Erythrocyte sedimentation rate (ESR) test is a blood test that checks if you have any inflammation. It can also track the progress of specific diseases. It is often called the “sickness index”. Read on to find out how ESR works, what can impact ESR levels in your body, and how it all relates to your health.
What Is the Erythrocyte Sedimentation Rate (ESR)?
Erythrocyte sedimentation rate (ESR) was discovered in 1987 [1, 2].
The ESR is the rate at which red blood cells (erythrocytes) sink to the bottom (sedimentation) of a tube in one hour [3, 4].
The main factors affecting ESR are hematocrit (percentage of red blood cells in your blood) and blood proteins, such as fibrinogen [5].
The ESR test has many functions.
ESR Blood Test
Erythrocyte sedimentation rate (ESR) test or “sed rate test”, is a blood test that checks for inflammation. It measures the distance in millimeters that red blood cells fall in one hour (mm/hr) [6, 7].
There are a few ways that this is measured, such as the Westergren method, Wintrobe Method, MicroESR, and automated methods [8, 9, 10].
Westergren Method
The Westergren method is considered the gold standard in measuring ESR [11].
The blood sample is mixed with sodium citrate (4:1). Then it is mixed into a Westergren-Katz tube (2.5 mm diameter) until the 200 mm mark.
Next, the tube is set vertically, at room temperature (18 – 25 °C), for one hour.
At the end of an hour, they measure how far the red blood cells have settled. This distance is ESR.
In the modified Westergren method, edetic acid is used instead of sodium citrate [8, 9, 10].
Other methods:
The Wintrobe method is less sensitive than the Westergren method and the maximal values may be misleading [12, 13].
The micro ESR method is quick (20 min) and popular for babies, as the test requires very little blood. It is also useful for diagnosing neonatal sepsis [14, 15, 16].
Automated methods are faster, easy to use, and could be better predictors for autoimmune diseases. Yet, their sensitivity to technical procedures (blood mixing, tube sizes, etc.) could influence the test results [17, 18, 19, 20, 21, 22, 23, 24].
What Can The ESR Test Reveal?
1) Inflammation
The ESR test checks if you have an inflammation [3].
In inflammation, certain proteins will appear in the blood, such as fibrinogen. These proteins cause red blood cells to cling together and form clumps. This makes them heavier, so they fall faster, which increases the ESR [5, 25, 3].
Therefore, high ESR shows inflammation. The higher the ESR level, the higher the inflammation [5, 25, 3].
But, the ESR test is not very sensitive (so it can’t pick up all inflammation) nor specific, so it can not diagnose specific diseases [6].
2) Screen for Specific Diseases
The ESR test could help with the diagnosis of certain diseases:
- Polymyalgia rheumatica (an inflammatory disease which causes muscle pain and stiffness) [26, 27, 28]
- Giant cell arteritis (inflammation of blood vessels) [29, 30, 31, 32, 33]
- Cancer [34, 35]
- Bone infections [36, 37, 38]
- Subacute thyroiditis (inflammation of the thyroid) [39, 40, 41]
- Ulcerative colitis [42]
3) Progression of Specific Conditions
The ESR test cannot diagnose diseases, but it can track the progress of specific conditions [43]:
- Heart disease [44, 45, 46]
- Cancer [47, 5, 48]
- Rheumatoid arthritis [49, 50, 51]
- Systemic lupus erythematosus (SLE) [52, 53]
- Sickle-cell disease [54, 55, 56]
4) Serious Conditions
ESR levels higher than 100 mm/hr could suggest a serious disease, such as infection, heart disease, or cancer [57, 5, 3, 6].
ESR levels higher than normal may predict cancer or cancer progression, like metastasis [58, 59, 60, 61, 62].
When to Get a Sed Rate Test
Your doctor may order an ESR test if you have the following symptoms [63]:
- Headache
- Fever
- Joint or shoulder pain
- Abnormal weight loss
- Anemia
Normal ESR Levels
| Age | Men | Women |
| Younger than 50 | 0-15 mm | 0-20 mm |
| Older than 50 | 0-20 mm | 0-30 mm |
Children should have an ESR lower than 10mm [3].
