Cholesterol – a balanced view on a sticky topic

General Healthcare

  12 Minutes

Cholesterol is a waxy, fatty substance which is naturally found in our blood and in most of our cells. A large proportion is made ‘in-house’ in our livers, but we also consume it through our diet.

The cholesterol hypothesis and birth of the statins

The cholesterol hypothesis of cardiovascular disease has dominated medical opinion and has been universally accepted for decades. It claims that lowering fats/lipids in the circulatory system reduces the chance of developing cardiovascular disease and atherosclerosis, i.e. fatty build up in arteries leading to blockages, heart attacks and strokes.

Lovastatin was the first drug designed to lower cholesterol more than 40 years ago, marking the birth of a group of cholesterol lowering drugs known as the ‘statins’. Since then, a plethora of variations thereon have been developed, including simvastatin, atorvastatin, rosuvastatin and many others easily recognisable by the presence of the term ‘statin’ in their chemical name.

Recently published statistics from more than 83 countries confirm that the use of lipid modifying agents (LMAs) has increased between 2008 and 2018, from just more than 7,500 units per 1,000 people per year in 2008, to over 11,000 units per 1,000 people per year in 2018, of which statins being the most common form of LMA. In 2018 more than 173 million people are reported to have used these types of drugs.

The good, the bad and the ugly

Cholesterol and its role in the human body is commonly misunderstood. The narrative for decades has been simply that cholesterol is bad, it’s essentially something you don’t want, and the lower your level, the better. In reality however, cholesterol is no mistake, it’s actually a vitally important substance in human physiology; every cell requires it to function normally. Not only does it play an important structural role in cell membranes (we have 30 trillion of these, by the way) but it also facilitates transport of things in and out of our cells, signalling between cells, as well as playing a crucial role in nerve conduction in the nervous system. Most don’t know either that our brains are the richest source of cholesterol in our whole body. Our bodies also need cholesterol to make vitally important hormones such as oestrogen, testosterone and cortisol as well as other important things like bile and vitamin D.

Within our blood, cholesterol is transported around bound to carrier substances called lipoproteins. These fall generally into two categories, namely high-density lipoprotein cholesterol (HDL-C) i.e., ‘the good’ and low-density lipoprotein cholesterol (LDL-C), and ‘the bad’ cholesterol. The best way to remember which is which is ‘H’ stands for happy and ‘L’ stands for lousy! It’s the ‘lousy’ LDL-C which is the ‘bad’ cholesterol and thought to contribute to cardiovascular disease, the one that blocks arteries. The ‘happy’ HDL-C, on the other hand, is the ‘good’ cholesterol because it carries LDL-C back to the liver and is protective against cardiovascular disease.

So, who’s ‘the ugly’ then you might ask? It’s the triglycerides, another fatty substance which just makes things worse especially when LDL-C levels are high and HDL-C are low. It further increases the risk of blockages which can lead to heart attacks and strokes.

Types of Cholesterol

So, if you have elevated LDL-C, does this guarantee an increased risk? The answer may not be as cut and dry as we think. Newer types of tests can actually analyse how ‘bad’ your ‘bad cholesterol’ is, by measuring your LDL-C particle number (LDL-P), the particle size and whether or not the LDL has been negatively modified or not. This information can give us a better idea of how bad your individual LDL is and of course a better indication of your actual risk.

Ideally to reduce risk you want the lowest LDL particle number, the biggest particle size and as little modification of LDL as possible. This is because smaller, more densely packed particles of LDL can get into and block arteries easier than larger, fluffier counterparts, and when modified, they become even more risky. In fact, some research suggests that if your LDL is made up mostly of small dense particles, your risk of cardiovascular disease is up to 3 times greater even if your LDL is within ‘normal’ range!

So not all cholesterol is bad then, even some types of LDL-C are not as bad as we thought, and of course higher levels of HDL-C is actually considered protective and may even lessen the risk posed by elevated LDL-C. Later in this article we will discuss ways in which you can increase HDL-C levels (increase the good guys), and possibly try and make the bad LDL-C guys, well, less bad.

