How to Raise Your Cardioprotective HDL [Rev. 12-22-11, 04-18-12, 05-17-16]

Note: Revisions or additions are in red  font.

What is HDL?

HDL stands for high density lipoprotein and its importance in being a key player in preventing atherosclerosis (artery clogging) is more and more evident.[1],[16] It has even been seen that when LDL, (the ‘bad' or 'lousy' cholesterol), is very low, it is the HDL which is the deciding parameter on whether or not heart attacks (and other events) occur.[2] I, for one, am very insistent with my patients in raising this factor.

How does it work?

HDL promotes the mobilization and clearance of excess cholesterol via the series of reactions collectively termed ‘‘reverse cholesterol transport.’’[3] This is where cholesterol in the wall of the artery (and elsewhere) is removed before it is incorporated into the wall (or elsewhere) pathologically and irreversibly (it is a normal/natural constituent of cell structures and substances). Another mechanism cited is that HDL possesses many antioxidant capabilities, and thereby pre-empting the oxidation reactions inherent in development of atherosclerosis.[3] Another mechanism is HDL stimulates endothelial nitric oxide production and thence increases vasodilatation (opening up of blood vessels) and heart muscle blood flow. HDL also significantly impacts the capacity of inflammatory white blood cells to enter and take up residence in the sub-endothelial spaces of arteries.[4][5] This last factor is a probable player in removal of cholesterol molecules by engulfing them and removing them to safer dispositions.

My personal conviction is that the first phenomenon of reverse cholesterol transport is the most important one. There are other described mechanisms outlined in the figure which I won't go into.[6]

Conceptually from Figure 1 in reference [6]

The actual steps to take for increasing HDL are as follows:

• Increase healthy oils intake - olive oil, fish oil, coconut oil, butter and animal fats. Concerning the last two it applies to organic products and not those which come from animals enhanced by bovine growth hormones and whose products will contain supernatural levels of IGF (such as present in the USA). This last may be the factor which increases heart related events occurring in those consuming relatively high levels of animal fats in some people in the USA.[7] I say this because there is solid evidence that fat intake of animal origin is associated with lower cardiac mortality compared to the USA as in the French population[8] and the Eskimos[9]. Their food products are organic predominately. I (personally), target a 45% calorie quota for fats and oils of an overall calorie intake, and I emphasize the organic or natural status of said  fats. 45% is mid-way between the French and Eskimos.[8],[9] Here I would like to add that I use calories as a practical measure only, as the scientific basis of their translation into body energy is very shaky at this point in time (6-17-12, 5-17-16). 
• Increase low glycemic index foods – in other words avoid sugars (sucrose and high fructose corn syrup), and foods containing starch. This may also be described as a low-carbohydrate diet, with a relatively high consumption of fat and protein.[10]
• Fatty tissue weight loss if needed by controlling overall calorie intake as follows: if the person is at a healthy body mass index (BMI) then intake should be equal to calorie expenditure. If the BMI is high resulting from high body fat then intake should be less than expenditure. If the BMI is low then one should increase overall calorie intake.
• Engage in more aerobic exercise regularly, daily.[16]
• Tobacco and smoking cessation if applicable.[11],[16]
• Ensure intake of good quality protein (preferably animal origin that hasn’t been treated with bovine growth hormone – BST). Target a minimum of 1 gram per kilo body weight per day. This is because protein is a building block for HDL. As mentioned previously HDL stands for high density lipoprotein.
• With your physician’s consent and instruction – take niacin 500 – 2000 mg in the morning depending on how low your HDL is. This is also known as nicotinic acid. Be ready for the flushing and itching. This will occur 5 – 30 minutes after ingestion and happens in most people. Lasts around 10 – 45 minutes. Use the immediate release form. It is worth the flush. This medicine (which is also a vitamin) has been shown to decrease heart attack incidence. [6],[12],[13],[14],[15]
• Take vitamin C (ascorbic acid) as a supplement orally to the tune of 250 mg daily.[11],[17]
• Other agents are available that may raise HDL such as statins (unusually), fibrates and more novel agents in the pipe line[3]. That being said I am not too enthusiastic about all cholesterol ester transport protein inhibitors (CETP-I).[18] My lack of enthusiasm here is because of their mechanism of action. They work by essentially preventing HDL from reaching its end-point target environment, and as such will increase the level in the blood, but won't remove LDL. Bad idea. It astounds me how much money is being/was spent on developing such a non-nonsensical drug. 
• Of all current options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins [VLDL] and VLDL remnants), LDL-C, and lipoprotein(a). The European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L).[6] I prefer a target of 60 mg/dL or higher.