A low ESR is normal and does not cause any symptoms [63].
Factors That Increase ESR Levels
Disorders and diseases:
- Inflammation, infection, or malignant diseases can increase ESR rates [3, 5, 25, 64, 65, 66]
- Women tend to have higher ESR rates [3, 6, 5, 67]
- Old age [3, 6, 5, 67, 68]
- Anemia; reduced hematocrit increases ESR levels [3, 5, 6, 65]
- Macrocytosis (large red blood cells) [3, 5]
- Polycythemia (increased production of red blood cells) [3, 5, 69, 8, 70]
- Increased fibrinogen levels [3, 5]
- Pregnancy [71, 72]
- Diabetes [3, 5, 73]
- Kidney failure [74]
- Chronic heart failure [75]
- Obesity [6, 5]
- Hyperlipidemia (high concentrations of fats in the blood) [76]
- Heart disease [77, 44, 45]
- Polymyalgia rheumatica (an inflammatory disorder where there is muscle pain around the shoulders and hips) [78, 27, 79]
- Subacute thyroiditis [39]
- Alcoholic liver disease, which can cause decreased albumin production, and thus increase ESR [80]
- Crohn’s disease and ulcerative colitis [81, 82]
- Kidney failure [74]
- Temporal/giant cell arteritis (inflammation in blood cells around the scalp) [83, 84]
- Multiple myeloma [85]
- Waldenstrom’s macroglobulinemia (tumors that make large amounts of immunoglobulins) [86, 87]
- Atherosclerosis (plaque buildup in the arteries) and stroke [88]
- Cancer risk, progression, and death [34, 89, 90]
Drugs and supplements:
- Iodine, when it causes thyroid problems [91]
- High ginger consumption, when it’s linked to subacute thyroiditis [92]
- Birth control [93]
- Smoking [94, 95, 96, 97]
- Alcohol [80, 98]
- Dextran [99]
Technical errors during the test such as a tilted tube or dilution error can also give a false high ESR result [3].
Factors That Decrease ESR Levels
When red blood cells are smaller, they will drop slower, hence a lower ESR.
- Red blood cells diseases: extreme leukocytosis, polycythemia, microcytosis, sickle cell disease, spherocytosis, acanthocytosis, and anisocytosis [3, 5, 69, 8, 54]
- Protein abnormalities: hypofibrinogenemia, hypogammaglobulinemia, and dysproteinemia with hyperviscosity state [3, 5, 8, 65, 100, 70]
- NSAIDs, cortisone, anesthetic drugs, levamisole, and prednisone [101, 5, 8, 102, 84]
What Happens If Your ESR Is High?
Conditions Associated With High ESR
The conditions we discuss here are commonly associated with high ESR test values, but this single symptom is not enough for a diagnosis. Work with your doctor to discover what underlying condition might be causing your unusually high value in this test and to develop an appropriate plan to improve your health.
1) Polymyalgia Rheumatica
Polymyalgia rheumatica is an inflammatory condition that affects people over 50. It causes pain and stiffness in the neck, shoulders, upper arms, and hips, or pain all over the body [103, 104].
The ESR test is often used as a diagnostic tool for polymyalgia rheumatica, as high ESR levels show inflammation [27, 79].
In multiple studies on almost 900 people with polymyalgia rheumatica, most people had ESR above 30 mm/h. Only 6% to 22% of them had ESR lower than 30 mm/h [105, 26, 106, 107, 108, 109].
High ESR (> 30-40mm/h) may show polymyalgia rheumatica. Yet, normal ESR rates cannot exclude the condition and more tests should be done [106, 110, 111, 112].
2) Giant Cell/Temporal Arteritis
Temporal arteritis or giant cell arteritis is when there is inflammation of the blood vessels. It affects people over 50 and is more common among women. It can cause headaches, pain in the joints, fever, eye pain, blindness, and even stroke. It is often related to polymyalgia rheumatica [113, 31, 30, 114, 115].