Testing cholesterol levels

The most common test done is called a Total Cholesterol test, this = HDL-C + LDL-C + 20% of triglyceride levels and gives a broad snapshot of cholesterol status. Now, if you have high HDL-C and normal LDL-C and triglycerides, you could still have an elevated total cholesterol level, which is certainly not a bad thing at all. Similarly, a ‘very high’ total cholesterol could be dominated by high HDL-C and less so by more modest amounts of LDL-C, making the total count not as ominous as it seems at face value. A Total Cholesterol test in isolation then is not sensitive enough to accurately define risk, and it’s even less reliable if it’s tested without fasting for 12 hours.

When your doctor orders a Lipogram/Lipid profile, however, the pathology lab measures HDL-C, LDL-C and Triglycerides and calculates Total Cholesterol. This gives a better reflection on the composition of the Total Cholesterol value. With this more detailed assessment you can calculate your cholesterol ratio, i.e. Total Cholesterol ÷ HDL-C (the ideal ratio is less than 3.5 : 1, the higher the ratio the higher the risk i.e. the more LDL-C dominates the total profile). A lipogram/lipid profile should always be done in a fasting state, i.e. nothing to eat from dinner the night before (+-12 hours) to be considered accurate.

So, you’ve had a lipogram and your LDL-C is elevated, pushing your total cholesterol to high levels, as a result of this you’re told you have too much ‘bad’ cholesterol. If possible, ask your doctor to measure your LDL particle size and density to give a more accurate idea of the actual risk. One example of this in South Africa is the LipidPro LDL test. If your LDL is mostly the large, fluffy type, you are less at risk.

Is cholesterol the ‘be all and end all’?

The risk of cardiovascular disease, i.e. strokes, heart attacks etc. from blocked arteries is far more complex than a simple cholesterol report. One must consider other very important contributing factors such as family history, blood pressure, smoking, stress, body weight, and very importantly the level of inflammation in your body.

More and more research is pointing to the fact that inflammation is as much, if not more, of a driver of cardiovascular disease than cholesterol. A test that helps determine this inflammatory risk is called a high-sensitivity C-reactive protein, i.e. hsCRP. This is a simple blood test available from all pathology labs but very seldom used or even mentioned to patients. Has your GP offered you this test? Some argue that this is an even more sensitive test to determine cardiovascular risk, and that life insurers should be using this as a far better predictor of risk than a good old cholesterol test.

If you are essentially healthy and non-diabetic, a useful tool to holistically calculate your cardiovascular risk is the Reynolds Risk Score. It’s a free online calculator designed to predict your risk of having a future heart attack, stroke, or other major heart disease in the next 10 years. To complete the calculation, you will need the following information:

  • Age (maximum 80yrs)
  • Gender
  • Smoker or not?
  • Systolic blood pressure (the upper number)
  • Total cholesterol value
  • HDL-C levels (good cholesterol)
  • hsCRP (mentioned above)
  • Parents history (heart attacks or strokes before age 60?)

Once you have all the data, plug it all in and press calculate!

Another useful test to ask about is a homocysteine test. High levels of this amino acid are also associated with heart attacks and strokes as well as other serious illnesses such as dementia. It’s worthwhile getting this done at some stage to see if this is not silently elevated in the background. The levels are easily lowered with good quality folic acid and B vitamins.

The controversy

Despite the dominant school of thought strongly linking high total cholesterol levels and LDL-C with cardiovascular disease and regarding it as the major contributing factor, recently more and more scientists have begun to challenge this decade-old doctrine leading to fierce debate on the topic and two camps strongly standing their ground. Essentially, the dissident camp suggests that cholesterol is not the ‘be all and end all’ or the root cause of cardiovascular disease i.e., it’s possibly not as much of a risk as it was previously thought to be, but rather one of many contributing factors, and that simply lowering these levels does not significantly reduce risk. In some recent articles researchers even directly challenge the validity of the historical evidence supporting the cholesterol hypothesis. We don’t take sides in this article but do encourage readers to make informed medical decisions, this means reading reliable sources of information and making up your own mind about this topic.

