Bibliography for Reference Ranges

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Reference Ranges Overview

Lab Reference Ranges

Lab reference ranges refer to the ranges found next to each marker on the bloodwork. Each lab across the country defines their own reference ranges. They are typically referred to as the “normal” or “healthy” ranges but in reality, they just represent 95% of the population tested at that lab and have no basis for defining optimal health. See optimal reference ranges section for more details.

Lab reference ranges used in LabSmarts are taken from two types of sources (in order of priority):

  • Clinical research (with links to PubMed)
  • National averages and/or ranges from labs and clinical textbooks
  • LabCorp, Quest Diagnostics, Mayo Clinic Medical Laboratories, and Lab Tests Online (created by the American Association for Clinical Chemistry)
  • McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
  • Kaushansky K, Lichtman MA, Prchal J, et al. Williams Hematology. 9th ed. New York: McGraw-Hill; 2015.
  • Wintrobe MM, Greer JG, Rodgers GM, et al. Wintrobe’s Clinical Hematology. 14th ed. Philadelphia: Wolters Kluwer; 2019.
  • Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
  • Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in Clinical Practice. 5th ed. New York: McGraw-Hill Medical; 2010.
  • Hoffbrand AV, Steensma DP. Hoffbrand’s Essential Haematology. 8th ed. Hoboken, NJ: Wiley; 2020.

Optimal Reference Ranges

As mentioned, labs define their reference ranges based on 95% of the population they test. The majority of the population is unhealthy, values in the low and high ends of the lab range justifiably represent suboptimal health and indicate an imbalance in a body system function. Optimal body system function happens when values are within the “optimal” range, which is inside the low and high ends of the lab range, closer to the average (mean) population.

The optimal range for each marker is defined using validated clinical research correlating threshold values to imbalances in body system function. If evidence for the optimal range is not listed below, the optimal range minimum and maximum values are calculated using one standard deviation from the lab mean. This range covers 68% of the population, a much more realistic range for representing optimal body system function than the lab range which is two standard deviations from the lab mean representing 95% of the population. Learn more about the 68-95-99.7 rule here.

Alarm Reference Ranges

The alarm reference range minimum and maximum values used in the software are three standard deviations away from the mean, unless otherwise noted below. These values should be given serious consideration as they are a clear indication that the body system associated with that marker may not be functioning properly.

Age Ranges Supported

Reference ranges used in LabSmarts are for adults only, with one exception. References ranges for infants and children are defined for the seven red blood cell related makers on the CBC based on the study below. Use with infants and children at your own risk.

Red Blood Cells (RBC) Reference Ranges

Lab reference ranges adjusted based on gender and age

  • LabSmarts uses the reference ranges for each gender and age group found in the study below as the lab reference ranges for the seven red blood cell related markers on the CBC.
  • This study is a better representation of a slightly healthier population than the reference ranges found on your client’s bloodwork.
  • This study used the values from 44K “healthy” people from a large nationally representative, population-based, cross-sectional NHANES database to determine “normal/healthy” reference ranges. They started with 65K people then excluded 21K who had 1 of over 15 different health conditions, such as heart disease, stroke, and cancer.
  • The ranges from this study still do not represent optimal ranges. Optimal ranges are defined below as 1 standard deviation from the mean of the ranges in this study.

Red Blood Cells (RBC)

    • Lab Min and Max (using gender and age specific ranges from this study): “The large sample size (44K) of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean

Hemoglobin (HGB)

