# Can HDL Cholesterol be TOO high? **URL:** \ **Category:** Factual Questions\ **Created:** [May 5, 2015, 3:26am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291 "2015-05-05T03:26:34Z")\ **Posts on this page:** 14\ **Page:** 1
**Author:** ![Enola\_Gay](https://avatars.discourse-cdn.com/v4/letter/e/3ab097/32.png) [@Enola\_Gay](https://boards.straightdope.com/u/Enola_Gay)\ **Post date:** [May 5, 2015, 3:26am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/1 "2015-05-05T03:26:34Z")
I first had my cholesterol tested in my 20s and my HDL was 92. I am 50 now and just got it tested again (hadn’t had a test since my 20s!). Anyway my numbers now are as follows: HDL 121, LDL 90, for a total of 211. My doctor thought it was great and said he’d never seen an HDL so high (he’s an internist not a cardiologist). I did some googling and found sites that said that HDL too high is a bad thing so now I’m confused. Is there a doctor or other expert in the house who can give me the straight dope? ---
**Author:** ![KarlGauss](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/karlgauss/32/3713_2.png) [@KarlGauss](https://boards.straightdope.com/u/KarlGauss)\ **Post date:** [May 5, 2015, 4:21am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/2 "2015-05-05T04:21:31Z")
By and large the only liability associated with having high levels of HDL cholesterol is that you’re liable to live to 100 (or more) so be sure to take care of yourself. In every study I’ve seen, there has been a clear and direct relationship between HDL level and longevity. Perhaps not too surprisingly is the consistent observation that people with high HDL levels are overrepresented in centenarians compared to people with lower HDL levels. I suppose there may be exceptionally rare variants where a person’s HDL is dysfunctional and not only doesn’t work as it should, but also resists being cleared out of the system (i.e. it would build up and cause high levels even though it wasn’t doing the usual good things that HDL is thought to do). I emphasize that such variants are RARE. How does HDL confer protection against atherosclerosis (and against other aspects of aging)? - HDL carries cholesterol away from the tissues and then to the liver for excretion from the body (this is the classic mechanism, so-called 'reverse cholesterol transport) - HDL cholesterol being elevated is in part an epiphenomenon, i.e. the HDL got so high by virtue of taking cholesterol away from LDL (and other cholesterol containing particles) - HDL may have on it various antioxidant (and possibly other protective) molecules - HDL elevation is usually associated with low triglyceride levels - HDL elevation may also be a marker for other, generally healthy factors e.g. non-smoking, non-obese, non-hyperinsulinemic, physically fit individuals ---
**Author:** ![Surreal](https://avatars.discourse-cdn.com/v4/letter/s/eada6e/32.png) [@Surreal](https://boards.straightdope.com/u/Surreal)\ **Post date:** [May 5, 2015, 5:05am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/3 "2015-05-05T05:05:41Z")
High HDL does appear to be associated with abnormal liver enzymes, even after adjusting for alcohol consumption: > **[Low LDL-C and High HDL-C Levels Are Associated with Elevated Serum...](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0085366)** > > Background Dyslipidemia, typically recognized as high serum triglyceride, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels, are associated with nonalcoholic fatty liver disease (NAFLD).... > [@](#): > > We examined the associations between alanine aminotransferase (ALT), aspartate aminotransferase (AST) and major components of serum lipid profiles in a nationally representative sample of 23,073 individuals, who had no chronic viral hepatitis and were not taking lipid-lowering medications, from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. ALT and AST exhibited non-linear U-shaped associations with LDL-C and HDL-C, but not with triglyceride. After adjusting for potential confounders, individuals with LDL-C less than 40 and 41–70 mg/dL were associated with 4.2 (95% CI 1.5–11.7, p = 0.007) and 1.6 (95% CI 1.1–2.5, p = 0.03) times higher odds of abnormal liver enzymes respectively, when compared with those with LDL-C values 71–100 mg/dL (reference group). **Surprisingly, those with HDL-C levels above 100 mg/dL was associated with 3.2 (95% CI 2.1–5.0, p\<0.001) times higher odds of abnormal liver enzymes, compared with HDL-C values of 61–80 mg/dL.** ---
