Today’s guest post is from my friend John Hanson, who has provided a dialogue about cholesterol followed by a short discussion – “food for thought”, if you will. Thanks John!
“Good morning Doctor. You are here today to provide expert witness for the court to help us understand cholesterol measurements.”
“Yes. I am a cardiologist.”
“Tell me about the basic cholesterol blood test, the one we all get every year. Tell me in as simple terms as you can what this test is.” The prosecutor stood aside, leaned on the rail, and let him address the full audience.
“It’s a simple test. A technician places your blood sample in a machine that spins it. The centrifugal forces separate the various components, then we measure those components.”
“Do we use a microscope and count all the particles?”
“Oh no, there are many millions of particles in blood samples. We could never sort and count them all individually. We simply measure the quantites of these separated drops of … goo.”
“Goo?” The prosecutor raised his eyebrows and looked at the doctor questioningly over his reading glasses.
“It looks like, like something that ran out of your nose when you have a cold,” the audience chuckled cautiously with him.
“OK, we have various drops of goo, then you give us numbers for those drops, a number that equals their mass?”
“More or less, yes”
“More or less? Are there are other considerations?”
The doctor paused to think for several seconds, “Well, yes. You see not all the particles in each drop are the same. There’s a little variation in size. Some particles are smaller and some are bigger. The calculation we make is based on a standard sized particle, but there can be some variation.”
“How much variation?” the lawyer asked.
“We allow plus or minus 10 percent.” The doctor was sitting up straight, relaxed, and confident in his answer.
“Do we know anything about these particles, why they vary, and what they mean?”
“Yes we do. There’s strong evidence that smaller particles are more dangerous than bigger ones because …”
“Thank you doctor. I don’t want to get into dangers just yet. Maybe we’ll cover that this afternoon. This morning I want to stick with just our calculations. So you say that particle size variations can result in variations in our measurements.”
“That is correct.”
“Can you also tell us, without going into great detail, how these size variations come about? Is there a known cause?”
“Well yes there is. We know the reasons. It’s food.
“One of the big causes is how we make triglycerides. These are packages of fat. When our liver makes triglyceride packages, it borrows a protein from our HDL particles to create the VLDL carrier particles.”
“Carrier particles being particles that carry the fats to cells for consumption.”
“That is correct. And when these VLDLs return to the liver, the liver cuts them up with enzymes in a process called hepatic lipase.”
“Am I correct in thinking that enzymes are like knives?”
“Yes, they are our bodies’ knives. When we break up complex components into base components, we use enzymes to do the work.”
The prosecutor now leaned on the rail in from of him and focused my attention on him, “and what happens to VLDLs when our livers break them apart?”
“Well, it depends on the type of triglyceride, but these VLDLs created by our livers, because they have this APO-B100 protein from the HDL particle, well, they are converted into small, dense LDL particles. They can make our LDLc value look smaller than it really is.”
“APO-B100, that’s the protein that the liver stole from our HDLs?”
“Yes. The 100 indicates that it has 100% of the attributes of an active lipoprotein.”
Lawyers like to vary their posture to maintain jury focus in complex discussions. He started walking around now and using his hands more. “Ahh, I see. But why are these lipoproteins smaller than others?”
“They are created in a different process and lack a few other components.”
“So they are smaller.”
“Yes, and more dangerous.”
“Dangerous?” he walked towards the jury for effect.
“Theoretically yes. Since they are smaller, it’s thought they more easily penetrate the arterial wall, the endolethium…”
He interrupted the doctor again and walked back towards him. “Thank you doctor, but we’ll discuss dangers this afternoon. Can you please confirm the points we just covered, which are that liver production of triglycerides both reduces our HDL number and increases our small LDL number?”
“That may be correct.”
“Your saying there’s doubt?”
“Of course. This is not an exact measurement.”
“And each of our numbers is represented by a distinct … drop of goo?”
He paused to review the coverage, “Well, actually no. We don’t have a drop of goo for our LDLc number. We have to calculate it.”
