Lipid Transport

(Jenna Ericson) #1

I’ve always had a hard time understanding the differences between types of cholesterol and their role in fat metabolism. I found these great videos that clarified things a lot:

My question after watching these is, what determines how much LDL is made by the liver? This seems important as LDL is often seen as the culprit in contributing to risk for certain diseases. I understand that the topic of LDL as a marker of disease is a controversial one, but maybe whether it is or not has to do with what is causing the demand for it.

(Bacon is a many-splendoured thing) #2

The purpose of LDL, as I understand it, is to convey fatty acids from adipose tissue to cells that need energy. The cholesterol, according to Dave Feldman in a couple of his presentations, is pretty much just along for the ride, in case it is needed. Dave’s analogy is that the lipoprotein is like the ship, the fatty acids are like the passengers (i.e., the reason the ship is travelling in the first place), and the cholesterol is like the lifeboats. Most cells are capable of making their own cholesterol, so the LDL-cholesterol is mostly there for emergencies. Or so I understand it.

This was all very well explained at, the last time I visited, and Dave has given a number of talks at Low Carb Down Under events that are available on YouTube.

(Jenna Ericson) #3

I just found this video on how cholesterol is made. I thought it was interesting that the process starts when you have too much Acetyl CoA, which can be used to make either cholesterol or ketones. The video also clarifies where hydroxymethylglutaryl-CoA reductase is used, which is the enzyme inhibited by statins.

(Luza Hazel) #4

Palmitic Acid intake determines how much LDL is made by the liver however this isn’t an issue on a ketogenic diet because there’s no crazy amounts of sugar in the blood to stick to LDL transport proteins.
Palmitic acid - Wikipedia

Atherosclerosis is due to a multitude of toxicity factors. Hyperglycemia and/or Hyperlipidemia from overeating. Intake of lipid peroxides and/or pesticides and/or persistent organic pollutants and/or air pollution causing inflammation in the endothelium. Hyperglycemia also leads to the creation of advanced glycation ends products and these AGEs can cause atherosclerosis.

(KM) #5

Um, this was not in the wiki you quoted. Source?

(Luza Hazel) #6

Glycation - Wikipedia

Fruits have Antiglycation compounds like polyphenols and carotenoids however I doubt they can protect against the formation of advanced glycation end products if mixed with meat (high protein) like we see online in those who advocate an animal-based diet with fruit. And they can’t protect against temporary ketoacidosis if our ketones are high from being in ketosis and then we decide to consume too much fruit.

(KM) #7

What I’m questioning is the idea that glucose in the blood sticks to LDL or that LDL is somehow involved in the transportation of glucose into cells. Not a concept I’m familiar with, at least not the way it’s phrased. Not to say I’m right, I just don’t think I’ve ever heard this, I thought the process was basically a sort of osmosis facilitated by insulin.

(Luza Hazel) #8

LDL isn’t involved in the transportation of glucose into cells.

Susceptibility of LDL and its subfractions to glycation - PubMed (

Is there a minimum blood glucose level for glycation to occur?


Yes, there is a minimum blood glucose level for glycation to occur. Glycation is a non-enzymatic process that involves the reaction between glucose and proteins or lipids in the body, resulting in the formation of advanced glycation end products (AGEs).

Glycation can occur at any blood glucose level, but it becomes more significant when blood glucose levels are elevated. The likelihood and extent of glycation increase with higher blood glucose concentrations over an extended period. In individuals with poorly controlled diabetes, who may have chronically high blood glucose levels, the risk of glycation and the subsequent formation of AGEs is higher.

It is important to note that glycation is a natural process that occurs in the body to some extent, even in individuals with normal blood glucose levels. However, chronic hyperglycemia (high blood glucose levels) can accelerate and amplify the glycation process, leading to increased formation of AGEs, which may contribute to various complications associated with diabetes, such as cardiovascular disease, neuropathy, and nephropathy.

(Bacon is a many-splendoured thing) #9

It’s not, so far as I understand. Every cell has glucose receptors on its membrane, so they just take what they need (if any) from the glucose circulating in the blood.