    • Lab Min and Max (using gender and age specific ranges from this study): “The large sample size of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. “Hemoglobin values ≤12.0 g/dL (and possibly ≤13.0 g/dL) in females age 50+ (but not age <50) and hemoglobin values ≤13.0 g/dL in all males are associated with progressively increasing mortality risk independent of the contribution of other test values. Increased risk is also noted for hemoglobin values >15.0 g/dL (and possibly >14.0 g/dL) for all females and for hemoglobin values >16.0 g/dL for males.” Fulks M, Dolan VF, Stout RL. Hemoglobin Screening Independently Predicts All‐Cause Mortality. J Insur Med. 2015;45:75–80. [PubMed]
    2. “Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women.” Kabat GC, Kim MY, Verma AK, Manson JE, Lessin LS, Kamensky V, Lin J, Wassertheil-Smoller S, Rohan TE. Association of Hemoglobin Concentration With Total and Cause‐Specific Mortality in a Cohort of Postmenopausal Women. Am J Epidemiol. 2016;183(10): 911–19. [PubMed]
    3. “An inverse J-shaped relationship between hemoglobin and all-cause mortality was observed; the lowest risk for mortality occurred at hemoglobin values between 130 to 150 g/L (13.0 to 15.0 g/dL) for women and 140 to 170 g/L (14.0 to 17.0 g/dL) for men.” Culleton BF, Manns BJ, Zhang J, Tonelli M, Scott Klarenbach S, Hemmelgarn BR. Impact of anemia on hospitalization and mortality in older adults. Blood. 2006; 107:3841-3846. [PubMed]
    4. “…subjects with hemoglobin < 14.0 g/dL showed higher mortality rate than those with hemoglobin 14.0-14.9 g/dL or ≥ 15.0 g/dL. The subjects with hemoglobin ≥ 15.0 g/dL showed a lower survival rate than those with 14.0-14.9 g/dL… “ The low number of red blood cells is an important risk factor for all-cause mortality in the general population. Kim YC, Koo HS, Ahn SY, Oh SW, Kim S, Na KY, Chae DW, Kim S, Chin HJ. Tohoku J Exp Med. 2012;227(2):149-59. [PubMed]

Hematocrit (HCT)

    • Lab Min and Max (using gender and age specific ranges from this study): “The large sample size (44K) of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. “The lowest risk for all-cause mortality was seen in quartile 2 for men (range, 0.421-0.440) and women (range, 0.381-0.400). In absolute Hct values, Hct >0.44 in either men or women is associated with increased risk of death. However, at the lower end of the scale, in men risk of death increases at approximate Hct <0.42, whereas in women the risk of death increases only at a lower threshold of Hct <0.38.” Paul L, Jeemon P, Hewitt J, McCallum L, Higgins P, Walters M, et al. Hematocrit Predicts Long‐Term Mortality in a Nonlinear and Sex‐Specific Manner in Hypertensive Adults. Hypertension. 2012;60:631–638. [PubMed]
    2. “Low and high levels of HCT are associated with increased mortality in the general population.” Boffetta P, Islami F, Vedanthan R, Pourshams A, Kamangar F, Khademi H, et al. A U‐shaped relationship between haematocrit and mortality in a large prospective cohort study. Int J Epidemiol. 2013;42(2):601–615. [PubMed]

High Elevation (Altitude) Adjustments to RBC, HGB, and HCT Reference Ranges

    • Find the elevation of your client’s city HERE
    • The barometric pressure of the atmosphere decreases with each incremental increase in elevation or altitude causing oxygen molecules in the air to get further apart. As a result, the oxygen content of each breath is reduced incrementally the higher up one lives from sea-level.
    • Because people living at higher elevations take in less oxygen with each breath, their bodies have to overcompensate by generating more red blood cells to capture more of the oxygen they take in. This means their normal levels of RBC, HGB, and HCT are higher than those living closer to sea-level.
    • If the ranges for these markers are not adjusted upward, you may miss out on identifying suboptimal blood oxygen delivery as a possible root cause of your client’s fatigue or incorrectly identify dehydration as a condition your client should address.
    • This is why LabSmarts adjusts these ranges for clients living at elevations above 3,280 feet using correction factors recommended by the World Health Organization at elevation increments based on the study from Sullivan and others.
    1. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, World Health Organization, 2011 (WHO/NMH/NHD/MNM/11.1). Website or PDF. Accessed February 19, 2020.
    2. Sullivan KM, Mei Z, Grummer-Strawn L, Parvanta I. Haemoglobin adjustments to define anaemia. Trop Med Int Health. 2008;13(10):1267-1271. [PubMed]
    • If vacationing in a higher elevation location, wait at least 3 days before getting blood drawn.

WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, World Health Organization, 2011 (WHO/NMH/NHD/MNM/11.1). Website or PDF.

