Lose the belly fat to live longer and healthier:
Source Papers:
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Full paper here:
Adult Immunizations as Part of Cardiovascular Care: 2026 ACC Concise Clinical Guidance
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The higher rate of rapid progression of atherosclerosis in healthy keto dieters with high lipids aside (KETO-CTA vs. NATURE-CT).
Children with FH under statin treatments vs. their parents with FH. Are people going to pretend the parents as children were âmetabolically unhealthyâ?
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Iâm here to share the results of my statin experiment and to ask my super smart friends for advice on what my next steps might be.
As some of you know, I used to be statin intolerant and went years with nothing for my lipids.
Iâm currently on Repatha, ezetimibe, colchicine, and bempedoic acid. I donât technically need more, but Iâm high risk, and Iâd still like my lipids to be lower to make up for all the time I wasnât on anything.
After using some very old Livalo a couple of months ago with success, on 7/10/26 I started taking Livalo 1 mg per day. Unlike in the olden days, this time I feel fine and it no longer makes me feel sofa-bound.
Now on to potential myopathy⌠GAH
Oddly, I almost never get sore when I workout. Over this past month, Iâm getting more and more sore. I canât be sure itâs related, but itâs looking that way.
My first thought was, well, Iâm more concerned with my heart than being pain free, so hurting during workouts is a fine trade offâŚâŚ BUT, itâs now to the point that I canât lift as much weight, and I simply donât have muscle to spare (osteoperios and tiny)
Before I go off Livalo to see if that is truly the cause, I wanted to mention that Opus told me colchicine has the potential to make Livaloâs effective dose higher. Apparently combining it with bempodoic acid might also be a contributing cause.
If you were me, would you go off Livalo for a month to see if it was a coincidence or not? If it winds up being causal, would you then just add back, perhaps, 1mg 2x per week?
Or, is the statin potentially more beneficial than colchicine and/or bempodoic acid on someone with already good lipids? If so, instead of touching Livalo yet, would youâd pause each of those for a month to see if itâs the combo creating the issue?
If my pre-Livalo lack of soreness from working out is helped by colchicine, pausing it while being on Livalo might not tell me much. For all I know itâs the LDN though⌠not sure.
Open to any suggestions!!
There is potential of pitavastatin interaction with colchicine. Dropping colchicine should be looked at in the context of overall inflammatory biomarkers, hsCRP, IL-6, GlycA etc. - if those are low, then dropping colchicine might be an option, if not, Iâd keep it. In other words, if given a choice Iâd rather take pitavastatin and drop colchicine as long as my inflammatory markers are low, if not, Iâd keep the colchicine and drop the pitavastatin given that you are controlling your lipids pretty well already. If you have myalgia, my suspicion would fall on pitavastatin (Livalo), because while the effect of pitavastatin on muscles is much less than other statins, itâs still a statin and there are reports (including from users on this site). You might just be very sensitive to statins, and in your place, if pitavastatin is giving you problems, Iâd drop it - there are other drugs coming down the pike which you can get on once theyâre available. I love statins, pitavastatin especially, but they are not for everybody, and if you are getting such serious side effects as you describe, I would drop them without hesitation. Remember, the goal is to safely drop your ApoB, the goal is not to simply be on a statin, and you can drop your ApoB/LDL with other classes of drugs. Iâm not a doctor and this is not medical advice etc. just my thoughts as a lay student of lipids and CVD.
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You should replace the statin with equivalent compound if you get myopathy even if in the majority of cases itâs the nocebo effect. First itâs a real effect even if itâs not from the statin, so you canât wish it away, and second I think it increases your risk of the very rare incidence of rhabdo which is dangerous. Colchicine has many interactions some which are dangerous, so itâs something you should go over with a doctor carefully, and search for drug interactions in the literature/websites.
Obicetrapib is available in Europe soon, which you might be able to order in some way if youâre comfortable with not waiting for outcome trials, but if you do, do check for drug interactions for novel compounds!
Is there any statin you havenât tried? There could still be one that works for you and doesnât have drug interactions.