My understanding isn’t so much that lipoproteins get glycacted as that they get oxidised. Not that they can’t also be glycated, but oxidation can make lipoproteins unrecognisable and therefore difficult to clear from the blood. The long dwell time of LDL when the diet is high in carbohydrate increases the risk of oxidative damage. Also, the hyperinsulinaemia resulting from a high-carb diet interferes with the production of nitric oxide, which the body uses to lower blood pressure. So when arteries get damaged, it is easier for oxidsed LDL particles to get into the arterial wall.

(Luza Hazel) #10

Learn something new every day. Thanks for sharing.

ChatGPT says that its hyperglycemia and not hyperinsulinemia which inhibits nitric oxide production. Is it really correct to say hyperinsulinemia when the hyperglycemia is causing the issues?

(Bob M) #11

Can you ask Chat GPT to cite its sources?

(Luza Hazel) #12

Not anymore for some reason.

(Bacon is a many-splendoured thing) #13

ChatGPT is wrong.

Hyperglycaemia causes other problems. If it reaches too high a level, we die, hence the insulin reaction to drive excess glucose out of the blood and into muscle to be metabolised and into fat cells to be stored as fat. Hyperinsulinaemia interferes with a great many processes. Insulin is a powerful hormone and has many effects throughout the body.

I imagine that ChatGPT also thinks that the way to lose fat is to eat less, move more, avoid meat and saturated fat, and eat lots of carbs. Unless, of course, one of its teachers was a secret ketonian. But a trained AI is only as good as the reference material it’s been fed.

(KM) #14

Whole grains, the answer to everything. :scream:

(Jenna Ericson) #15

What’s crazy is I found that ChatGPT made a similar error when I asked something having to do with measuring insulin. It kept saying that you could measure insulin levels depending on blood glucose levels. It was a while ago that I asked that. Strange times!

(Luza Hazel) #16


The cause of hyperinsulinemia is always excess consumption of calories. Especially carbohydrates.

Why are you blaming excess Insulin?

One important molecule for maintaining vessel function, including relaxation of the arterial smooth muscle layer, is nitric oxide (NO) which is generated by endothelial NO synthase (eNOS). Insulin increases NO production via posttranslational modification of eNOS via PI3K/AKT activity; however, this mechanism is suppressed during insulin resistance.
Insulin: too much of a good thing is bad | BMC Medicine | Full Text (

Does hyperglycemia or hyperinsulinemia inhibit nitric oxide production?


Both hyperglycemia (high blood glucose levels) and hyperinsulinemia (high insulin levels) can have effects on nitric oxide (NO) production, albeit through different mechanisms.

Hyperglycemia: Hyperglycemia can directly inhibit NO production and impair its bioavailability through several mechanisms:

  1. Reduced endothelial nitric oxide synthase (eNOS) activity: High glucose levels can decrease the activity of eNOS, the enzyme responsible for producing nitric oxide in endothelial cells. This can lead to reduced nitric oxide synthesis and availability.
  2. Increased oxidative stress: Hyperglycemia promotes the production of reactive oxygen species (ROS) and oxidative stress. These ROS can react with nitric oxide, forming peroxynitrite, a highly reactive compound. The formation of peroxynitrite not only reduces nitric oxide availability but also contributes to endothelial dysfunction.
  3. Advanced glycation end products (AGEs): Prolonged hyperglycemia leads to the formation of advanced glycation end products (AGEs), which are harmful compounds formed by the reaction between glucose and proteins. AGEs can interfere with nitric oxide signaling pathways and reduce eNOS activity, further compromising NO production.

Hyperinsulinemia: Hyperinsulinemia, on the other hand, is not known to directly inhibit nitric oxide production. However, it can indirectly affect NO availability and function through various mechanisms:

  1. Insulin resistance: Prolonged hyperinsulinemia can contribute to insulin resistance, where cells become less responsive to the effects of insulin. Insulin resistance is associated with reduced nitric oxide production, potentially affecting endothelial function and vasodilation.
  2. Oxidative stress: Hyperinsulinemia can promote oxidative stress, which can scavenge nitric oxide and impair its bioavailability. This can result in reduced NO-mediated signaling and vasodilation.
  3. Endothelial dysfunction: Insulin resistance and hyperinsulinemia can contribute to endothelial dysfunction, impairing the normal production and release of nitric oxide from endothelial cells. This can impact vascular function and NO availability.

It’s important to note that the relationship between hyperglycemia, hyperinsulinemia, and nitric oxide production is complex and can be influenced by various factors. Additionally, individual variations and the specific context of the condition can impact the interactions between hyperglycemia, hyperinsulinemia, and nitric oxide. Therefore, it is advisable to consult with a healthcare professional for a comprehensive understanding of your specific situation and its implications on nitric oxide function.

