The new BMJ review of high cholesterol and mortality in the elderly


High cholesterol ‘does not cause heart disease’ new research finds, so treating with statins a ‘waste of time’ – or at least that’s the headline in the UK papers following the Just published paper in the BMJ . This, the latest study to question the established view that high cholesterol is always a bad thing, looked at the relationship between serum LDL-cholesterol and mortality in observational studies of people aged 60 and older

“We identified 19 cohort studies including 30 cohorts with a total of 68 094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.”[1]

In other words, in free-living populations without pre-existing disease, higher LDL-cholesterol predicts a lower risk of death in those over 60, and (with more limited evidence) does not predict an increased risk of death from heart disease or stroke.

This has been known for a long time – this review, which collated these studies for the first time, should not have been controversial. To be more exact, it has been known for a long time that higher levels of total cholesterol are protective in the elderly, and this knowledge predates the use of statins (which, if they are given to elderly with high cholesterol, and do prevent heart attacks, have been proposed as a confounder). Data about LDL-cholesterol levels in the elderly is more recent in most cases, and that is specifically what this review investigates.

The results are not just academic; old people are medicated, and are fed poorly in rest homes and hospitals, on the premise that high cholesterol is bad for them and everything must be done to lower it if it is high. As Professor R.D. Feinman says, “remind me again why we have a medical literature?” – because it’s obviously not there so that anyone can learn from it!

The latest review was published in the UK. Meanwhile the reigning monarch, Queen Elizabeth II, now 90 years old, remains healthy and hard-working on a completely different diet to that recommended and fed to her elderly subjects. She likes her food cooked in butter and cream, eats meat regularly, and skips the carbs.


Her Majesty knows what’s good for her – LCHF!

Criticisms of the study

So, how solid is the latest review? Are there other explanations for the correlations, or lack thereof? The Committee for Evidence Based Medicine launched an attack on Ravnskov et al’s review when it was published, in the form of a post-publication peer review. This is worth reading as it gives insights into possible confounders and errors in interpretation.
Yet it does not really disagree with the evidence or refute or overturn the conclusions.
The main issues are:

Limitations of the study: the search was restricted by being limited to PubMed and English-language publications.

Our response: PubMed is a large data resource, and as can be seen the search turned up many relevant studies. It is not usual to include foreign-language papers in, for example, Cochrane collaboration meta-analyses. The search also retrieved the references from the papers found, a process which would have turned up most of the relevant papers stored outside the PubMed archive.

The limitations of the review are probably related to the limited resources available for research which is merely a matter of public interest.

HDL cholesterol: “only three out of the 19 included studies appear to have controlled for HDL-C level in their analyses. It is highly possible that the observed inverse association for LDL-C and mortality is entirely mediated by a high HDL-C in the included cohorts.”

Our response: the 3 papers that controlled for HDL all found that high LDL-C was significantly associated with reduced mortality.

Statins: “The issue is that those who have high LDL-C are much more likely to be prescribed statins during the period of observation than the low LDL-C group. This would lead to an overall protective effect in the group with high LDL-C, making it appear that LDL-C is correlated with reduced all-cause mortality, when, in fact, it may be the effect of statin therapy.”

Our response: observational studies showing a protective effect of high cholesterol in the elderly date from before the statin era. Statins are expected to reduce cardiovascular mortality; there is no evidence from RCTs that they reduce death from other causes. It is total mortality, not cardiovascular mortality that is most strongly negatively associated with serum LDL-C in this review.  Of the three studies we found in Ravnskov et al. that controlled for statin use, two found a strong protective effect of higher LDL-C and one found no association, a pattern typical of the review as a whole.

Data extraction errors: The reviewers identified a small number of data extraction errors. Unfortunately these are common occurrences; almost all the diet-heart meta-analyses, for example, contain such errors. Hopefully the errors in this review can be corrected. However, using the correct figures does not alter the conclusions of the review.

The CEBM review asks us to reject the conclusions of Ravnskov et al, but fails to supply alternative evidence to support a different conclusion.

More insight:

We pulled up at random one of the studies used in Ravnskov et al’s review to see whether it gives more insight into lipids and risk. This study followed people 50+, so may be of interest to more readers.[2]

Bathum L, Depont Christensenc RD, Engers L et al. Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease: A population-based register study. Scandinavian Journal of Primary Health Care. Volume 31, Issue 3, 2013. full-text:  DOI:10.3109/02813432.2013.824157

Objective. This study aimed to investigate the association of lipoprotein and triglyceride levels with all-cause mortality in a population free from diabetes and cardiovascular disease (CVD) at baseline. The European Guidelines on cardiovascular disease prevention state that in general total cholesterol (TC) should be < 5 mmol/L (190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) should be < 3 mmol/L (115 mg/dL).

