#1

This is a wiki page dedicated to all things hsCRP. For optimizing other biomarkers see Easy Hacks Guide Targeting Different Biomarkers (BMI, apoB, blood pressure, HbA1c, eGFR, etc)
Feel free to add to it but try to keep the associated discussion on topic.

C-Reactive Protein

Wikipedia page

C-reactive protein is a biomarker of systemic inflammation and is considered an independent risk factor for cardiovascular diseases such as heart attack and stroke. Elevated CRP levels are associated with an increased risk of atherosclerosis, diabetes, hypertension and other inflammatory conditions. It’s also a marker of inflammaging.

The associated blood test is hsCRP for High sensitivity CRP.

What are the recommended hsCRP levels?

CRP levels should be as low as possible in general excepted in acute cases like infection, wound healing, etc


Chronic CRP levels are considered as follow

  • above 3 is a very high risk of cardiovascular disease.
  • 1 to 3 is considered elevated risk.
  • 1 and below is considered normal
  • 0.5 and below is considered optimal. It should be as low as possible though.

Supplements reducing CRP

1. Omega-3 Fatty Acid Supplements

Examples: Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA).
Mechanism: Possess anti-inflammatory properties and lower triglyceride levels.
Effect on hsCRP: May reduce hsCRP levels by 10–15%.
Clinical Evidence: The REDUCE-IT trial showed cardiovascular benefits with high-dose EPA.

2. Boswellia serrata extract

Effect on hsCRP: Substantial reduction.
Clinical Evidence: A pilot, randomized, double‐blind, placebo‐controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee

Medications That Reduce hsCRP

1. Statins (HMG-CoA Reductase Inhibitors)

Examples: Rosuvastatin, Atorvastatin, Simvastatin, Pitavastatin, Pravastatin.

Statin Reduction
Rosuvastatin 20-40%
Atorvastatin 20-35%
Simvastatin 15-25%
Pitavastatin 15-25%
Pravastatin 10-20%

Mechanism: Statins inhibit the enzyme HMG-CoA reductase, reducing cholesterol synthesis and exerting anti-inflammatory effects.
Effect on hsCRP:
Rosuvastatin: Reduces hsCRP by up to 37–50% depending on the dose.

Dose Reduction
5 mg 15-20%
10 mg 25-30%
20 mg 35-40%
40 mg 40-45%

Atorvastatin: High doses can reduce hsCRP by 36%.
Pitavastatiin: Moderate reduction in CRP, generally 15-25%
Simvastatin and Pravastatin: Moderate reductions in hsCRP levels.
Clinical Evidence: The JUPITER trial demonstrated significant hsCRP reduction with rosuvastatin, leading to reduced cardiovascular events.

3. PCSK9 Inhibitors

Examples: Alirocumab, Evolocumab.
Mechanism: Monoclonal antibodies that inhibit PCSK9, increasing LDL receptor availability and lowering LDL cholesterol.
Effect on hsCRP: May modestly reduce or increase hsCRP levels.
Clinical Evidence: Trials like ODYSSEY OUTCOMES have shown cardiovascular benefits, with some reduction in hsCRP.

4. Niacin (Vitamin B3)

Mechanism: Lowers LDL cholesterol and triglycerides, raises HDL cholesterol, and has anti-inflammatory properties.
Effect on hsCRP: Can reduce hsCRP levels by 15–25%.
Clinical Considerations: Use is limited due to side effects like flushing and gastrointestinal discomfort.
Clinical Evidence:

5. Fibrates

Examples: Fenofibrate, Gemfibrozil.
Mechanism: Activate peroxisome proliferator-activated receptor-alpha (PPAR-α), influencing lipid metabolism.
Effect on hsCRP: Can reduce hsCRP levels by 10–20%.
Clinical Considerations: Beneficial in patients with high triglycerides and low HDL cholesterol.
Clinical Evidence:

6. Antidiabetic Medications

Metformin
Mechanism: Improves insulin sensitivity and has anti-inflammatory effects.
Effect on hsCRP: Can reduce levels by 10–20%.
Clinical Evidence:

Thiazolidinediones (TZDs)
Examples: Pioglitazone, Rosiglitazone.
Mechanism: Activate PPAR-Îł, reducing inflammation.
Effect on hsCRP: Reduction of 30–50%.
Clinical Evidence:

