Good Calories, Bad Calories, by Gary Taubes

Refined carbohydrates are digested exceptionally quickly and cause blood sugar spikes which in turn cause the liver to release LDLs that initially carry a large payload of cholesterol.

Percy, can you peek at the cites at the back of the book and find a couple of papers I can look up re: this point?

Thanks, Percy.

I feel your pain. My service went up and down for months and no tech could fix it ... until piece by piece they replaced every last thing ... the modem, the cable from the street to the house, the splitter, the ethernet cable and the ground plate.

The ground plate did the trick (*knock on wood*).

I did a bit of poking around ... and I can't find a link between insulin and elevated LDL and TG levels. And I can't find a link between carbs and obesity other than that's what folks overeat. Nor can I find anything about the "myth of the balanced diet".

For what it's worth, my off the cuff impression is that assuming carbs with a high glycemic index are inherently bad (and lead to obesity and CHD) is overstating the case in the extreme.

Japanese folks eats loads of high GI food (rice) and yet they have very low rates of obesity and CHD.

And, although it isn't really on point, I wanted to mention a recent 60 Minutes report on bariatric surgery. Folks who have gastric bypass are, in many cases, relieved of their diabetes instantly -- the day of their surgery.

Fasting plasma glucose and glycosylated hemoglobin concentrations returned to normal levels (83%) or markedly improved (17%) in all patients. A significant reduction in use of oral antidiabetic agents (80%) and insulin (79%) followed surgical treatment.

Here.

This led an Italian surgeon to disconnect and reconnect the duodenum of a diabetic rat to assess the surgical procedure's effect. Answer? It was like an off/on switch. (Study.)

This spontaneous remission puzzled Italian surgeon Francesco Rubino, now at New York Presbyterian Weill Cornell Medical Center. "We wanted to know what is making diabetes remit. We thought it could have been something to do with the small bowel," Dr. Rubino says. So he began performing the bypass on diabetic rats, and realized that when he disconnected the top of the small intestine, an area called the duodenum, the diabetes disappeared. Then, he reversed the operation. When he reattached it, the diabetes came back. This was a pivotal discovery. By merely blocking food from traveling through the duodenum, Rubino sent diabetes into remission, proving the effect was independent from weight loss. This meant diabetes could essentially be removed with a scalpel.

Here.

What this means, I haven't the foggiest. But it's odd.

Which leads me to believe that the diet-diabetes link is missing a big chunk of something. There's no question that obesity = type 2 diabetes. But why the instantaneous results?

Even if they did, considering the wealth of other evidence, the Japanese experience would merely be an unexplained anomaly.

They aren't the only ones.

Up until last year, the French had an extremely low obesity rate. Since 2007, tho, their obesity rates have doubled. This dramatic increase in obesity cannot be attributed to "an increase in carbs".

The French also have a historically low rate of CHD.

The same is true of the Italians and the Greeks.

Whatever one might believe science demonstrates to be the case, reality is that while western countries have increasingly focused on fat as the cause of obesity and heart disease ...

True. But devious marketing is beside the point.

Stating categorically that refined carbs are very, very bad is just as deceptive as stating categorically that fats are very, very bad.

Glycemic index can be a very misleading measure of the goodness/badness of carbohydrates.

Then how does one distinguish between good and bad?

Other than "common sense" -- which, as you pointed out upthread, is a poor way to judge dietary needs.

Edited by molbiogirl, : grammar

I have a feeling that individual papers aren't going to tell the whole story as the process is fairly complicated and probably took time to tease out.

Neither of your cites has anything to do with insulin.

The first talks about different kinds of LDL particles.

The second talks about how to measure LDL levels.

Both cites are open access, so you can read them if you'd like.

Why are you asking, by the way? Is there something controversial about that characterization of the liver's response to elevated blood sugar levels?

Because you (and the author) claim that insulin levels are related to elevated LDL levels.

The problem with refined carbohydrates is that they're rapidly digested and cause blood sugar spikes, which in turn cause an insulin response from the pancreas, which in turn causes the liver to produce LDLs with a high payload of cholesterol. The eventual destiny of these LDLs is to give up their cholestrol and end up as small, dense LDLs which have a greatly heightened ability to leave deposits on blood vessel walls, and they have a deleterious effect generally on cell metabolism.

Insulin spikes are perfectly normal.

It's the link to LDL and CHD that are in question.

I can't find any supporting evidence in the literature.

I did find this:

No consensus has been obtained for the notion that hyperinsulemia or insulin resistance contributes significantly to the risk of coronary heart disease (CHD) similarly to major risk factors, high total and LDL cholesterol, elevated blood pressure, smoking, low HDL cholesterol, diabetes and aging.

Metabolic Syndrome in the 21st Century, Jose Antonio Gutierrez, 2005.

Available here.

I have also found plenty of evidence that insulin suppresses VLDL synthesis (VLDL = the small, dense LDLs you mention).