Design. A population-based register study in the period 1999–2007 including 118 160 subjects aged 50 + without statin use at baseline. All-cause mortality was related to lipoprotein and triglyceride levels and adjusted for statin use after inclusion.

Results. All-cause mortality was lower in the groups with TC or LDL-C above the recommended levels. Compared with subjects with TC < 5 mmol/L, adjusted hazard ratios for the group aged 60–70 years ranged from 0.68 (95% confidence interval (CI) 0.61–0.77) for TC 5–5.99 mmol/L to 0.67 (95% CI 0.59–0.75) for TC 6–7.99 mmol/L and 1.02 (95% CI 0.68–1.53) for TC ≥ 8 mmol/L in males and from 0.57 (95% CI 0.48–0.67) to 0.59 (95% CI 0.50–0.68) and 1.02 (95% CI: 0.77–1.37) in females. For triglycerides, ratios compared with the group < 1 mmol/L in the females aged 60–70 years ranged from 1.04 (95% CI 0.88–1.23) to 1.35 (95% CI 1.10–1.66) and 1.25 (95% CI 1.05–1.48) for triglycerides 1–1.39 mmol/L, 1.4–1.69 mmol/L, and ≥ 1.7 mmol/L, respectively. Statin treatment after inclusion provided a survival benefit without correlation to cholesterol level.

Conclusion. These associations indicate that high lipoprotein levels do not seem to be definitely harmful in the general population. However, high triglyceride levels in females are associated with decreased survival.


In Bathum et al, higher LDL-cholesterol is associated with lower mortality in all age groups over 50.

Our comment: Bathum et al was a study of a Danish population, and the Danes have access to good quality dairy and other animal foods. Thus higher LDL-C, in as far as this has anything to do with diet, may mainly distinguish the well-fed from those subsisting on the ersatz concoctions of the budget food industry. Very high HDL was not protective in “younger” men, but this is something you mainly see in those drinking lots of alcohol. This research does not suggest that the lipid patterns associated with LCHF diets (low TG, high HDL, moderate or high LDL-C) will lead to an increased rate of mortality as people age (which is, of course, when most mortality occurs).

So in the end, we will go with the British headlines – yes High LDL cholesterol isn’t a problem in normal older people – unless it’s low! There are a group of epidemiologists, and nutrition scientists in New Zealand and around the world, who have based their whole career around the idea that high LDL cholesterol is a problem.  What do you have to say?

And, the queen got at least one thing right – low carb.


[1] Ravnskov U, Diamond DM, Hama R. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open 2016;6:e010401. full-text: doi:10.1136/bmjopen-2015-010401

[2] Bathum L, Depont Christensenc RD, Engers L et al. Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease: A population-based register study. Scandinavian Journal of Primary Health Care. Volume 31, Issue 3, 2013. full-text:  DOI:10.3109/02813432.2013.824157




  1. christine mccarthy · · Reply

    what are you trying to say….that we are elderly On 14/06/2016 4:12 pm, “The Science of Human Potential” wrote:

    > puddleg58 posted: ” High cholesterol ‘does not cause heart disease’ new > research finds, so treating with statins a ‘waste of time’ – or at least > that’s the headline in the UK papers following the Just published paper in > the BMJ . Its the latest study to question the establi” >

  2. It’s a good question – what does this say, if anything, about risk in younger people?
    IMO cholesterol in young people is a little more likely to be affected by risks the young are exposed to (like high sugar diets, trans fats, smoking, infections, workplace toxins like lead or PCBs); and people who make it to old age were exposed to less of these things or move away from them as they grow up and take fewer risks.
    However, what you do find is that mortality increases with age; and age, even though it’s a continuous variable, is used as a risk factor in heart disease calculations. So old age is where more people are likely to be treated according to cholesterol numbers; so that’s where it’s most important to get their meaning right.

    1. I agree George, high LDL in younger people presents an indicator of some small CVD risk, but why? Is eating less butter the solution? I doubt it because of the ApoA v ApoB debate. Its probably LDL pushed up as a poor lifestyle choice and ApoB is well up.