**Author:** ![Enola\_Gay](https://avatars.discourse-cdn.com/v4/letter/e/3ab097/32.png) [@Enola\_Gay](https://boards.straightdope.com/u/Enola_Gay)\ **Post date:** [May 5, 2015, 6:10pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/4 "2015-05-05T18:10:25Z")
Well damn, I first read **KarlGauss** ’s post and rejoiced. Then I read **Surreal** ’s and now I’m back to being confused. FYI my liver enzymes were “normal”… so hopefully I’ll just live to be 100. But if anyone else would like to weigh in, I would appreciate it. ---
**Author:** ![KarlGauss](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/karlgauss/32/3713_2.png) [@KarlGauss](https://boards.straightdope.com/u/KarlGauss)\ **Post date:** [May 5, 2015, 9:30pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/5 "2015-05-05T21:30:29Z")
> [@Enola\_Gay](#): > > Well damn, I first read **KarlGauss** ’s post and rejoiced. Then I read **Surreal** ’s and now I’m back to being confused. FYI my liver enzymes were “normal”… so hopefully I’ll just live to be 100. Although there seems to be a link at a population level between high HDL and elevated liver enzymes, it’s worth noting that the elevation of the latter was very, very modest. Moreover, although called “live enzymes” in the study, the same enzymes are found in other tissues including muscle. So, for example, it is possible that some of the association between high HDL and high “liver enzymes” is really an association between high HDL and a minor degree of muscle inflammation - around the degree seen after vigorous exercise, an activity that leads to higher HDL (and thus which provides a possible mechanism for the association). Most importantly, even if the elevation in enzymes does reflect some degree of liver inflammation, the bottom line is that, on average, people with high HDL liver longer than those with lower levels. In other words, any putative liver abnormality associated with high HDL levels would seem to be of marginal, if any, clinical significance. ---
**Author:** ![Leo\_Bloom](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/leo_bloom/32/10377_2.png) [@Leo\_Bloom](https://boards.straightdope.com/u/Leo_Bloom)\ **Post date:** [May 6, 2015, 12:12am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/6 "2015-05-06T00:12:19Z")
I look forward to OP self-Zombie in 2064. ---
**Author:** ![Surreal](https://avatars.discourse-cdn.com/v4/letter/s/eada6e/32.png) [@Surreal](https://boards.straightdope.com/u/Surreal)\ **Post date:** [May 6, 2015, 12:38am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/7 "2015-05-06T00:38:45Z")
> [@KarlGauss](#): > > Most importantly, even if the elevation in enzymes does reflect some degree of liver inflammation, the bottom line is that, on average, people with high HDL liver longer than those with lower levels… That may be true for HDL levels of 50 or 60 mg/dl, but the OP has an HDL of **121**. It’s pretty silly to extrapolate the data to that extent. ---
**Author:** ![KarlGauss](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/karlgauss/32/3713_2.png) [@KarlGauss](https://boards.straightdope.com/u/KarlGauss)\ **Post date:** [May 6, 2015, 1:11am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/8 "2015-05-06T01:11:37Z")
> [@Surreal](#): > > That may be true for HDL levels of 50 or 60 mg/dl, but the OP has an HDL of **121**. It’s pretty silly to extrapolate the data to that extent. The Framingham study and its scientists may disagree with your characterization of an HDL level of 121 as “silly”. Specifically, Framingham data had the upper limit of HDL for men at 129 and, for women, at 139. ([CITE](http://atvb.ahajournals.org/content/8/6/737.full.pdf)). In any case, in the absence of evidence suggesting a deleterious effect of very high HDL levels (the “liver enzyme” cite above notwithstanding), and in the presence of a mountain of data linking high HDL to reduced atherosclerosis and to longevity, it does not seem unreasonable to extrapolate by saying that people with very high HDL levels, similar to those with merely high levels of HDL, are likewise at reduced risk of atherosclerosis. And, please note, I am not trying to say that acting to raise HDL levels (whether achieved by medical or non-medical means) confers a benefit. I am simply saying that I am unaware of evidence to suggest that very high HDL levels differ from merely high HDL levels in terms of health benefits. As always, I stand to be corrected. ---