GLP-1 Receptor Agonists
Examples: Liraglutide, Exenatide.
Effect on hsCRP: Modest reductions, along with cardiovascular benefits.
Clinical Evidence:

SGLT2 Inhibitors
Examples: Empagliflozin, Canagliflozin.
Effect on hsCRP: Potential anti-inflammatory effects contributing to cardiovascular risk reduction.
Clinical Evidence:

7. Anti-Inflammatory Medications

Colchicine
Mechanism: Inhibits microtubule polymerization, reducing inflammatory responses.
Effect on hsCRP: Can significantly reduce hsCRP levels.
Clinical Evidence: The COLCOT trial demonstrated reduced cardiovascular events with colchicine in patients with recent myocardial infarction.

Canakinumab
Mechanism: Monoclonal antibody targeting interleukin-1ÎČ, reducing inflammation.
Effect on hsCRP: Substantial reduction.
Clinical Evidence: The CANTOS trial showed decreased cardiovascular events but is limited by high cost and infection risk.

8. ACE Inhibitors and ARBs

Examples: Ramipril (ACE inhibitor), Losartan (ARB).
Mechanism: Lower blood pressure and exhibit anti-inflammatory properties.
Effect on hsCRP: May modestly reduce hsCRP levels.
Clinical Considerations: Benefits are more pronounced in patients with hypertension and high cardiovascular risk.

References

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials

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Easy Hacks Guide Targeting Different Biomarkers (BMI, apoB, blood pressure, HbA1c, eGFR, etc)
#2

The above post is a wiki so feel free to add to it. It’s linked from Easy Hacks Guide Targeting Different Biomarkers (BMI, apoB, blood pressure, HbA1c, eGFR, etc)

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#3

Any known connection between omega index and hsCRP? My omega index is ~10% (one measurement) and hsCRP is 0.2-0.3 (last few measurements, including tests with a 0.3 lower limit).

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#4

Re: statins, I don’t see pitavastatin on the list, but various studies show it lowering hsCRP very significantly, with only rosuvastatin lowering more, though I’ve seen studies showing pitavastatin ahead of even rosuvastatin. Regardless, seems worth mentioning in the statin group, I think.

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#5

Added to the list of statins

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#6

Not much: Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials 2024

image

Not all (see above).

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#7

Updated and added the link to that interesting paper.
BTW it’s a wiki page so feel free to hack it.

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#8

I’m quite active on Wikipedia, but for whatever reason, I’m not convinced the Wiki model will work here (even though I advocated for it initially and also contributed to the Longevity Wiki). I think it’s because all our discussions here are about topics that are controversial or still at the stage of research and not confirmed. Anyway, I won’t edit :slight_smile:

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#9

Rapamycin is not listed: it doesn’t lower hsCRP? (@RapAdmin @John_Hemming any thoughts/experience on this?)

#10

I had my CRP really low before starting on rapamycin.

I think baseline CRP is a representation of the senescence burden. I dont’t think Rapamycin hits this directly. Hence over a period of time it may have some benefit, but not an obvious one.

The other issue is that people don’t often try to measure the baseline. They simply take a single value at one time.

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#11

I hate to even bring it up, but if in the case of CRP, there is the obvious distinction between just lowering the marker itself, hsCRP, without changing the underlying inflammation, and lowering hsCRP, by actually lowering the underlying inflammation the marker is measuring, how do we know which of the interventions listed in the wiki is which?

Unless we have some other way of measuring inflammation, we can’t be sure that an intervention isn’t simply gaming the hsCRP number.

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#12

If an intervention acted to inhibit IL-6 to stop the liver creating CRP your point would be correct. However, if the intervention reduces the underlying generation of IL-6 because inflammation is lower (which is what most interventions do) then it is a good outcome. I am pretty certain that is what is happening.

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#13

I know PQQ and Ashwagandha can possibly lower CRP as well

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#14

Has anyone here experienced hsCRP reduction with omega 3? The literature seems to conclude that omega 3 is useless when it comes to hsCRP:

#15

In reviewing an unrelated paper, I came across this. Is anyone deep on this mutation?

“. . . alleles in the HNF1A gene associated with lower CRP levels have been linked to an increased risk of cardiovascular disease, indicating that low CRP levels do not always correlate with reduced disease risk.”

