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C-Reactive Protein: What's Optimal? A Comprehensive Review

hs-crp optimal range

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#1 Michael Lustgarten

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Posted 25 April 2021 - 10:24 AM




Papers referenced in the video:

 

The baseline levels and risk factors for high-sensitive C-reactive protein in Chinese healthy population: https://immunityagei...omedcentral....

 

Bioanalytical advances in assays for C-reactive protein: https://pubmed.ncbi....ih.gov/26717...

 

Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians: https://pubmed.ncbi....ih.gov/26629...

 

High-sensitivity C-reactive protein predicts mortality but not stroke: https://www.ncbi.nlm...gov/pmc/arti...

 

Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg Cohort Study, 1984-1998: https://pubmed.ncbi....ih.gov/18156...

 

High sensitive C-reactive protein (hsCRP), cardiovascular events and mortality in the aged: a prospective 9-year follow-up study: https://pubmed.ncbi....ih.gov/25456...

 

Plasma Biomarkers of Inflammation, the Kynurenine Pathway, and Risks of All-Cause, Cancer, and Cardiovascular Disease Mortality: The Hordaland Health Study: https://pubmed.ncbi....ih.gov/26823...

 

Troponin T, B-type natriuretic peptide, C-reactive protein, and cause-specific mortality: https://pubmed.ncbi....ih.gov/23228...

 

Association between C reactive protein and all-cause mortality in the ELSA-Brasil cohort: https://pubmed.ncbi....ih.gov/32102...

 

C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study: https://pubmed.ncbi....ih.gov/15821...

 

High-sensitivity C-reactive protein and cystatin C independently and jointly predict all-cause mortality among the middle-aged and elderly Chinese population: https://pubmed.ncbi....ih.gov/30592...

 

Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study: https://pubmed.ncbi....ih.gov/23821...

 

High-Sensitivity C-Reactive Protein and Risks of All-Cause and Cause-Specific Mortality in a Japanese Population: https://pubmed.ncbi....ih.gov/27268...

 

Beta2-microglobulin for risk stratification of total mortality in the elderly population: comparison with cystatin C and C-reactive protein: https://pubmed.ncbi....ih.gov/18227...

 

Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population: https://pubmed.ncbi....ih.gov/18790...

 

Impact of systemic inflammation on the relationship between insulin resistance and all-cause and cancer-related mortality: https://pubmed.ncbi....ih.gov/29191...

 

High-sensitivity C-reactive protein and coronary heart disease in a general population of Japanese: the Hisayama study: https://pubmed.ncbi....ih.gov/18403...

 

An epigenetic biomarker of aging for lifespan and healthspan: https://pubmed.ncbi....ih.gov/29676...

 

DNA methylation GrimAge strongly predicts lifespan and healthspan: https://pubmed.ncbi....ih.gov/30669...


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#2 albedo

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Posted 27 April 2021 - 08:41 AM

Highly interesting Michael and well researched! Thank you for your efforts to educate us!

Comments and questions:

  • I just realize hr-CRP gets top score in Levine’s PhenoAgeAcc vs. Phenotypic Age. Now this seems more logical to me as linked to chronic inflammation. In the latter it scored (even if Levine herself said you cannot really compare as weights were not standardized – private com.) 9% (log-CRP) vs 33% (RDW) in weight. Maybe you can further elaborate on this.
  • What would you recommend as lifestyle, nutrition and specific supplementation to try and lower hr-CRP?
  • I looked once at my baseline for IL-6 and TNF-alpha but realize now I should rather look at IL-18 and IL-1beta on the non-infection DAMP path. Would you agree?
  • How would you characterize and measure “tissue damage”? I wonder if you can check correlation with LDH, the latter goes high with cancer based tissue damage, hence maybe not really appropriate for chronic non-cancerous conditions.
  • The DAMP path is (very logically I guess) linked to adipose tissue. Chronic inflammation decreases if you decrease adipose tissue and increase lean body mass. Would you agree and how would you measure adipose tissue?
  • Definitively I retain we should target for hr-CRP less than 1 for optimal (not ref ranges). I am not happy with my recent numbers. I had for many years about 0.3 in average with a rising trend I attribute also to a chronic infection I have got. Past two years measurements at 1 and 1.3 now at 65+
  • Did not check (sorry): is Ahmed-Anhari 2013 hr-CRP or CRP?
  • (not in the video, I know from other posts) It is good and maybe not a coincidence I understand you will be testing inflammation prior to Covid-19 vaccination. I did the same
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#3 Michael Lustgarten

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Posted 27 April 2021 - 06:38 PM

Thanks albedo. Even though RDW has a greater contribution to calculating biological age, I try to optimize all of the 9 variables, not just RDW (or hs-CRP).

I looked for RCTs that reduced CRP, but I saw reductions from ~7 to 4.5, which isn't relevant if you've got much lower values. From my n=1 experience, higher blood levels of cholesterol (including HDL) are correlated with lower hs-CRP (see https://youtu.be/U0nTtDmCwSQ?t=429),so I aim to prevent my TC and HDL from being too low, which I always seem to have a propensity for.

Because hs-CRP is induced by each of those cytokines, it may be worthwhile to only measure hs-CRP, and the output for all those inputs. Alternatively, I understand the argument to measure the individual cytokines, too.