**Author:** ![Surreal](https://avatars.discourse-cdn.com/v4/letter/s/eada6e/32.png) [@Surreal](https://boards.straightdope.com/u/Surreal)\ **Post date:** [May 8, 2015, 10:20pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/9 "2015-05-08T22:20:01Z")
Let’s back up for a minute here. The OP’s internest said that he’d never seen an HDL level so high. I don’t know how much experience the OP’s physician has, but right away that’s red flag. Extreme values (high or low) for any biomarker are more likely to indicate disease rather than superb health. Mortality curves are often “U” shaped. > [@KarlGauss](#): > > . Specifically, Framingham data had the upper limit of HDL for men at 129 and, for women, at 139. ([CITE](http://atvb.ahajournals.org/content/8/6/737.full.pdf)). Note that they lump a huge range of HDL values into the top quintile. For men the top quintile had an HDL range of 55 mg/dl all the way to 159 mg/dl. That’s from 0.75 standard deviations above the mean to 8.5 SDs above the mean. There’s insufficient data to make any specific claims about HDL levels higher than 3 SDs above or below the mean. If the OP is a male, his 121 HDL would be 5.7 SDs above the mean. If she is female, her HDL is 4.1 SDs above the mean. Extremely rare. From the Merck Manual: > **[Dyslipidemia - Dyslipidemia - Merck Manual Professional Edition](https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/dyslipidemia)** > > Dyslipidemia - Etiology, pathophysiology, symptoms, signs, diagnosis & prognosis from the Merck Manuals - Medical Professional Version. > [@](#): > > Elevated High-Density Lipoprotein Levels > > \*\*Elevated high-density lipoprotein (HDL) level is HDL cholesterol \> 80 mg/dL \*\*(\> 2.1 mmol/L). > > Elevated HDL cholesterol levels usually correlate with decreased cardiovascular risk; however,\*\* high HDL cholesterol levels caused by some genetic disorders may not protect against cardiovascular disease, probably because of accompanying lipid and metabolic abnormalities\*\*. > > Primary causes are single or multiple genetic mutations that result in overproduction or decreased clearance of HDL. Secondary causes of high HDL cholesterol include all of the following: > > \*\*Chronic alcoholism without cirrhosis > > Primary biliary cirrhosis > > Hyperthyroidism\*\* > > Drugs (eg, corticosteroids, insulin, phenytoin) > > **The unexpected finding of high HDL cholesterol in patients not taking lipid-lowering drugs should prompt a diagnostic evaluation for a secondary cause with measurements of AST, ALT, and thyroid-stimulating hormone** ; a negative evaluation suggests a possible primary cause. [http://atvb.ahajournals.org/content/15/11/1849.full](http://atvb.ahajournals.org/content/15/11/1849.full) > [@](#): > > Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state accompanied by a longevity syndrome. However, we reported the cases of markedly hyperalphalipoproteinemic subjects with juvenile corneal opacification. These patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities, and one of them has recently been identified to be homozygous for a missense mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP) gene. In the current study, to elucidate the clinical significance of and atherogenicity in marked HALP, we determined the incidence of atherosclerotic cardiovascular disease (ACD) in patients with marked HALP and characterized the lipoprotein abnormalities in those who had ACD, focusing especially on CETP and HTGL. The subjects were 201 patients (111 males and 90 females) with **marked HALP (≥2.58 mmol/L [100 mg/dL])**, 67% of whom were demonstrated to have the CETP gene mutations in the intron 14 splice donor site or in exon 15. Their mean age was 54±15 years. Plasma levels of total cholesterol, HDL cholesterol, and triglyceride in all subjects were 6.28±1.78, 3.15±0.90, and 1.08±0.53 mmol/L, respectively. Ten of the male patients (9.0%) and two of the female patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris, and