Blood Cholesterol

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Questions Received:

  1. Why do saturated fats raise blood cholesterol levels by increasing LDLs but polyunsaturated fats do not? What happens in the liver to cause this difference? I know it's something to do with the presence/absence of double bonds but can't find out what! Do we lack enzymes to degrade saturated fats, hence they are converted to cholesterol and so cause elevated LDLs? Can you put me out of my fat misery please?!

  2. I work as a health promotion nurse, mainly looking at prevention of CHD. I take a lot of fasting lipid profiles and am aware of the implications of raised LDL and low HDL, but our results always provide a total chol:HDL ratio. I can't seem to find a 'normal' or 'target' level/value for this or indeed anything to clarify the implications of this - should this be the 'treatable' figure rather than total cholesterol measurement as it is probably more realistic?

Responses:

Why do saturated fats raise blood cholesterol levels by increasing LDLs but polyunsaturated fats do not? What happens in the liver to cause this difference? I know it's something to do with the presence/absence of double bonds but can't find out what! Do we lack enzymes to degrade saturated fats, hence they are converted to cholesterol and so cause elevated LDLs? Can you put me out of my fat misery please?!

18th August 1999

There are several potential mechanisms by which an intake of saturated fat could lead to increased blood cholesterol:

unsaturated fatty acids tend to favour the formation of HDLs. Presumably this is linked to the reaction involving the enzyme lecithin cholesterol acyl transferase (LCAT) in which unsaturated fatty acids are transferred from plasma lecithin (a phospholipid) onto the cholesterol molecule to form an ester. HDL then transports this cholesterol to the liver where it is broken down. Hence unsaturated fatty acids would tend to reduce plasma cholesterol. Conversely saturated fatty acid or low levels of unsaturated fatty acid would elevate cholesterol levels in plasma because HDL levels relative to LDL have decreased.

low-density lipoprotein (LDL) particles tend to contain cholesterol esters rich in saturated fatty acids, whereas high-density lipoprotein (HDL) contains unsaturated fatty acids. Thus a high proportion of saturated fatty acids in the diet could (in theory at least) increase LDLs

saturated fatty acids and cholesterol tend to be present together in foods such as animal fat. Hence consumption of food rich in saturated fatty acids would raise cholesterol levels concurrently. (However, a recent study by Kromhaut (1999) indicates that this does not apply in the case of stearate which does not raise LDL)

saturated fatty acids may have some regulatory effects on cholesterol synthesis which tends to raise plasma cholesterol levels (via LDL), an effect which is not produced by unsaturated fatty acid.

There is clear epidemiological evidence that diets rich in cholesterol and saturated fats lead to an increased risk of coronary heart disease as a consequence of high plasma cholesterol levels promoting the development of atherosclerotic plaques in blood vessel walls. Polyunsaturated fatty acids are regarded as being protective because they reduce the risk of atheroma development.

Saturated fats taken in with the diet are incorporated into cholesterol esters (and triglycerides) which form part of the LDL complexes in the blood, whereas polyunsaturated fatty acids are taken up mainly into cholesterol esters in HDL. The chemical composition of these two particles is quite different: LDL contains 80% fat, of which 50% is made up of cholesterol, and 20% protein. HDL contains 55% fat, of which 25% is cholesterol, and 45% protein. Increased levels of LDL have been linked to an increased risk of coronary heart disease and led to its description as "bad cholesterol". Conversely increased HDL levels reduce the risk of coronary heart disease and HDL is referred to as "good cholesterol". Since cholesterol is an essential component of cells and has numerous other roles throughout the body, for example providing a raw material for the synthesis of steroid hormones, we must be careful in the way we attach such labels and keep in mind the need for an appropriate balance.

A large proportion of LDL cholesterol is in the form of esters containing saturated fatty acids, whereas HDL contains unsaturated fatty acids. HDL lipoproteins tend to transport excess cholesterol from peripheral tissues back to the liver where it is broken down. HDL is assembled from apolipoprotein-AI, phospholipid, and free cholesterol discs secreted by the liver and intestines. The free cholesterol is esterified in the mature HDL and can then be transferred to LDL or taken up by the liver or steroid-metabolising tissues.

Diagram showing biosynthesis of HDL< Diagram showing biosynthesis of HDL

In contrast, LDL particles are involved in the uptake of cholesterol into tissue cells via a receptor-mediated process. A decrease in the number of LDL receptors on tissue cells has been linked to high circulating levels of plasma cholesterol. Decreased receptors means decreased cholesterol uptake and the raised LDL levels that ensue increase the risk of atheroma. About 20 years ago it was discovered that mutations in the gene that encodes the LDL receptor protein causes familial hypercholesterolaemia. In this condition there are high levels of LDL but tissue cells are unable to take up cholesterol from the blood. People affected by this mutation are at a much higher risk of coronary heart disease and stroke than other people (Brown 1984).

 

 

 

 

 

 

 

Several factors can influence the levels of circulating HDL (Scott, 1999). For example, there is a difference in levels between women and men: women have higher levels of HDL than men up until the menopause, and this offers them some protection against heart disease. Levels of HDL can also be increased by exercise, weight loss, moderate alcohol intake, and chemicals such as fibric acid derivatives, nicotinic acid, and tamoxifen.

References

I work as a health promotion nurse, mainly looking at prevention of CHD. I take a lot of fasting lipid profiles and am aware of the implications of raised LDL and low HDL, but our results always provide a total chol:HDL ratio. I can't seem to find a 'normal' or 'target' level/value for this or indeed anything to clarify the implications of this - should this be the 'treatable' figure rather than total cholesterol measurement as it is probably more realistic?

11th May 2005

Thank you for your interesting enquiry. The ratio of total cholesterol to HDL (high density lipoprotein) is considered to be a useful predictor of atherosclerosis and thus cardiovascular disease more generally. The number is obtained by dividing total blood cholesterol - HDL, low density lipoprotein (LDL), and very low density lipoprotein (VLDL) - by HDL, with higher ratios indicating higher risks of heart attacks, stroke, etc and low ratios indicating lower risk.

The total cholesterol/HDL ratio is not as accurate as the LDL/VLDL:HDL ratio, but the former is more commonly carried out because the total cholesterol is easier and cheaper to measure than the LDL and VLDL levels.

The reference values used in western industrialised countries differ slightly from one source to another, but the following table is probably representative:

Ratio of total cholesterol to HDL
Risk Level Females Males
Very low (50% average) <3.3 <3.4
Low 3.8 4.0
Average 4.5 5.0
Moderate (2 x average) 7.0 9.5
High (3 x average) >11 >23

You are right to think that the actual cholesterol values are probably more realistic than the ratio when it comes to treatment. The American Heart Association recommends that the absolute numbers for total blood cholesterol and HDL cholesterol levels be taken into account because they are more useful than the ratio in determining appropriate treatment for patients. It is probably best to view the total cholesterol:HDL ratio as a useful, practical, and cost-effective screening device to identify those people most at risk of cardiovascular disease, and then progress to more precise tests for those who will need treatment.

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