Durrington PN, Newton RS, Weinstein DB, Steinberg D. 1982 Effects of insulin and glucose on very low density lipoprotein triglyceride secretion by cultured rat hepatocytes. J Clin Invest. 70:63–73.

Patsch W, Franz S, Schonfeld G. 1983 Role of insulin in lipoprotein secretion by cultured rat hepatocytes. J Clin Invest. 71:1161–1174.

Lewis GF, Uffelman KD, Szeto LW, Steiner GP. 1993 Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. Diabetes. 42:833–842.

Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. 1995 Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest. 95:158–166.

Nor have I found any evidence for the notion that ...

The cause of obesity is levels of insulin ...

If you can find any other cites in the book, that would help. I would love to look at the author's evidence.

I have a feeling that individual papers aren't going to tell the whole story as the process is fairly complicated and probably took time to tease out.

I'd be happy with a paper that gives me just a piece of the puzzle. Something that looks at insulin and LDL levels, for example.

Edited by molbiogirl, : No reason given.

The problem with refined carbohydrates is that they're rapidly digested and cause blood sugar spikes, which in turn cause an insulin response from the pancreas, which in turn causes the liver to produce LDLs with a high payload of cholesterol. The eventual destiny of these LDLs is to give up their cholestrol and end up as small, dense LDLs which have a greatly heightened ability to leave deposits on blood vessel walls, and they have a deleterious effect generally on cell metabolism. The cause of obesity is levels of insulin in combination with other hormones and a person's individual metabolism sufficient to encourage fat cells to emphasize the fatty acid=>triglyceride process, rather than the reverse triglyceride=>fatty acid process. Triglyerides are stored in the fat cells for later use as energy. Significantly, this process of storage of triglycerides in fat cells in the presence of insulin will take place at the expense of other demands of the body for energy, for example, hunger and exercise. And most importantly, the presence of fatty acids by themselves is insufficient to cause their net conversion into triglycerides - that takes insulin, whose levels are driven by blood sugar levels, whose levels are in turn driven by carbohydrate intake.

I addressed a couple of these points in my previous post, but I'd like to add one more thing.

To jump from "glucose = insulin spike" to "insulin = LDL" to "insulin = CHD risk factor" is way off the deep end.

As is "insulin + hormones/metabolism = obesity".

My point is, the author has jumped the gun big time. His theories aren't supported by the evidence. And if his theories aren't supported by the evidence, what are we to make of them?

His book sounds like it's just another in a long line of scare tactic diet books.

In fact, it sounds an awful lot like Eat Right For Your (Blood) Type.

Your inquiry didn't mention insulin, so there should be no surprise that the papers I provided don't mention insulin.

I thought it was clear that my question concerned the link between insulin and LDL/CHD.

Here's a brief summary of HDL/LDL/VLDL.

HDL High-density lipoprotein * Makes up 20%–30% of total cholesterol * The “good” cholesterol * Moves cholesterol from arteries to the liver. LDL Low-density lipoprotein * Makes up 60%–70% of total cholesterol * Main form of “bad” cholesterol * Causes build up of plaque inside arteries. VLDL Very-low-density lipoprotein * Makes up 10%–15% of total cholesterol * With LDL, the main form of “bad” cholesterol * A precursor of LDL

http://www.health.harvard.edu/fhg/updates/update0205c.shtml

Here's a picture of the pathway.

Please note that VLDL is a precursor of LDL. Therefore, anything that suppresses the biosynthesis of VLDL will necessarily suppress the biosynthesis of LDL.

And insulin suppresses VLDL biosynthesis.

Specifically, the results of studies, both in vitro and in vivo have demonstrated that insulin acutely inhibits hepatic (liver) VLDL secretion.

Hyperinsulinemia and in vivo very-low-density lipoprotein-triglyceride kinetics, Am J Physiol Endocrinol Metab 246: E187-E192, 1984.

Percy writes: I've not heard of "HMG-CoA reductase", but apparently it encourages the production of LDL's.

HMG coA is part of the mevalonate pathway.

Please note that insulin upregulates the LDL receptor gene, not the synthesis of LDL particles. (The dotted lines on the left refer to insulin's role in the pathway.)

Percy writes: But I'm not sure VLDL and small, dense LDLs and the same thing, so I'm not sure I'm making the claim you think I am. I just don't know.

It appears that I was wrong. VLDL particles are not the same as small, dense LDL particles.

LDL particles are heterogeneous respective sizes, densities, and lipid compositions. LDL particles have been divided into 2 distinct phenotypes: pattern A, with a higher proportion of large, more buoyant LDL particles, and pattern B, with a predominance of small dense LDL particles.

http://www.medscape.com/viewarticle/446747

However, small, dense LDLs cannot be reliably measured.

There is no standardization of the methods for assessment of small dense LDL, so different assays can give different results, with agreement between methods in only 8% of patients.

So they measure VLDL levels and TG levels.

Samples from the Familial Metabolic Syndrome Study in Saxony were used to assess the determinants of small dense LDL levels. After correction for degree of hyperglycemia, hyperinsulinemia, age, gender and BMI the strongest correlates of particle size were the levels of VLDL triglyceride or plasma triglycerides (TG).