      1. That’s right Grant, if we look at the epidemiology of butter and dairy saturated fats there’s no evidence of CVD risk, yet these fats are supposed to elevate LDL.
        Insulin resistance can elevate LDL because insulin downregulates the ApoCIII gene (ApoCIII makes LDL more persistent) although LDL hyperlipidemia is not usually seen in IR syndromes, and low LDL may predict them.
        This might explain why LDL does rise in a minority on insulin-lowering diets – they’re maybe too effective in some cases!.
        Malcolm Kendrick (an author of Ravnskov et al) has recently proposed that not only short-term cardiovascular risk (which is relatively uncontroversial), but also the underlying pathology, is a clotting disorder.
        Sugar is well known to increase clotting, the Mediterranean diet (polyphenolic antioxidants, fish oil omegas, etc) to decrease it. As do statins.
        Guess what – a standard lipid-lowering diet doesn’t help.
        Kendrick’s hypothesis matches well with the list of things that harm, and of things that help. The LDL hypothesis doesn’t match so well. For example, the effect of statins is independent of their effect on the LDL level; aspirin has no effect on LDL, vitamin D and fish oil can raise LDL, dairy raises LDL but has no effect on risk (and in some studies slight benefit).
        Diabetes is, of course, a “hypercoagulable state”.

  3. What about the under-60’s? What do we know for this group?

    1. Hi David,

      See the Danish paper in the post for 50+ in that country – but in most studies the cut-off for total cholesterol benefit is higher. See my response to Jeffry Gerber as to one explanation for the difference.
      In middle age, LDL-C is an independent risk factor, but is often modified to insignificance when adjusted for HDL, TGs, HbA1c, insulin, and so on.
      There are a few studies of lipid-lowering medicines in heart disease patients which show that a) there is a cardiovascular risk benefit from lowering LDL-C in these populations, b) those individuals with highest HDL (and lowest TG) at baseline have lowest risk, c) individuals with highest HDL at baseline do not gain extra benefit from intensive LDL-C lowering. As we are talking about baseline HDL and TGs, this is not the level as affected by drugs (drugs that increase HDL are not usually beneficial), but is a sign of metabolic good health, which may relate to diet, exercise, and other environmental and lifestyle factors.

      1. thanks – especially also for the additional links. Very helpful.

  4. Thanks George. The findings demonstrate the higher LDL-C serves as an associated marker for decreased all cause mortality in the elderly. I think it’s important to mention that this is not necessarily a cause and effect phenomenon. The higher LDL-C wasn’t necessarily making them live longer, but simply associated with good health and longevity.

    1. That’s exactly right IMO Jeffry – the proposed mechanism of LDL-C being involved in immune defense is plausible, but would only account for a small part of the mortality difference, though perhaps a slightly larger proportion as age increased, as we do see.
      My guess is that higher LDL-C is a marker of more robust liver and endocrine function, and is thus associated with lower HbA1c (this is the case in Framingham, where high LDL has a highly protective association with future diabetes diagnosis), very low or no risk of serious liver disease (seen in Japan), and likely lower outputs of TG-VLDL.
      However in younger people very high LDL can also be the result of (e.g.) a pathology (such as hypothyroidism), chronic toxic exposures, or of genetic factors, all of which can be atherogenic or otherwise life-shortening, so we see this age-related gradient, which varies between populations.

  5. Brilliant George. Thanks for your additional thoughts.

  6. Maguerita Zondagh · · Reply

    Sorry doctors, you people never ever look at the best guinea pig of all. WE the ones with heterozygous Familial hypercholesterolemia. So my son at 34 got QUINTUPLE bypass surger. Other son al has disease. The women have longevity (my mom with total chol of 13 is now 85). I went onto extreme KETO and ppl though I wld drop dead any moment and my cholesterol plunged to normal (though I DO take fibrates – with statins my family all get rhabdomyoleses within the week). But my boys are at massive risk. WHY NOT WORK ON US then you will know all these things for sure. I took a chance and ate serious animal fat 70% a day on a cholesterol of 13 and something wonderful happened. Only my GP was impressed – said the blood doesn’t lie. Tell my cardiologst who was quite furious and thought I was being obtuse.