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Some with Statin Associated Myopathy benefit from CoQ10 supplementation (200mg/d)
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For several reasons, this study may not be relevant in this case.
(1)The statins examined did not include pitavastatin, therefore the relevance is in question.
From the study:
âDepending on the inclusion criteria of each RCT, different types of statins were administered (Simvastatin, Atorvastatin, Rosuvastatin, Lovastatin, Pravastatin, Fluvastatin), ranging from a dosage of 10 mg/d to 80 mg/d.â
(2)The causative mechanism of statin associated myalgia that is examined in this study is based on statins depleting CoQ10 levels:
From the study:
âSeveral causative mechanisms are discussed for the development of SAMS,(9) but a statin-induced reduction of Coenzyme Q10 (CoQ10) levels is of particular interest.(13) Statins (3-Hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit the endogenous synthesis of cholesterol by inhibiting the rate-limiting enzyme of the mevalonate pathway.(14) Thus, statins intervene very early in the mevalonate metabolic pathway and inhibit the formation of intermediary products including geranylgeranyl pyrophosphate. This isoprenoid is essential for the endogenous synthesis of CoQ10.(15) As CoQ10 is only supplied in small quantities with food and is predominantly synthesised endogenously,(16,17) statin intake can lead to reduced CoQ10 levels.(17)â
Re: (2) Pitavastatin uniquely among statins does not deplete serum levels of CoQ10, (I posted studies showing this elswhere in this site) therefore the mechanism examined by this study is irrelevant in the case of pitavastatin.
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No expert by any measure but I would drop colchicine for reasons others have indicated (might make statin sides worse) plus Iâve read some bad stories about it especially if taken for longer periods. Then after youâve waited for couple weeks and assessed the situation, I would drop PITA (if you really have to). Even though youâre saying youâre high risk youâre already doing a lot especially now that you are doing Rpatha in addition to EZe and BAcid. Donât overdo it just because you think youâre high risk. Three lipid lowering meds should be more than enough for you.
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From personal experience, most medications you take together with pitavastatin cause increased side effects. Take it isolated in the evening.
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Thank you all for taking the time to provide excellent feedback.
I decided to go off livalo to see if the pain subsides. If it does, I can then re-evaluate options when Iâm sure that was the cause (weighing another trial against BA and colchicine etc, or just closing the chapter).
Because itâs been getting worse, and the mention of rhabdo, I thought stopping to figure it out seemed like the conservative move.
My pilates instructor and my PT have individually been making comments at my lower ability to go hard due to pain, so whatever is going on is real.
And yessss, I want to get Obicetrapib the day my hot little hands can get a hold of it!!!
FYI, I take ubiquinol a few days per week
Iâll also reopen the can of worms better known as colchicine.
Thanks again everyone!!!
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I noticed no one has mentioned the potential root cause of your myalgia yet. Colchicine isnât the culprit here. You likely carry a malignant hyperthermia susceptibility gene, which leads to dysfunction in your ryanodine receptors (RyR). Pitavastatin contains a fluorophenyl structure, which can form a triad that targets these ryanodine receptors.
Note that this mechanism assumes your creatine kinase (CK) levels are NOT elevated. If your lab results come back showing normal CK, then this is almost certainly the issue. Switching to simvastatin or pravastatin should directly resolve the problem.
muscle-related adverse reactions signals were meaningful when the two drugs were combined in the order of colchicine combined with fluvastatin (ROR 187.38, 95% CL 96.68-363.17; IC 6.99 95% CL 1.65-5.68); colchicine combined with simvastatin in 135 cases (ROR 30.08. 95% CL 25.25-35.85; IC 4.80 95% CL 3.96-5.12); and colchicine combined with rosuvastatin (ROR 25.73, 95% CL 20.16-32.83; IC 4.59 95% CL 3.38-4.98) versus colchicine combined with atorvastatin (ROR 25.73, 95% CL 22.33-29.66; IC 4.59 95% CL 3.97-4.91) with almost identical signal intensity, followed by colchicine combined with pravastatin (ROR 13.67, 95% CL 9.17-20.37; IC 3.73 95% CL 1.87-4.47), whereas no signals were generated for lovastatin or pitavastatin.
