Like most healthcare practitioners, you may see patients concerned about elevated levels of blood fats (namely cholesterol and/or triglycerides), especially if their attention has been drawn to this from a recent test result. If you’re considering options to support these patients, you may find this article interesting, because it summarises the evidence for some commonly prescribed nutritional supplements for such individuals, in order to complement the medical interventions prescribed by the GP or lipidologist.
Here’s what a healthy serum lipid panel looks like (NHS reference ranges in mmol/L, 2022):
- Triglycerides (TG): 1.7 or below fasting, 2.3 or below non-fasting
- Total cholesterol (TC): 5 or less
- Low density lipoprotein cholesterol (LDL-c): 3 or less
- High density lipoprotein cholesterol (HDL-c): 1 or above in men, 1.2 or above in women
- Ratio of total cholesterol to HDL-cholesterol (TC:HDL-c ratio): as low as possible, greater than 6 being too high
Cholesterol is, of course, a vitally important molecule for cell membrane function, steroid synthesis, bile production and nervous system health. The liver makes LDL-c to carry the cholesterol around the body in order to perform these important roles; and after completion, the cholesterol is transferred to HDL-c to return it to the liver for excretion (see fig. 1). Note that other lipid-related particles are also considered important predictors of cardiovascular disease (CVD) risk, in particular the level of lipoprotein (a) – Lp(a) – and the ratio of apolipoprotein B to A-1 (The Apo B/Apo A-1 ratio[i]). These are not covered here because they are not typically measured by GPs and so they will less often be seen in practice.
[i] Apolipoproteins are surface proteins involved in lipoprotein metabolism, Apo B being found on the surface of all atherogenic lipoprotein particles – VLDL and all LDL sub-fractions, and Apo A-1 being found on HDL particles, which are anti-atherogenic because they carry cholesterol back to the liver.
Elevated cholesterol per se may not be damaging to health, providing there is sufficient HDL-c in circulation to carry the cholesterol from LDL-c back to the liver before it has a chance to oxidise and cause damage to arteries. Damage to arteries can lead to heart attacks, strokes and other cardiovascular (CV) issues. Hence the pattern of the relative blood lipids (such as the TC:HDL-c ratio) is more important than simply the level of TC (see Figure 1).
Figure 1: The process of cholesterol transport: Triglycerides from dietary fats and sugars are transported to the liver, where they are packaged, together with cholesterol, into LDL-c for transport around the body through the blood stream. After the cholesterol has fulfilled its role, it is transferred to HDL-c, which transports it back to the liver for excretion via bile.
Dietary supplements to consider
Here’s a selection of key nutritional supplements worth considering if your patient needs more than diet and lifestyle to support a healthy pattern of blood lipids. Note that diet and lifestyle are not covered in this article, because there is a plethora of information elsewhere on these crucial inputs for managing blood fats. Suffice it to say that a wholefoods, low glycaemic load, Mediterranean-style diet, high in brightly coloured plant foods, olive oil, oily fish, pulses and nuts/seeds is a good starting point; together with moves towards optimising sleep, physical activity, stress, a sense of purpose and good connections with people and with nature.
EPA + DHA
Despite some studies reporting null findings, a sizeable body of evidence suggests that blood levels of the long-chain omega-3 fatty acids EPA and DHA (from fish oil) are inversely related to the risk of total mortality and fatal CVD events.(1) In terms of blood lipids, a systematic review of 18 studies reported that using EPA/DHA at more than 2g/day lowered TG concentration (with DHA having a greater effect), increased HDL-c and, although there was no reduction in LDL-c, increased LDL particle size, making the LDL-c less atherogenic.(3)
Specific mechanisms of EPA and DHA in blood lipid health include inhibiting hepatic synthesis of triglycerides, increasing LDL’s resistance to oxidation, and supporting the functioning of LDL-c membrane receptors.(4) In fact, these fatty acids can be so effective that prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia.(5)
Dosages used in studies typically range from 0.5-1.8g/day, although higher dosages of 3-4g/day have been required for reducing elevated triglycerides. Increasingly, evidence is pointing towards aiming for a specific ‘Omega-3 index’ as being more useful than a ‘one-size-fits-all’ dosing approach. This requires determining the daily dosage according to the baseline status of cell membrane EPA and DHA for the individual. Studies suggest that individuals with more than 8% of their red cell membrane fatty acids comprising EPA and DHA may have a 90% lower risk of sudden cardiac death compared to individuals with an ‘index’ of less than 4%. It’s also worth knowing that the current European average is less than 4% and that a study of 3,500 people found that those at the optimal 8% and above were not only eating oily fish but were also supplementing EPA and DHA. The conclusion was so strong that the researchers went as far as recommending that the need for supplementation for most people should be reflected in institutional guidelines.(6)
CoQ10
Coenzyme Q10 is essential for the mitochondrial production of ATP, especially in busy organs like the liver and the heart. Although CoQ10 is an endogenous compound, the liver’s ability to synthesise it tends to reduce with age, such that by the age of 40, the heart typically gets less than 70% of the Q10 it was getting at the age of 20. There are many mechanisms by which supplemental Q10 may reduce the risk of CVD (such as modulating blood pressure and blood glucose control and inflammation) and in particular by supporting healthy blood lipids. For example, studies have reported Q10 to:
- Increase HDL-c through stimulation of the Apo A-1 gene;
- Work as an antioxidant within LDL-c, helping to prevent LDL-c oxidation;
- Exert antioxidant activity within cell membranes, supporting LDL receptor function.(7)
In human trials, Q10 has been shown to improve blood lipids. However, the specific lipid changes tend to be variable between different types of cohorts and different Q10 preparations and dosages. For example:
- A 2018 review of 8 trials reported significantly reduced total cholesterol and increased HDL-c but no change to TGs nor LDL-c in patients with coronary artery disease.
