CRP plays an important role in infections. However, this protein is also a marker of low-grade inflammation and a predictor of your cardiovascular disease risk. Find out how this protein links stress, emotional and socioeconomic cues to physiological ones, and how to keep your CRP levels at bay.

Introduction

crp

http://www.jbc.org/content/279/47/48487.full

CRP, short for C-reactive protein, is a ring-shaped protein whose levels rise in response to inflammation (R).

CRP is currently considered as the key biomarker of systemic inflammation (R).

Its production is regulated by cytokines such as interleukin-6 (IL- 6), interleukin-1β (IL-1β), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) (R,R).

CRP is mainly produced in the liver in response to inflammation and tissue damage, but it can also be produced locally by other tissues, such as arterial tissue, lungs, and kidneys (R,R,R).

CRP’s is one of the pattern-recognition proteins. Its main function is the non-self recognition (R,R).

CRP plays a key role in the host’s defense against infection. CRP binds the cell surface of many pathogenic microbes, thereby activating the innate immune system (more specifically the classical complement pathway) (R,R). CRP also binds dead or dying cells (R). These microbes and cells are then ready to be devoured by white blood cells.

crp_mechanism

http://www.nature.com/nrrheum/journal/v7/n5/fig_tab/nrrheum.2011.37_F1.html

This process of is also called “the acute-phase reaction/response”, and represents an early reaction of the organism to a variety of injuries such as bacterial, viral or parasitic infection, mechanical or thermal trauma, ischemic necrosis or malignant growth (R).

These changes are called ‘acute’ because most are observed within hours or days following the onset of infection or injury (R).

The purpose of these responses is to restore balance within our bodies and to remove the cause of its disturbance (R).

Why Are Higher Levels of CRP Bad?

Apart from acute infection/injury, CRP is also an indicator of chronic/systemic inflammation. Increases in levels of CRP are part of the biological response to chronic stress (R).

Increased CRP levels have been found in a number of chronic conditions, such as prediabetes, prehypertension (elevated blood pressure), obesity, diabetes, hypertension and cardiovascular disease (CVD) (R,R).

CRP levels are associated with smoking and periodontal (gum) disease (R).

Elevated CRP levels can predict the development of type 2 diabetes and glucose disorders (R).

Studies show a statistically significant association of CRP with the onset of cardovascular disease (CVD) (R) and suggest that CRP levels can predict future cardiovascular (CV) risk in apparently healthy men and women (R).

When both CRP and cholesterol levels are high, a person’s overall risk of developing a CV event increases up to 9-fold compared with that of a person with low CRP and cholesterol levels (R).

CRP is positively correlated with measures of insulin resistance, obesity, and circulating triglyceride and negatively correlated with HDL cholesterol concentrations (R).

Apart from being a marker of inflammation, CRP also has a direct proinflammatory effect. In endothelial cells, CRP was shown to decrease nitric oxide and prostacyclin release and increase the levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1) (R).

In monocyte-macrophages, CRP increases reactive oxygen species and proinflammatory cytokine release (R).

Also in blood vessel muscles, CRP has been shown to increase inducible nitric oxide (iNO), NF-kB, mitogen-activated protein kinase, and angiotensin type-1 receptor (AGTR1), resulting in increased reactive oxygen species and blood vessel muscle cell proliferation (R).

CRP can also directly inhibit insulin signaling and action in skeletal muscles (R).

Optimal Reference Range For CRP

CRP is found in traces in overtly normal, healthy individuals (R).

The normal CRP levels vary between populations, with mean values from under 1.0 up to 3.0 mg/l (R). The median value of CRP in the blood is 0.8 mg/l, with an interquartile range of 0.3 to 1.7 mg/l (R).

The CRP baseline concentration is partially genetically regulated. Genetics accounts for 25–40% of the variation in CRP levels between people (R).

CRP secretion is increased by infections (bacterial, fungal, mycobacterial, or severe viral), tissue necrosis, trauma, cancer, and other inflammatory disorders, including atherosclerosis (R).

CRP concentration increases 4 to 6 hours after acute tissue injury or inflammation and declines rapidly with the resolution of the inflammatory process (R).

CRP levels can increase up to up to 1000-fold or even more, reaching a peak at 48 h (R,R).

CRP has a constant half-life of 18-19 h under all conditions of health and disease, so the sole determinant of circulating CRP concentration is the production rate (R,R). CRP can be degraded by macrophages (R).

