HDL cholesterol: can you get too much of a good thing?

​If you've ever heard of high density lipoprotein (HDL) you probably know it as the ‘good cholesterol.’ It transports cholesterol from our body back to the liver, but unlike the name suggests, it has no causal link to heart health improvement, only associated benefits (1).

To test this association, a controlled drug trial was set up to artificially raise HDL (2) to hopefully lower the number of people dying from the worlds number one killer - cardiovascular disease. Unfortunately, ' the trial was terminated prematurely because of an increased risk of death,' quite the opposite of what they hoped for. Other trials have been completed which did not show any positive or negative overall impacts (3).

To add to this, individuals with genetically high HDL from birth also seem to have no protection from CVD (4) so HDL's impact may simply be neutral and is simply an association. ​A recent study looked at associations between HDL and all-cause mortality, interestingly they found a U shaped relationship (5). Meaning it may be similar to weight, too low or high and it causes problems. They summarised by stating that 'our results indicate that the common belief that, the higher the concentration of HDL cholesterol the better, does not hold.' It will be interesting to see if trials are completed to test this U shaped association.

As mentioned in previous posts, raised LDL levels causes atherosclerosis which is the narrowing of our arteries, high levels of it can even double our CVD risk (6). Research indicates the lower the level, the better (7). So what diets that people are currently following provide the greatest reduction in risk? 1. Vegetarian, 2. Pescatarian and 3. Omnivore (8).

So it seems our grannies were onto something when they encouraged us to eat our greens.

1) Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. Jama 2009;302:1993–2000.

2) Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B, Investigators I. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109–2122.

3) Keene D, Price C, Shun-Shin MJ, Francis DP. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. Bmj 2014;349:g4379.

4) Voight, B.F., Peloso, G.M., Orho-Melander, M., Frikke-Schmidt, R., Barbalic, M., Jensen, M.K., Hindy, G., Hólm, H., Ding, E.L., Johnson, T. and Schunkert, H., 2012. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. The Lancet, 380(9841), pp.572-580.

5) Christian M. Madsen, Anette Varbo, Børge G. Nordestgaard, Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies, European Heart Journal, Volume 38, Issue 32, 21 August 2017, Pages 2478–2486, https://buff.ly/2VtNADI

6) Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–e220. doi: 10.1161/CIR.0b013e31823ac046

7) J H O’Keefe Jr, L Cordain, W H Harris, R M Moe, R Vogel. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004 Jun 2;43(11):2142-6.

8) S G De Biase, S F Fernandes, R J Gianini, J L Duarte. Vegetarian diet and cholesterol and triglycerides levels. Arq Bras Cardiol. 2007 Jan;88(1):35-9.