“This is the number that doctors use most, is it not?”
“Yes. We primarily use LDL values to determine risk of heart disease and to prescribe various drugs like statins.”
“How to we calculate this value?”
“We know the total cholesterol, the HDL, and the triglycerides values. We take the total cholesterol, subtract the known HDL, then add an estimate of the triglyceride impact, about twenty percent of our triglycerides are added to come up with our LDL value.”
“We add twenty percent of our triglycerides? It seems to me that increasing our triglycerides must also be considered bad then.”
“Our liver produced ones only.”
“So triglycerides are made elsewhere. Where are these other triglycerides made?”
“When we eat fat, they are converted to triglycerides in the intestines.”
“All fats that we eat?”
“Fats cannot be transported through the bloodstream otherwise.”
“And they use a different protein than the APO-B100?”
“They use the APO-B48 which has a 48% lipoprotein expression.”
“And the VLDLs are cut apart by our livers after they deliver their load?” The prosecutor knew all this but wanted the jury to understand the significance of their lack of lipoprotein expression.
“Correct, but they do not become LDL particles?”
“They do not become LDL particles? You mean those small dangerous ones?”
“That’s right, they just get broken up and recycled for many uses.”
“Are any of these uses dangerous?”
“No. We don’t think so.”
“But saturated fats are dangerous?”
The doctor stared into the balcony pondering their discussion.
“Are you confused doctor?”
“Well, yes actually. We’ve always been taught that fats are the source of liver produced triglycerides, but they can’t be because they are already packaged when they get into the blood stream. We know that small LDLs are the dangerous ones, but obviously fat can’t be the source of the danger. We do know that fructose is nearly all converted to triglycerides because our bodies don’t otherwise recognize it. Excess glucose does too. It’s most likely that these sugars are the source of our dangerous LDLc particles.”
“You just mentioned that twenty percent of triglycerides get included with our LDL values. Please tell us how we get this number, this twenty percent.”
“It represents the portion of the triglycerides that will be converted to LDLs”
“But not all triglycerides get converted to LDLs.”
“That is correct. It’s an estimate”
The prosecutor upped the intensity by walking and speaking. “Are there conditions where this estimate becomes invalid?”
“Yes as levels of triglycerides get higher, the numbers become less certain.”
“Can very low levels of triglycerides make numbers less certain?” he stopped walking and stared at the doctor.
“No they cannot.”
“You said earlier that some VLDLs are not converted to lipoproteins. What if all our triglycerides were of this type?”
“We never see such cases. It’s not possible.”
“You didn’t answer my question sir.”
The judge, who had been sitting motionless, now shuffled around the papers on his desk, and leaned forward, resting his chin on a hand who’s elbow was braced on the corner of his dais.
The doctor looked at the judge then looked at the prosecutor. “If such a case were to exist, which it couldn’t, then that person’s LDL value would be grossly overstated by about twenty percent of their triglyceride value.”
“Now tell me doctor, what is a low triglyceride value?”
“About 100 is the lowest I see.”
“If a person’s triglycerides were all made in their intestines, that is they all came from fat, would that number be higher or lower?”
“Their triglyceride value would likely be much lower.”
“And their LDL overstated?”
Another pause, “possibly.”
“But this doesn’t happen.”
“It can’t happen.”
“Why can’t it happen?”
“Because it doesn’t.”
“But it could?”
“If such a person existed, a person with only these ‘good’ triglycerides, what would you expect their triglyceride values to be?”
The doctor sure was pausing a lot today, “I estimate around 50 mg/dl or less.”
The attentive judge finally butted in, “Doctor. My triglycerides are 42. Does that mean my LDL value is overstated?”
The doctor was now fidgeting uncomfortably, “I suppose it could be.”
“You don’t know these things?”
“There is a test which looks at the APO-B levels in the blood which should be more accurate than the calculation I’ve described, but as far as I know, the two haven’t been compared in detail.”
“Thank you doctor,” and the judge sat back, finished with his question but not satisfied with the answer. He grunted under his breath.