peripheral vascular diseases. Ten patients with HALP who had ACD were identified to be heterozygotes for CETP deficiency. To further clarify the characteristics of marked HALP in patients with ACD, we compared the plasma lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP deficiency who were with and without ACD. There was no significant difference in plasma lipids, lipoproteins, and CETP between the two groups, whereas HTGL activities were significantly lower in the heterozygotes for CETP deficiency with ACD than in the heterozygotes without ACD and in control subjects. **These results suggest that marked HALP may not always be a beneficial state and that people who are heterozygotes for CETP deficiency and who have low HTGL may be susceptible to ACD**. ---
**Author:** ![Surreal](https://avatars.discourse-cdn.com/v4/letter/s/eada6e/32.png) [@Surreal](https://boards.straightdope.com/u/Surreal)\ **Post date:** [May 12, 2015, 1:03am UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/10 "2015-05-12T01:03:58Z")
> [@KarlGauss](#): > > In every study I’ve seen, there has been a clear and direct relationship between HDL level and longevity. You must have missed these: > **[High density lipoprotein cholesterol and longevity.](https://jech.bmj.com/content/42/1/60.short)** > > In the Twin Cities Prospective Study, executive men aged 45 to 55 and "healthy" at the entry examinations in 1948 were re-examined yearly to 1975. Follow-up through 1983 lost only one man. High density lipoprotein cholesterol (HDL) in the serum was... > [@](#): > > In the Twin Cities Prospective Study, executive men aged 45 to 55 and “healthy” at the entry examinations in 1948 were re-examined yearly to 1975. Follow-up through 1983 lost only one man. High density lipoprotein cholesterol (HDL) in the serum was measured in 1955 with a method checked with recent standard methods. Among 217 men, 130 were dead by 1983, 56 from coronary heart disease (CHD) and 27 from neoplasms. Survivors did not differ in mean HDL from the men who died but they had higher values than the men dead from CHD. Men dead from neoplasms had significantly higher HDL than men dead from CHD. Men dying early did not differ in HDL from those dying later but they had higher blood pressures. HDL was unrelated to age at death from all causes but was related to age at death from CHD. HDL was not related to age, total cholesterol, smoking, or respiratory function but was negatively correlated with measures of body fatness. Multiple regression and multiple logistic analyses showed no difference in HDL between survivors and men dead from all causes, but men dead from CHD tended to have lower HDL. **The data indicate that longevity is not related to HDL in middle age.** > **[HDL Serum Cholesterol and 24–Year Mortality of Men in Finland](https://academic.oup.com/ije/article-abstract/13/4/428/814884)** > > Abstract. Keys A (Laboratory of Physiological Hygiene, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA), Karvonen M J, Punsar > [@](#): > > Solution of the multiple logistic equation using all those variables found \*\*the probability of 24-year coronary death was not significantly related to HDL \*\*but was significantly related, positively, to the non-HDL cholesterol concentration. > [@KarlGauss](#): > > Perhaps not too surprisingly is the consistent observation that people with high HDL levels are overrepresented in centenarians compared to people with lower HDL levels. Perhaps but there are conflicting reports: [http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2001.4911234.x/abstract;jsessionid=76195DDB47A9AC4BB0C352FAED00B68F.f02t01?deniedAccessCustomisedMessage=&userIsAuthenticated=false](http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2001.4911234.x/abstract;jsessionid=76195DDB47A9AC4BB0C352FAED00B68F.f02t01?deniedAccessCustomisedMessage=&userIsAuthenticated=false) > [@](#): > > In comparison with older people, the centenarians had low concentrations of total and low-density lipoprotein cholesterol (LDL-C) and a relative predominance of high-density lipoprotein 2 cholesterol. No environmental factor, except the number of apo E ε2 alleles, was a significant determinant of LDL-C and apo B, suggesting that the low apo B–containing lipoprotein in centenarians may be attributable to a genetic cause. **Centenarians had elevated levels of lipoprotein (a) and decreased high-density lipoprotein cholesterol (HDL-C), which seem to be an unfavorable lipoprotein profile.** Lower levels of HDL-C in the centenarians were associated with decreased serum albumin, elevated CRP and IL-6 levels, and cognitive impairment, suggesting that HDL-C could be a sensitive marker for frailty and comorbidity in the oldest old. ---
