#496

I just stumbled upon this 2022 study saying too low LDL (and also too high LDL) is associated with higher mortality. I lean on thinking it isn’t biased if they’re also saying too high LDL is bad.

Seeing how my recent LDL was 32, I am going to drop Ezetimibe and just remain on 5mg Rosuvastatin.

https://www.ahajournals.org/doi/full/10.1161/JAHA.121.023690#:~:text=However%2C%20recent%20observational%20studies%20indicated,mortality%20and%20other%20adverse%20outcomes.

#497

Pretty much all of the autoinjector pen medications end up being a fixed cost, regardless of dose. So on Mounjaro - I find a lot of patients do well on weight loss in the 3.75 mg/week range (always start no higher than 2.5 mg/week for first 4 weeks is the manufacturer’s recommendation) … so getting 4 doses out of a 15 mg pen is markedly more cost effective, if self paying. But you have to have the skills to do this safely and with sterility.

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#498

It’s an observational study which does not take cofounding factors such as cancer, infections or other health issues into account. When adjusted for those, lower LDL-C (or rather apoB) is always better. That’s why I’m using both 10mg of rosuvastatin and ezetimibe which I tolerate relatively well.

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#499

I tolerate 5mg rosu and 10mg eze well too. What is your ApoB or LDL?

#500

My LDL-C is in the low 60s. Don’t know about my apoB as I couldn’t find any inexpensive tests for it.

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#501

You’re absolutely right. I forgot they probably didn’t account for the fact people in disease states have low LDL which probably accounts for this result. I’ll stick with my 32 LDL and remain on Ezetimibe.

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#502

Why would you remain on rosuvastatin if your LDL is 32?

#503

Well if there’s no downside of having a very low LDL, why stop? It was always around 90-105 before Rosuvastatin and Ezetimibe.

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#504

Low-density lipoprotein (LDL) cholesterol, often referred to as “bad” cholesterol, plays a crucial role in our health. While we often focus on reducing high LDL levels to mitigate heart disease risk, it’s essential to consider the lower end of the spectrum as well.

Here’s what we know:

  1. Very Low LDL Levels: There is no consensus on precisely how to define “very low” LDL cholesterol. However, if LDL falls below 40 milligrams per deciliter of blood, it would be considered very low. Although rare, extremely low LDL levels may be associated with increased risks:

    • Cancer: Some studies suggest a potential link between very low LDL and certain cancers.
    • Hemorrhagic Stroke: Extremely low LDL levels might be associated with an increased risk of hemorrhagic stroke¹[1] ²[2].

  2. Safety and Effectiveness: Recent research indicates that lowering LDL below 70 mg/dL is both safe and effective in reducing cardiovascular disease risk. However, this level is still significantly higher than the very low threshold mentioned earlier³[5].

In summary, while extremely low LDL levels are uncommon, maintaining a balance is crucial. Always consult with a healthcare professional to assess your individual risk factors and determine the optimal cholesterol levels for your health. :herb:

Source: Conversation with Bing, 4/27/2024
(1) Cholesterol level: Can it be too low? - Mayo Clinic. Cholesterol level: Can it be too low? - Mayo Clinic.
(2) Can LDL Cholesterol Be Too Low? - HealthCentral. Can Cholesterol Be Too Low?.
(3) LDL cholesterol: How low can you (safely) go? - Harvard Health. LDL cholesterol: How low can you (safely) go? - Harvard Health.
(4) Can My Cholesterol Be Too Low? - Verywell Health. Can Cholesterol Be Too Low?.
(5) Cholesterol Can Be Too Low? Causes, Consequences, and Treatment - WebMD. Cholesterol Can Be Too Low? Causes, Consequences, and Treatment.

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#505

If you for example look at your Harvard source they don’t seem to agree with the conclusion that low LDL is bad, see for example the section “No apparent danger of very low LDL cholesterol” and the section after it.

Association studies are one thing - but if someone for example has cancer and therefore as often is the case ends up with low LDL that leads to an association and correlation between low LDL and mortality but the cause is not low LDL it is the cancer.

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#506

Different studies point into different directions. Often in the opposite directions. The question is which opinion to choose for your wellbeing. My logic guides me to choose moderation, not extremes like too high or too low. There’s an opinion that LDL lower than 40 may bring unwanted outcomes. Unless it’s disproved, I wouldn’t cross the line.

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#507

@LaraPo Different studies have materially different value

Randomized controlled trials and Mendelian Randomization studies are massively better at identifying true causal relationships than association studies

Just make sure you weigh the studies based on the type of data they are based on

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#508

IMG_7198
IMG_71981179×2556 216 KB

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#509

Does this study answer how low to go?

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#510

The main paper does not seem to. They have a ton of supplements thought, not sure if that would help answer that question even if it was not the focus of the paper.

Full paper here:

https://www.nature.com/articles/s42003-024-05887-2

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#511

@AnUser Did we ever discuss these two papers (1) and (2)

Together, these lines of evidence strengthen the hypothesis that APOB is implicated in longevity via modulation of healthspan and build on the findings by Perrot et al. (2020)2 and Richardson et al. (2021)1. Like us, Perrot et al. 2 performed MR analyses of circulating metabolites on lifespan using the Kettunen21metabolite instruments. They found evidence that higher APOB and APOB-containing lipoproteins shorten lifespan. We extend their observation about APOB and longevity by showing that APOB shortens healthspan. Moreover, we also extend the work by Richardson et al.1, who observed that APOB is implicated in type 2 diabetes. Like AD, type 2 diabetes ends healthspan.

In addition, we found that circulating APOB (but not LDL) increases risk for AD.

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#512

Btw re AD, there seems to be more open questions

This finding for APOB in relation to AD conflicts with that by Williams et al. (2020)33, who sought to identify genetic support for the repurposing of mipomersen (an antisense oligonucleotide inhibitor of APOB34) for AD prevention. Like us, Williams and colleagues used IGAP GWA study data for the AD outcome source in their two-sample MR. Their study differed from ours in the construction of their genetic instrument, though. Whereas our instruments for APOB contained more SNPs, which were clumped to prevent LD, they used a principal-components-based MR method. We attempted a partial replication of our MR of APOB on AD using a substantially larger GWA study containing more than triple of the number of AD cases. Although our partial replication succeeded in the sense that the results revealed that higher levels of APOB increased risk for AD, the effect estimate attenuated towards the null. Future MR studies of AD, ideally with a larger number of clinically defined cases (and not including IGAP cases) are needed to confirm whether the relationship between APOB and AD is causal.

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#513

I don’t remember discussing this paper. But again: what does “higher” mean? Higher than what? I think we all know that too high ApoB is bad, but how low should we go? Or does “higher” just mean “everything else being equal, higher is worse”?

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#514

Yes. Some MR studies show the curves, but the first one above in the main paper only focus on the point estimates. Not sure about the supplement or the other two papers or their supplements. Perhaps @AnUser or @Virilius have / can answer.

#515

I have mentioned that The Lancet paper elsewhere a couple of times.

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