Pregnancy Adjustments to RBC, HGB, and HCT Reference Ranges

    • Normal physiological changes in pregnancy result in a reduction of hemoglobin concentration.
    • “Red cell mass (driven by an increase in maternal erythropoietin production) also increases, but relatively less, compared with the increase in plasma volume, the net result being a dip in hemoglobin concentration. Thus, there is dilutional anemia.” Chandra S, Tripathi AK, Mishra S, Amzarul M, Vaish AK. Physiological changes in hematological parameters during pregnancy. Indian J Hematol Blood Transfus. 2012;28(3):144-146. [PubMed]
    • LabSmarts adjusts the reference ranges for these three markers based on the correction factors in the study from Sullivan et al. See the table from this study above.
    1. Sullivan KM, Mei Z, Grummer-Strawn L, Parvanta I. Haemoglobin adjustments to define anaemia. Trop Med Int Health. 2008;13(10):1267-1271. [PubMed]

Mean Corpuscular Volume (MCV)

    • Lab Min and Max (using gender and age specific ranges from this study): “The large sample size (44K) of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. “Patients with PAD (peripheral arterial disease) displayed a significantly higher mean corpuscular volume level (94.5 fl) than control subjects (90.9 fl, p<0.001).” Mueller T, Haidinger D, Luft C, Horvath W, Poelz W, Haltmayer M. Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study. Angiology. 2001;52(9):605–613. [PubMed]
    2. “…elevated MCV level in non-anemic cancer-free individuals was associated with increased all-cause mortality in both men and women, and with cancer mortality, in particular liver cancer mortality in men.” Yoon, Hyung‐Jin, Kyaehyung Kim, You‐Seon Nam, Jae‐Moon Yun, and Minseon Park. Mean Corpuscular Volume Levels and All‐Cause and Liver Cancer Mortality. Clinical Chemistry and Laboratory Medicine. 2016;54(7):1247–57. [PubMed]
    3. “…larger erythrocytes in older adults are associated with poorer cognitive function.” Gamaldo, Alyssa A., Luigi Ferrucci, Joseph Rifkind, Dan L. Longo, and Alan B. Zonderman. The Relationship between Mean Corpuscular Volume and Cognitive Performance in Older Adults. Journal of the American Geriatrics Society. 2013;61(1):84–89. [PubMed]
    4. Anderson JL, Ronnow BS, Horne BD, Carlquist JF, May HT, Bair TL, et al. Usefulness of a complete blood count‐derived risk score to predict incident mortality in patients with suspected cardiovascular disease. Am J Cardiol. 2007;99:169–174. [PubMed]

Mean Corpuscular Hemoglobin (MCH)

    • Lab Min and Max (using gender and age specific ranges from this study): “The large sample size (44K) of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. Anderson JL, Ronnow BS, Horne BD, Carlquist JF, May HT, Bair TL, et al. Usefulness of a complete blood count‐derived risk score to predict incident mortality in patients with suspected cardiovascular disease. Am J Cardiol. 2007;99:169–174. [PubMed]

Mean Corpuscular Hemoglobin Concentration (MCHC)

    • Lab Min and Max (using gender and age specific ranges from this study): “The large sample size (44K) of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. Anderson JL, Ronnow BS, Horne BD, Carlquist JF, May HT, Bair TL, et al. Usefulness of a complete blood count‐derived risk score to predict incident mortality in patients with suspected cardiovascular disease. Am J Cardiol. 2007;99:169–174. [PubMed]

Red (Blood) Cell Distribution Width (RDW)