Besides tissue damage, CK as a marker of muscle damage, elevated ALT, AST for liver damage, as examples.

Adipose tissue can be measured with DXA, which I've done 3x. Many labs offer it as a service to the public for a fee (usually < $100).

Based on the data in the video, one can make the argument that as low as possible, ~ 0.2 mg/L or less, may be optimal for hs-CRP.

Which reference is Ahmed-Anhari 2013, just so that I don't have to click on every link in the video?

Yes, my response to the vaccine will be interesting. I'll have blood test data in the morning tomorrow before the shot, but not after. I will have RHR, HRV, and sleep though.



 


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#4 albedo

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Posted 27 April 2021 - 07:22 PM

...
Which reference is Ahmed-Anhari 2013, just so that I don't have to click on every link in the video?
...

 

 

It is: Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study, https://pubmed.ncbi....h.gov/23821244/

I did not read but looks like CRP and not hr-CRP

Attached File  A-A 2013.PNG   45.44KB   0 downloads

 

 



#5 albedo

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Posted 27 April 2021 - 07:25 PM

I keep doing the same mistake: hs-CRP (high sensitivity CRP) NOT hr-CRP (mixing with high-resolution CRP which might not exist) ... sorry



#6 Michael Lustgarten

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Posted 27 April 2021 - 07:26 PM

As, so that test isn't geared towards measuring very low levels of CRP, so it may cast doubt on the actual levels (0.1 - 0.5 mg/L) quantified in that study...


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#7 albedo

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Posted 28 April 2021 - 12:29 PM

 

Highly interesting Michael and well researched! Thank you for your efforts to educate us!

Comments and questions:

  • ...
  • What would you recommend as lifestyle, nutrition and specific supplementation to try and lower hr-CRP?
  • ...

 

I am reading LE's protocol on chronic inflammation and you might find it useful:

https://www.lifeexte...ic-inflammation

 

Also this:

"...An inflammatory index, developed by a group from the Arnold School of Public Health at the University of South Carolina, scored 42 common dietary constituents based on their ability to raise serum CRP.122 Constituents (such as saturated fat, tea polyphenols, or vitamin D) were given either a positive (anti-inflammatory) or negative (pro-inflammatory) score, the magnitude of which was weighted based on the volume of inflammation research on the isolated ingredient. Human clinical data was weighted more than animal data, and clinical trials more than observational studies. The scores were then verified by comparing them to nutrient intakes and CRP levels from a group of 494 volunteers over the course of one year. Amongst the most anti-inflammatory nutrients (based on the model and study data) are magnesium, beta-carotene, turmeric (curcumin), genistein, and tea; the most pro-inflammatory included carbohydrates, total- and saturated fat, and cholesterol. The index may provide a useful metric for accessing the overall inflammatory potential of an individual diet..."

 

We are using much of the same nutrients.

 

Ref 122 in the quote is: Cavicchia, P. P., Steck, S. E., Hurley, T. G., et al. A new dietary inflammatory index predicts interval changes in serum high-sensitivity C-reactive protein. Journal of Nutrition. 2009;139(12):2365–2372.

The study provides a tool for assessing the inflammatory potential of the diet but I do not like much the hs-CRP clinical cut-off at 3.
 


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#8 Michael Lustgarten

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Posted 28 April 2021 - 02:18 PM

Yes, that's interesting, but note that my saturated fat intake (almost exclusively from cacao beans, coconut butter) is correlated with lower hs-CRP (https://youtu.be/U0nTtDmCwSQ?t=431).

Unfortunately, most don't eat those foods, so it's unknown if large populations would react similarly.


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#9 albedo

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Posted 29 April 2021 - 09:11 AM

Yes, that's interesting, but note that my saturated fat intake (almost exclusively from cacao beans, coconut butter) is correlated with lower hs-CRP (https://youtu.be/U0nTtDmCwSQ?t=431).
...

 

Do I understand correctly your saturated fat intake is reflected into TC and the most significant (inverse) correlation with hs-CRP is seen with the HDL fraction, which is good, right?


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#10 Michael Lustgarten

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Posted 29 April 2021 - 10:55 AM

Yes albedo, those are the correlations. Also, higher HDL is correlated with lower Lp(a) in my data, which further suggests that getting HDL into the 50s, whether by more saturated fat (cacao/coconut) or other mechanisms may be good for health.


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#11 albedo

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Posted 29 April 2021 - 03:30 PM

I see a similar correlation between TC and hs-CRP but much less significant. Maybe this is due to the higher variance in my hs-CRP data because of infections as it is acute phase protein. So data should be corrected by that. Indeed the significance increases when removing what I consider "outliers". The variance on TC is probably less important due to its lesser response to dietary and other changes in the same period of time.


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#12 albedo

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Posted 29 April 2021 - 07:37 PM

Next to the hs-CRP:

Attached File  Labs Inflammation.PNG   1.07MB   0 downloads

https://drjockers.co...ory-lab-markers



#13 Michael Lustgarten

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Posted 29 April 2021 - 08:43 PM

 

He notes that 0 - 1 mg/L is optimal for hs-CRP, but as I noted in the video, there are many studies showing that as close to 0 may be optimal.


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#14 albedo

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Posted 02 May 2021 - 12:42 PM

As you definitively touch on hs-CRP in your last video, this should be also posted here:

https://www.longecit...ndpost&p=905951


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