One of the diagnostic criteria of temporal arteritis is when ESR is equal or higher than 50 mm/hr [30, 29, 31, 32, 33].
In multiple studies on almost 400 people with temporal arteritis, most people had ESR above 40 mm/h [116, 84, 117, 118, 119, 120].
High ESR (> 40-50mm/h) can show temporal arteritis, but ESR < 40mm/h cannot exclude the condition. Other tests, like C-reactive protein, are more sensitive in diagnosing the disease [116, 121].
3) Heart Disease
In multiple studies with over 262,000 people, those with high ESR had higher chances of developing heart failure, heart attack or atherosclerosis (hardening of the arteries) compared to people with normal ESR levels [42, 122, 44, 45, 123, 88].
In multiple studies with almost 21,000 people, those with high ESR had increased risk of dying from heart disease or stroke [44, 45, 124, 125, 126].
In multiple studies with almost 500 heart disease or stroke patients, most patients had increased ESR levels [127, 128, 129].
In two studies on almost 1,000 patients who had heart surgery, people with ESR above 40 mm/h had longer periods of hospital stay and intensive unit care, and increased risk of adverse effects [46, 125].
4) Cancer
In a study of almost 240,000 Swedish men, those with ESR above 15 mm/hr had a 63% higher risk of colorectal cancer compared to those with ESR of < 10 mm/hr [34].
In a study on 5,500 people, those with weight loss, anemia, and high ESR had a 50% chance of cancer. Patients with weight loss and high ESR, but not anemia, had a 33% chance of cancer [35].
In a study of almost 4,500 people, breast cancer patients had much higher ESR levels (> 35 mm/h) compared to healthy women and those with benign cancer [130].
In multiple studies with 1.2 million prostate cancer patients, those with ESR above 50 mm/h had lower survival rates and a higher risk of metastasis [131, 47, 61].
In two studies with almost 1,500 kidney cancer patients, high ESR increased the risk of death [132, 89].
In 854 Hodgkin disease patients, those with ESR above 30 mm/h had active disease and a higher risk of death [133, 58].
In 139 skin cancer patients, those with ESR higher than 22 mm/h had lower survival rates and a higher risk of metastasis [134].
In 97 patients with blood cancer (mycosis fungoides), those with high ESR levels had 52.83% chance of surviving the disease [90].
In 220 patients with stomach cancer, men with ESR above 10mm/h and women with ESR above 20 mm/h had lower survival rates, more metastases and larger tumors [135].
In 410 patients with a type of bladder cancer (upper urinary tract urothelial carcinoma), ESR levels higher than 22 mm/h for men and 27 mm/h for women were associated with cancer progression and death [48].
Patients with skin disease (dermatomyositis) and ESR levels higher than 35 mm/h had higher chances of developing cancer [136].
In 94 patients with glioma (tumor in the brain or spinal cord), those with ESR above 15 mm/h had higher chances of dying [137].
In 42 patients with multiple myeloma, those with increased ESR had lower survival rates [138].
Patients with high ESR had lower chances of survival compared to patients with low ESR in a study on 189 lung cancer patients [139].
5) Rheumatoid Arthritis Progression
Rheumatoid arthritis (RA) is an autoimmune disease. It causes pain, stiffness, and swelling in joints. Increased ESR often suggests active RA or disease progression [49, 50, 51].
In a 25-year study on almost 1,900 rheumatoid arthritis patients, 64% of the patients had ESR levels higher than normal [140].
In multiple studies with 373 people with a 2-year study on 251 patients with rheumatoid arthritis, higher ESR levels showed worse disease status or lower treatment response [141, 142, 143].
But, in a 1-year study on 159 children with rheumatoid arthritis, the ESR levels did not relate to disease progression [144].
6) Bone Infections & Inflammations
ESR levels higher than 70 mm/hr in adults and above 12 mm/h in children can suggest bone infections [36, 37, 38, 145].