Compared to the acute sharp rise in CRP levels, low-grade chronic inflammation, a condition underlying insulin resistance and associated with cardiovascular disease and type 2 diabetes, produces minor elevations of CRP in the 3- to 10-mg/L range (R).

crp_risk-large

http://circ.ahajournals.org/content/108/12/e81

To measure your CRP levels, normally you would want the high-sensitivity C-reactive protein (hs-CRP) test, not the CRP test. The CRP test is ordered for people with symptoms of serious bacterial infection or chronic inflammatory disease. It measures CRP in the range from 10 to 1000 mg/L, while hs-CRP test measures CRP in the range from 0.5 to 10 mg/L.

Elevated levels of CRP (>3 mg/L) are associated with cardiovascular event risk (R). The risk of developing cardiovascular disease is quantified as follows (R):

  • Low risk: hs-CRP level under 1.0 mg/L
  • Average risk: between 1.0 and 3.0 mg/L
  • High risk: above 3.0 mg/L
  • Very high risk: 5-10 mg/L
  • Above 10 mg/L – clinically significant inflammatory states (R).

CRP levels increase with age (R,R).

CRP can be elevated in pregnancy (median value of 4.8 mg/L, interquartile range of 0.63 – 15.7 mg/L), and these elevations are evident from even the earliest gestational ages and can persist throughout gestation. Fluctuations are common (R).

Viral infections and any mild inflammation elicit a smaller increase in CRP level (10–40 mg/L), while bacterial infection, as well as active inflammation, can elicit much higher responses of between 40–200 mg/L. In some severe bacterial infections and burns, the level can increase more than 200 mg/L (R).

CRP peaks at about 15:00 hours each day, with a 1% variation in CRP level attributed to the daily and seasonal effects. Very small changes occur during the menstrual cycle in females (R).

A lack of CRP elevation in inflammation may be seen with liver failure, as well as during flares of conditions such as systemic lupus erythematosus (R).

Elevations of CRP in the absence of clinically significant inflammation can occur in renal failure (R).

CRP and Disease

CRP in Infections

crp_infections

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120012

CRP plays a protective role in infection, activating the immune response, and helping the body defend itself from viruses and bacteria (R,R).

Viral infections elicit a smaller increase in CRP (10–40 mg/L), while bacterial infection can elicit much higher responses of between 40–200 mg/L, or in severe cases well above 200 mg/L (R).

Point-of-care tests that perform a CRP test within 4 minutes have now become available, and therefore CRP can assist in diagnosing serious infections in hospital settings (R).

CRP in Cardiovascular Disease

crp_atherogenesis

http://www.nature.com/nrcardio/journal/v2/n1/fig_tab/ncpcardio0074_F2.html

CRP is not only a systemic inflammatory marker. It is also a local pro-atherosclerotic factor. It can cause the hardening of arteries (R).

CRP has proinflammatory effects on blood vessel cells and may play a causal role in the pathogenesis of heart artery disease (R).

CRP can activate the cells that line the interior of blood vessels and can cause their dysfunction (R).

CRP reduces nitric oxide (NO) release from arterial and venous cells (R). Nitric oxide is important because it relaxes narrowed blood vessels, increasing oxygen and blood flow. (R).

CRP was found to cause atherosclerosis (hardening of the arteries). Furthermore, the plaque buildup within the arteries is capable of releasing CRP in the bloodstream and modifying local blood CRP levels perpetuating the cycle (R).

Similarly, increased levels of low-density lipoprotein (LDL) cholesterol in patients with cardiovascular risks induce blood vessels to express CRP, which may, in turn, promote the uptake of LDL into blood vessel cells (R).

In healthy subjects CRP can predict myocardial infarction mortality, peripheral blood vessel disease, heart failure, and arrhythmias, including sudden heart death (R,R).

CRP levels <1 mg/L are considered low-risk, 1 to 3 mg/L as average risk, and >3 mg/L as high risk for cardiovascular disease (CVD) (R).

In the Women’s Health Study, CRP was additive to low-density lipoprotein (LDL) cholesterol and the Framingham 10-year risk score in predicting future CVD in healthy American women (R).

The American Heart Association and Centers for Disease Control and Prevention recommended using CRP as a risk marker for cardiovascular diseases in individuals with a Framingham risk score between 10% and 20%. This subgroup of patients may benefit from high-sensitivity (hs)-CRP testing, mainly because physicians are often undecided about the treatment for a patient who is considered at intermediate risk (R).

A controversial trial named JUPITER, in which statins were administered to healthy individuals with > 2 mg/L CRP levels (see optimal reference ranges above), resulted in a significant 44% reduction in the risk of myocardial infarction, stroke, admission to hospital for unstable angina, or death from CVD (R). This study has, however, received a lot of critiques and should be taken with a grain of salt (R).

CRP in Elevated Blood Pressure

CRP may change the blood  vessel system toward a proinflammatory and narrowed-blood-vessel (vasoconstrictive) state with increased arterial stiffness, resulting in elevated blood pressure (hypertension) (R).

