What are evidence-based methods to lower elevated C-Reactive Protein (CRP) levels?

Evidence-Based Methods to Lower High-Sensitivity CRP

The most effective evidence-based interventions to lower hs-CRP are regular structured exercise (reducing CRP by 16-41%), statins in appropriate populations, and adherence to a Mediterranean dietary pattern, with exercise showing reductions independent of weight loss. 1, 2

Lifestyle Interventions

Physical Activity and Exercise

• Structured exercise programs lower CRP levels by 16-41% in clinical trials, with effects that may be independent of baseline CRP levels, body composition, or weight loss 2
• Higher levels of physical activity and cardiorespiratory fitness are consistently associated with 6-35% lower CRP levels in cross-sectional studies 2
• A 6-month exercise program in rheumatoid arthritis patients lowered CRP levels, likely related to reduction in body fat 1
• The CRP reduction from physical activity appears at least as effective as pharmacological interventions in similar populations 2
• High-intensity exercise is not contraindicated and should be encouraged in those already accustomed to activity, as no adverse effects have been demonstrated 1
• Physical activity that is enjoyable is more likely to be sustained long-term 1

Dietary Modifications

Mediterranean Diet:

• A Mediterranean diet (high in fruits, vegetables, legumes, cereals, with olive oil as primary fat source, less red meat, more fish) shows inverse correlation with CRP concentration even after adjusting for age, gender, hypertension, metabolic syndrome, BMI, and statin treatment (p=0.041) 3
• Specific components associated with lower CRP include:
  • ≥2 servings of vegetables per day (p=0.003) 3
  • ≥3 pieces of fruit per day (p=0.003) 3
  • ≥3 servings of fish/seafood per week (p=0.058) 3
  • Lower consumption of butter, margarine, or cream (p=0.041) 3

Plant-Based Dietary Patterns:

• A vegan lifestyle intervention including fresh fruits, vegetables, whole grains, legumes, nuts, and seeds significantly reduced CRP levels 4
• The degree of CRP improvement was associated with baseline CRP levels—higher baseline levels predicted greater decreases 4
• Males with higher baseline CRP appeared to have more robust CRP decreases than females 4
• Healthy plant-based diet index (whole grains, fruits, vegetables, tea, coffee) significantly reduced hs-CRP and TGF-β (p<0.0001) 5
• The vegetable and high fiber content of plant-based diets likely reduces CRP in the presence of obesity 4

Smoking Cessation

• Smoking approximately doubles the risk of elevated CRP 6
• Patients should be advised to stop smoking and directed toward evidence-based smoking cessation programs, even if they have failed previously 1

Pharmacological Interventions

Statins

• Rosuvastatin is FDA-approved to reduce major adverse cardiovascular events in adults without established coronary heart disease who have hs-CRP ≥2 mg/L plus at least one additional CV risk factor 7
• The JUPITER trial demonstrated rosuvastatin lowered CVD event rates by 50% while decreasing CRP by 37% 8
• In women >60 years with estimated CHD risk >10%, statins could be considered if hs-CRP is >2 mg/L after lifestyle modification and no acute inflammatory process is present 1
• Statins reduce CRP in adults, though minimal information is available on their effect on CRP in children 1

Other Lipid-Lowering Agents

• Niacin or fibrate therapy can be useful when HDL-C is low (<50 mg/dL) or non-HDL-C is elevated (>130 mg/dL) in high-risk women after LDL-C goal is reached 1

Important Clinical Caveats

CRP as a Marker vs. Causal Factor

• Genetic studies of CRP polymorphisms have not shown corresponding differences in CVD event rates, suggesting CRP is a marker of inflammation rather than a direct causal factor 8
• No clinical trials have specifically demonstrated that achieving low CRP levels independently prevents atherosclerosis progression 8
• Current guidelines do not recommend serial testing of hs-CRP to monitor treatment effects 8

When to Investigate Further

• If CRP >10 mg/L with elevated TSH, investigate for concurrent acute infection, subacute thyroiditis, or other inflammatory disease 6
• Bacterial infections cause the highest CRP elevations (high inflammatory range), while viral infections cause moderate elevations 6
• Screen for acute illness by checking temperature and symptoms; examine liver enzymes to rule out fatty liver disease 6

Populations Requiring Special Consideration

• The American Heart Association notes there is currently no clinical role for measuring CRP routinely in children when assessing CVD risk factors 1
• Asian patients initiating rosuvastatin should start at 5 mg once daily due to increased plasma concentrations 7