    • “The sizes (volumes) of red cells vary within a certain range in which the number of cells of particular volumes form a bell-shaped or Gaussian distribution; the standard deviation of the cell volumes divided by the mean cell volume gives what is called the red cell distribution width, or RDW, measured as a percent. As it happens, the RDW is a parameter that helps to further classify an anemia because it reflects the variation of red blood cell size. It can be helpful in differentiating causes of microcytosis, because moderate to severe iron deficiency anemia is associated with an increased RDW, whereas thalassemia and anemia of chronic disease (ACD) are associated with a normal RDW.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017. p. 85.
    • Lab Max (using gender and age specific ranges from this study): “The large sample size (44K) of NHANES provided a high degree of statistical power in determining age- and sex-specific partitions in reference intervals.  A major strength of our study is the use of a large nationally representative population-based sample (NHANES), use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop objectively/statistically defined breakpoints. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
    • Alarm Max = 3 standard deviations from lab mean
    • Optimal Max – anything below this value is considered optimal as low RDW has no clinical significance
    1. “For every 1-unit increase of RDW, there is an increased risk of occurrence of ACM (all-cause mortality) and MACEs (major adverse cardiac events). This study indicates RDW may be a prognostic indicator for CVD outcomes.” Hou H, Sun T, Li C, et al. An overall and dose-response meta-analysis of red blood cell distribution width and CVD outcomes. Sci Rep. 2017;7:43420. Published 2017 Feb 24. [PubMed]
    2. “High RDW (≥15% variation, n = 6,050) compared to low (<12.5% n = 20,844) was strongly associated with mortality. Higher RDW was also associated with incident CAD, heart failure, peripheral vascular disease, atrial fibrillation, stroke, cancer, colorectal cancer, and especially leukemia. Pilling LC, Atkins JL, Kuchel GA, Ferrucci L, Melzer D. Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years. PLoS One. 2018;13(9):e0203504. Published 2018 Sep 13. [PubMed]
    3. “Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001).” Patel KV, Semba RD, Ferrucci L, et al. Red cell distribution width and mortality in older adults: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2010;65(3):258–265. [PubMed]
    4. “…a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors.” Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatientsArch Pathol Lab Med 2009;133:628–32. [PubMed]
    5. “RDW, which is recently considered as an inflammatory marker with a significant predictive value of mortality in diseased and healthy populations, is significantly higher in diabetic patients than healthy subjects and is particularly higher in uncontrolled glycemia.” Nada AM. Red cell distribution width in type 2 diabetic patients. Diabetes Metab Syndr Obes. 2015;8:525–533. Published 2015 Oct 30. [PubMed]
    6. “Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B(12) deficiency, RDW remained strongly associated with mortality. Red blood cell distribution width is a widely available test that is a strong predictor of mortality in the general population of adults 45 years or older.” Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med. 2009;169(5):515–523. [PubMed]
    7. Titcomb CP. Red Cell Distribution Width (RDW): An Underappreciated Marker for Increased Mortality. ON THE RISK Journal of The Academy of Life Underwriting. 2017;33(1):30-46. [Article] [Full Issue]

Corrected Reticulocyte Count (CRC)

    • Reticulocytes are immature red cells that lose their RNA a day or so after reaching the blood from the marrow.
    • A reticulocyte count provides an estimate of the rate of red blood cell production.
    • LabSmarts corrects the value entered for reticulocyte count and plots a corrected reticulocyte count (CRC) on a bar graph in the RBC Analysis section.
    • CRC = reticulocytes % x (HCT %/mean HCT %), mean HCT % is determined based on gender and age.
    1. “A very useful measurement in determining the cause of normocytic anemia is the reticulocyte count. Reticulocytes are newly formed red blood cells that have recently lost their nuclei but retain high levels of cytosolic mRNA dedicated to the synthesis of hemoglobin. In cases, prominently in hemolytic anemia, where there is a loss of red blood cells due to peripheral destruction of these cells, there is an increased synthesis in bone marrow of red blood cells and an early release of red blood cell precursors, especially reticulocytes.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017. p. 86.
    2. “Reticulocytes should rise in anaemia because of erythropoietin increase, and be higher the more severe the anaemia. This is particularly so when there has been time for erythroid hyperplasia to develop in the marrow as in chronic haemolysis. After an acute major haemorrhage there is an erythropoietin response in 6 hours, and the reticulocyte count rises within 2-3 days, reaches a maxiumum in 6-10 days and remains raised until the haemoglobin returns to the normal level. If the reticulocyte count is not raised in an anaemic patient, this suggests impaired marrow function or lack of erythropoietin stimulus.” Hoffbrand AV, Steensma DP. Hoffbrand’s Essential Haematology. 8th ed. Hoboken, NJ: Wiley; 2020.
    • Lab Min and Max
    1. “The normal percentage is 0.5-2.5%.” Hoffbrand AV, Steensma DP. Hoffbrand’s Essential Haematology. 8th ed. Hoboken, NJ: Wiley; 2020.
    2. “The normal reticulocyte count at birth ranges from 3% to 7% during the first 48 hours, during which time it rises slightly. After the second day, it falls rather rapidly to 1% to 3% by the seventh day of life.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
    3. “Typical Reference Interval: 0.5% – 1.5% McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017. p. e22.
    4. “The normal reticulocyte count for both the automated and new methylene blue methods is 1% with a range of 0.6%–2.0%.” Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in Clinical Practice. 5th ed. New York: McGraw-Hill Medical; 2010.
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean

Reticulocyte Production Index (RPI)

    • RPI corrects the CRC with respect to the proportion of reticulocytes present in a patient without anemia and the premature release of reticulocytes into the peripheral circulation. Therefore, RPI is a more meaningful expression of erythropoiesis.
    • LabSmarts uses RPI to help distinguish between iron insufficiency and blood loss as a possible root cause of suboptimal blood oxygen delivery.
    • The RPI is calculated by dividing the corrected reticulocyte count (CRC) by a correction factor that’s based on an estimated maturation time of reticulocytes in the blood.
    • See Reticulocyte production index in Wikipedia for the RPI formula and maturation correction table used in the formula.
    • Lab Min and Max
    1. “Bone marrow response to anemia may be appropriate (hyperproliferative), with an RPI over 3 generally indicating marrow red cell hyperproliferation; however, the anemia may be due to defective red blood cell production or marrow failure (hypoproliferative), which is generally indicated by an RPI less than 2.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
    2. “Optimal Marrow Response: Reticulocyte Production Index Greater Than Two: If the output of reticulocytes has exceeded two times normal, as determined by the absolute reticulocyte count, or RPI, it can be assumed that the marrow has reached an optimal response. The cause for the anemia is then acute blood loss or hemolysis. If blood loss cannot be proved, evidence that hemolysis is in fact present must be sought.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017. p. 600.
    3. “Bone marrow response to anemia may be appropriate (hyperproliferative), with an RPI over 3 generally indicating marrow red cell hyperproliferation; however, the anemia may be due to defective red blood cell production or marrow failure (hypoproliferative), which is generally indicated by an RPI less than 2.” Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in Clinical Practice. 5th ed. New York: McGraw-Hill Medical; 2010.

Iron Panel Reference Ranges

Iron

Serum iron reflects iron that is bound to serum proteins such as transferrin. Serum iron levels will begin to fall somewhere between the depletion of the iron stores and the development of anemia.

  • Decreased levels are associated with poor iron intake or absorption (hypochlorhydria or vitamin C insufficiency), chronic blood loss, internal bleeding, chronic inflammation and/or infection, increased blood loss during menses, free radical pathology, renal dysfunction, chronic renal failure, hypothyroidism, liver inflammation as a result of dysfunction and/or damage, and association with progesterone birth control pills.
  • Increased levels excess are associated with iron intake (food, supplementation, exposure), liver inflammation as a result of dysfunction and/or damage, premature red blood cell breakdown, conditions of iron overload (hemochromatosis and hemosiderosis), infections, and iron conversion issues as a result of nutrient insufficiencies such as B6, B12, folic acid, zinc and/or copper.
    • Lab Min and Max: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    • Serum iron is not a reliable indicator of iron status, but below are a few studies that support using the tighter optimal range:
    1. “In this large cohort of persons aged > or =71 years, there was consistent evidence of increasing risk of mortality at lower serum iron levels. In fact, lower serum iron levels were associated with an increased risk of CAD, cardiovascular disease, and all-cause mortality. The results are compatible with the possibility that in an older population, there is an inverse association between serum iron levels and risk of mortality.” Corti MC, Guralnik JM, Salive ME, Ferrucci L, Pahor M, Wallace RB, et al. Serum iron level, coronary artery disease, and all‐cause mortality in older men and women. Am J Cardiol. 1997;79: 120–127. [PubMed]
    2. “We found an association between serum iron and risk of fatal acute myocardial infarction, with rate ratios for males and females in the highest category of serum iron (> or = 175 micrograms per dl) of 2.18 [95% confidence intervals (CI) = 1.01-4.74] and 5.53 (95% CI = 1.69-18.12), respectively.” Morrison HI, Semenciw RM, Mao Y, Wigle DT. Serum iron and risk of fatal acute myocardial infarction. Epidemiology. 1994;5: 243–246. [PubMed]

TIBC (Total Iron Binding Capacity)

Total iron binding capacity (TIBC) is an approximate estimation of the serum transferrin level. The transferrin protein carries most of the iron in the blood.