- Another 2018 review of 21 trials concluded CoQ10 significantly reduced TGs but not TC in patients with metabolic diseases.
- And another 2018 review of 7 trials reported CoQ10 reducing TC and LDL-c in patients with chronic kidney disease.(8)
It’s also worthwhile considering Q10 supplementation in individuals taking statin medication. This is because statins work by interrupting the hepatic mevalonate pathway. This pathway is responsible for both cholesterol and Q10 production, so interrupting it can result in a significant reduction in Q10.(9)
Most CoQ10 supplements are difficult to absorb because the molecule is so large. Studies with the best results have tended to use a form of Q10 that has been processed into a smaller and more bioavailable ‘snowflake-shaped’ molecule. It is this form, for example, that was shown to result a 43% reduction in cardiovascular death in a RCT of 420 heart failure patients(10) and a 54% reduction (together with selenium) in a RCT of 443 generally healthy ageing individuals.(11)
Red Yeast Rice
Red yeast rice is made by culturing rice with various strains of the yeast Monascus purpureus. Some preparations of red yeast rice are used in food products in Chinese cuisine, including Peking duck.
Red yeast rice has been referred to as ‘…the most effective cholesterol-lowering nutraceutical on the market’.This is due to the active component monacolin K, which works in a similar way to statins (blocking HMG-CoA reductase enzyme within the hepatic mevalonate pathway). Although red yeast rice is milder than synthetic statins, and tends consequently to be better tolerated, it is still worth supplementing CoQ10 alongside, in order to negate any potential depletion of this important cardiovascular molecule.
Red yeast rice has been reported to reduce LDL-c by 15-25% within 6 to 8 weeks. This reduction was also accompanied by a similar reduction in TC, non-HDL-c, ApoB and inflammatory markers (matrix metalloproteinases 2 and 9, and hsCRP). What’s more, this translated into improved markers of vascular ageing, measured as improvements in pulse wave velocity and endothelial function.(12)
Vitamin E
Antioxidants are important generally for cardiovascular health and vitamin E, being fat-soluble, has some good evidence for supporting healthy blood lipids.
In a study of 363 randomly chosen CVD patients, for example, a strong association was found between good levels of HDL-c and vitamin E. What’s more, the lower the vitamin E status, the higher the participants’ levels of TG, TC and LDL-c. The researchers concluded: ‘Vitamin E monitoring might be used as a useful prognostic and therapeutic agent in dyslipidemia disorder.'(13)
Kidney disease patients undergoing hemodialysis typically experience low levels of protective HDL-c. A study of 40 such patients has found that vitamin E (300mg/day) significantly improved HDL-c levels.(14)
Others to consider
Aged garlic, bergamot, resveratrol, niacin, plant sterols – all of these have some mechanistic evidence in managing blood lipids, so could be considered as an adjunct to, or in place of, the nutrients of focus in this article. The fact that each of us is unique, means that the efficacy of supplement combinations will vary between individuals. Sometimes it is only by trialling them, usually for a period of several weeks, that one can determine the best combination for any given individual.
It’s also crucial, of course, to get a full list of any pharmaceutical medications the patient is taking, to cross-check for any potential interactions between these medications and the supplements under consideration (avoiding any supplements with a listed potential interaction) and to advise the patient to keep their GP informed of the recommended supplements.
In summary, dyslipidaemia significantly increases the risk of CVD. Dyslipidaemia refers to imbalances in blood lipids, namely TG, TC, HDL-c, LDL-c and their ratios. Poor diet and lack of certain micronutrients are key modifiable influencers of blood fats. In addition, there are some key micronutrients evidenced to support healthy blood lipids, including EPA + DHA, CoQ10, red yeast rice and vitamin E.
by Lorraine Nicolle Nutr BANT MAAC RBAF – Acupuncturist, Registered Nutritional Therapist, Registered Nutritionist.
