Written by the SiPhox Health Research Team

Reviewed by Michael Lustgarten PhD, Human Nutrition Research Center on Aging

 

There are two main types of inflammation. Acute (short-term) and chronic inflammation (long-term, low-level).

Classically, inflammation is viewed as an acute response to tissue injury, infection, or another disease state that produces characteristic symptoms (swelling, redness, and warmth). In most cases, this is a functional and useful immune response. However, in some cases, the inflammatory system can be operating at a persistently elevated level, which is known as chronic inflammation.

The medical community has been aware of chronic inflammation for a long time, but only in recent decades has it become possible to track low levels of inflammation using high-sensitivity blood tests. This has shed light on chronic, systemic inflammation as a highly destructive process that drives disease pathogenesis and the aging process itself. It contributes so significantly to the deterioration associated with aging that it has been coined “Inflammaging.”

Chronic inflammation contributes to the development of at least 7 of the 10 leading causes of death in the United States. It may go undetected for years or even decades without proactive tracking, silently threatening your health.

C-Reactive Protein, or CRP, is used to measure acute inflammation, but with the advent of hsCRP (high-sensitivity CRP) testing, it became possible to use it for tracking chronic inflammation as well. CRP is one of several proteins rapidly produced by the liver during an inflammatory response. Its primary goal in acute inflammation is to coat damaged cells and bacteria to make them easier to recognize by other immune cells.

Chronically elevated CRP may signal an increased risk for practically all noncommunicable diseases (NCDs), including heart disease, cancer, diabetes, stroke, Alzheimer’s disease, chronic kidney disease, osteoporosis, chronic lower respiratory disease, and more - even if you are asymptomatic. However, conventionally, it is not treated on its own until it occurs in association with another medical condition (e.g., rheumatoid arthritis.)

CRP, in recent years, has also become understood as an active cause of inflammation in addition to simply being a marker of inflammation.

Chronically elevated CRP: A Direct Link to Decreased Longevity

CRP is an immune system protein produced by the liver in response to injury, infection, or other inflammatory events. Physicians often look at CRP as one of the major markers of chronic and acute inflammation.

Meta-analyses of all-cause mortality studies find that for longevity, the ideal baseline CRP is essentially as low as possible.

Source: https://pubmed.ncbi.nlm.nih.gov/28327451/

This empirical evidence agrees well with aging clocks like the Morgan Levine PhenoAge clock, where baseline CRP is a major component, and with leading Inflammaging research.

Chronic inflammation is a contributing factor to cancer, heart disease, lung disease, chronic obstructive pulmonary disease, chronic kidney disease, Alzheimer’s disease, and irritable bowel syndrome. It is also connected to an array of metabolic disorders, including pre-diabetes and diabetes, obesity (animal studies suggest that high levels of CRP may even directly cause weight gain by interfering with metabolism), and high blood pressure (CRP causes chronic contraction of blood vessels).

This is why tracking and optimizing baseline CRP using high-sensitivity CRP (hsCRP) tests is just as important for longevity and healthspan as blood glucose tracking (diabetes prevention), and lipid (ApoA1, ApoB, HDL, LDL) tracking (cardiovascular risk reduction).

How can I better understand my results?

The CDC/AHA divides the risk of cardiovascular events into the 3 following categories [3]

• Low risk: less than 1.0 mg/L

• Average risk: 1.0 to 3.0 mg/L

• High risk or acute inflammation: above 3.0 mg/L (consider discussing with your physician)

It is important to note that research supports targeting baseline CRP levels below 0.5 mg/dL. Commonly, lab tests will report "<0.2 mg/L" if you have an ideal/ undetectable value.

For example, a study of 27,939 women, showed that hsCRP and cardiovascular risk are proportional, meaning that lower hsCRP was linked to reduced risk—even at the lowest levels measured (<0.5 mg/L).

 

hsCRP vs. CRP

You may have seen CRP and hsCRP in your test results. These both refer to the same inflammation protein. CRP, or C-reactive protein, is also called “standard CRP.” CRP is also used in the diagnosis of severe inflammation related to acute conditions. The standard CPR test measures it in the range of 10 to 1000 mg/L. An hsCRP or “high sensitivity CRP” accurately detects lower levels of the protein and is used to evaluate individuals for low-grade inflammation and risk of heart disease. hsCRP measures CRP in the range from 0.2 to 10 mg/L.

 

Note: A high CRP value alone cannot be used to diagnose any specific issue. Consult your physician for any interpretation of your CRP test results.

What are the causes of persistently high baseline CRP?

Short-term CRP can spike for many reasons including intense exercise, infection, and other factors. Putting those aside, persistently elevated CRP (e.g. above 1mg/L) can have many underlying causes.