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You can measure creatinine kinase as well, I remembered now I did this before/after taking a statin, Gil Carvalho did the same.
Not sure what the guidelines are.
If you notice mild muscle pain after you start to take a statin, contact your healthcare professional. You may have a blood test to measure levels of an enzyme called creatinine kinase. This test can diagnose rhabdomyolysis or milder forms of muscle pain.
edit: I saw Kawaii posted about this now as well
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Mogging
This is what peak performance looks like
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What is interesting is that rosuvastatin and pravastatin not only cause myalgia in me but also make me feel like Iâve been hit by a car or something. Pitavastatin and atorvastatin only cause myalga in my feet when Iâve been taking them at too high doses or too low without break or in combination with other medications.
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HDL Under the Microscope: Setting the Record Straight with Dr. Lipid
I. Executive Summary
In this National Lipid Association presentation, lipidologists Dr. Peter H. Jones and Dr. Thomas Dayspring dismantle the long-standing clinical misconception of High-Density Lipoprotein Cholesterol (HDL-C) as the âgood cholesterolâ and establish a modern, physiologically rigorous framework for evaluating high-density lipoproteins (HDLs). Historically, observational epidemiology demonstrated an inverse correlation between plasma HDL-C levels and atherosclerotic cardiovascular disease (ASCVD). However, extensive randomized controlled trials (RCTs) evaluating HDL-C-raising pharmacotherapiesâincluding niacin, fibrates, and early cholesteryl ester transfer protein (CETP) inhibitorsâconsistently failed to demonstrate reductions in major adverse cardiovascular events (MACE). Furthermore, Mendelian randomization studies confirmed that genetic variations raising plasma HDL-C do not confer causal cardiovascular protection (Voight et al., 2012).
HDLs represent 90% of all circulating lipoprotein particles in plasma, yet they carry a minor fraction of overall plasma lipids compared to ApoB-containing âdump truckâ lipoproteins (LDL, VLDL, IDL). Instead of acting primarily as cholesterol transporters, HDLs are heterogeneous, pleiotropic platforms carrying over 200 distinct proteomic and lipidomic species. They participate in innate immunity, antioxidant defenses, endothelial maintenance, and anti-thrombotic activity. Plasma HDL-C tests measure solely the mass of cholesterol contained within HDL particles, completely failing to reflect HDL functionality or cellular cholesterol efflux capacity.
The dynamic lifecycle of HDL involves complex lipid remodeling. Apolipoprotein A-1 (ApoA-1) undergoes phospholipidation and esterification via Lecithin-Cholesterol Acyltransferase (LCAT) to form mature, spherical HDLs. Crucially, 60% of HDL-C originates directly from hepatic lipidation and 20â30% from enterocytes, while macrophage/arterial plaque efflux accounts for less than 10%. Furthermore, CETP-mediated lipid exchange between HDL and ApoB particles, combined with renal catabolism of shrunken, triglyceride-rich HDLs, drives particle clearance. Novel, potent CETP inhibitors like obicetrapib significantly reduce ApoB and LDL-C while generating massive HDL1 particles (up to 18 nm). These large particles cause Nuclear Magnetic Resonance (NMR) spectral overlap, creating false-positive elevations in small LDL particle counts. Ultimately, clinical lipid management must abandon HDL-C treatment targets, focusing strictly on ApoB and non-HDL-C reduction, alongside lifestyle optimization to preserve endogenous HDL particle functionality.
II. Insight Bullets
- ApoB vs. Non-ApoB Classification: Lipoproteins are divided into ApoB-containing particles (VLDL, IDL, LDL, chylomicrons) and Non-ApoB particles (HDL, characterized structurally by ApoA-1).
- ApoA-1 Structural Dynamics: ApoA-1 is an amphipathic, transferable helical peptide containing 22-amino-acid repeats; individual HDL particles carry between 1 to 5 copies of ApoA-1 depending on maturation state.