Detection of small dense LDL-cholesterol: is it necessary to determine particle size? www.futuremedicine.com/doi/pdf/10.2217/17460875.3.1.23

But the fact remains. Insulin downregulates VLDL biosynthesis; therefore, it necessarily downregulates LDL biosynthesis.

Percy writes: But he presents the evidence that supports a connection between hyperinsulemia and heart disease.

Hyperinsulemia is insulin resistance.

wiki writes: Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin resistance in fat cells results in elevated hydrolysis of stored triglycerides ... Increased mobilization of stored lipids in these cells elevates free fatty acids in the blood plasma. Insulin resistance in muscle cells reduces glucose uptake (and therefore increases local storage of glucose as glycogen), whereas insulin resistance in liver cells reduces storage of glycogen, making it unavailable for release into the blood when blood insulin levels fall. High plasma levels of insulin and glucose due to insulin resistance often lead to metabolic syndrome and type 2 diabetes. Metabolic syndrome (aka Syndrome X) is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.

A blood sugar spike (and its attendant insulin release) is not the same thing as insulin resistance.

The cause of insulin resistance is largely unknown, but it tends to run in families, suggesting a strong genetic component.

3 mutations are associated with hyperinsulemia: insulin receptor mutations (Donohue Syndrome), LMNA mutations (Familial Partial Lipodystrophy) and mitochondrial mutations.

All 3 are heritable, of course.

Here's a brief summary of the mitochondrial mutations and their link to hyperinsulemia.

To explore the metabolic origin of insulin resistance, Shulman and his colleagues recruited young healthy volunteers who tested positive for insulin resistance and who were the offspring of patients with type 2 diabetes. They also recruited a second, control group of volunteers who exhibited insulin sensitivity who were matched for age, height, weight and physical activity.

According to Shulman, the researchers had to distinguish between two possible causes of the fat accumulation in the muscle that could trigger insulin resistance. “Either there were defects in the fat cells, called adipocytes, in which there was increased release of fatty acids to muscle cells,” said Shulman. “And/or, there was a defect in mitochondrial function in the muscle cells which would lead to decreased metabolism of these fatty acids. So, we designed the study to look at both of these possibilities.”

“We found that these lean insulin-resistant offspring—who have a high probability of later developing type 2 diabetes—had muscle insulin resistance, but no detectable abnormalities in their fat cells compared to the insulin-sensitive subjects,” said Shulman.

“Using this method we found that rates of ATP production in the muscles of the insulin-resistant offspring was decreased by thirty percent compared to normal subjects,” said Shulman.

Shulman and his colleagues are now performing muscle biopsy studies to determine whether the mitochondrial impairments are due to defects in the mitochondria themselves, or due to a reduced number of mitochondria in the subjects' cells.

It is important to distinguish between hyperinsulemia and normal insulin response (which is all a blood sugar spike induces -- a perfectly normal insulin response).

If you could post a couple of cites that support the author's assertion that a normal insulin response (not hyperinsulemia) is linked to elevated LDL levels (either form -- A or B), that would be great. Or a cite that supports the author's contention that a blood sugar spike (and its perfectly normal insulin response) is directly linked to CHD.

What Taubes is actually saying is that blood sugar spikes encourage the liver to temporarily store fatty acids away as triglycerides, and these are later released into the bloodstream as VLDLs.

First. Glucose is stored in the liver as glycogen, not triglycerides. Glycogen is a complex carbohydrate. A triglyceride is a fat, formed from three fatty-acid molecules and one glycerol molecule. Triglycerides are stored in adipose tissue.

Second. There are "triglyceride storage diseases" that result in fatty deposits in the liver. But these are not related to blood sugar spikes. They are metabolic defects.

Third. Blood sugar spikes don't "encourage" anything but an insulin response. If you have evidence to the contrary, I would be interested in hearing it.

Fourth. The release of glycogen as VLDL is not "inevitable". Glycogen is released from the liver as glucose, not VLDL.

Fifth. FFAs are released from adipose tissue (fat), not the liver.

Sixth. FFAs are packaged into VLDL by the liver ... from blood plasma FFAs derived from dietary fat, not carbohydrates.

In the absence of insulin (in other words, when you haven't eaten or you're exercising a lot), the action of its counter hormone glucagon is dominant. Glucagon stimulates the liver to provide glucose for the rest of the body, initially via glycogenolysis (breaking down glycogen) and later by gluconeogenesis (making new glucose) as liver glycogen supplies are depleted. To provide the energy (ATP) needed for gluconeogenesis the liver oxidizes fats derived from the adipose tissue. In the absence of insulin, the adipose hormone sensitive lipase is active, releasing fatty acids (from adipose tissue) to the blood, where they are transported in association with albumen to the liver (and other tissues).

http://www.usd.edu/med/som/somdept/biochem/courses/bioc520/b520c6.htm

Here's a picture:

(Note: Acetyl CoA derived from glycogen stores in the liver can be used to synthesize FFAs (box at top of figure). Acetyl CoA is produced when it is needed for fatty acid synthesis, but normally the gene is inactive and has certain transcriptional factors that activate transcription when necessary. Necessary means when there's a shortage of FFAs.)