**Author:** ![Surreal](https://avatars.discourse-cdn.com/v4/letter/s/eada6e/32.png) [@Surreal](https://boards.straightdope.com/u/Surreal)\ **Post date:** [November 4, 2016, 8:09pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/11 "2016-11-04T20:09:01Z")
A recent cohort study of over 600,000 Canadians demonstrates that I was right about the risks of high HDL and KarlGauss was wrong: [https://content.onlinejacc.org/article.aspx?articleID=2572335](https://content.onlinejacc.org/article.aspx?articleID=2572335) > [@](#): > > Results A total of **631,762 individuals** were included. The mean age of our cohort was 57.2 years, 55.4% were women, and mean HDL-C level was 55.2 mg/dl. There were 17,952 deaths during a mean follow-up of 4.9 ± 0.4 years. The overall all-cause mortality rate was 8.1 per 1,000 person-years for men and 6.6 per 1,000 person-years for women. Individuals with lower HDL-C levels were more likely to have low incomes, unhealthy lifestyle, higher triglycerides levels, other cardiac risk factors, and medical comorbidities. Individuals with lower HDL-C levels were independently associated with higher risk of CV, cancer, and other mortality compared with individuals in the reference ranges of HDL-C levels. **In addition, individuals with higher HDL levels (\>70 mg/dl in men, \>90 mg/dl in women) had increased hazard of non-CV mortality.** ---
**Author:** ![kayaker](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/kayaker/32/441_2.png) [@kayaker](https://boards.straightdope.com/u/kayaker)\ **Post date:** [November 4, 2016, 8:22pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/12 "2016-11-04T20:22:37Z")
> [@Surreal](#): > > A recent cohort study of over 600,000 Canadians demonstrates that I was right about the risks of high HDL and KarlGauss was wrong: > > [https://content.onlinejacc.org/article.aspx?articleID=2572335](https://content.onlinejacc.org/article.aspx?articleID=2572335) :eek: Don’t worry. I checked, and the OP posted earlier today. He lives on in open defiance of those 600,000 Canucks. ---
**Author:** ![Enola\_Gay](https://avatars.discourse-cdn.com/v4/letter/e/3ab097/32.png) [@Enola\_Gay](https://boards.straightdope.com/u/Enola_Gay)\ **Post date:** [November 4, 2016, 9:41pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/13 "2016-11-04T21:41:38Z")
Yes 17 months after that test, I’m still alive & kicking. FTR I’m female, so Surreal, please dumb it down for me. What non-CV events/diseases can kill me due to my high HDL? And is there a way to reduce your HDL? My diet mostly consists of lean meats, fish, & vegetables & I exercise almost every day. Should I eat less fish? I have an extremely healthy lifestyle (except for the booze I consume on weekends), so I’d like to live til 100 if at all possible. ---
**Author:** ![Surreal](https://avatars.discourse-cdn.com/v4/letter/s/eada6e/32.png) [@Surreal](https://boards.straightdope.com/u/Surreal)\ **Post date:** [November 7, 2016, 8:36pm UTC](https://boards.straightdope.com/t/can-hdl-cholesterol-be-too-high/719291/14 "2016-11-07T20:36:48Z")
> [@Enola\_Gay](#): > > And is there a way to reduce your HDL? My diet mostly consists of lean meats, fish, & vegetables & I exercise almost every day. Should I eat less fish? I have an extremely healthy lifestyle (except for the booze I consume on weekends), so I’d like to live til 100 if at all possible. I don’t think it’s the HDL itself that puts you at risk, more likely it’s just a marker of some type of underlying pathology. Similarly there have been a number of trials of drugs designed to raise HDL in people with low HDL in order to reduce cardiovascular events and none of them have worked. That said, once I found out that my HDL is in the high range (80-100 mg/dl, male), I cut back on foods high in lauric acid (coconut oil, palm oil, etc.) in order to keep my HDL down.