- Centrifugal Buoyancy Mechanics: High-density lipoproteins sink during ultracentrifugation because they are protein-dense with minimal lipid volume, whereas ApoB particles float due to carrying massive lipid payloads proportional to the third power of their particle radius (V=34âĎr3).
- Epidemiological Correlation Fallacy: Early observational studies showed an inverse correlation between HDL-C and coronary heart disease, creating the unproven hypothesis that raising plasma HDL-C mass would directly prevent atherogenesis.
- Pharmacological Failure of HDL Elevation: Multiple RCTs testing agents designed to raise HDL-C (e.g., niacin, fibrates, torcetrapib, dalcetrapib) failed to show reductions in MACE, disproving the therapeutic strategy of targeting HDL-C elevation (Keene et al., 2014).
- Mendelian Randomization Disproof: Human genetic analyses show that single-nucleotide polymorphisms (SNPs) specifically elevating plasma HDL-C do not decrease cardiovascular risk, proving HDL-C is non-causal (Voight et al., 2012).
- Numerical Dominance of HDL Particles: HDLs account for approximately 90% of all circulating lipoprotein particles in human plasma, whereas atherogenic ApoB-containing particles make up only 10%.
- Disproportionate Lipid Payload: Despite comprising only 10% of total particles, ApoB lipoproteins transport the overwhelming majority of circulating cholesterol and triglycerides due to their substantially larger volumetric capacity.
- Extensive Proteomic Heterogeneity: Proteomic profiling identifies over 200 distinct proteins associated with the HDL particle family, although an individual HDL particle accommodates a maximum of ~42 protein molecules simultaneously.
- Innate Immunity and Pleiotropic Roles: HDLs function as immunomodulatory, antioxidant, antithrombotic, and anti-inflammatory platforms, carrying immune proteins to sites of vascular injury as part of the innate immune response.
- Absence of Clinical Functionality Assays: Commercial lipid panels quantify only the mass of cholesterol contained in HDL (HDL-C), offering zero information regarding functional quality, proteomic composition, or cholesterol efflux capacity.
- Initial Lipidation Steps: Nascent ApoA-1 acquires surface phospholipids via cellular ABCA1 transporters as the mandatory first step of particle assembly prior to accepting unesterified free cholesterol.
- Biochemical Function of LCAT: Lecithin-Cholesterol Acyltransferase (LCAT) transfers a fatty acid from phosphatidylcholine to free cholesterol, generating non-polar cholesteryl esters that migrate into the core to convert disc-like HDL into a mature sphere.
- Major Endogenous Sources of HDL-C: Approximately 60% of circulating HDL cholesterol is derived directly from hepatic lipidation, 20â30% from intestinal enterocytes, and less than 10% from peripheral extrahepatic tissues.
- Forward Cholesterol Transport Pathways: Mature HDLs deliver cholesterol to steroidogenic organs (adrenal cortex, gonads) for steroid hormone synthesis and to adipocytes (via SR-BI and local CETP) for tissue storage.
- Direct vs. Indirect Reverse Cholesterol Transport: Direct RCT involves hepatic SR-BI uptake of HDL cholesterol; indirect RCT occurs when CETP transfers cholesteryl esters from HDL to ApoB particles for clearance via hepatic LDL receptors.
- Insignificance of Plaque Efflux to Serum Mass: Cholesterol effluxed from arterial macrophages and foam cells (macrophage RCT) represents a negligible portion of systemic cholesterol flux and contributes zero measurable mass to standard plasma HDL-C levels (Rosenson et al., 2012).
- Triglyceride-Driven Catabolism: In hypertriglyceridemic states, CETP exchanges HDL cholesteryl esters for ApoB triglycerides; hepatic and endothelial lipases hydrolyze the TG, leaving unstable, shrunken HDLs that are filtered and degraded by renal tubules.