What insulin does do more directly is influence fat cells to tilt the balance of conversion back and forth between fatty acids and triglycerides toward the production of triglycerides...

Elevated TG levels are correlated to insulin resistance, not normal insulin response. In other words, hyperinsulemia is correlated to elevated TGs, not blood sugar spikes. And, as I said before, the causes of hyperinsulemia are probably genetic, not behavioral (aka carb intake).

In other words, even if you're starving, or even if you're in the middle of 5 set tennis match under a hot sun, if you elevate your insulin levels then fat cells will steal from the rest of the body by gobbling up the available fatty acids that other cells (muscle cells, for example) might use for energy.

When under stress from starvation, the body uses protein and fat as energy. Because no glucose is available.

When under stress from overexertion, the body uses glycogen stores in the liver. That's just plain old glucose.

(Glycogen is also stored in the muscles. It is used up in the first 10 minutes or so of heavy exercise, tho.)

Fat cells (adipose tissue) don't "steal" anything from anywhere. They are storage depots. That is all.

Probably Taubes' most important point is that the conventional wisdom about obesity, that it is a simple result of too many calories in and too few calories out, that the obese simply eat too much and exercise too little, is wrong.

I have yet to see any evidence of that.

If you'd like to post some cites, I'd be happy to read the papers.

http://www.nytimes.com/2007/10/07/books/review/Kolata-t.html

But the problem with a book like this one, which goes on and on in great detail about experiments new and old in areas ranging from heart disease to cancer to diabetes, is that it can be hard to know what has been left out.

For example, Taubes argues at length that people get fat because carbohydrates in their diet drive up the insulin level in the blood, which in turn encourages the storage of fat. His conclusion: all calories are not alike. A calorie of fat is much less fattening than a calorie of sugar.

It’s known, though, that the body is not so easily fooled. Taubes ignores what diabetes researchers say is a body of published papers documenting a complex system of metabolic controls that, in the end, assure that a calorie is a calorie is a calorie. He also ignores definitive studies done in the 1950s and ’60s by Jules Hirsch of Rockefeller University and Rudolph Leibel of Columbia, which tested whether calories from different sources have different effects. The investigators hospitalized their subjects and gave them controlled diets in which the carbohydrate content varied from zero to 85 percent, and the fat content varied inversely from 85 percent to zero. Protein was held steady at 15 percent. They asked how many calories of what kind were needed to maintain the subjects’ weight. As it turned out, the composition of the diet made no difference.

My point exactly.

Here's insulin signaling.

Click to enlarge

http://www.genome.ad.jp/kegg/pathway.html

I'm not going to post the carbohydrate diagrams. There are too many.

Here's a list, tho.

1.1 Carbohydrate Metabolism
Glycolysis / Gluconeogenesis
Citrate cycle (TCA cycle)
Pentose phosphate pathway
Pentose and glucuronate interconversions
Fructose and mannose metabolism
Galactose metabolism
Ascorbate and aldarate metabolism
Starch and sucrose metabolism
Aminosugars metabolism
Nucleotide sugars metabolism
Pyruvate metabolism
Glyoxylate and dicarboxylate metabolism
Propanoate metabolism
Butanoate metabolism
C5-Branched dibasic acid metabolism
Inositol metabolism
Inositol phosphate metabolism

Each of those is just as hairy looking as insulin signaling. And they are all interconnected.

Same story for lipid metabolism.

That KEGG site is worth a look.

NYT writes: Cascades are especially common in medicine as doctors take their cues from others, leading them to overdiagnose some faddish ailments (called bandwagon diseases) and overprescribe certain treatments (like the tonsillectomies once popular for children).

He acknowledges that that hypothesis is unproved, and that the low-carb diet fad could turn out to be another mistaken cascade.

Second NYT article.

Here's the glutamate pathway.

Click to enlarge

Each of those numbers refers to another metabolic pathway. For a more realistic picture, check this out:

http://www.genome.jp/kegg/atlas/metabolism

It's truly stunning.

Glutamate is used for a lot of things.

A metabolite isn't an on/off switch. It just isn't.

If you'd like to browse scholar.google, "glutamate metabolism review" produced a lot of useful articles. So did "monosodium glutamate metabolism review".

Edited by Admin, : Fix image width.

So you're disputing that the liver converts glucose into triglycerides, so we can look into that.

The top box in the diagram labeled "Liver" seems consistent with Taubes description of glucose having a role in the production of VLDL.

No. I am not disputing that the liver can biosynthesize triglycerides from glucose. If you will recall ...

(Note: Acetyl CoA derived from glycogen stores in the liver can be used to synthesize FFAs (box at top of figure). Acetyl CoA is produced when it is needed for fatty acid synthesis, but normally the gene is inactive and has certain transcriptional factors that activate transcription when necessary. Necessary means when there's a shortage of FFAs.)

