicron remnants derived from olive, corn, palm and fish oil and butter fat was compared by adding each lipoprotein separately to the perfusate of isolated livers from rats fed on a normal diet. Labelled remnants from butter fat and fish oil were removed more rapidly from the perfusate than remnants derived from olive, corn and palm oil. The oxidation of labelled remnant fatty acid from olive oil, fish oil or butter fat was four to seven times greater than that from corn and palm oil. Labelled fatty acid in fish oil remnants was incorporated into phospholipid significantly more efficiently than the labelled fatty acid in olive, corn or palm oil remnants, with butter fat giving an intermediate value. For all the remnants, there was a significant amount of hydrolysis of labelled esterified cholesterol by the liver which was dependent on the magnitude of hepatic uptake of each type of remnant. The recovery of remnant [3H]cholesterol label in the bile was 50% less with palm oil remnants than with all the other remnants studied. The results indicate that the fatty acid composition of chylomicron remnants has a major impact on their uptake and metabolism by the liver.

Berneis and Krauss 2002

LDLs in humans comprise multiple distinct subspecies that differ in their metabolic behavior and pathologic roles. Metabolic turnover studies suggest that this heterogeneity results from multiple pathways, including catabolism of different VLDL and IDL precursors, metabolic remodeling, and direct production. A common lipoprotein profile designated atherogenic lipoprotein phenotype is characterized by a predominance of small dense LDL particles. Multiple features of this phenotype, including increased levels of triglyceride rich lipoprotein remnants and IDLs, reduced levels of HDL and an association with insulin resistance, contribute to increased risk for coronary heart disease compared with individuals with a predominance of larger LDL. Increased atherogenic potential of small dense LDL is suggested by greater propensity for transport into the subendothelial space, increased binding to arterial proteoglycans, and susceptibility to oxidative modification. Large LDL particles also can be associated with increased coronary disease risk, particularly in the setting of normal or low triglyceride levels. Like small LDL, large LDL exhibits reduced LDL receptor affinity compared with intermediate sized LDL. Future delineation of the determinants of heterogeneity of LDL and other apoB-containing lipoproteins may contribute to improved identification and management of patients at high risk for atherosclerotic disease.

DeFronzo 1992

Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal. With time, however, the beta-cell fails to maintain its high rate of insulin secretion and the relative insulinopenia (i.e., relative to the degree of insulin resistance) leads to the development of impaired glucose tolerance and eventually overt diabetes mellitus. The cause of pancreatic "exhaustion" remains unknown but may be related to the effect of glucose toxicity in a genetically predisposed beta-cell. Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered beta-cell function in NIDDM. Insulin resistance in NIDDM involves both hepatic and peripheral, muscle, tissues. In the postabsorptive state hepatic glucose output is normal or increased, despite the presence of fasting hyperinsulinemia, whereas the efficiency of tissue glucose uptake is reduced. In response to both endogenously secreted or exogenously administered insulin, hepatic glucose production fails to suppress normally and muscle glucose uptake is diminished. The accelerated rate of hepatic glucose output is due entirely to augmented gluconeogenesis. In muscle many cellular defects in insulin action have been described including impaired insulin-receptor tyrosine kinase activity, diminished glucose transport, and reduced glycogen synthase and pyruvate dehydrogenase. The abnormalities account for disturbances in the two major intracellular pathways of glucose disposal, glycogen synthesis, and glucose oxidation. In the earliest stages of NIDDM, the major defect involves the inability of insulin to promote glucose uptake and storage as glycogen. Other potential mechanisms that have been put forward to explain the insulin resistance, include increased lipid oxidation, altered skeletal muscle capillary density/fiber type/blood flow, impaired insulin transport across the vascular endothelium, increased amylin, calcitonin gene-related peptide levels, and glucose toxicity.

So what you're looking for is citations to research supporting the view that elevated glucose levels encourage the production of triglycerides.

...this one, the box at the top shows glucose being converted to fatty acids, which it does not specify are free or bound up in triglycerides...

It would really help keep the discussion on a constructive footing if you could just focus on the topic, and if you could think of us as partners on an adventure of exploration instead of as enemies on opposite sides of a battle line.

The present review summarises the effects of different carbohydrate and fat structures on food intake and appetite and the differences in response at various levels of processing of macronutrients. Several physico-chemical properties of carbohydrate and fat molecules appear to influence the short-term satiating properties.However, long-term substantiation of these findings expressed in terms of food intake or body weight is not currently available.Such studies will be required to make clear recommendations regarding dietary composition to aid satiety.

Three major areas associated with fat structure have been investigated with regard to their satiating effectiveness.Chain length and degree of saturation of fats have a large impact on their physico-chemical properties and several studies have investigated the role of these factors on appetite and eating behaviour.The final area that has received some attention relates to the functionality of specific fat molecules, particularly conjugated linoleic acid (CLA), mainly in terms of weight regulation and metabolism, but also recently on food intake and appetite.

A number of studies have shown MCT (medium chain length TAGs) to be more satiating than long-chain triacylglycerols in both animals and S24 S. French human subjects (Stubbs & Harbron 1996; Wymelbeke et al. 1998). Furthermore, MCT added to a very-low energy diet have been shown to speed the rate of weight loss and enhance satiety in the first 2 weeks of weight loss (Krotkiewski, 2001).

Within the C18 fatty acids, linoleic acid was found to be more satiating when infused into the upper small intestine in human subjects than oleic or stearic acids (French et al. 2000). Similar findings have been noted when oils are incorporated into foods (Lawton et al. 2000).