Elevated CRP value preceded new-onset hypertension at an early stage among an elderly healthy population (R).

Individuals with highest CRP levels had a twofold increased risk of developing elevated blood pressure compared to those with the lowest CRP levels (R).

CRP in Metabolic Syndrome

Metabolic syndrome (MetS) is a proinflammatory state characterized by increased CRP levels (R).

There is a linear relationship between the number of metabolic features and increasing levels of CRP (R).

CRP is positively correlated with BMI, waist circumference, blood pressure, triglycerides, cholesterol, LDL cholesterol, blood glucose, and fasting insulin, and it was inversely correlated with HDL cholesterol and insulin sensitivity (R).

Strong associations are observed between CRP levels, central obesity, and insulin resistance (R).

Additionally, CRP in the setting of MetS confers an increased risk of future cardiovascular events (R).

CRP in Obesity

Elevated CRP is associated with obesity and abnormal fat metabolism in adults and children (R).

There is a significant correlation between CRP and BMI and CRP and total calorie intake (R).

Schoolchildren who were overweight/obese had higher levels of CRP and IL-6, whereas individuals with waist circumference (WC) and body fat percentage (BF%) alterations had higher levels of CRP only (R).

Furthermore, CRP concentration can predict the change in BMI during childhood (R).

Higher CRP concentrations correlate with lower concentrations of adiponectin, a protein that enhances insulin sensitivity and prevents atherosclerosis (hardening of the arteries) (R).

CRP in Stroke

High CRP levels were associated with the development of stroke (R).

CRP level was associated with the severity of stroke, and the mortality and brain hemorrhage after stroke (R).

CRP > 3 mg/ml was associated with increased risk of incident stroke by 40% as compared with CRP<1 mg/l over a 15-year follow-up period. The risk was greater in men with elevated blood pressure (R).

CRP in Obstructive Sleep Apnea

CRP is also increased in obstructive sleep apnea (OSA), when breathing is suspended during sleep. Patients with OSA have higher blood CRP concentrations that increased corresponding to the severity of their apnea (R,R,R).

Treatment of OSA with CPAP (continuous positive airway pressure) significantly alleviated the effect of OSA on CRP levels (R).

Low levels of magnesium (Mg) are associated with chronic inflammatory stress and higher CRP concentration in patients with OSA (R).

CRP in Systemic Lupus Erythematosus (SLE)

Reduced clearance of dying cells by macrophages and/or increased cell death cause accumulation of cellular fragments in various tissues. Autoimmunity was reported to develop in many animal models with defects of the clearance of dying cells and cell material, especially that of nuclear origin (R).

CRP has the ability to bind nuclear debris and autoantigens and promote the clearance of dying cells, and may protect against autoimmunity (R,R).

Insufficient CRP levels are implicated in the development of systemic lupus erythematosus (SLE) (R).

In human SLE, there is relative failure of the acute-phase CRP response during active disease despite evident tissue inflammation (R).

A mutation in the CRP gene has been detected in SLE patients, but its significance is not known. However, this mutation leads to a decreased CRP level in SLE patients (R).

In parallel, low CRP level may also be induced by IgG antibodies to CRP which are found in up to 78% of SLE patients (R).

It has been shown that an injection of CRP can delay the onset of SLE and the development of kidney inflammation in mice (R).

The link between CRP and SLE is not that straightforward because elevated CRP was found to correlate with disease activity in SLE in a number of other studies (R).

There was also an association between vitamin D deficiency and elevated CRP in lupus patients (R).

CRP in Rheumatoid Arthritis

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CRP is found in the joint cavity fluid of rheumatoid arthritis (RA) patients and can bind to white blood cells and other inflammatory cells (R).

Inflammation in RA is closely related to the production of CRP and pro-inflammatory cytokines. Studies of patients with rheumatoid arthritis (RA) document a correlation between high CRP and worsening of RA symptoms (R).

Levels of CRP correlate with changes in inflammation/disease activity, tissue damage and progression, and functional disability (R).

CRP level is one of the best predictive markers for joint destruction and disease progression in early RA and is a strong risk predictor of non-traumatic fractures (R).

CRP is also associated with various manifestations of RA, such as the induction of atherosclerosis (hardening of the arteries) and osteoporosis (R).

Changes of CRP within the first 2 weeks of treatment with an anti-TNF agent can determine whether this RA treatment will be successful (R).

CRP in Periodontal (Gum) Disease

Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and bone loss. CRP levels are elevated in patients with chronic periodontitis (R).

CRP tends to increase with the gum destruction marked by alveolar bone loss (R). Patients with aggressive periodontitis had significantly higher CRP compared to the localized aggressive periodontitis and non-periodontitis groups (R).

Treatment of gum infections, whether by intensive mechanical therapy, drug therapy or extraction, can significantly lower CRP (R).

