Cholesterol

Struggling to understand the science on cholesterol. It seems to be controversial. Both sides seem to be saying that the other side is using flawed research.

So. Is there scientific evidence that high LDL increases the risk of heart disease?

And is there scientific evidence that high LDL increases the risk of stroke?

 

@Jonathan Edwards ?

 

@Sarah94 my understanding is that it is based on 3 factors, your LDL, HDL, triglycerides, ratios and risk factors. Your BP and glucose fasting comes into play too. It can be a bit confusing.

 

According to my GP, cholesterol is only a concern if you have other risk factors in addition to high cholesterol (ie high blood pressure, high triglycerides, Diabetes, etc).

 

I don't follow the detail of this. I am pretty sure that high cholesterol is a risk factor, even on its own. I am not sure about LDL though. The cholesterol carried by LDL is supposed to be the bad part but I am not sure what LDL level on its own means.

I don't think things are so much controversial as complicated. What I think is controversial is the value of drug treatment - or at least what proportion of the population can reasonably be considered likely to benefit.

Somebody else is likely to know more than I do.

 

Especially for women.

 

That's not really what it says. The post only relates to HDL-cholesterol:

 

My sister has high LDL and is overweight, her GP wanted to put her on Statins, but she refused and is trying to lower it with diet.

When my LDL was high my GP told me she would put me on 'meds' if I was pre-diabetic and had high BP. My LDL is still on the higher end but she no longer mentions it. My HDL is high, my triglycerides low and I'm not overweight.

 

check out fat emperor who has some good videos on this, also on adipose tissue signalling (or how you can be fat and metabolically healthy)
https://thefatemperor.com/whats-the-real-story-with-cholesterol-and-heart-disease-podcast-ep9/

https://www.youtube.com/watch?v=OvuGm8VYkQY

ETA 2 different videos. First one informative on ll/ hdl/ triglycerides

 

Regarding treating high cholesterol with statins: I've read that statins help statistically, but the number needed to treat - that is,
(number people with x risk profile taking statin) / (adverse events avoided) is well over 25.

So you may have x risk factors but were not going to have an adverse effect without it, or you may have the risk factor, take the statin, and also have the adverse event despite it. You also might be a person who doesn't have a stroke because taking the statin. The way I understand it is that it shifts the odds in your favor, but there's no certainty it's going to benefit you in particular.

 

The aspect that few doctors divulge is that of all cause mortality. Typically the effect of side effects / overall efficacy is not divulged.

Statins don't do well on this.
Being female is also an impact.

 

Canadian guidelines. It’s all about your risk factors (weight, comorbidities such as diabetes, family history), and lipids. https://www.onlinecjc.ca/article/S0828-282X(16)30732-2/pdf

 

Some links from the NNT (Number needed to treat) website http://www.thennt.com/ you might find interesting :

Cardiac Interventions That Work

Cardiac Interventions That Don't Work

Cardiac Interventions That Need More Study

 

I think there are a lot of myths about cholesterol being bad not bad etc.


It is a bit complicated but I will try and simplify what I know of it. Sorry if this is too long/simple.

1). There have been lots of studies that show correlation with heart disease and stroke with a diets high in saturated fat.
2). Studies have also shown than a diet high in unsaturated fat (mono and polyunsaturated fats) have low correlation e.g. the Mediterranean diet
3) other studies have shown correlation between high triglyceride levels in the blood and heart disease and stroke.
4) other studies have shown a link to consumption of saturated fat and cholesterol in the bloodstream
5) high cholesterol was and is still thought to clog arteries forming plaque and be the cause of heart disease and stroke due to restricted blood flow through ‘hardened arteries”
6) newer studies then showed that LDL (low density lipoprotein) was more directly linked to heart disease
7) high HDL is thought to lower the risk of depositing cholesterol on artery walls
8) men have a higher risk of heart disease and have lower levels of HDL on average

There seems a reasonably robust amount of studies that make us believe that the facts are true...but in most instances they are only correlations and we don’t yet know the exact mechanisms, although recent work has started to challenge the view that saturated fat and cholesterol are the main culprits per se.

So how does cholesterol come into it?

To understand the significance of this requires a bit of food chemistry... simplified from my addled brain:

Unsaturated means a fatty acid with double bonds between its carbon back bone, saturated have none. Monounsaturated means the fatty acid has one double bond, polyunsaturated, many.

Before digestion the fatty acids are bound together as triglycerides (3 fatty acids glued together with a glycerol molecule). The combination of fatty acids gives the triglyceride its properties. Complex fats can have many different types of triglyceride in them.

Generally though, we call fats either saturated (solid at room temperature (lard, butter, coconut/palm oil)) or unsaturated (liquid (rapeseed oil etc)). However most fats Have both saturated and unsaturated fatty acids in them when they are broken down. This is important because it shows that there aren’t good fats or bad fats ..they are normally a combination of good and “bad” fatty acids. Some have more unsaturated in them than others though (like seeds, nuts/oils from seeds/nuts). The fatty acids themselves aren’t “bad” either.

We don’t absorb fats until they are broken down into their constituent parts (fatty acids/glycerol) but they are then rebuilt later for different uses and transportation around the body. The body rebuilds the absorbed fatty acids from the gut into new triglycerides for use in cells etc. These then need to be transported via blood to the parts of the body that need them.

Cholesterol is also a fat and is used by the body to transport the triglycerides around. It is mainly produced by the liver during digestion (about 20% of cholesterol we need comes directly from the food we eat, the rest is made and secreted with bile). The liver can make cholesterol from carbohydrate as well as fat. So most of the cholesterol in blood comes from the digestion process not from the type of food eaten.

It is also useful in itself because it is essential for making cell membranes. So the body has found a neat way of getting both triglycerides and cholesterol around the body.

But fat doesn’t do well in blood. To make it easily transportable the body binds a protein to the outside of the cholesterol/triglyceride.

So our triglycerides are made, they are bound to cholesterol which in turn helps bind to the protein to make the main transport lipoprotein complex.

The lipoprotein complex then circulates around the body, dropping off the triglycerides to various parts of the body.

LDL is a lipoprotein that has lost its triglyceride and is as a result high in cholesterol. It isn’t pure cholesterol since it has protein with it.

HDL is also a lipoprotein with less fat in it and more protein than LDL. It is thought that HDL is produced by the liver to return cholesterol back to the liver. It is thought to lower the risk of heart disease by removing cholesterol from the arterial walls as it passes through.


So in terms of conflicting evidence. It still remains true that ldl will increase with increased fat consumption and this is still thought to be a bad thing due to it hardening arteries. However we also know that eating unsaturated fat is still good advice. Whether the two are linked is yet to be proven definitively. This may be due to the omega in it rather than the unsaturated part but that’s a whole other story.

So from the evidence so far ...we should still eat fat in moderation and monitor blood ldl and hdl levels in relation to triglyceride as per the current guidelines.

I think of this as evolving science rather than a u-turn like some pro paleo advocates are stating. There certainly isn’t much evidence that eating a high fat diet is good for you.

 

Thank you, for that It is so hard to get explanations that have enough detail but are not way above my head.

 

A gut-derived hormone regulates cholesterol metabolism
Xiaoli Hu; Fengyi Chen; Liangjie Jia; Aijun Long; Ying Peng; Xu Li; Junfeng Huang; Xueyun Wei; Xinlei Fang; Zihua Gao; Mengxian Zhang; Xiao Liu; Ye-Guang Chen; Yan Wang; Huijie Zhang; Yiguo Wang

The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice).

It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.


Link | PDF (Cell)