- Subparticle Sizing as Metabolic Biomarker: Depletion of large HDL particles (HDL2) alongside elevated small dense HDLs/VLDLs serves as a surrogate biomarker signature for hyperinsulinemia and insulin resistance.
- Paradoxical U-Shaped Mortality Curve: Extremely high serum HDL-C levels (>80â90 mg/dL) paradoxically correlate with increased all-cause and cardiovascular mortality, often signaling dysfunctional particles or genetic clearance defects (Madsen et al., 2017).
- CETP Inhibition with Obicetrapib: Modern selective CETP inhibitors like obicetrapib lower ApoB and LDL-C by 40â50% while markedly elevating HDL-C and generating oversized HDL1 particles (up to 18 nm diameter) (Nicholls et al., 2022).
- NMR Diagnostic Artifact: Oversized HDL1 particles produced during potent CETP inhibition cause spectral overlap on NMR spectroscopy platforms, triggering false-positive elevations in small LDL particle (small LDL-P) counts.
- Clinical Priority of ApoB Verification: Clinicians managing patients on CETP inhibitors must rely on direct immunoassays for ApoB or non-HDL-C rather than NMR particle concentrations to monitor atherogenic particle burden accurately (Marston et al., 2021).
- Bacterial and Viral Neutralization: HDLs bind bacterial lipopolysaccharides (LPS) and viral proteins, facilitating reticuloendothelial neutralization and clearance as part of systemic host defense.
- Absence of Guidelines for HDL-C Elevation: No major international cardiovascular guidelines establish a target lower limit or treatment goal for raising HDL-C, reinforcing that ApoB/LDL-C suppression is the sole evidence-backed therapeutic focus.
IV. Actionable Protocol (Prioritized)
High Confidence Tier (Level A/B Evidence)
- Target ApoB and Non-HDL-C as Primary Metrics: Focus clinical interventions exclusively on lowering atherogenic ApoB-containing particle concentrations and non-HDL-C using statins, ezetimibe, PCSK9 inhibitors, or bempedoic acid (Marston et al., 2021).
- Mitigate Insulin Resistance to Protect HDL Remodeling: Implement lifestyle modifications (e.g., Mediterranean dietary pattern, physical exercise, and visceral adiposity reduction) to lower plasma triglycerides, prevent hyper-catabolism of HDLs, and normalize particle size distribution (Estruch et al., 2018).
- Use ApoB Immunoassays for Patients on CETP Inhibitors: Discontinue reliance on NMR-derived small LDL particle counts in patients taking novel CETP inhibitors due to spectral interference from oversized HDL1 particles.
Experimental Tier (Level C/D Evidence / High Safety Margin)
- Selective CETP Inhibitor Utilization for ApoB Lowering: Evaluate novel selective CETP inhibitors (e.g., obicetrapib) as adjunctive agents for aggressive ApoB and LDL-C reduction in high-risk ASCVD patients, pending outcome results from Phase 3 cardiovascular trials (Nicholls et al., 2022).
- Advanced Subparticle Profiling as an Auxiliary Metabolic Marker: Use large HDL particle (large HDL-P) depletion and small VLDL/LDL-P excess strictly as secondary diagnostic markers to evaluate underlying insulin resistance in complex dyslipidemias.
Red Flag Zone (Debunked / Lacking Safety Data)
- Prescribing Pharmacotherapy to Raise HDL-C: Avoid prescribing niacin, fibrates, or off-label agents specifically to raise serum HDL-C levels. Level A evidence demonstrates no MACE reduction and potential off-target adverse effects (Keene et al., 2014).
- Misinterpreting High HDL-C as âCardioprotectiveâ: Do not assume elevated HDL-C (>80â90 mg/dL) provides immunity against atherosclerosis or justifies withholding ApoB-lowering therapy. Extremely high HDL-C displays a U-shaped risk curve and frequently reflects dysfunctional particles (Madsen et al., 2017).
- Relying on NMR Small LDL-P Under CETP Inhibition: Do not base clinical decisions on NMR small LDL particle readouts during CETP inhibitor therapy, as spectral overlapping produces false-positive results.
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