6 months after the completion of gum therapy, a median decrease in CRP of 0.5 mg/l  was observed (R).

CRP in Inflammatory Bowel Disease (IBD)

Elevated CRP can be observed in inflammatory bowel disease (IBD), but this is not always the case.

In one study, CRP before diagnosis was associated with risk of incident Crohn’s disease and ulcerative colitis (R).

In another study CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis but had no influence on CRP levels in patients with Crohn’s disease (R).

In another study, however, CRP concentration was not associated with colonic inflammation (R).

CRP of ≤0.5 can exclude IBD in patients with IBS symptoms (R).

CRP in Fatigue

Low-grade inflammation has a role in the development of fatigue (R,R).

Fatigue was associated with higher CRP concentrations in healthy adults (R), and disease-free survivors of breast cancer (R).

Higher CRP was also prospectively associated with new-onset fatigue (R).

CRP in Depression

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Low-grade inflammation is linked to depression.

A number of studies found a significant association between increased CRP and depressive symptoms (R,R,R).

Elevated CRP was found to be significantly more frequent in patients with recurrent depressive disorders and was further associated with overweight/obesity and lowered high-density lipoprotein (R).

CRP levels were associated with a history of suicide attempts in depressed patients. The risk of suicide attempts increased with higher levels of CRP (R,R).

Increased levels of hostility were also associated with increased levels of CRP (R).

CRP in Age-related Macular Degeneration

Macular degeneration is a medical condition which may result in blurred or no vision in the center of the visual field.

Several studies suggest a close association between CRP and eye blood vessel disorders. A significant association between the incidence of age-related macular degeneration (AMD) and CRP levels was found, especially between the occurrence of AMD and CRP levels higher than 3 mg/L (R).

High levels (> 3 mg/L) of CRP are associated with a two-fold likelihood of late onset AMD, compared to low levels (< 1 mg/L) (R).

Furthermore, more than threefold higher incidence of AMD was found in women with CRP levels exceeding 5 μg/mL (R).

CRP in Dementia

In the oldest-old, high CRP levels are associated with increased odds of all-cause dementia (memory decline), particularly in women (R).

CRP in Cancer

Some organs of the body show a greater risk of cancer when they are chronically inflamed (R). It is therefore not surprising that an association between increased CRP and the risk of developing cancer was found (R).

CRP elevation has been associated with the progression of skin, ovarian, and lung cancer, and CRP has been used to detect recurrence of cancer after surgery (R).

Persistent elevation of CRP has also has been reported in colorectal cancer, and is associated with the increased risk of colorectal cancer and overall cancer risk (R).

Preoperative CRP >10 mg/L was a strong predictor of compromised survival in colorectal cancer patients with liver metastases (R).

Factors that Elevate CRP

1) Sleep Disturbances

crp-sleep

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643002/

There is an established, yet complex, relationship between CRP and sleep. Excess sleep, insufficient sleep, frequent napping and infrequent napping can all be linked with elevated CRP, but these relationships depend on both nocturnal and daytime sleep patterns (R).

Insufficient sleep has been linked to inflammation. For example, CRP increases with both sleep deprivation and poor self-rated sleep quality in a dose-dependent manner (R).

Both total (88 hours) as well as partial (4.2 hours during 10 consecutive nights) sleep restriction significantly increased blood concentrations of CRP (R).

Sleep deprivation in pregnancy significantly increases CRP (R).

CRP concentration was elevated immediately after sleep restriction, and since this peptide has a half-life of 19h, this elevation was sustained after two days of recovery sleep (R).

On the other hand, several investigations have linked long sleep (≥9 hrs/night) with higher CRP in individuals with Obstructive Sleep Apnea and type 2 diabetes (R).

Elevated levels (>3.0mmol/l) of CRP were observed in both ≤6h and ≥10h sleep in aging men (R).

In men, long sleep duration and greater sleep disturbance were associated with raised CRP levels (R).

The relationship between daytime naps and CRP is also ambiguous. Self-reported nappers had increased CRP, and the authors suggested that frequent naps may actively elevate CRP, possibly via enhanced blood pressure upon waking (R).

On the other hand, a recent investigation focusing on young adults who nap infrequently reported IL-6, the precursor to CRP, increases following sleep deprivation, but decreases after subsequent naps (R).

A study looked at interdependence in couples’ sleep (sleep-wake concordance i.e., whether couples are awake or asleep at the same time throughout the night). Men and women with higher sleep-wake concordance also had lower CRP values (R).

2) Smoking

Cigarette smoking was found to increase CRP (R,R).

CRP increases directly after smoking in chronic obstructive pulmonary disease patients (R).

Studies have shown that increased CRP levels are a secondary effect of smoking and reflect tissue injury (R).