These studies have shown that daily intake of CLA (conjugated linoleic acid) can reduce total body fat (Blankson et al. 2000) or abdominal fat (Riserus et al. 2001). In addition, two studies have also shown significant reductions (Medina et al. 2000) or inverse associations (Belury et al. 2003) with circulating leptin levels.Of these studies, however, only one has attempted to assess appetite effects of CLA in human subjects without significant findings (Medina et al. 2000).

In a recent review (Raben, 2002) of thirty-one short-term studies, fifteen studies demonstrated that low-GI foods reduce hunger or increase satiety, fourteen found no effect and two actually found lower satiety following the low-GI test compared with the high-GI test.As with many areas of research, a wide variety of methodologies have been employed, making a systematic analysis of the key factors potentially accounting for differences difficult.Certainly, the physiological profile of low-GI diets (slower gastric emptying, digestion and absorption, lower peak insulin and glucose followed by slower declines and less severe nadirs in glucose levels) would fit with scientific knowledge concerning appetite suppression (Pawlak et al. 2002).Further well-controlled, appropriately powered, randomised intervention trials are needed to critically address this question (Astrup, 2002).

I think this study is in the general neighborhood of the initial part of the process that Taubes describes, that elevated glucose levels cause increased triglyceride output from the liver: Effects of dietary fructose or glucose on triglyceride production and lipogenic enzyme activities in the liver of Wistar fatty rats, an animal model of NIDDM.

Transcription of a number of genes involved in lipogenesis is stimulated by dietary carbohydrate in the mammalian liver. Both insulin and increased glucose metabolism have been proposed to be initiating signals for this process, but the pathways by which these effectors act to alter transcription have not been resolved...For many lipogenic enzyme genes, these two factors may provide an integrated signaling system to support the overall nutritional response to dietary carbohydrate.

This is consistent with Taubes premise, which is that repeatedly abusing the body's metabolic processes with blood sugar spikes causes insulin resistance and obesity, creating an environment where elevated blood sugar levels cause increased triglyceride production by the liver. This is the part that I've been saying is not controversial, and it doesn't appear to be an incredibly rare process as you've been claiming.

There has been considerable progress over the past few years in unravelling the mechanisms of insulin action, and the molecular defects that give rise to insulin resistance.Recent advances dissecting the signalling pathways, cellular architecture and spatial compartmentalization of proteins, coupled with the sophisticated genetic analysis of the system, have yielded quantum leaps in our insight into how proteins and tissues interact to control glucose and lipid metabolism.But many gaps remain in our understanding of these processes, and in the pathophysiology underling insulin resistance.We need to define the missing steps in the insulin-signalling network, elucidate the mechanisms of cross-talk in the system, and determine the genetic susceptibility of insulin resistance and the interactions between genes and environment.

Despite periods of feeding and fasting, plasma glucose remains in a narrow range between 4 and 7 mM (milli molar) in normal individuals.This tight control is governed by the balance between glucose absorption from the intestine, production by the liver and uptake and metabolism by peripheral tissues.

Up to 75% of insulin-dependent glucose disposal occurs in skeletal muscle, whereas adipose tissue accounts for only a small fraction.

Although insulin does not stimulate glucose uptake in liver, it blocks glycogenolysis (breaking down glycogen) and gluconeogenesis (making glucose), and stimulates glycogen synthesis, thus regulating fasting glucose levels.

Insulin action in tissues not normally considered insulin sensitive, including brain and pancreatic beta-cell, may also be important in glucose homeostasis

So the big central question is what accounts for this huge disconnect between what it is claimed the research indicates, and the actual experience of the western world.

But the mainstream health establishment is claiming that dietary fat is the big bugaboo of modern health. They claim that the research supports a conclusion that dietary fat is the primary culprit behind heart disease, diabetes and obesity.

Pollan echos Taubes on another point concerning nutrition as religion.

Pollan next agrees with Taubes about the health dilemma, and provides a little information about the "French contradiction" that is consistent with the carbohydrate hypothesis.

You gave me the impression that Pollan was going to contradict Taubes.

Pollan even traces the origin of our current dilemma back to the 70s, just like Taubes, perhaps back to the same McGovern committee as Taubes.

Nutrition science in my view is sort of where surgery was in the year 1650.

I think examination of scientific issues like this requires objectivity and emotional detachment. If you've got your mind made up already and have only entered into this discussion to take jabs at Taubes at every opportunity then this isn't really a dialogue and there's no point in me responding anymore.

You're driving both me and you crazy jumping with a big "Aha!" on every little detail, and you've been mostly wrong with your citations so far and wasting both our time.

Taubes doesn't have any metabolic pathways of his own, he's just trying to present the research, and I've just been trying to present what he presents.

Diabetes is one of the oldest diseases known to science. It is described in ancient Egyptian writings from 5000 bee as a disease with frequent urination as a primary symptom. In 100 ad a Greek physician, Areteus the Cappadocian, described it as a chronic condition, "the melting down of flesh and limbs into urine," and named the condition diabetes after the Greek word for "siphon" or "going through." Mellitus, the Latin for "sweet," was added because the urine of people with diabetes was sweet. Thus, diabetes became known as diabetes mellitus the "sweet water" disease. In fact, until the 1800s, when the first chemical test for measuring sugar in urine was developed, diabetes was diagnosed by tasting the urine for sweetness when someone was suspected of having diabetes mellitus (Canadian Diabetes Association [CDA], 2006).