That is the "liver box at the top".

I need to rearrange your post a bit to try and untangle all this.

Taubes says that it is triglycerides that are packaged into VLDL, not FFAs.

An FFA is a part of a triglyceride. (The proper name of triglyceride is triacylglycerol.)

Free fatty acid = "Fatty acids can be bound or attached to other molecules, such as in triglycerides or phospholipids. When they are not attached to other molecules, they are known as "free" fatty acids.

The uncombined fatty acids or free fatty acids may come from the breakdown of a triglyceride into its components (fatty acids and glycerol)." (Wiki)

A triglycerides with its glycerol removed = 3 "free" fatty acids.

And triglycerides aren't "packaged" into anything except fat tissue.

FFAs are used in the packaging of VLDLs.

Percy quoting Taube writes: "After we eat a carbohydrate-rich meal, the bloodstream is flooded with glucose, and the liver takes some of this glucose and transforms it into fat—i.e., triglycerides—for temporary storage."

Temporary storage, yes. In your adipose tissue (aka your butt and thighs). BUT THEY ARE NOT SYNTHESIZED FROM GLUCOSE. Not under ordinary conditions. Take a closer look at the wiki graf you quoted.

Here is the text in its entirety (broken into chunks and capped for clarity).

Triglycerides, as major components of very low density lipoprotein (VLDL) and chylomicrons, play an important role in metabolism as energy sources and transporters of DIETARY FAT.

Right off the bat it says: From dietary fat. Not from carbs.

They contain more than twice as much energy (9 kcal/g) as carbohydrates and proteins. In the intestine, triglycerides (FROM DIETARY FAT) are split into glycerol and fatty acids (this process is called lipolysis) (with the help of lipases and bile secretions), which are then moved into the cells lining the intestines (absorptive enterocytes).

The triglycerides are rebuilt in the enterocytes from their fragments and packaged together with cholesterol and proteins to form chylomicrons. (IN THE LIVER).

These are excreted from the cells and collected by the lymph system and transported to the large vessels near the heart before being mixed into the blood. Various tissues can capture the chylomicrons, releasing the triglycerides to be used as a source of energy.

Fat and liver cells can synthesize and store triglycerides.

Yes. Can synthesize. Not does synthesize as a normal part of carb metabolism. As I pointed out earlier, the genes for this process are INACTIVE (aka downregulated) and require a host of transcriptions factors (a cascade of signals from the body telling it to turn the gene on).

When the body requires fatty acids as an energy source, the hormone glucagon signals the breakdown of the triglycerides by hormone-sensitive lipase to release free fatty acids (FROM THE ADIPOSE TISSUE).

As the brain can not utilize fatty acids as an energy source, the glycerol component of triglycerides can be converted into glucose, via gluconeogenesis, for brain fuel when it is broken down. Fat cells may also be broken down for that reason, if the brain's needs ever outweigh the body's.

The brain runs on glucose and glucose alone. And the brain is the body's number one priority.

When the body is under stress (usually starvation), the adipose tissue is broken down into its component parts: FFAs and glycerol. The liver then takes the glycerol and manufactures glucose to send to the brain.

Here's a picture of glycolysis (breaking down glucose) and gluconeogenesis (making glucose).

Please note that they are simply the reverse of one another for the most part.

Glycolysis is the normal breakdown of glucose.

Gluconeogenesis happens only under starvation/overexertion conditions.

The body doesn't like to make sugar from fat. It is very metabolically expensive and it has as "side products" some pretty nasty things called ketone bodies.

Please also note that to make sugar, you have to start with pyruvate (at the bottom of the figure).

Please note that the glycerol from the triglyceride is converted into pyruvate.

OK.

Now that we have all that sorted out, let's unpack your Taube quote.

Taube writes: After we eat a carbohydrate-rich meal, the bloodstream is flooded with glucose, and the liver takes some of this glucose and transforms it into fat—i.e., triglycerides—for temporary storage.

No. It doesn't.

These triglycerides are no more than droplets of oil. In the liver, the oil droplets are fused to the apo B protein and to the cholesterol that forms the outer membrane of the balloon.

The source of these triacylglycerols is dietary fat.

The triglycerides constitute the cargo that the lipo-proteins drop off at tissues throughout the body. The combination of cholesterol and apo B is the delivery vehicle.

This is perfectly normal. In fact, it is vital. Your body uses cholesterol in its cell membranes and to manufacture hormones.

The resulting lipoprotein has a very low density and so is a VLDL particle, because the triglycerides are lighter than either the cholesterol of the apo B. For this reason, the larger the initial oil droplet, the more triglycerides packaged in the lipoprotein, the lower its density.

This is gobbledygook. There is no "for this reason". The name VLDL just describes the particle. That's all.

And a VLDL particle is perfectly normal. Like I said, your body needs cholesterol and VLDL/IDL/LDL/HDL is the way it moves cholesterol around the body so that it can be used in lots of very important metabolic processes.