Nearly every common chronic disease has an inflammatory component. Even mental health conditions such as anxiety and depression tend to be associated with elevated CRP. As scientists learn more about the brain-body relationship, new connections of this type between blood biomarkers and mental health conditions are being found.

Chronic inflammation can last for months or indefinitely. It can be driven by underlying issues including pathogens (like a fungus or parasite), foreign material (such as a toxic chemical), or autoimmune disorders (like IBD or rheumatoid arthritis). However, for many modern Americans, lifestyle factors such as poor diet, nutritional or hormonal imbalance, cigarette, and alcohol use, and disrupted sleep can be the main driver of long-term inflammation.

Evidence-Based Approaches to Lowering Baseline CRP

Proactively making an effort to lower CRP levels is both feasible and recommended. Lifestyle has a direct impact on CRP levels. For example, the consumption of trans-fatty acids can increase CRP levels within the 0.9 - 2.3 mg/L range. Whereas moderate exercise has been shown to be a means of lowering high CRP.

Below are diet, lifestyle, and supplementation protocols that have strong evidence (references included) for improving elevated baseline CRP levels. Note that where possible we generally only reference Randomly Controlled Studies (RCTs) and Meta-analyses of RCTs.

Note: The information below is provided for reference, please consult your physician before starting any new health regimen.

Evidence for commonly suggested dietary and lifestyle changes that lower CRP:

1. Improved sleep

• Complete and partial sleep deprivation has been shown to increase CRP levels in healthy adults. [8]
• Quantify user data shows a strong -0.46 inverse correlation between the Quantify sleep score (based on wearable device sleep data) and hsCRP.
• Top Quantify sleep insight:

“Consider leaving your smartphone and any other screens outside your bedroom before going to bed. This will help you fall asleep faster and improve your sleep efficiency.”

2. Weight loss (if overweight) and improved diet

• Following a Mediterranean-style diet for a duration of 12 weeks has been shown to decrease CRP levels. [2]
• Weight loss is correlated with lowered CRP levels. [2]

3. Exercise

• Medium-intensity exercise (20 minutes to 1 hour of running) is known to lower your CRP levels [4]
• Quantify user data shows a significant -0.3 inverse correlation between daily steps taken (based on wearable device activity data) and hsCRP.

4. Cessation of smoking

• When levels of CRP were compared in smoking status groups for 1926 men aged 40 to 69 years, it was found that long-term cessation brought CRP levels down to non-smoker levels. [11]

5. Removal of processed foods and refined sugars from your diet

• A low-glycemic index and low glycemic load diet (eating less simple carbohydrates and lower portions of carbs) has been shown to decrease CRP levels. [1]

6. Heat Exposure

• Sauna usage [4-7x a week for 10-15 minutes] is associated with decreased hs-CRP levels. [13]

Evidence for Commonly Used Supplements for Reducing CRP Levels:

1. Curcumin

• (0-3 mg per kilogram of body weight, or roughly 0-1.4 mg per pound.) supplementation is associated with lower CRP levels. [5] [14]

2. Zinc

• A meta-analysis of 35 Randomized Control studies comprising 1995 participants has displayed a decrease in CRP following Zinc supplementation. ****[6]

3. Vitamin D

• Increasing sun exposure (15-20 minutes a day) or supplementing with Vitamin D over the counter may increase your Vitamin D levels and increase your Inflammation Score. [3]

4. Omega 3

• Omega 3 or fatty fish consumption is associated with lower CRP levels. [10]

5. Probiotic

• Probiotic supplementation has been shown to decrease CRP levels in a meta-analysis of 31 studies. [9]

6. Vitamin E (alpha-tocopherol)

• Supplementing vitamin E (15mg/day) can lower inflammation. A meta-analysis of 246 participants suggests that supplementation with vitamin E in the form of either α-tocopherol or γ-tocopherol would reduce serum CRP levels. [15]

7. Quercetin

• Supplementing quercetin at doses above 500 mg/day can lower inflammation levels. This meta-analysis showed a significant effect of quercetin supplementation on the C-reactive protein-especially at doses above 500 mg/day and in patients with CRP <3 mg/l. [16]

 

🗒️ Note: All of the lifestyle, diet and supplementation approaches to lowering chronic inflammation have been shown to work for the average person. To know which ones work for you, tracking your hsCRP on a regular basis is the most effective approach. 

Options for tracking your hsCRP:

Revolutionizing hsCRP tracking:

In 2023 SiPhox Health will be launching (for investigational use) our 3-minute at-home hsCRP test that uses only 5 microliters of blood, just like a glucometer. This will cut the cost, time, and difficulty of tracking hsCRP by a factor of ten. Quantify test kit subscribers will be the first to get access to our at-home device via a beta-tester study. 