3) Saturated Fatty Acids and Trans Fats

There is a potential positive association of saturated fatty acids (SFA) with CRP levels (R).

Lauric and myristic acids and high saturated/polyunsaturated fatty acid (SFA/PUFA) ratio are associated with elevated CRP concentrations in men (R).

A study of over 700 nurses showed that those with the highest trans fat consumption had blood levels of CRP that were 73% higher than those with the lowest consumption (R).

4) Vitamin Deficiency

Elevated CRP was associated with vitamin D deficiency in the urban elderly (R).

Elevated CRP was associated with prenatal vitamin A deficiency (R).

A significant negative correlation was found between retinol (vitamin A) level and CRP in children (R).

Vitamin A-deficient subjects exhibited a significant risk of elevated CRP in a sub-Saharan African study (R).

CRP had a negative correlation with vitamin K concentration in older men and women (R).

CRP concentrations were positively correlated with vitamin K deficiency status in young adult women (R).

5) Stress

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CRP is elevated in chronic stress and may be the link between stress and low-grade inflammation related diseases.

Psychological and social stress significantly impacts CRP (R). In a study that examined job stress and CRP levels among Chinese workers, effort, overcommitment, and effort-reward imbalance were significantly correlated with higher CRP; and reward was significantly related with lower CRP (R).

Positive engagement coping was associated with lower CRP in the context of interpersonal stress (e.g., arguments with parents or siblings, conflict between adults in the home, friendship ended) or frequency of arguments with others reported in daily diaries (R).

A correlation was found between high CRP levels, chronic stress, and burnout experience in women with psoriasis (R).

Individuals with more children had significantly higher levels of CRP than individuals without children or than individuals with a low number of children. This association could reflect the known associations between high CRP and higher economic stress, exhaustion, episodic stress and chronic stress (R).

6) Socioeconomic Factors

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CRP levels have been associated with many social and economic factors, which, in many cases, can be translated into chronic stress.

Children whose parent had less than a high school degree had 35% higher CRP than those with a college graduate parent; and, poor children had 24% higher CRP than those with high family income (R).

Children living in neighborhoods with high levels of poverty or crime had elevated CRP levels compared to children from other neighborhoods (R).

Furthermore, there was an association between childhood social isolation and CRP (R).

As neighborhood and family’s socioeconomic status (SES) increased, CRP decreased (R,R,R).

Being married is weakly associated with lower CRP level (R).

Both higher education and household income predicted lower CRP levels over the 13 years of a follow-up study (R).

In a Swiss sample, a linear association was found between education and CRP (R).

Depending on the study, associations with CRP and race were observed (R), or not found (R).

Several studies have demonstrated that women have higher levels of CRP compared to men (R).

Among heterosexuals, women had higher levels of CRP than men. However, sexual-minority men had higher levels of CRP than heterosexual men and sexual minority women. Lesbians had lower levels of CRP than heterosexual women (R,R,R).

7) Substance Abuse

CRP levels were higher in the presence of nicotine, alcohol, and cannabis use and nicotine dependence (R).

A U-shaped cross-sectional relationship between CRP and alcohol consumption is widely documented. Whereas alcohol in moderation is beneficial, alcohol users showing abuse or dependence have elevated CRP (R).

8) Altitude

While a short-term stay at moderate altitude (2590 m) can decrease CRP levels (R), higher altitudes increase CRP and systemic inflammation.

Circulating CRP is upregulated in response to low pressure and low oxygen conditions at high altitude (R).

Hypoxia (decreased body oxygen) at high altitude was also associated with elevated CRP (R).

In a 2-week mountaineering expedition (at 3200-3616 m), participants had increased CRP concentrations (R).

High CRP is associated to neurological cognitions in high altitude, and it may be a potential biomarker for the prediction of high altitude induced cognitive dysfunction (R).

9) Extreme Cold

In temperatures below 0°C, CRP level increases with decreasing temperature. A reverse association, however, was observed above 0°C (R).

Hormones/Pathways That Increase CRP

10) Leptin

Leptin is able to promote CRP production from liver cells and cells lining blood vessels (R).

Positive correlations between blood leptin and CRP concentrations with increasing obesity have been reported. Administration of leptin to humans was also shown to increase blood CRP levels (R).

On the other hand, CRP can bind leptin in the blood, and the restriction of leptin may cause leptin insufficiency in the hypothalamus which, in turn, promotes fat accumulation (R).

11) Estrogen

Oral estrogen therapy increased CRP levels in women (R,R).

Postmenopausal women using hormone replacement therapy (HRT) have higher CRP levels (R).