Back to your post.

This is one point that I didn't manage to garble. Both mine and Taubes' descriptions said that triglycerides, not glycogen, are released in VLDL.

Triacylglycerols are not packaged into VLDL particles. FFAs are. And they come from dietary fat.

Here is your original quote.

What he does say is that once triglycerides are stored in the liver that their release is inevitable. The more often you spike your blood sugar, the more often the liver will sock away triglycerides, and the more VLDLs the liver will eventually produce.

No. Triacylglycerol is not stored in the liver.

If it is, you have liver disease.

Glycogen (which is just a complex carb made from glucose) is stored in the liver.

This is perfectly normal.

And, one more time, VLDLs are packaged by the liver from dietary fat.

You couldn't function without either glycogen in your iver or VLDL in your bloodstream.

Triacylglycerols, when released from adipose tissue, are used to manufacture sugar (from the glycerol) and as evergy (from the FFAs).

They are not packaged into VLDLs.

And their release is not inevitable. My big butt is evidence of that.

This is another point upon which both I and Taubes were clear. Neither of us said that free fatty acids are released from the liver.

FFAs are part of triacylglycerols.

What insulin does do more directly is influence fat cells to tilt the balance of conversion back and forth between fatty acids and triglycerides toward the production of triglycerides... MBG writes: Elevated TG levels are correlated to insulin resistance, not normal insulin response. In other words, hyperinsulemia is correlated to elevated TGs, not blood sugar spikes. And, as I said before, the causes of hyperinsulemia are probably genetic, not behavioral (aka carb intake). Percy writes: Are you talking about elevated TG levels in the bloodstream? I don't believe Taubes makes any claims about insulin's influence on triglyceride levels in the bloodstream, and if he does then I missed them. I certainly wasn't trying to say anything about insulin's influence on TG levels in the bloodstream.

You said that Taube said "insulin influences" adipose tissue to push toward a greater release of TAGs. This means "elevated TAGs". If the metabolic process is "pushed" toward one end, it is abnormal and TAG levels are increased above and beyond normal conditions.

And, as I said before, that is a marker of disease.

And insulin does not do that.

You can prove to yourself that the absence of intake of glucose in the form of carbohydrates isn't stress or starvation with a simple personal experiment: Eat only meat for an entire week.

Yes. To the body, it is starvation.

The brain runs only on glucose. (See above.) If you don't eat carbs, your body is under stress. It needs a heckuva lot of glucose to run your brain.

And by manufacturing glucose from fat (and by using only protein for energy for the other vital metabolic processes), you produce those nasty ketone bodies I mentioned earlier.

I'm sure you've heard of ketoacidosis. It's what killed Madeline Neumann.

wiki writes: This happens in untreated Type I diabetes (see diabetic ketoacidosis), and also in alcoholics after binge drinking, subsequent starvation, and the alcohol-induced impairment of the liver's ability to generate glucose (see alcoholic ketoacidosis).

Percy writes: The body can draw upon glucose, fatty acids and protein for energy.

Under normal conditions, only glucose and FFAs.

If you are using protein, you are starving.

wiki writes: During starvation or a prolonged fasting state, the glycogen storage is used up and the level of insulin in the circulation is LOW and the level of glucagon is very high. The main means of energy production is lipolysis (fat breakdown). Gluconeogenesis (glucose manufacture -- above) converts glycerol and fatty acids via the TCA cycle via acetyl CoA to produce energy. Proteolysis (protein breakdown -- the source is your muscles) provides alanine which also enters gluconeogenesis. Lactate produced from pyruvate enters the gluconeogenesis pathway too. Too much Acetyl CoA produces ketone bodies which can be detected in a urine exam. The brain starts to use ketone bodies as source of energy.

Percy writes: In the absence of insulin the fat cells in the body will tilt the balance of the FFA/triglyceride conversion process toward the production of FFAs which are released into the bloodstream for use as energy.

See? You said it again. "Tilt toward TAGs". No, it does not. Not not not. Elevated TAGs = a disease condition, like hyperinsulemia.

Also. The body can manufacture lipids (not FFAs -- there's a difference). That's known as lipogenesis. But it does so in order to manufacture things like cell membranes. Again. A perfectly normal process.

The body DOES NOT manufacture FFAs from the dietary intake OF ANYTHING.

It digests dietary fat and RELEASES FFAs.

In the presence of insulin, fat cells are a net drain upon fatty acids in the blood stream as they convert it to stored triglycerides.

Percy, this just isn't true. Adipose tissue is just storage. Your body uses all the FFAs it needs then it socks away the excess.

Percy writes: So in light of the national experience over the past century with obesity, diabetes and heart disease, how's your theory that it's primarily due to dietary fat working out for you?

Hey. If I could untangle the root cause(s) of the national obesity epidemic (by uncovering some heretofore unknown metabolic link or some such), I'd get the FN Nobel.

That doesn't mean that Taube isn't "idea-mining" legit scientific papers. He's ripping stuff out of context and completely distorting it.