People with diabetes and ESR above 70 mm/hr have an increased risk of developing diabetic foot osteomyelitis (bone infection) [36].
In 61 patients with an untreated foot infection, ESR levels higher than 67 mm/hr indicated osteomyelitis (bone infection) [37].
In bone inflammation (spondylodiscitis), more than 90% of the patients have ESR levels between 43 mm/h and 87 mm/hr [38].
In 259 children with limb pain, ESR above 12 mm/hr and C-reactive protein (CRP) above 7 mg/L were related to orthopedic infection [145].
In patients after hip replacement surgery, increased ESR may show joint infection [146].
In 285 patients with knee osteoarthritis, those with ESR above 20 mm/h had lower muscle strength compared to patients with normal ESR levels [147].
A decrease of ESR during treatment may show good treatment response and improvement in disease status [148].
7) Systemic Lupus Erythematosus (SLE)
Systemic lupus erythematosus (SLE) is an autoimmune condition. It can affect joints, the nervous system, the kidneys, the skin, the heart, and the lungs. People with lupus have periods of health (remission) and periods of illness (flares) [53, 149].
In patients with active lupus, ESR is usually high. High ESR in lupus patients may indicate flares [52, 150].
In multiple studies with over 1,000 people with lupus, abnormally high ESR showed flares, infections or disease progression [151, 152, 153, 154].
8) Sickle-Cell Disease
In two studies with 139 children with sickle-cell disease, their normal ESR levels were below 8 mm/h. ESR above 20 mm/h showed crisis or infection [55, 56].
If ESR is high (> 20 mm/h) in people with sickle-cell disease, it indicates infection or painful crisis [54, 55, 56].
9) Ulcerative Colitis
In a 7-year study on almost 241,000 healthy men, those with higher than normal ESR levels had a higher incidence of ulcerative colitis [42].
ESR above 15 mm/h may predict relapse in patients with ulcerative colitis [155].
10) Subacute Thyroiditis
Subacute thyroiditis is an inflammation of the thyroid. It causes pain and swelling of the thyroid, fever, and tiredness. In most patients with subacute thyroiditis, ESR levels are higher than 50 mm/h [39, 40, 41, 156, 157, 158, 91].
Ginger and iodine may cause subacute thyroiditis, which increases ESR [156, 91].
11) Reduced Cognitive Ability
In a study on almost 50,000 men, those with ESR above 7 mm/h had decreased cognitive abilities at age 18 – 20 [159].
In 368 stroke patients, increased ESR were related to reduced hippocampal volume (part of the brain responsible for memory) and lower cognitive abilities [160].
Higher ESR was associated with a lower IQ in a study of 638,000 men [161].
12) Schizophrenia
Higher ESR was also related to an increased risk for schizophrenia in the same study of 638,000 men [161].
Causes of High ESR
1) High Fibrinogen
High fibrinogen levels make the red blood cells to clot together and fall faster, thus increasing ESR levels [3].
Diets high in iron, sugar, and caffeine were related to increased fibrinogen levels in 206 people [162].
Protein, in particular, may be necessary for healthy levels of fibrinogen. Protein-deficient animals have low fibrinogen compared to their properly-nourished counterparts [163].
In a study on 16 people, a protein shake or a balanced-meal shake doubled fibrinogen levels [164].
2) High Triglycerides (Association)
In 101 people with high cholesterol and triglycerides, most of them had higher ESR levels [165].
- A low-fat, high-carbohydrate diet increased blood triglycerides in healthy adults [166, 167, 168, 169].
- Low-fat, high-carbohydrate, sugar-rich diets increase the production of Very-Low-Density Lipoprotein (VLDL), and blood triglycerides [170, 171, 172].
- Lack of exercise and sugar consumption, including fructose and glucose, can increase blood triglyceride levels [173, 174, 175].
3) Birth Control
In 42 healthy women who were taking oral contraceptives, 45% of them had much higher than normal ESR levels [93].
4) Alcohol Consumption
Chronic alcohol consumption can cause inflammation [98].