References:
[1] P Natarajan, KK Ray, CP Cannon (2010) High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol 55: 1283-1299. Doi:10.1016/j.jacc.2010.01.008.
[2] P Barter, AM Gotto, JC LaRosa, J Maroni, M Szarek, SM Grundy et alHDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events. N Engl J Med 357: 1301-1310.
[3] PT Peter (2009) Novel Therapies for Increasing Serum Levels of HDL. Endocrinology and metabolism clinics of North America 38: 151-170.
[4] X Li (2000) Protective effect of high density lipoprotein on endothelium-dependent vasodilatation. Int J Cardiol 73: 231 236. Doi:10.1016/S0167-5273(00)00221-7.
[5] B Levkau, S Hermann, G Theilmeier, M van der Giet, J Chun, O Schober et al (2004) High-Density Lipoprotein Stimulates Myocardial Perfusion In Vivo. Circulation 110: 3355-3359. Doi:10.1161/01.CIR.0000147827.43912.AE.
[6] MJ Chapman, G Assmann, JC Fruchart, J Shepherd, C Sirtori, European Consensus Panel on HDL-C (2004) Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C. Curr Med Res Opin 20: 1253-1268. Doi:10.1185/030079904125004402.
[7] TT Fung, RM van Dam, SE Hankinson, M Stampfer, WC Willett, FB Hu Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality. Annals of Internal Medicine 153: 289-298. Doi:10.1059/0003-4819-153-5-201009070-00003.
[8] MH Criqui, BL Ringel (1994) Does diet or alcohol explain the French paradox? Lancet 344: 1719-1723.
[9] H Bang, J Dyerberg, N Hjøorne (1976) The composition of food consumed by Greenland Eskimos. Acta Med Scand 200: 69-73.
[10] GD Foster, HR Wyatt, JO Hill, AP Makris, DL Rosenbaum, C Brill et al (2010) Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet. Annals of Internal Medicine 153: 147-157. Doi:10.1059/0003-4819-153-3-201008030-00005.
[11] J Hallfrisch, VN Singh, DC Muller, H Baldwin, ME Bannon, R Andres (1994) High plasma vitamin C associated with high plasma HDL- and HDL2 cholesterol. Am J Clin Nutr 60: 100-105.
[12] PL Canner, KG Berge, NK Wenger, J Stamler, L Friedman, RJ Prineas et al (1986) Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. Journal of the American College of Cardiology 8: 1245-1255.
[13] K. G. Berge1 Contact Information,P.L.Canner2 and Coronary Drug Project Research Group, (1) Mayo Clinic, 55905 Rochester, Minnesota,USA, (2) Maryland Medical Research Institute, Baltimore, Maryland,USA (1991) Coronary drug project: Experience with niacin. European Journal of Clinical Pharmacology: S49-S51; S49.
[14] JB Segal, J Eng, LJ Tamariz, EB Bass (2007) Review of the Evidence on Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism. Ann Fam Med 5: 63-73. Doi:10.1370/afm.648.
[15] Clofibrate and niacin in coronary heart disease. (1975) JAMA 231: 360-381.
[16] Anonymous Association of High-Density Lipoprotein Cholesterol With Incident Cardiovascular Events in Women, by Low-Density Lipoprotein Cholesterol and Apolipoprotein B100 Levels . http://annals.org/content/155/11/742.abstract. Accessed 12/22/2011 2011. 

[17] Jacques, PF. “Ascorbic acid, HDL, and total plasma cholesterol in the elderly.” Journal Of The American College Of Nutrition, v. 6 issue 2, 1987, p. 169-174.

[18] J Poss, M Bohm, U Laufs (2010) HDL and CETP in atherogenesis. Dtsch Med Wochenschr 135: 188-192. Doi:10.1055/s-0030-1247862.