12) Cytokines IL- 6, IL-1β, IL-17 and TNF-α

CRP production is regulated by interleukin-6 (IL- 6), interleukin-1β (IL-1β), IL-17 and tumor necrosis factor-α (TNF-α) (R,R).

These cytokines are produced in response to, for example, steroid hormones, thrombin, other cytokines, UV-light, neuropeptides and bacterial components (R).

Lifestyle to Decrease CRP

Taking into account that CRP reflects chronic stress levels, it is not surprising that a balanced lifestyle and activities that can help us counter/reduce stress have beneficial effects on CRP levels.

1) Exercise

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Regular physical activity was shown to reduce CRP levels in several studies (R).

In an analysis of 20 studies involving 1,466 patients with coronary artery disease, CRP levels were found to be reduced after exercise. Among those studies, higher CRP concentrations or poorer fat profiles before beginning the exercise were associated with greater reductions in CRP (R).

The amount of exercise needed to lower CRP levels is relatively modest, total energy expenditure needed was estimated to be just 368 – 1050 kcal/week (R).

CRP level in healthy people and those with cardiovascular disease will decrease following twenty weeks of training with the intensity of 75% maximum oxygen consumption on ergometer bike (R).

Small-sided games (SSG) or cycling (CYC) training were both effective at improving CRP in sedentary, middle-aged men (R).

However, CRP levels can also increase post-exercise when the exercise is stressful and causes tissue damage. The amount of production of CRP depends on the duration, intensity, type of exercise and the distance traveled by an individual. CRP increases more in exercises with more distance traveled (R).

CRP level in aerobic exercise increases more than in anaerobic exercise (R).

The exercise of all-out intensity and relatively short duration, no matter what type, does not elicit a significant change in CRP for the 1h to 5h period of rest following the exercise (R).

After a marathon (42.195 Km) CRP levels were unchanged, they increased ¾ times the next day, and after four days were back to original levels (R).

On the other hand, CRP level after an ultra-marathon (200 km) increased 40 times and it remained at the same level up to six days after the race (R).

2) Weight Loss

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Weight loss and fat reduction were showed to induce favorable changes in CRP levels (R).

Intentional total body fat mass reduction was associated with significant reductions in CRP in obese adults with osteoarthritis (R).

The odds of achieving desirable CRP levels more than doubled with intentional 5% loss of total body weight and fat mass (R).

Some studies suggest that global, rather than regional, fat loss are better predictors of change in inflammatory burden (R).

Other studies indicate that fat stored in the abdominal region and thigh muscles is associated with higher circulating levels of CRP independent of total fat mass, suggesting that greater reduction of fat in these regions may be associated with greater improvement in CRP levels (R).

3) Balanced Diet

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The quality of diet was independently and significantly associated with lower CRP levels, showing that diet is associated with systemic inflammation (R).

Diets high in dietary fiber and rich in fruits and vegetables are associated with lower CRP levels, while consumption of a Western diet, a diet high in fat, sugar, sodium, and refined grains can elevate CRP levels (R).

In one study, participants received a 45% fat 1,000 Kcal Mediterranean-like meal (monounsaturated 61% of fat) or a Western-like (saturated 57% of fat) meal. The Mediterranean-like meal resulted in a 2-hour post-meal decrease in CRP (R).

4) Alcohol in Moderation

Light alcohol intake rather than abstention or abuse is associated with lower CRP levels (R,R).

Not surprisingly, red wine intake was associated with decreased CRP (R).

Among women, moderate wine consumers had significantly lower levels of CRP than women who drank no or little wine (R).

Combined consumption of white wine and extra-virgin olive oil also decreased CRP in chronic kidney disease patients (R).

However, the association between alcohol and CRP concentration appears to be mediated primarily by ethanol and was independent of the type of alcoholic beverage consumed (R).

5) Yoga, Tai Chi, Qigong, and Meditation

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Yoga, Tai Chi, and Qi Gong are multi-dimensional behavioral therapies that integrate moderate physical activity, deep breathing, and meditation to promote stress-reduction and relaxation, which beneficially influence the immune system and overall health (R).

7 to 16 weeks (1 to 3 times/week totaling 60 to 180 minutes weekly) of these so-called “mind-body therapies” causes statistically significant improvements in CRP levels, especially pronounced in individuals with disease (R).

Evidence suggests that yoga may help decrease inflammatory mediators including CRP (R).

When long-term expert hatha yoga practitioners and novices were compared in a study, expert practitioners had lower CRP levels (R).

An 8-week regimen of yoga in addition to standard medical therapy significantly reduced CRP levels in patients with heart failure (R).

A simplified, gentle form of tai chi chuan in patients with type 2 diabetes who were also obese decreased CRP levels (R).

A decrease in CRP was also observed in older depressed participants receiving escitalopram when they also practiced tai chi chih (R).

