"When your cholesterol is stuck - what then"

Professor Mark L. Wahlqvist AO, FTSE

BMedSc MD (Adelaide) MD (Uppsala) FRACP, FAIFST, FACN, FAFPHM
Chair, Australian Academy of Science Nutrition Committee
Director, Asia Pacific Health & Nutrition Centre, Monash Asia Institute, Melbourne, Australia

1. What does blood cholesterol represent?
2. How important is blood cholesterol alone?
3. Protection against CVD
4. Drugs versus lifestyle
5. When drugs fail, lifestyle still matters
6. Older and Newer drugs

1. What does blood cholesterol represent?
Cholesterol is one of several fats transported in the blood. Others are triglycerides, phospholipid and "free fatty acids". They all have to be linked to protein as "lipoproteins" since they will not otherwise dissolve in the plasma or serum. Most cholesterol is also actually linked, like other fats, to fatty acids which may be saturated, monounsaturated or polyunsaturated, and the polyunsaturated fatty acids, may be "omega 6" or "omega 3", sometimes called n-6 or n-3.

Lipoproteins not only carry fats, they also carry fat-soluble vitamins like the Vitamin A precursor carotenoids (and other carotenoids), and various forms of vitamin E. This means lipoproteins have many functions. These functions include cell membrane structure and related receptor and signalling activities, steroid hormone production and vitamin D production from cholesterol itself, provision of fuel for tissues from triglycerides (as important as glucose, especially for sustained activity), anti-oxidant and other vitamin functions through carotenoids and vitamin E. Some tissues like the brain and nervous system, and the eye, are very rich in "essential" polyunsaturated fatty acids (n-3 and n-6) which must be provided by plasma lipoproteins containing cholesterol.

The blood cholesterol comes from what we eat and what we make (in all cells, but especially in the liver). But actually factors other then cholesterol in the diet are more important than dietary cholesterol itself in determining the blood cholesterol, especially saturated fats from animal sources. Even here, if the animal is monogastric (has one stomach like us and pigs) rather than ruminant (sheep and cows), the animal fat type will represent what the animal eats, so it may be more or less favourable to health.

In the case of plant foods, the fat content may be accompanied by a host of other, often health-favourable compounds, depending on how refined or unrefined the plant item is. Generally nuts, seeds and grains are nutritious (nutrient dense) forms of fat, compared with refined products which are made from them. Another consideration is whether an unsaturated fat (especially polyunsaturated) has been hydrogenated and then becomes a significant source of "trans fatty acids" themselves capable of damaging arteries and causing thrombosis, and may increase the risk of diabetes.

We must have some blood cholesterol and the lipoproteins of which it is part, but not too much, because the excess can get into the inner artery wall, damaging and thickening it. This is more likely if the lipoprotein is oxidisable - and this in turn will depend on the rest of the lipoprotein molecule and what we eat to influence it. Fruits, vegetables and wholegrains provide anti-oxidant capacity in lipoproteins and are therefore in their own right as CVD protective foods.

There are also different kinds of lipoproteins when they are characterized by their density - very low (VLDL), low (LDL) and high (HDL). These have very different effects on the risk of cardiovascular disease (CVD). Put simply, the VLDL (which contains most of the triglycerides) and LDL which contain most of the cholesterol increase the risk of artery damage, and HDL decreases it (by providing a reverse transport system to take cholesterol back to the liver so that it can be excreted in the bile either as such or as bile acids. Thus, one's blood cholesterol may be increased, not by VLDL or LDL, but by HDL and this is a "good" rather than a "bad" thing.

2. How important is blood cholesterol?
Just measuring or managing the blood cholesterol is not the whole story in relation to heart disease, stroke, peripheral vascular disease (PVD) affecting the limbs, or other organ disease where arteries are damaged by accumulation of cholesterol (eg. kidneys, eye, penis). And this is without considering any more than the serum lipoprotein molecules that transport cholesterol between different tissues and dietary factors than affect these molecules.

There is much more to the cardiovascular disease because
(1) other factors make a particular lipoprotein disorder more or less risky. These include:
(i) diet in general and not just how it affects cholesterol containing lipoproteins
(ii) how physically active we are - this helps us "burn up" the triglycerides and reduce VLDL, and to increase HDL
(iii) whether we smoke, which affects not only lipoproteins adversely, but directly damages arteries.

(2) of our family history
- what may reflect genetic make-up, how our genes express themselves, and our behaviour

(3) of whether we have high blood pressure

(4) of whether we are prone to have diabetes or its precursor known as "impaired fasting glycaemia"

(5) of whether we are abdominally obese, because this represents fat which enters the liver circulation and stimulates lipoprotein metabolism, and increases the risk of diabetes and of hypertension (high BP)

(6) maternal nutrition, which affects the birth weight, and growth in the first year of life programme our genes for or against the risk of CVD especially when marginal nutrition is followed by a nutritional surfeit.

3. Protection against CVD (Cardiovascular Disease)
Food and beverage can provide considerable protection against CVD. But, there are a number of pathways that connect the way we eat to the risk of CVD and this knowledge encourages a more general nutritional approach to CVD protection.