References:

1. Anette E Buyken, Janina Goletzke, Gesa Joslowski, Anna Felbick, Guo Cheng, Christian Herder, Jennie C Brand-Miller. “Association between Carbohydrate Quality and Inflammatory Markers: Systematic Review of Observational and Interventional Studies.” Oxford Academic, The American Journal of Clinical Nutrition, Volume 99, Issue 4, April 2014, Pages 813–833, https://academic.oup.com/ajcn/article/99/4/813/4637862.

2. Basu, Arpita, et al. “Dietary Factors That Promote or Retard Inflammation.” Arteriosclerosis, Thrombosis, and Vascular Biology, 16 Feb. 2006, https://www.ahajournals.org/doi/10.1161/01.atv.0000214295.86079.d1.

3. Chen N;Wan Z;Han SF;Li BY;Zhang ZL;Qin LQ; “Effect of Vitamin D Supplementation on the Level of Circulating High-Sensitivity C-Reactive Protein: A Meta-Analysis of Randomized Controlled Trials.” Nutrients, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/24918698/.

4. CL;, Fedewa MV;Hathaway ED;Ward-Ritacco. “Effect of Exercise Training on C Reactive Protein: A Systematic Review and Meta-Analysis of Randomised and Non-Randomised Controlled Trials.” British Journal of Sports Medicine, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/27445361/.

5. Gorabi AM;Abbasifard M;Imani D;Aslani S;Razi B;Alizadeh S;Bagheri-Hosseinabadi Z;Sathyapalan T;Sahebkar A; “Effect of Curcumin on C-Reactive Protein as a Biomarker of Systemic Inflammation: An Updated Meta-Analysis of Randomized Controlled Trials.” Phytotherapy Research : PTR, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/34586711/.

6. Jafari A;Noormohammadi Z;Askari M;Daneshzad E; “Zinc Supplementation and Immune Factors in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.” Critical Reviews in Food Science and Nutrition, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/33356467/.

7. Luan, Ying-Yi, and Yong-Ming Yao. “The Clinical Significance and Potential Role of C-Reactive Protein in Chronic Inflammatory and Neurodegenerative Diseases.” Frontiers in Immunology, Frontiers Media S.A., 7 June 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008573/.

8. Meier-Ewert HK;Ridker PM;Rifai N;Regan MM;Price NJ;Dinges DF;Mullington JM; “Effect of Sleep Loss on C-Reactive Protein, an Inflammatory Marker of Cardiovascular Risk.” Journal of the American College of Cardiology, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/14975482/.

9. Milajerdi A;Mousavi SM;Sadeghi A;Salari-Moghaddam A;Parohan M;Larijani B;Esmaillzadeh A; “The Effect of Probiotics on Inflammatory Biomarkers: A Meta-Analysis of Randomized Clinical Trials.” European Journal of Nutrition, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/30854594/.

10. Mortazavi, Akramsadat, et al. “The Effect of Omega-3 Fatty Acids on Serum Apelin Levels in Cardiovascular Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.” Reports of Biochemistry & Molecular Biology, Varastegan Institute for Medical Sciences, Oct. 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175591/.

11. Ohsawa M;Okayama A;Nakamura M;Onoda T;Kato K;Itai K;Yoshida Y;Ogawa A;Kawamura K;Hiramori K; “CRP Levels Are Elevated in Smokers but Unrelated to the Number of Cigarettes and Are Decreased by Long-Term Smoking Cessation in Male Smokers.” Preventive Medicine, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/15917065/.

12. Sadura-Sieklucka, Teresa, et al. “Effects of Whole Body Cryotherapy in Patients with Rheumatoid Arthritis Considering Immune Parameters.” Reumatologia, Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie, 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091479/.

13. T;, Laukkanen JA;Laukkanen. “Sauna Bathing and Systemic Inflammation.” European Journal of Epidemiology, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/29209938/.

14. Tabrizi R;Vakili S;Akbari M;Mirhosseini N;Lankarani KB;Rahimi M;Mobini M;Jafarnejad S;Vahedpoor Z;Asemi Z; “The Effects of Curcumin-Containing Supplements on Biomarkers of Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Phytotherapy Research : PTR, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/30402990/.

15. Saboori S;Shab-Bidar S;Speakman JR;Yousefi Rad E;Djafarian K; “Effect of Vitamin E Supplementation on Serum C-Reactive Protein Level: A Meta-Analysis of Randomized Controlled Trials.” European Journal of Clinical Nutrition, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/25669317/.

16. Mohammadi-Sartang M;Mazloom Z;Sherafatmanesh S;Ghorbani M;Firoozi D; “Effects of Supplementation with Quercetin on Plasma C-Reactive Protein Concentrations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” European Journal of Clinical Nutrition, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/28537580/.