In cancer patients, medical qigong improved CRP levels, reduced the side effects of cancer (R), and improved the quality of life (R).

A practice of mindfulness in faculty staff with elevated CRP lowered their CRP levels. Although not statistically significant, at 2-months the CRP level was one mg/ml lower – a change which may have clinical significance (R).

In IBD patients attending a Breath-Body-Mind Workshop (BBMW) (breathing, movement, and meditation), by week 26 there was a significant decrease in CRP values (R).

Both a novel Buddhism-based walking meditation and the traditional walking exercise reduced CRP levels in depressed elderly (R).

6) Sexual Activity

Men who were sexually active with a partner (more than once a month) were less likely to be in a higher CRP category five years later than men who were sexually inactive. Yet, higher frequency of sex (i.e., 2–3 times a month or once a week or more) was not related to CRP for men (R).

Women with sexual partners had significantly lower CRP at midcycle, and higher CRP at other phases; in contrast, sexually abstinent women had little cycle-related change in CRP (R).

7) Optimism

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Inflammatory markers including CRP were increased in pessimism (R).

Self-rated health was associated with elevated CRP even among apparently healthy individuals (R).

Poor self-rated health was significantly associated with elevated CRP levels in women (R).

Nutritional Factors That Decrease CRP

Food/nutrients that return our body’s natural balance and reduce inflammation have beneficial effects on CRP levels.

8) Vitamin A, C, D, K Sufficiency

Blood vitamin C concentrations were found to be associated with lower CRP levels in both men and women, primarily among non-smokers, non-overweight women and postmenopausal women (R).

Supplementation with VitC+Ca+F reduced CRP and oral pathogens in a rural population with periodontitis (R).

Elevated CRP was associated with vitamin D deficiency in the urban elderly (R).

Elevated CRP was associated with vitamin A deficiency (R,R,R).

CRP was elevated in vitamin K deficiency in older men and women (R) and young adult women (R).

9) Vitamin E

Several studies showed a significant reduction in CRP levels in vitamin E-treated individuals (R).

In one study, participants who regularly ingested more than 78 mg vitamin E/d, had 22% lower CRP levels compared to those who were not exposed to any vitamin E supplementation (R).

Vitamin E-coated dialyzer can reduce CRP levels in hemodialysis patients (R).

10) Niacin

Niacin has been shown to reduce CRP levels and cardiovascular risk in patients with high cholesterol and triglycerides (R,R). Not all studies recorded significant effects though (R).

Lower dose extended administration of niacin can be used safely to decrease CRP successfully in non-ST elevated acute coronary syndrome (NSTE-ACS) patients. Study shows that at the 3rd day CRP levels were similar between the groups; but 1 month later, CRP levels were significantly lower in the niacin group of patients (R).

Niacin significantly decreased CRP levels when added to simvastatin therapy, compared to simvastatin alone (R).

11) Folate

Folate can decrease CRP levels (R).

Higher concentration of folate in the blood was associated with lower CRP concentration in pregnancy (R).

Folate had beneficial effects on CRP levels in patients with metabolic syndrome (R) and reduced CRP levels in overweight and obese women (R).

12) Carotenoids

High beta-Carotene was related to low CRP in several studies (R). In one of these studies, an increase of 2 mg/L in CRP was associated with a 1.3% decrease in β-carotene in middle-aged women (R).

Preterm infants supplemented with carotenoids had lower CRP (R).

Study participants who received astaxanthin had lower CRP at Week 8 (R).

Higher blood alpha-carotene and beta-carotene concentrations were significantly associated with lower CRP in Japanese men (R).

13) Selenium

The relationship of high CRP and low blood selenium was significant for well-nourished patients (R).

Selenium supplementation significantly decreased insulin levels and CRP in patients with diabetes and heart disease (R).

Selenium administration decreased CRP in women with polycystic ovary syndrome (PCOS) (R).

Selenium supplementation in pregnant women with gestational diabetes had beneficial effects on glucose metabolism, CRP levels, and biomarkers of oxidative stress (R).

Selenium and coenzyme Q supplementation decreased CRP and reduced cardiovascular mortality in the elderly (R).

14) Magnesium

A systematic review indicates that higher dietary magnesium intake is significantly associated with lower CRP levels. The potential beneficial effect of Mg intake on chronic diseases may be, at least in part, explained by inhibiting inflammation (R).

Oral magnesium supplementation decreased CRP levels in apparently healthy subjects with prediabetes and low magnesium (R).

Smoking causes a significant increase in CRP concentration, associated with a decrease in magnesium concentration (R).

15) Chromium

In women with polycystic ovary syndrome (PCOS), taking chromium for 8 weeks led to a significant reduction in CRP (R).