And I'd like to remind you of something, Percy.

The French have historically had very low obesity rates and very low CHD rates. In fact, Taube mentions it in the book.

"The French Paradox".

The French have historically eaten LOADS of fat and LOADS of refined carbs. Just LOADS.

So.

Why, in the past year and a half, have French obesity rates doubled?

Just to be clear. A chylomicron ≠ VLDL particle.

Chylomicron on the right. VLDL/IDL/HDL on the left.

How are chylomicrons formed? * The triglycerides, phospholipids and cholesteryl esters are combined with an apolipoprotein, known as apolipoprotein (apo) B48, in the enterocyte. The lipoproteins formed in this manner are secreted into the lymph (chyle) and are termed chylomicrons. * They are large (diameter >75 nm; density <950 g/L) and rich in triglycerides, but contain only a relatively small amount of protein

What is the role of lipoprotein lipase? Lipoprotein lipase is located on the vascular endothelium of tissues that have a high requirement for triglycerides, for example: * skeletal and cardiac muscle (for energy); * adipose tissue (for storage); and * lactating mammary gland (for milk). Lipoprotein lipase releases triglycerides from the core of the chylomicron by hydrolysing them to fatty acids and monoglycerides, which are taken up by the tissues locally. In this way, the circulating chylomicron becomes progressively smaller, its triglyceride content decreases and it becomes relatively richer in cholesterol and proteins. As the core shrinks, its surface materials (phospholipids, free cholesterol and apo Cs) become overcrowded and are transferred to HDL. The relatively cholesterol ester-enriched, triglyceride-depleted product of chylomicron metabolism is known as the chylomicron remnant. The apo B48, present from the time of assembly, remains tightly anchored to the core throughout.

http://www.cmglinks.com/asa/lectures/Part_2/lecture/2.htm

VLDL particles, on the other hand, contain 3 sorts of "apo" particles: apoB (100), apoC (I & II) and apoE. These apo particles are made of triglycerides, phospholipids, cholesterol and cholesteryl esters.

VLDL is the body's transport mechanism for these apo particles (which carry the TAGs, P-lipids and cholesterol).

Click to enlarge

Please note that the triacylglycerides are that yellow thing -- which represents the apo particles. The red thing represents the cholesterol. Don't take that representation of the particles literally. It's just drawn that way to show the proportions of the various components.

Here's another figure.

Click to enlarge

See the apo particles being added on the right to form the mature VLDL? See that the FFAs are immediately released by lipoprotein lipase?

OK.

Now to the "package" comment.

You will notice that I had no problem with Taube's description of apoB in my last post:

The triglycerides constitute the cargo that the lipo-proteins drop off at tissues throughout the body. The combination of cholesterol and apo B is the delivery vehicle. This is perfectly normal. In fact, it is vital. Your body uses cholesterol in its cell membranes and to manufacture hormones.

Nor did I have any problem with this statement...

These triglycerides are no more than droplets of oil. In the liver, the oil droplets are fused to the apo B protein and to the cholesterol that forms the outer membrane of the balloon. The source of these triacylglycerols is dietary fat.

...except to correct the source of the TAGs.

Also.

Take a look at this figure again. See FFAs in the "liver box" at the top? See how the arrow points to VLDL? See how the VLDL arrow points to adipocytes (fat cells)? See how the FFAs are PACKAGED into TAGS in the adipocytes?

One last thing.

Just for future reference, here are the 2 disease processes that Taube keeps talking about as if they were normal responses to carb intake: hypertriglyceremia and dyslipidemia.

Here's a comparison of normal VLDL metabolism and abnormal metabolism aka hypertriglyceridemia (hyper = too much ... triglyceride = TAGs ... emia = disease).

Those yellow and red balls are just to represent the proportions of the particle's components. They shouldn't be taken literally.

Hypertriglyceremia, btw, is what you keep talking about (elevated TAG levels).

The ppt slide also mentions the small, dense LDLs.

Here's a look at another abnormal metabolic cycle that produces the small, dense LDLs.

This is a dyslipidemia.

See the comment down in the lower left corner? "Fatty liver" aka adiposopathy?

If you have fatty liver, you have a disease. A very serious disease, actually.

OK.

Are we all set on VLDL and chylomicrons?

And do you concede that the FFAs that are used to produce the VLDL particles come from dietary fat and not carbs?

Edited by Admin, : Adjust image width.

Edited by Admin, : Typo.

And neither I nor Taubes ever claimed that (to use your words) "the FFAs that are used to produce the VLDL particles come from...carbs."

I'm sorry, Percy, but yes you did.

Message 27.

The Taube quote.