Here are some good quality journal articles on this controversy for bedtime reading if you are interested:

  • LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature – by Ravnskov et al. (2018) published in Expert Review of Clinical Pharmacology Journal.
  • Inflammation, not cholesterol is the cause of chronic disease – by Tsoupras et al. (2018) published in Nutrients Journal. https://www.mdpi.com/2072-6643/10/5/604

In many of these types of situations, the truth is somewhere in the middle. Blatantly disregarding cholesterol status would be irresponsible. Similarly, ignoring new diagnostic options and possible chronic inflammation in the body and focusing only on the cholesterol numbers would be a very short-sighted approach.

Managing cholesterol

If your main goal is to get the cholesterol numbers down, statin drugs work wonderfully. As with many chronic medications, however, these drugs are not side-effect free, and some patients do not tolerate them, especially at higher doses. As with most medical decisions, one must carefully weigh up the benefits versus the risks in discussion with your healthcare provider. Irrespective of whether you use statins or other LMA drugs, diet and lifestyle interventions should always be incorporated too. Many patients who go onto drugs like statins or diabetic medication fall into the trap of relying totally on medication and neglect to make any healthy lifestyle choices.

Whether you take statins or not, if your cholesterol levels are an issue creeping upward or you have a family history of cholesterol problems and cardiovascular disease, there are several evidence-based interventions through diet, complementary medicines and supplements you can use to holistically address the problem.

Lifestyle choices

It goes without saying that regular physical exercise is a must, specifically if you are overweight. This is key to the long-term management of cholesterol and cardiovascular health in general. Smokers, getting the diagnosis of high cholesterol is just another sign that you should quit!

Cholesterol modification and lowering inflammation through diet

The Lyon Diet Heart Study found that, in people who had had a previous heart attack, the Mediterranean diet reduced the risk of recurring heart disease by 50-70% compared to a simple low-fat diet. The Mediterranean diet was also 3 times more effective than statin drugs in preventing a second heart problem.

The Mediterranean diet is probably the most researched diet, with dozens of published studies on its benefits in various aspects of health, unlike many other fad diets which come and go, the evidence on this way of eating is impressive and continues to grow!

Mediterranean Diet

In this diet, most calories and protein come from plant-based foods (nuts, seeds, legumes, fruit and vegetables), and consumption of healthy fats in moderate amounts is permitted i.e. olive oil, nuts etc. Animal protein is limited to poultry and ideally, fish and red meat are very limited.

In addition to simply following the Mediterranean diet, you can do a little more by adding in the additional requirements described by the Portfolio Diet. This ‘bolt-on’ module in addition to the Mediterranean diet foundation is also science-based and has proven possibly as effective as 20mg of lovastatin i.e., it can reduce LDL-C by up to 30%.

Add in the following on top of your Mediterranean Diet foundation daily:

  • 30g almonds (+-23 almonds, raw unsalted).
  • 20g thick, sticky fibre from oats, barley, psyllium, linseeds etc.
  • 50g soy protein from tofu, soy products or soy milk (ideally non-GMO!).
  • 2g plant sterols available from health shops as a supplement or derived from avocado, soybeans, olive oil and green leafy veg.
  • Legumes daily (peas, beans, lentils etc.).

Looking for an anti-inflammatory diet? The good news is that a Mediterranean diet has you covered already.

The most pro-inflammatory foods are:

  • Sugar – the most inflammatory food!
  • Refined carbohydrates
  • Fizzy drinks
  • Processed foods and fast foods
  • Red meat and dairy (in excess)
  • Alcohol (in excess).

Some foods have also shown to favourably influence LDL-C particle number and size; these include:

  • Olive oil
  • Psyllium
  • Fish oils (EPA & DHA)
  • Flaxseed oil
  • Avocado
  • Strawberries
  • Nuts (pistachio, almonds, hazelnuts)
  • Turmeric
  • Plant sterols.
Herbal remedies

One of the most important herbs, also a food of course is good old garlic (Allium sativum). It’s shown to reduce total cholesterol and specifically triglyceride levels. There is also some research that confirms that artichoke leaf extract (Cynara scolymus) can significantly lower cholesterol levels. One study reported a reduction in LDL-C by 23% over 6 weeks of supplementation. A.Vogel Boldocynara contains an extract of fresh Artichoke leaf and is a Western herbal medicine which acts as a tonic to support the function of the liver, gallbladder, and digestive system. Supporting liver health is a good idea since most cholesterol is made ‘in-house’ by our livers.