References:
[I] Apolipoproteins are surface proteins involved in lipoprotein metabolism, Apo B being found on the surface of all atherogenic lipoprotein particles – VLDL and all LDL sub-fractions, and Apo A-1 being found on HDL particles, which are anti-atherogenic because they carry cholesterol back to the liver.
[2] Jackson KH, Harris WS. Blood Fatty Acid Profiles: New Biomarkers for Cardiometabolic Disease Risk. Curr Atheroscler Rep. 2018 20(5), 2018, 22.
[3] Innes JK, Calder PC. The Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Cardiometabolic Risk Factors: A Systematic Review. International Journal of Molecular Science, 19(2) 2018, 532. doi: 10.3390/ijms19020532. PMID: 29425187; PMCID: PMC5855754.
[4] Sherratt SCR, Juliano RA, Mason RP. Eicosapentaenoic acid (EPA) has optimal chain length and degree of unsaturation to inhibit oxidation of small dense LDL and membrane cholesterol domains as compared to related fatty acids in vitro. Biochim Biophys Acta Biomembr. 2020 Jul 1;1862(7):183254; Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KH, Summerbell CD, Worthington HV, Song F, Hooper L. Omega-3 Fatty Acids for the Primary and Secondary Prevention of Cardiovascular Disease. Cochrane Database Syst Rev, 3(2), 29 February 2021: CD003177)
[5] Backes J, Anzalone D, Hilleman D, Catini J. The Clinical Relevance of Omega-3 Fatty Acids in the Management of Hypertriglyceridemia. Lipids Health Dis. 15(1), 22 July 2015, 118.
[6] Siscovick DS, Barringer TA, Fretts AM, et al. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. 135(15) 11 April 2017, e867-e884; Jackson KH, Harris WS (2018). Blood Fatty Acid Profiles: New Biomarkers for Cardiometabolic Disease Risk, Curr Atheroscler Rep. 20(5), 20 March 2018, 22; Jackson KH, Polreis JM, Tintle NL, et al. Association of Reported Fish Intake and Supplementation Status with the Omega-3 Index, Prostaglandins Leukot Essent Fatty Acids, March 2019, 142:4-10.
[7] Suárez-Rivero JM, Pastor-Maldonado CJ, de la Mata M, Villanueva-Paz M, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Suárez-Carrillo A, Talaverón-Rey M, Munuera M, Sánchez-Alcázar JA. Atherosclerosis and Coenzyme Q10, International Journal of Molecular Science, 20(20), 2019, 5195.
[8] Bakhshayeshkaram M, Lankarani KB, Mirhosseini N, et al. The Effects of Coenzyme Q10 Supplementation on Metabolic Profiles of Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials, Curr Pharm Des., 24(31), 2018, 3710-3723; Sharifi N, Tabrizi R, Moosazadeh M, et al. The Effects of Coenzyme Q10 Supplementation on Lipid Profiles Among Patients with Metabolic Diseases: A Systematic Review and Meta-analysis of Randomized Controlled Trials, Curr Pharm Des,. 24(23), 2018, 2729-2742; Jorat MV, Tabrizi R, Mirhosseini N, Lankarani KB, et al. The Effects of Coenzyme Q10 Supplementation on Lipid Profiles Among Patients with Coronary Artery Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials, Lipids Health Dis, 17(1), 2018, 230.
[9] Arch. Neurol., 61(6), 2004, 889-92.
[10] Mortensen S, Rosenfeldt F, Kumar A, Dolliner P, Filipiak K, Pella D et al. The Effect of Coenzyme Q 10 on Morbidity and Mortality in Chronic Heart Failure, JACC: Heart Failure, 2(6), 2014, 641-649.
[11] Alehagen U, Peter Johansson et al. Cardiovascular Mortality and N-Terminal-proBNP Reduced After Combined Selenium and Coenzyme Q10 Supplementation: A 5-year Prospective Randomized Double-blind Placebo-controlled Trial Among Elderly Swedish Citizens, International Journal of Cardiology, 2012.
[12] Cicero AFG, Fogacci F, Banach M. Red Yeast Rice for Hypercholesterolemia. Methodist Debakey Cardiovascular Journal, 15(3), 2019, 192-199.
[13] Barzegar-Amini M, Ghazizadeh H, Seyedi SMR, et al. Serum Vitamin E as a Significant Prognostic Factor in Patients with Dyslipidemia Disorders. Diabetes Metab Syndr, 13(1), 2019, 666-671.
[14] Mune M, Uto-Kondo H, Iteya I, et al. Vitamin E Supplementation Improves High-density Lipoprotein and Endothelial Functions in End-stage Kidney Disease Patients Undergoing Hemodialysis . Clinical Nephrology, 90(3), 2018, 212-221.