“So doctor, please confirm this is what you are telling us. If I eat lots of fructose, sugar, then my liver will create lots of triglycerides, these will cannibalize my HDL particles, and make smaller LDL particles. My HDL value will go down, and my LDL value will go down. It may look lower than it really is.”
“Yes … that is correct.”
“Conversely if I eat very little fructose and other sugars, my LDL may look higher because I’m not making them look smaller. I am also adding extra estimates for triglyceride created LDLs which won’t happen because I have very few of them.”
“That sounds correct, but it hasn’t been shown in research or practice.”
“And lower cholesterol is good for us. Isn’t that correct doctor?”
“Lower cholesterol, lower LDL that is, is good for us, But doing it this way isn’t.”
“Please tell the jury sir, what the good way is.”
“The good way is by lowering our saturated fats.”
“But you just told us that saturated fats don’t create lipocentric VLDL particles. If it doesn’t create small dangerous particles, then it must result in bigger, benign particles.”
“I think I’ll have to have some discussions with my colleagues.”
“So when I read a study in the paper that eating high saturated fats increases my cholesterol and is bad for me, Should I believe it or not?”
The doctor was silent.
The prosecutor raised his voice adamantly, “When my doctors tells me that I should eat no saturated fats, should I believe him?”
The doctor finally spoke, “Such statements, ones that say eating fats make our cholesterol numbers bigger, are true, BUT … I don’t see any reason to believe that saturated fats make our cholesterol dangerous.”
“Thank you doctor!”
We’ve been following recommendations of eating lower amounts of fat for almost four decades. We’ve all had the concept that high cholesterol is bad for us burned into our psyches. Articles about people making great changes to their diets such as this one to lower fat intake are prevalent. Websites promoting reduction of meat and fat intake are everywhere. Studies ‘suggesting’ the evil of meats and fats have a long history. Celebrity doctors write books, create websites, and go on TV extolling the virtues of low fat diets. All of these messages use the same logic: high cholesterol causes heart disease, so therefore anything that increases your cholesterol levels, specifically your LDLc levels, must increase your heart risk. They never demonstrate mechanisms.
Association is not proof. Firefighters are highly associated with house fires, yet nobody can or will prove that firefighters are responsible for causing them. My dialogue suggests reasons why these judgements about high cholesterol levels are wrong; it actually suggests that the reverse is true: the less fat and more sugar we eat, the sicker we become. Take a look around you; look in the mirror. During these last decades we’ve gotten fatter and sicker.
Real evidence indicates this basic cholesterol assertion is not only questionable but completely wrong. A recent compelling analysis by a leading lipidologist found no indications that saturated fat consumption leads to increased CVD risk. Statistical studies like this one indicate LDLc levels are very poor predictors of risk. Over the last couple of decades, our understanding of the mechanisms of heart disease are leading us down a different road. My dialogue above identifies some of these ideas. Arterial plaque is a problem, but it is not due to simple lipid numbers. Particle sizes and inflammatory/oxidization pressures are where real science points. Science points to the fires, not the firefighters.
When you look at all the science objectively, when you start putting all the puzzle pieces together, it points to causes other than fat and red meat. 80% of us diabetics will die from heart disease. Diabetes is a disease of sugar control, not fat control. Yes Bill Clinton has lost 25lbs and reduced his CVD risk by following one of these low fat diets, but he has also eliminated sweets. He has reduced his carbohydrate intake. People on calorie reduction diets all reduce sugar and carbohydrate intake as well as fats and proteins. Are we missing the boat by avoiding fats? The cholesterol issue hasn’t hit the courts yet. Will it?
For the record, I eat about 30-50g of carbohydrates a day. At least 60% of my calories come from fat. I’ve lost 25lbs, my A1C is 5.6%, HDL is 2.21mmol/l (85.5 mg/dl), LDL is 2.24 (86.6), and my triglycerides are 0.45 (39.8). I don’t take any cholesterol drugs.