Supplements for healthy cholesterol levels and cardiovascular health

There are various supplements which can lower cholesterol levels which are supported by scientific evidence. These include:

  • Red yeast rice extract – fermenting rice with a yeast called Monascus purpureus produces substances called mevinic acids which can lower the amount of cholesterol manufactured in the liver. The extract also contains other potential cholesterol-lowering agents like beta-sitosterol and isoflavones.
  • Niacin (vitamin B3) – has also been shown to reduce total cholesterol, triglycerides and LDL-C. The problem is, at the doses needed to do so, it can cause irritating hot flushes. Non-flushing options (inositol hexaniacinate) are available, but they may not be as effective as their flush-producing counterparts.
  • Essential fatty acids (EFAs) – specifically Omega 3 fatty acids from fish oil or flaxseed oil can lower cholesterol levels as well as reduce the risk of fatal heart attacks. Omega 3 supplements containing EPA and DHA at the correct dosages can also lower triglyceride levels. Fish oils and EPA/DHA have also been shown to increase LDL-C particle size and reduce levels of small dense LDL-C. Very important when it comes to fish oil supplements… don’t be tempted by the cheap and nasty special offers, this is one supplement you don’t cut corners on. Why? Because cheap fish oil will typically be of poor quality and could contain heavy metals which build up in predatory fish, particularly those not sourced from unpolluted waters. Buy the best quality you can afford and check labels about heavy metals and purification protocols or even simpler use a non-fish source of EPA and DHA such as the A.Vogel VegOmega3, a vegan source of Omega-3 essential fatty acids DHA, EPA and ALA which helps support and maintain normal heart and cardiovascular health and function.
  • Grapeseed extract has been shown in several studies to not only lower levels of oxidised LDL-C, but even lower other important makers like hsCRP and homocysteine. It also has the much-needed anti-inflammatory action and may offer a protective effect in blood vessel inflammation and protect against atherosclerosis.
  • Curcumin extracted from turmeric also has some good data confirming its positive effects on lipid profile, anti-inflammatory effects and cardiovascular protective action. It’s also been shown to reduce small dense LDL-C levels.
  • Berberine is a bioactive compound extracted from certain well-known medicinal plants, including Goldenseal and Oregon grape. Research confirms that it has various cardiovascular benefits, including the ability to lower LDL-C without affecting HDL-C, as well as lowering triglyceride levels. There is also some evidence which suggests that berberine might also favourably influence LDL particle number and particle size.
  • If you have high homocysteine levels, the best supplements are folic acid, specifically activated folate known as 5-Methyltetrahydrofolate (5-MTHF), B vitamins, specifically B12, B6, B2, N-acetylcysteine (NAC), Zinc, and trimethyl glycine (TMG). People with high homocysteine may be deficient in folate, zinc and B-vitamins or simply don’t absorb them properly. Bio-Strath contains 61 nutrients in a highly bioavailable format, meaning you absorb them much easier including B12, B6, B2, folic acid and zinc. It’s also shown to significantly increase the absorption of nutrients.
Other leads to follow up on

If you’re told your cholesterol is high, even more so if your HDL-C is too low and your triglycerides too high, this may be a clue that you have something called metabolic syndrome. Simply lowering cholesterol or taking a blood pressure pill is not enough to combat this properly. Metabolic syndrome is a combination of some of the following (not necessarily all):

  • Abnormal lipid profile (classically high LDL-C, low to normal HDL-C, and raised triglycerides).
  • Borderline to high blood pressure.
  • Overweight, specifically carrying weight around the belly.
  • Insulin resistance (high fasting insulin levels).
  • A fatty liver.
  • Prone to gout.

Metabolic Syndrome

Sluggish or declining thyroid function may also negatively affect the lipid profile. Have your thyroid checked and compare levels with historical data to see if this is the case.