In a study on 250 people, people with alcoholic fatty liver disease and alcoholics had the highest ESR levels compared to the other groups [80].
Alcohol can also cause macrocytosis (large red blood cells), a condition which increases ESR [3, 5, 176].
5) Smoking
Smoking produces free radicals which increase inflammatory proteins, such as fibrinogen. This leads to increased ESR levels [95, 96].
In 550 arthritis patients, smokers had higher ESR levels and lower immunoglobulin levels, independent of their treatment or condition [94].
In 105 healthy men, smokers had higher ESR compared to non-smokers, but the number of cigarettes did not play any role in ESR [97].
6) Immunoglobins (IVIG)
High doses of immunoglobulin injections (IVIG) increased the ESR levels in 63 children with Kawasaki disease on a 7-day study [177].
In another 7-day study on 21 patients with an autoimmune disease, a high dose of immunoglobulin injections (IVIG) increased their ESR levels [178].
Potential Benefits of High ESR
1) May Increase Survival In Heart Failure
In a study of 242 people with chronic heart failure, those with high ESR levels had higher survival rates compared to patients with low or normal ESR levels [75].
2) May Increase Survival In Cancer
In a study on 300 people with prostate cancer, ESR levels between 40 – 50 mm/hr were associated with a lower risk of death [47].
Diseases Associated With Low ESR
The conditions we discuss here are commonly associated with low ESR test values, but this single symptom is not enough for a diagnosis. Work with your doctor to discover what underlying condition might be causing your unusually low value in this test and to develop an appropriate plan to improve your health.
1) Sickle-Cell Anemia
Sickle-cell anemia is a genetic blood disorder. People with sickle-cell anemia have abnormal hemoglobin (sickle hemoglobin), making their red blood cells crescent-shaped. These cells block blood flow in the vessels and die faster than normal red blood cells, which causes low hematocrit levels [179].
The deformed sickle cells fall down more slowly. Hence, people with sickle-cell anemia usually have low ESR levels (< 5 mm/hr) [180, 181, 182, 55].
In a study on 44 children with sickle-cell disease, their average ESR levels were 7.9 mm/hr when they were healthy [56].
2) Red Blood Cells Abnormalities
Red blood cells that have different shapes or sizes decrease the sedimentation (falling) rate. These conditions include [3, 5, 8, 183]:
- Spherocytosis (red blood cells are shaped like circles)
- Polycythemia (increased production of red blood cells)
- Acanthocytosis (red blood cells with spikes)
- Anisocytosis (red blood cells of unequal size)
- Microcytosis (very small red blood cells)
3) Extreme Leukocytosis
Leukocytosis is a condition in which the body produces a high amount of white blood cells, which decreases the ESR [184, 3, 5, 8, 183].
4) High Fibrinogen
High fibrinogen levels make the red blood cells clot together and fall faster, which increases ESR levels [3].
In hypofibrinogenemia, the body produces less fibrinogen than normal, which decreases ESR [3, 5, 8, 183].
Benefits of Low ESR
May Predict Cancer Survival
In a study on 220 people with stomach cancer, men with ESR lower than 10mm/hr and women with ESR lower than 20 mm/hr had higher survival rates [135].
Ways to Decrease ESR
If your ESR value is too high, the most important thing is to work with your doctor to find out what’s causing your high ESR and to treat any underlying conditions. The additional lifestyle changes listed below are other strategies you may want to discuss with your doctor. None of them should ever be implemented in place of what your doctor recommends or prescribes!
1) Preventing Infections
Living a healthy and hygienic lifestyle can help protect the body against infections. People with infections can have a high sedimentation rate. Thus, preventing infections can help prevent increases in ESR [66, 83].
2) Exercise
Exercise can decrease inflammation [185, 186].
In two studies with over 1,000 people, light or moderate exercise decreased their ESR levels [187, 188].
In an animal study, ESR decreased more when the training intensity increased [189].
3) Diet and Nutrition
In a clinical trial on 27 people, a gluten-free vegan diet and a lacto-vegetarian diet decreased their ESR levels [190].