I can’t disagree with this but I’d rather not throw the baby out with the bath water.

(Bacon is a many-splendoured thing) #17

The cause is not excess consumption of calories, it is excess consumption of carbohydrate, since carbohydrates are nothing more than glucose molecules arranged in various ways. (If the carbohydrate is indigestible, we call it fibre.) Eating carbohydrate raises serum glucose, and the rise in glucose past a certain point is dangerous, possibly even fatal, to the body. Thus, the pancreas secretes insulin to drive the excess glucose out of the blood stream.

But it is not only hyperglycaemia that damages the body, hyperinsulinaemia does also. Hyperinsulinaemia results from insulin-resistance, and it is implicated in the various forms of metabolic dysfunction: hypertension, elevated heart rate, atherosclerosis, Type II diabetes, gout, Alzheimer’s disease, breast cancer (and other cancers, as well), polycystic ovarian syndrome (PCOS), impotence (erectile dysfunction), visceral fat accumulation, and many other conditions. That is why I am blaming excess insulin. As your citation points out, an acute insulin rise can be helpful, but chronic hyperinsulinaemia interferes with NO production and thus causes hypertension (there are other factors at work that also cause arterial damage on a high-carb diet).

ChatGPT is only as good as the sources it was trained on, and those were selected by biased human beings. As with any human being, you have to ask the AI to show its sources, too, and then you can trace back the information to the studies that provided it. In a lot of cases, these studies are flawed in one way or another.

Note: protein has an effect on insulin secretion that is about half the effect of glucose (carbohydrate), but the result depends on whether the protein was consumed as part of a high-carb or a low-carb diet. If the former, the insulin response to protein is unchecked resulting in an even higher insulin response. In the context of the latter, however, the increase in insulin is matched by an increase in glucagon secretion, leaving the metabolic state of the body unchanged. (Insulin and glucagon regulate each other.)

Fat has no effect on insulin secretion, beyond the bare minimum needed for us to live.

(Luza Hazel) #18

It is the excess consumption of calories when consuming a standard mixed diet. Those consuming a high carb/low fat diet do not experience hyperinsulinemia because they don’t develop atherosclerosis but will eventually experience degeneration from a lack of fat.

And insulin resistance is an indication of Atherosclerosis. Atherosclerosis needs to be present in the endothelium before there’s insulin resistance.

Does excess insulin in the blood cause any damage?


Excess insulin in the blood, particularly when it is chronically elevated, can potentially cause damage and have negative effects on the body. Here are some potential risks associated with high insulin levels:

  1. Insulin Resistance: Prolonged hyperinsulinemia can lead to insulin resistance, a condition where the body’s cells become less responsive to the effects of insulin. Insulin resistance disrupts the normal regulation of blood sugar levels, potentially leading to chronically elevated blood sugar levels and an increased risk of developing type 2 diabetes.
  2. Weight Gain and Obesity: Insulin is involved in the regulation of metabolism and the storage of excess glucose as fat. Elevated insulin levels can promote fat storage and make it more challenging to lose weight or maintain a healthy weight. Excess body weight, particularly abdominal obesity, can further contribute to insulin resistance.
  3. Cardiovascular Risks: High levels of insulin have been associated with an increased risk of cardiovascular diseases. Insulin can influence various factors involved in cardiovascular health, such as blood pressure regulation, cholesterol metabolism, and the growth of smooth muscle cells in blood vessels. Prolonged hyperinsulinemia may contribute to the development of atherosclerosis (hardening and narrowing of the arteries), increasing the risk of heart attacks, strokes, and other cardiovascular complications.
  4. Hormonal Imbalances: Elevated insulin levels can disrupt the balance of other hormones in the body. For example, in women, hyperinsulinemia can stimulate the overproduction of androgens (male hormones), which can lead to symptoms such as acne, excessive hair growth, and menstrual irregularities.
  5. Inflammation: Hyperinsulinemia has been associated with chronic low-grade inflammation in the body. Inflammation plays a role in the development of various diseases, including cardiovascular diseases, type 2 diabetes, and certain types of cancer.

