HDL: What’s Optimal For Minimizing Disease Risk And Maximizing Longevity?

Meta-analysis for the association between HDL with all-cause mortality risk has identified HDL levels 55 – 60 mg/dL range as optimal. However, that data includes subjects up to 85y-in the video, I present data for 85y – 115yr olds that additionally suggests HDL in the 55 – 60 mg/dL range as optimal. In addition, I show my own HDL data over the past 15 years (n=34), the correlation for HDL with my diet, and how I plan on consistently increasing my 15-year average HDL of ~44 mg/dL to the 50’s.

9 thoughts on “HDL: What’s Optimal For Minimizing Disease Risk And Maximizing Longevity?

  1. Chicken Little

    I seem to have the opposite problem of too much HDL (ranging from 75-105 in US terms over 40 years, most recently 84mg/dL at age 71). For years doctors told me my HDL was so high that my total cholesterol “didn’t matter” (not that it was ever high). (I have only 1 recent hsCRP datapoint, which was .7, so not high, but not much of a correlation, either.) Recently, though, I read that there is such a thing as too much HDL, and these “all cause mortality” studies tend to confirm it.

    My efforts to find out more about the mechanism of harm in high HDL have not been wildly successful. But there does seem to be a distinction between people generally at low vs high risk of CVD. The Copenhagen and CANHEART studies on people at low risk showed much higher levels of HDL before non-cardiac causes of death kicked in…especially for women. By contrast, studies of people at higher risk of CVD events had elevated risk of cardiac events at lower thresholds of high HDL. https://www.uscjournal.com/articles/u-shaped-link-between-hdl-cholesterol

    So how does one lower HDL, anyway? It would be a pity to stop eating nuts, chocolate, ginger & turmeric, wouldn’t it? Even worse to stop drinking wine, exercising, or taking hormones? Is it too late to hope I can just outgrow it?

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    1. Michael Lustgarten Post author

      The reason that I focus on all-cause mortality is because if risk for CVD-related outcomes is reduced, but cancer (or other averse outcomes) risk is/are increased, is overall risk reduced? If terms of getting it closer to the ~55 mg/dL optimum, several other factors should be considered, including CRP, as you mentioned. Do you drink alcohol? That’s been reported to increase HDL.

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      1. Chicken Little

        You’ve certainly got me hooked on all-cause mortality as a sort of “first pass” way of focusing my attention. One can always drill down later on what seems to be happening at the outer ranges of the optimal mortality segment.

        In this case, I think CANHEART and Copenhagen seem to allow significantly higher optimal HDL levels–especially for women–for those otherwise at low risk of CVD: The CANHEART study which included >600,000 people age 55-105, did not find any increase in cardiac or non-cardiac events in women with HDL above 90 (for men, there was a slight uptick above 90 and the most common non-cardiac events are broken out). https://openheart.bmj.com/content/4/2/e000731 “The [Copenhagen] study also found excessive mortality for people with extremely low levels of HDL in the blood. The people with medium levels of HDL in the blood had the lowest mortality. For men, this level was 1.9 mmol/L. For women, it was 2.4 mmol/L.” 2.4 mmol/L equates to 93mg/dL https://www.sciencedaily.com/releases/2017/08/170823094124.htm FWIW both studies also raise questions about confounding and the appropriateness of regarding HDL as an independent indicator of cardiac health. They variously suggest LDL, TG or apolipo-A may be more telling.

        Meanwhile, yes, I agree alcohol intake is probably the most easily modifiable input for lowering high HDL…and may very well account for the higher readings I had at younger ages. It would be worth giving up wine for a few weeks before my next test to see if it makes a detectable difference.

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      2. Michael Lustgarten Post author

        That’s for the association between HDL with cardiac events, but our health isn’t that reductionist. What good is having a lower CVD-related mortality risk, but a potentially higher risk of other death? That’s why looking at all-cause mortality risk is more important than isolated outcomes, imo.

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  2. Chicken Little

    Of course, most people won’t care whether the lowest all-cause mortality risk HDL level is.54-58 as shown in the 2020 Zhong meta-analysis you discussed, or 93/ 2.4 mmol/L for women as shown (it clearly says “all-cause mortality” https://academic.oup.com/view-large/figure/99579397/ehx163f6.tif ) in the Copenhagen study I linked. The Copenhagen study does reference 2 other studies with lower values and speculates what might account for the difference: https://academic.oup.com/eurheartj/article/38/32/2478/3608700 But it’s good to know there is a range of data and opinion on this point.

    For better or worse, there could also be genetic factors in play. My siblings and one cousin who is built like us all have conspicuously high HDL, though we eat and drink differently. Our other cousins struggle with it like everyone else. Since I have recently ordered my whole genome, I may soon have more insight into how this actually bears on health risks.

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    1. Michael Lustgarten Post author

      Hey Chicken Little, you’re citing data from 1 paper, whereas in the video I cited meta-analysis data from 3+ million subjects (24 studies) that shows HDL ~60 mg/dLto be optimal for women. Do you have other data, like CRP, albumin, glucose, etc? I favor looking at the whole picture, rather than just 1 marker, HDL.

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  3. Chicken Little

    Of course…I have mountains of data, and foothills (at least) of papers. Being retired and seriously underemployed, several years ago I started looking at all my lab values (not just blood), and other biometric and performance data, as a “report card” to be improved upon…even though most people would consider me ridiculously healthy (BP 108/72, BMI 20.6 hsCRP .7, fGLU 4.6, Alb 38, e-GFR 79, proteinuria 0..and the biggest laugh RDW 11.7–until discovering phenotoypic age on your website I would never have known the significance…I actually had made a notation “low normal” to follow up!).

    Though not nearly as meticulous and disciplined as you about recording inputs, I had some early successes with raising my eGFR and urine pH, and have just gone from there. It probably was researching how to improve albumin that led me to all this wonderful and varied research you are doing and sharing on your website. I normally hate videos, but yours are among the most clear and succinct I have ever seen…on some very complex topics. I usually end up doing further research after seeing each one.

    OTOH, like most thin old ladies, I am also slipping slowly towards osteoporosis and sarcopenia in spite of my grudging efforts to become a late-life muscle builder. I don’t have much information on my microbiome or hormones, but I’m sure they’re important. As is sunlight and sleep. So blood markers are important, but perhaps they occupy a smaller portion of my dashboard. And genomics, when I get my report, is likely to push everything aside for awhile. But I understand that HDL is highly heritable, not only as to level but also as to particle sizes. Whether mine is pathological or protective is more likely to be revealed by my genome than by a meta-analysis of any size.

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