In a nutshell then

Despite the controversy, high cholesterol should not be ignored, it’s one of many factors which can lead to cardiovascular disease, but it should not be the only factor you tackle if you want to avoid illness. Get properly assessed to gain a holistic view of your actual cardiovascular risk and know where you stand, and then take a holistic approach. Medication is not the only answer here and should not be relied on solely. Make healthy lifestyle and dietary choices and explore some of the many evidence-based complementary approaches. To find an integrative doctor who can assist, visit the South African Society of Integrative Medicine (SASIM) and find a doctor in your area.

  Listen to the podcast here: Cholesterol podcast

Reference

  1. Anjom-Shoae, J., et al., Effects of grape seed extract on dyslipidaemia: a systematic review and dose–response meta-analysis of randomised controlled trials. British Journal of Nutrition, 2020. 124(2): p. 121-134.
  2. Asbaghi, O., et al., The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials. Phytother Res, 2020. 34(2): p. 239-253.
  3. Bundy, R., et al., Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: A randomized, double-blind placebo-controlled trial. Phytomedicine, 2008. 15(9): p. 668-675.
  4. Blais, J.E., et al., Trends in lipid-modifying agent use in 83 countries. Atherosclerosis, 2021. 328: p. 44-51.
  5. Doggrell, S.A., Berberine–a novel approach to cholesterol lowering. Expert Opin Investig Drugs, 2005. 14(5): p. 683-5.
  6. Engelhart-Jentzsch, K., I. Schlöffel, and S. Winter, Plasmolysed herbal yeast (Strath®) improves micronutrient bioavailability – An in vitro study using Caco-2 intestinal epithelial cells. AgroFOOD Industry Hi Tech, 2018. 29(2).
  7. Fallah Huseini, H., S. Kianbakht, and R. Heshmat, Cynara scolymus L. in Treatment of Hypercholesterolemic Type 2 Diabetic Patients: a Randomized Double-Blind Placebo-Controlled Clinical Trial. Journal of Medicinal Plants, 2012. 11(41): p. 58-65.
  8. Fatima, K., et al., Mediterranean Diet and its Effect on Endothelial Function: A Meta-analysis and Systematic Review. Irish Journal of Medical Science (1971 -), 2022.
  9. Jenkins, D.J.A., et al., Effects of a Dietary Portfolio of Cholesterol-Lowering Foods vs Lovastatin on Serum Lipids and C-Reactive Protein. JAMA, 2003. 290(4): p. 502-510.
  10. Kong, W., et al., Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nature Medicine, 2004. 10(12): p. 1344-1351.
  11. Kris-Etherton, P., et al., Lyon Diet Heart Study. Circulation, 2001. 103(13): p. 1823-1825.
  12. Lippi, G., C. Mattiuzzi, and G. Cervellin, Statins popularity: A global picture. Br J Clin Pharmacol, 2019. 85(7): p. 1614-1615.
  13. Panchal, S.K. and L. Brown, Cholesterol versus Inflammation as Cause of Chronic Diseases. Nutrients, 2019. 11(10): p. 2332.
  14. Ravnskov, U., et al., LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature. Expert Rev Clin Pharmacol, 2018. 11(10): p. 959-970.
  15. Rui, R., et al., Effects of Berberine on Atherosclerosis. Frontiers in Pharmacology, 2021.12.
  16. Silagy, C.A. and A. Neil, Garlic as a Lipid Lowering Agent—A Meta-Analysis. Journal of the Royal College of Physicians of London, 1994. 28: p. 39 – 45.
  17. Talebi, S., et al., The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review. Lipids in Health and Disease, 2020. 19(1): p. 66.
  18. Tang, C., et al., Mediterranean Diet and Mortality in People with Cardiovascular Disease: A Meta-Analysis of Prospective Cohort Studies. Nutrients, 2021. 13(8): p. 2623.
  19. University of Wisconsin – Dept. Family Medicine. 2012. Non-drug Ways to Promote Health by Lowering Cholesterol. [Online] Available: https://www.fammed.wisc.edu/files/webfm-uploads/documents/outreach/im/module_lowering_cholesterol_patient.pdf
  20. Warshafsky, S., R.S. Kamer, and S.L. Sivak, Effect of garlic on total serum cholesterol. A meta-analysis. Ann Intern Med, 1993. 119(7 Pt 1): p. 599-605.