This dietary approach includes:
(i) Food variety, especially of plant-derived food
(ii) Regular inclusion of fish (3-4 times/week) or its plant analogues for n-3 fatty acids (eg. linseed or flaxseed; rapeseed or canola)
(iii) Low fat ruminant meats or milk and milk products
(iv) Low sodium (Na+) (salt, MSG, sodium bicarbonate etc) intake, with a comparable molar intake of potassium (K+) as the Na/K ratio increases the risk of hypertension
(v) Not more than a modest alcohol intake as alcohol increases blood pressure, the risk of stroke and can displace other more nutritious foods from the diet.
(vi) Tea, whether black, oolong or green from Camelia Sinensis, the Chinese Camelia bush.

The physical activity approach to CVD protection requires special emphasis. It should be both aerobic, allowing endurance (eg. long walks) and strength (eg. gardening, cycling, swimming or weights for upper and lower body).

This has a favourable effect on potentially all known risk factors for CVD including mood (depression is a risk factor), insulin-resistance and diabetes, abdominal fatness, blood pressure and lipoprotein disorders.

Small cumulative and synergistic effects of food intake, physical activity and social activity (which in itself can prolong life) can outweigh single drastic measures, with their attendant risks, for single factors.

4. Drugs versus lifestyle
Lifestyle change provides an integrative and sustainable approach to CVD protection. The sum of the several factors exceeds that of its collective parts. Even for food, we know from studies of older people (FHILL, Food Habits in Later Life, and SENECA, Survey in Europe on Nutrition and the Elderly, a Concerted Action that an integral of food intake (rather than individual foods or nutrients) and an integral of lifestyle factors is a powerful way of prolonging life, even if one does not know what is happening to the blood cholesterol. Similarly, in the Lyon (French dietary intervention) study of de Lorgeril and colleagues in men with heart disease, even without changing the blood cholesterol, marked reductions over 4-5 years in coronary events and mortality, and in all cause mortality, were seen.

5. When drugs fail, lifestyle still matters
This is not to say that the blood cholesterol is unimportant and we now have powerful and highly selective drugs (the statins) to reduce the LDL cholesterol, with improvements in the LDL/HDL ratio. But sometimes, they cannot be used because of side effects, especially on liver and muscle.

And the quest for lower and lower LDL cholesterol is on, as other health problems increase, especially obesity and diabetes, as the need to intervene is greater. But these other body compositional and metabolic disorders also need to be dealt with in their own right not only because they adversely affect serum lipoproteins containing cholesterol, but also because otherwise the statins have limited efficacy on the endpoints of arterial, heart and cerebrovascular disease like stroke. The thing about lifestyle is that it tackles all of these problems at once and not just the LDL cholesterol.

It seems it is never too late to have recourse to lifestyle where CVD risk and high blood cholesterol levels are concerned - as the studies of older and of already affected individuals shows, even if the cholesterol level is unchanged.

6. Older and newer drugs
Increasingly, before the statins, which have indeed transformed blood cholesterol management, we had other, often awkward, medicinal approaches. The first of these back in the late 1950s was nicotinic acid (niacin or vitamin B-3) which is cheap and effective (for blood lipoproteins and for long-term survival), but has to be used several times a day and can produce flushing. The resins, like Questran (Cholestyramine) and Colestid (Colestipol), trapped cholesteroal and bile acids in the bowel for excretion, without themselves being absorbed. Fish oil consumption is also an established way to lower blood triglycerides.

The statins specifically reduce the formation of cholesterol in the body and, as a consequence, make the LDL Receptor (lock on the cell) which accepts and removes cholesterol from the circulation, more active (It is the recognition of LDL cholesterol by cells which may be impaired in many people).

Newer ways of reducing blood cholesterol are being explored, but it is arguable whether they will exceed the efficacy or safety record of the statins.

Other important mechanisms in arterial damage may be controlled with lifestyle (especially food) and drugs. These include:
(1) Inflammation in arteries with aspirin and related compounds (NSAIDS, non-steroids anti-inflammatory drugs). There are anti-inflammatory foods
(2) Arterial infection
Some evidence points to certain micro-organisms playing a role in arterial damage and cholesterol deposition. Foods play a role in maintaining and enhancing the body's defense mechanisms.

Over and above the arterial approaches, we already know that it is possible to reduce the susceptibility of organs (like the heart and kidneys) to reduction in blood flow. Here again fish (and n-3 fatty acids) play a role, for example, in reducing proneness to abnormal heart rhythms, like ventricular fibrillation, which cause sudden death - this is because the heart muscle membrane, enriched with n-3 fatty acids, is more electrically stable.

Conclusion
The blood cholesterol (and LDL) approach to CVD risk and management has been a major step forward. However a broader approach to the problem is warranted, very necessary where people struggle unsuccessfully or inadequately to correct their blood cholesterol, and reassuring where there are difficulties in lowering the blood cholesterol.

Last Updated: July 2003