It’s important to note that the negative effects of excess insulin often occur in the context of underlying conditions such as insulin resistance, metabolic syndrome, and obesity. Lifestyle modifications, including adopting a healthy diet, engaging in regular physical activity, and maintaining a healthy weight, can help manage insulin levels and reduce associated risks. If you have concerns about your insulin levels, it is advisable to consult with a healthcare professional for proper evaluation and guidance.

This doesn’t prove that excess insulin directly damages the endothelium.


You’re correct, my previous response did not specifically address the direct damage of excess insulin to the endothelium. When it comes to the direct effects of excess insulin on the endothelium, the relationship is complex and not fully understood. Here are some factors to consider:

  1. Endothelial Dysfunction: Endothelial dysfunction refers to impaired function of the endothelial cells lining the blood vessels. While hyperinsulinemia itself may not directly damage the endothelium, it is often associated with conditions such as insulin resistance, obesity, and diabetes, which can contribute to endothelial dysfunction. Endothelial dysfunction is characterized by reduced nitric oxide production, increased oxidative stress, inflammation, and impaired vasodilation, all of which can contribute to cardiovascular complications.
  2. Insulin’s Effects on Vasodilation: Insulin has vasodilatory effects, meaning it helps relax and widen blood vessels. In normal physiological conditions, insulin promotes vasodilation, which enhances blood flow and nutrient delivery. However, in the presence of insulin resistance or excess insulin, the vasodilatory response may be impaired, potentially contributing to endothelial dysfunction.
  3. Hyperinsulinemia and Atherosclerosis: Atherosclerosis is a condition characterized by the buildup of plaque in the arterial walls. While the direct impact of excess insulin on atherosclerosis is still a topic of research, hyperinsulinemia has been associated with various factors that contribute to the development and progression of atherosclerosis. These include increased oxidative stress, inflammation, stimulation of smooth muscle cell proliferation, and alterations in lipid metabolism. These factors can indirectly affect endothelial function and contribute to the development of atherosclerotic lesions.

It’s important to note that the effects of excess insulin on the endothelium are likely multifactorial and can vary depending on individual factors, such as overall health, genetic predisposition, and the presence of other underlying conditions.

Further research is needed to fully elucidate the direct effects of excess insulin on the endothelium and the mechanisms by which it may contribute to endothelial dysfunction and cardiovascular complications. If you have concerns about the impact of excess insulin on your health, consulting with a healthcare professional or a specialist in endocrinology or cardiology can provide you with more specific and personalized information.

Due to hyperglycemia.

Glycated Insulin Exacerbates the Cytotoxicity of Human Islet Amyloid Polypeptides: a Vicious Cycle in Type 2 Diabetes | ACS Chemical Biology

Glycated Insulin: R&D Systems (

Glycated insulin is broken down.

Molecular investigation of glycated insulin-induced insulin resistance via insulin signaling and AGE-RAGE axis - ScienceDirect

RAGE (receptor) - Wikipedia

(Bacon is a many-splendoured thing) #19

That is simply wrong. One of the signs of metabolic dysfunction from insulin-resistance/hyperinsulinaemia is indeed atherosclerosis.

Not to mention Type II diabetes, gout, dental caries, hypertension, other forms of cardiovascular disease, Alzheimer’s disease, a number of different types of cancer, irritable bowel, Crohn’s disease, fatty liver disease, obesity, polycystic ovarian syndrome, impotence, and a number of other conditions. Not everyone with hyperinsulinaemia/insulin-resistance (which Bikman says are synonymous terms) develops all these conditions, naturally, but they are all part of the metabolic syndrome/syndrome X/metabolic dysfunction, whatever you want to call it.

Insulin resistance is not an “indication” of atherosclerosis, it is the cause of athersclerosis. Insulin-resistance can exist independently from atherosclerosis, as was shown in the work of the late Dr. Joseph Kraft. Insulin-resistance is deduced from the insulin response to an oral glucose tolerance test.

If you are going to rely on ChatGPT for your information, then we’re done. Our first rule on these forums is “Show us the science.” So I challenge you to either produce actual studies from the medical literature to support your points, or else stop posting inaccurate information.

(Luza Hazel) #20

It seems like you misunderstood.

It isn’t because the only way to eat a high carb/low fat diet is to eat a whole food plant based diet and it hasn’t shown to cause atherosclerosis but reverse it.

Proof that insulin resistance is atherogenic?