In another study on 23 people, a 7-day fast reduced ESR levels [191].
Fish oil decreased the ESR levels in 2 trials with 60 people [192, 82].
Vitamin A and vitamin E decreased ESR levels in rats [193].
4) Weight Loss
Losing weight can help decrease ESR [194].
5) Supplements:
- Vitamin C [195]
- Boswellia serrata [196]
- Resveratrol [197]
- Goji berry [198]
- Curcumin [199]
- Fish oil/omega-3 fatty acids [82, 81]
- Green and black tea [200, 201]
- Goji berry [198]
6) Dental Hygiene
In 32 patients with gum disease, periodontal treatment decreased ESR levels after 2 months [202].
7) Drugs
In 64 patients who had surgery, their ESR levels decreased after they received propofol and thiopental (anesthetic drugs) [101].
In 2 meta-analysis studies, statin therapy decreased ESR levels in patients with rheumatoid arthritis [203, 204].
Drugs that fight inflammation and infection may also decrease ESR levels. These include:
- Tocilizumab [205, 206]
- Levamisole [102]
- NSAIDs (non-steroidal anti-inflammatory drugs) [5, 8]
- Cortisone [5, 8]
These drugs may help you lower your ESR value if you are already taking them for some other health condition, but never start taking them or increase your dose for this reason. Always follow the treatment plan prescribed by your doctor.
Genetics
Genes That Affect ESR
These SNPs/genes are associated with a higher ESR:
- rs3750996 (G/G) [207], rs3750996 (G-C) [207]
- rs2066865 (C>T) (minor allele) [208]
- rs3750994 (G-C) is related to higher ESR levels [207]
High fibrinogen levels make the red blood cells heavier and increase the ESR. So, genes increasing fibrinogen production could theoretically increase ESR levels. These include:
- rs2070006 (T>C) [209]
- rs2070011 (T>C) [209, 210]
- rs6050 (G>A) (major allele) [211, 212]
- rs1800790 (G>A) (minor allele) [211, 213, 214, 209]
- rs1800791 (G>A) [215, 210]
- rs2227399 (G>T) [209]
- rs4220 (G>A) [209, 210]
- rs7439150 (G>A) [215, 216]
- rs1049636 (T>C) [215, 210]
These SNPs/genes are associated with lower ESR levels:
- rs630337 (T/C) [217]
- rs11117956 (T/G) [217]
- rs11549407 (A/G) [217]
- rs650877 (G/A) [218]
- rs11118131 (T/C) [218]
- rs677066 (G/A) [218]
- rs6691117 (G/A) [218]
- rs12034383 (G/A) [218]
- rs1043879 [218]
- rs3091242 [218]
- rs873308 [218]
- rs10903129 [218]
- rs7527798 [218]
Low fibrinogen levels make the red blood cells lighter and decrease the ESR. So, genes decreasing fibrinogen production may theoretically reduce ESR levels:
- rs1800787 (C>T) is associated with low fibrinogen, slow initiation of the coagulation cascade, and possibly childhood pneumonia [210, 219].
- rs148685782 (G>C) is associated with low blood fibrinogen levels and hypofibrinogenemia [220, 221].
ESR and C-Reactive Protein (CRP)
In inflammation, the liver is producing a protein called C-reactive protein (CRP). The CRP blood test checks whether you have inflammation or infection. CRP levels higher than 10 mg/dL show infection [222, 223, 224].
CRP test is used most times together with the ESR test [225, 226, 227].
C-reactive protein is more sensitive than ESR and produces less false negative/false positive results than ESR [63].
CRP is better for checking and tracking the progress of acute inflammations, and infections [63, 225, 226].
ESR is better for checking and tracking the progress of chronic inflammations, and infections [63, 225, 226].
Limitations and Caveats
While there are many studies examining ESR, almost all of them are population-based, which means they can associate high or low ESR values with certain conditions but not establish them as their cause. Additional limitations of some of these studies include being based on older data or only conducted with men.
More clinical trials investigating ESR should be undertaken.