16) Calcium + Aspirin

Consumption of calcium supplement plus low-dose aspirin resulted in a significant decrease in CRP levels in pregnant women at risk for pre-eclampsia (R).

17) Polyunsaturated fatty acids

Higher intake of total polyunsaturated fatty acids (PUFAs) was associated with lower CRP levels. In this particular study, n-6 PUFAs were most beneficial (R).

In several studies, omega-3 fatty acids reduced the concentrations of CRP (R,R).

A high omega-3 diet significantly reduced CRP in older people (R).

Docosapentaenoic acid, a long-chain omega-3 acid, was associated with lower CRP (R).

18) Fiber

A high dietary fiber intake is associated with lower CRP levels (R,R).

Cereal fiber intake lowered CRP in women (R).

A 5-week high dietary fiber intake of oat bran, rye bran, and sugar beet fiber can reduce the low-grade inflammatory response measured as CRP (R).

Intervention with dietary fiber or fiber-rich food produced a slight, but significant reduction of CRP level among overweight and obese adults (R).

19) Probiotics

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A multispecies probiotic supplement (containing L. acidophilus, L. casei, L. rhamnosus, L. bulgaricus, B. breve, B. longum, S. thermophilus and fructooligosaccharide) for 8 weeks in diabetic patients resulted in a decrease in CRP and an increase in blood total GSH (R).

20) Coffee

Higher coffee consumption was associated with lower CRP (R,R).

Coffee consumption was associated with lower CRP among overweight/obese postmenopausal women (R).

One study found that CRP concentrations were progressively lower with increasing levels of coffee consumption in men, but not in women (R).

Another study showed that significantly lower levels of CRP were observed in the group of > or = 1 cup/day than in that of < 1 cup/day in Japanese women (R).

21) Green Tea

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Green tea extract reduces inflammatory biomarkers including CRP (R).

Green tea consumption in a multi-ethnic Asian population was associated with lower CRP concentrations (R).

Green tea catechins in the blood were shown to be weakly to moderately associated with lower CRP (R).

NOTE THAT: one study showed that hot tea consumers had lower levels of CRP compared to non-consumers of both sexes, whereas iced tea consumers had significantly higher levels of CRP compared to non-consumers (R).

22) Resveratrol

Wine polyphenols quercetin and resveratrol, dose-dependently suppress CRP production (R).

Sicilian red wine consumption was shown to reduce CRP levels (R).

23) Cocoa & Dark Chocolate

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Cocoa flavanols reduced CRP concentration in obese adults at risk for insulin resistance (R).

Dark chocolate reduced CRP levels in women (R), and patients with diabetes and elevated blood pressure (R).

A J-shaped relationship between dark chocolate consumption and CRP was observed; consumers of up to 1 serving (20 g) of dark chocolate every 3 d had CRP concentrations that were significantly lower than nonconsumers or higher consumers, suggesting that regular consumption of small doses of dark chocolate may reduce inflammation (R).

24) Cannabis

Recently active cannabis smokers among adults age 20–59 years old, had generally lower CRP levels than US community residents of the same age who had never smoked cannabis (R).

Another study found that the prevalence of elevated CRP (>0.5 mg/dl) was significantly higher among non-marijuana users than among past, current light or heavy users (R).

25) Botanical Extracts – Others

Milk thistle extract (Silybum marianum) significantly reduced CRP levels by 26.83% in type 2 diabetes patients (R).

Thirty days of pomegranate extract supplementation resulted in a significant decrease in CRP in overweight and obese individuals (R).

Aged garlic extract showed favorable effects on CRP in several studies (R).

Indian gooseberry (Phyllanthus emblica) extract decreased CRP levels after 12 weeks of supplementation in overweight and obese adults (R).

2-month treatment with Ginkgo biloba decreased CRP in metabolic syndrome patients (R).

A citrus polyphenolic extract of red orange, grapefruit, and orange reduced CRP levels (R).

Hormones/Pathways That Decrease CRP

26) Melatonin

Local melatonin application in patients with diabetes and periodontal disease resulted in a significant decrease in CRP (R).

Melatonin decreased augmented circulating levels of CRP in obese rats (R).

Medication That Decreases CRP

Cyclooxygenase inhibitors (aspirin, rofecoxib, celecoxib), platelet aggregation inhibitors (clopidogrel, abciximab), fat-lowering agents (statins, ezetimibe, fenofibrate, niacin, diets), beta-adrenoreceptor antagonists, as well as angiotensin converting enzyme (ACE) inhibitors (ramipril, captopril, fosinopril), reduce CRP (R).

Antidiabetic agents (rosiglitazone and pioglitazone) also reduce CRP levels, while insulin is ineffective (R).

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  • kathrin50

    I don’t agree, read [canyonranch]

    Sincerely, Kathrin

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