After we eat a carbohydrate-rich meal, the bloodstream is flooded with glucose, AND THE LIVER TAKES SOME OF THIS GLUCOSE AND TRANSFORMS IT INTO FAT--TRIGLYCERIDES--for temporary storage. These triglycerides are no more than droplets of oil. IN THE LIVER, THE OIL DROPLETS ARE FUSED TO THE APO B PROTEIN AND TO THE CHOLESTEROL that forms the outer membrane of the balloon. The triglycerides constitute the cargo that the lipo-proteins drop off at tissues throughout the body. The combination of cholesterol and apo B is the delivery vehicle. The resulting lipoprotein has a very low density and so is a VLDL particle, because the triglycerides are lighter than either the cholesterol of the apo B. For this reason, the larger the initial oil droplet, the more triglycerides packaged in the lipoprotein, the lower its density.

Here is what Taube said:

Carbs → TAGs → apoB (which is later incorporated into the mature VLDL -- see figure above)

Here is what really happens:

Fatty acids are usually ingested as triglycerides. They are broken down in the intestine into free fatty acids and monoglycerides by pancreatic lipase.

The short and medium chain fatty acids are then absorbed directly into the blood via intestinal capillaries. They then travel to a lot places -- one of which is the liver.

However, long chain fatty acids are too large to be directly absorbed by the tiny intestinal capillaries. Instead they are absorbed into the walls of the intestinal villi and reassembled again into triglycerides.

Once across the intestinal barrier, chylomicrons and VLDL particles are synthesized by the liver from the dietary fatty acids.

In summary.

Short and medium chain dietary fats: TAGs → FFAs → chylomicrons and VLDLs.

Long chain dietary fats: TAGs → FFAs → TAGs → chylomicrons and VLDLs.

Is that better?

And this is the question I asked in Message 31, concerning whether it is triglycerides or FFAs that are placed in VLDLs.

TAGs are in apo particles. Apo particles are in mature VLDLs.

And Taube is claiming that the TAGs come from carbs.

So if we can figure out the answer to this one issue then we can move on to the next item, which, if you like, can be whether glucose is involved at all in VLDL production.

Carbs can be converted into TAGs. That is not in dispute.

It is not the normal procedure. It only happens when one consumes excess carbs (in excess of the body's need for glycogen and energy, that is).

It is my impression that Taube thinks that every blood sugar spike = carbs into TAGs. And that this inevitably leads to the TAGs being incorporated into apo B particles.

IOW ... Carbs → TAGs → apoB.

Is that true? Or is he talking about excess carbs?

You're disputing almost everything that Taubes says ...

It's frustrating to see someone distort and/or misrepresent well-established science.

Like I said. The guy is idea-mining. With no regard for the metabolic realities.

You might want to take a look at this:

http://www.reason.com/news/show/28714.html

It details how Taube pissed off the scientists he quoted in a NYT Magazine article he wrote (published in 2003 -- a trial balloon before his book).

It details how he distorted their findings.

It details how he rejected out of hand literally hundreds upon hundreds of studies that don't support his theory.

Taubes presented University of Washington endocrinologist Michael Schwartz, whom he had interviewed, as a proponent of the idea that blood insulin levels as altered by carbohydrates could be a significant contributor to weight gain. But a commentary in the same magazine Taubes writes for, Science, sharply contradicted that position. "Although the concept that insulin triggers weight gain has little scientific merit, it remains a key selling point for advocates of diets that are low in carbohydrate and high in protein and fat," it read. "If hyperinsulinemia has adverse consequences, obesity does not appear to be among them," it concluded. Who wrote that? Michael Schwartz.

Since the publication of Taubes' article, numerous doctors, scientists, and health writers have picked apart various pieces of his argument. A fatlash has formed against Taubes, The New York Times Magazine, and Knopf. Originally riding an adulatory wave, Taubes complained bitterly to the weekly New York Observer in November that he was "being attacked by sleazebags."

The guy is just up to his same old tricks.

I'm sorry, Molbiogirl, but I cannot connect your answer to the question. I raised an issue concerning triglycerides, FFAs and VHDL, and your answer mentions none of those things.

Percy, you need to ask a different question.

I don't know how much clearer I can be.

Short and medium chain dietary fats: TAGs → FFAs → chylomicrons and VLDLs.

Long chain dietary fats: TAGs → FFAs → TAGs → chylomicrons and VLDLs.

In the case of short and medium chain carbs, FFAs are sent to the liver, processed into apo particles and incorporated into mature VLDL particles.

In the case of long chain carbs, TAGs are sent to the liver, processed into apo particles and incorporated into mature VLDL particles.

Sorry for another picture, but a picture is worth a thousand words.

The carbohydrate hypothesis may also be wrong, but Taubes makes a strong case that it has not been properly studied because of the hostility against it within the scientific community, of which you are currently providing a copious example.

I did quite a bit of research on this question last night.

And it is simply not true.

This question has been (and continues to be) studied exhaustively.

My dietary experience is probably nearly the identical one that all older people have, and the dietary fat, calorie intake/outgo hypothesis of obesity completely fails to explain this experience.

I hear you.

But my experience is the polar opposite (re: caloric intake).

Which is why we don't rely on just one person's experience, right?

But three weeks after cutting down on carbs I'm suddenly down 8 pounds, and I'm never hungry.

Water weight.

Protein laden diets leads to lots of water weight dropping off.