    1. Thanks very much Maguerita,
      Ufe Ravnskov who wrote the BMJ review has discussed the paradoxes of FH in some detail; I only know a little about this, but a couple of things you mention stand out.
      Why do you get rhabdomyolysis so quickly on statins?
      LDL-C particles carry not only cholesterol but also fat-soluble antioxidants and vitamins, including co-enzyme Q10. FH is caused by lack of LDL-C receptors; because these are missing from liver cells, and most LDL-C is taken up by the liver, FH causes very high levels of LDL-C to persist in the blood. These then oxidise (due to sugars and pro-oxidants and the presence of linoleic acid in LDL, something that statins decrease), and become atherogenic (are taken up by macrophages which accumulate in coronary artery lining).
      However, liver cells are not the only cells to have LDL-C receptors; the cells that line the blood vessels also have them, and there are LDL-C receptors in human skeletal muscle.
      This means that FH reduces the availability of cholesterol, COQ10, and other antioxidants from the blood. Generally this shouldn’t be a problem with regard to cholesterol and CoQ10 as cells can make these – but statins will inhibit the ability of cells to make their own, making them more dependent on the supply from LDL-C – which FH cells don’t have access to. So this might be the explanation for the risk of rhabdo.
      Why do males have higher risk from FH?
      I am not an expert in FH and it may be that genetic factors of FH are expressed differently between the sexes. However, if FH is a condition where LDL-C particles are over-exposed to oxidation, the difference in iron levels between men and women, due to both menstruation and the effects of testosterone vs estrogen, might explain some of the difference in outcomes.
      “Our results highly support the concept that the genetic mechanisms driven to hypertriglyceridemia also favor iron overload.”
      Iron overload can be diagnosed with a ferritin test, and treated easily by blood donation. You would want to get ferritin under 100 if possible, 50-80 would be ideal.
      These are just ideas and I am only a researcher, but hopefully we can get some clinicians on this thread with more knowledge and experience.
      Kudos to you for testing the effect of diet on yourself. The blood doesn’t lie – love it!

  7. Hi Mageurita,

    my friend is a geneticist and has sent me some comments about how a keto diet would affect FH

    “A person with heterozygous FH has about ~50% of the LDL-receptor on their cells.

    Keto forces lipid, the second fuel, to become the first fuel. So during the chylomicron phase much of the lipid is drawn off and is processed directly by lipoprotein lipase, etc. The upshot is that in many cases, much less lipid needs to be processed by the liver into VLDL. This can be confirmed by looking at the levels of TG. Consequently, much less apoB-100 is secreted and so there is much less of a burden on the LDL receptor to process LDL particles, and consequently there is less LDL particles that become old sick and oxidized.
    The goal is to decrease apoB.

    Chylomicrons (fat as it appears in the blood after being absorbed by the gut) have apoE so they are processed more speedily than LDL by the LDLR. It means the liver will process a chylomicron before it processes an LDL particle. Same applies for IDL. Plus, given the massive size of chylomicrons, and the load of unesterised cholesterol, this is a different league to exhausted tiny LDL that are still in circulation and the only cholesterol left is cholesterol esterised to linoleic acid.

    Note that because the LDL receptor isn’t working properly or there is less of it, endogenous cholesterol synthesis isn’t switched off by the activity of the LDLR, hence enhanced synthesis of cholesterol for these individuals. I guess this is why they are prescribed statins.”

    My comments – in this context, keto will reduce ApoB in most people, and restricting linoleic acid will help for two reasons – lower LA will slow oxidation of the LDL particles, and LA stimulates endogenous cholesterol synthesis in a way that isn’t down-regulated by the LDL-receptor.
    Keto can decrease endogenous cholesterol synthesis (and saturated fat doesn’t increase it), because the raw material for cholesterol synthesis is also the same used to make ketones.

    Here is some more information about iron

    In this study men with serum ferritin 200 mcg/l had a 2.2-fold (95% CI, 1.2-4.0; p<0.01) risk factor-adjusted risk of acute myocardial infarction compared with men with a lower serum ferritin. An elevated serum ferritin was a strong risk factor for acute myocardial infarction in all multivariate models. This association was stronger in men with serum low density lipoprotein cholesterol concentration of 5.0 mmol/l (193 mg/dl) or more than in others.

    If you look at figure 2 in this paper, serum ferritin of 200 or more increased risk of heart attacks 5-fold in men with LDL-C of 5 or more. I would imagine the values in FH of both are much higher than this. FH is a condition that will tend to promote iron accumulation, especially in men.

    This blog has a lot of information about iron and how to reduce it, the author has an ebook on the subject, but I think all the information about blood donation and its effect on ferritin levels is on the blog. Blood donation is free and by far the best way to lower iron.

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Richard David Feinman

Richard Feinman, the Other

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