I then took a quick look (no drilling down yet) using o1 and others to find:

Variants in the HNF1A (Hepatocyte Nuclear Factor 1 Alpha) gene, particularly those associated with lower C-reactive protein (CRP) levels, have paradoxically been linked to an increased risk of cardiovascular disease (CVD). The key variant in this context is:

  • rs1169288 (HNF1A-I27L, A allele)
  • rs1800574 (HNF1A-S487N, T allele)

Mechanism and Implications

  1. HNF1A and CRP Regulation
  • HNF1A is a transcription factor that regulates hepatic CRP expression. Loss-of-function variants in HNF1A lead to lower CRP production, independently of systemic inflammation levels.
  • This means that carriers of certain HNF1A variants may have genetically lower CRP, which can confound the use of CRP as a marker for systemic inflammation or cardiovascular risk.
  1. The Paradox: Lower CRP But Higher CVD Risk
  • In Mendelian randomization studies, individuals with these HNF1A variants have lower circulating CRP but a higher risk of cardiovascular disease.
  • The association between these variants and CVD risk suggests that CRP is not directly causal in ASCVD but rather a marker of inflammation and risk.
  • This supports the notion that CRP is reactive, rather than protective or directly harmful.
  1. Possible Biological Explanation for Increased CVD Risk
  • HNF1A has roles beyond CRP regulation, including glucose metabolism, lipid metabolism, and liver function.
  • HNF1A variants are associated with increased triglycerides, dyslipidemia, and type 2 diabetes (T2D)—all independent CVD risk factors.
  • The increased CVD risk in these individuals is likely mediated by metabolic dysfunction rather than inflammation per se.

Clinical Implications

  • CRP alone is not a perfect measure of cardiovascular risk—especially in individuals with HNF1A loss-of-function alleles.
  • Using CRP as a risk stratifier in patients with these variants could underestimate true cardiovascular risk.
  • The metabolic phenotype of these carriers suggests a need for aggressive lipid and glucose management, independent of CRP levels.

All interesting and deserving of follow up. My apologies if it is behind us. I did not see anything on HNF1As.

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#16

My hsCRP has gone from 0.9 to 0.26 in the past two years. I’m thinking the key things I’ve changed during that time is adding ezetimibe and Ashwagandha (if the first post in this thread is accurate).

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#17

Yes. Mine has declined similarly but over a 3-4 year period. However, I have made so many changes that it is no longer possible to assign attributions. I also think doing so doesn’t make sense at some point. It seems likely that many interventions will lower baseline inflammation, and by a significant amount but each succeeding addition lowers it less in absolute terms even though the percent change may be similar. Austin’s law of diminishing fleas or something like that I think.

The population data suggests it is worth following up on if ASCVD is a concern on one’s overall profile.

The frequency of HNF1A variants associated with lower CRP and increased cardiovascular disease (CVD) risk varies by population and specific allele.

1. rs1169288 (HNF1A-I27L, A allele)

  • Global Frequency: ~25-35%
  • European ancestry: ~27-30%
  • East Asian ancestry: ~30-40%
  • African ancestry: ~15-20%

This variant has been linked to lower CRP, increased triglycerides, and a higher risk of type 2 diabetes and ASCVD.

2. rs1800574 (HNF1A-S487N, T allele)

  • Global Frequency: ~5-10%
  • European ancestry: ~7-10%
  • East Asian ancestry: ~5-7%
  • African ancestry: <5%

This variant has a weaker effect on CRP but is still linked to metabolic dysregulation and cardiovascular risk.

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#18

I have a CAC of 950. hsCRP three months ago was .2 at Quest. (So they might have rounded down from .24.) What does this tell me about my CVD ‘risk’?

#19

If the above genetic variant issue is correct, it would depend on whether you are generically in the group of people who test low on CRP but actually have elevated risk. So far as I know, however, all of the knowable ASCVD risk is still subsumed by two markets: Lp(a) and Apo(b). This is likely a “to be continued” issue.

Assessing TNF-α & IL-10 will indicate the broader NF-ÎșB pathway activity. This should give you good indication of the balance between pro- and anti-inflammatory cytokines and provide a crosscheck on your low CRP level.

#20

I haven’t looked at these SNP’s but most complex traits are highly polygenic, with lots of SNP’s, so you have to sum up the effects of all the genes you have that are relevant (+ or -) for a total score or effect:

See this thread:

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What is your geneticgenie methylation profile?