  • Decreased levels are associated with chronic inflammation and/or infection, liver inflammation as a result of dysfunction and/or damage, and conditions of iron overload (hemochromatosis and hemosiderosis).
  • Increased levels are associated with iron insufficiency, late pregnancy, internal bleeding, blood loss, elevated estrogen, and liver inflammation as a result of dysfunction and/or damage.
    • Lab Min and Max: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean

% Saturation (% Transferrin Saturation)

The % transferrin saturation index is a calculated value that tells how much serum iron is bound to the iron-carrying protein transferrin. A % transferrin saturation value of 15% means that 15% of iron-binding sites of transferrin is being occupied by iron.

  • Decreased levels serve as a sensitive screening test for iron insufficiency.
  • Increased levels function as a sign of too much iron in the blood or iron overload.
    • Lab Min: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
    • Lab Max: Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max
    1. “The optimal TSAT ratio associated with the greatest survival is between 24% and 40%.” Stack AG, Mutwali AI, Nguyen HT, Cronin CJ, Casserly LF, Ferguson J. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population. QJM. 2014;107(8):623–633. [PubMed]
    2. “A level of 25 to 35 percent (transferrin saturation level) is typically considered healthy.” Mercola. January 09, 2019.
    3. “The optimal range of TS % is generally between 25–35%.” When the percentage is calculated to be less that about 17% or higher than 45%, a condition of either iron deficiency or iron overload is possible. Iron Disorders Institute.
    4. “Here we demonstrated that transferrin saturation ≥50% was associated with a two- to threefold increased risk of developing any form of diabetes, as well as type 1 diabetes and type 2 diabetes separately.” Ellervik C, Mandrup-Poulsen T, Andersen HU, et al. Elevated transferrin saturation and risk of diabetes: three population-based studies. Diabetes Care. 2011;34(10):2256–2258. [PubMed]
    5. “Individuals in the general population with TS≥50% vs <50% have an increased risk of premature death.” Ellervik C, Tybjaerg-Hansen A, Nordestgaard BG. Total mortality by transferrin saturation levels: two general population studies and a metaanalysis. Clinical chemistry. 2011;57(3):459–66. [PubMed]
    6. “…all-cause mortality is significantly greater for persons with a serum transferrin saturation of more than 55%…” Mainous AG 3rd, Gill JM, Carek PJ. Elevated serum transferrin saturation and mortality. Ann Fam Med. 2004;2(2):133–138. [PubMed]
    7. “…%TS was inversely associated with all-cause, cancer, and cardiovascular mortality in men or postmenopausal women aged 50 years or older. These results appear to show that a moderately high %TS may be protective against oxidative stress.” Kim KS, Son HG, Hong NS, Lee DH. Associations of serum ferritin and transferrin % saturation with all-cause, cancer, and cardiovascular disease mortality: Third National Health and Nutrition Examination Survey follow-up study. J Prev Med Public Health. 2012;45(3):196–203. [PubMed]

Ferritin

Ferritin is the main form of iron storage in the body. It is the ferrous form of iron (Fe2+) complexed with a protein, apoferritin, storing it in the ferric state (Fe3+). Most reliable indicator of total-body iron status. Ferritin is an acute phase reactant, in that it will increase during inflammation or infection.

  • Decreased levels are strongly associated with iron insufficiency where it is the most sensitive test to detect a growing trend towards iron insufficiency.
  • Increased levels are associated with iron overload, an increasing risk of cardiovascular disease, inflammation, and oxidative stress.
    • Lab Min and Max: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
    • Alarm Min = 1/2 of lab min
    • Alarm Max = 3 standard deviations from lab mean
    • Optimal Min and Max
    1. “Although serum ferritin is widely seen as an inflammatory biomarker, our understanding of its role as an intracellular iron storage protein gives no explanation of why it should even exist in serum. The view summarised here is that serum ferritin leaks from damaged cells, losing most of its iron on the way, and leaving that iron in an unliganded form that can impact negatively on health.” This unliganded iron can of course stimulate further cell damage. This overall view serves straightforwardly to explain the following, known observations. (1) Serum ferritin exists, despite the fact that ferritin is not synthesised in the serum. (2) Serum ferritin lacks most of the iron it contained when intracellular. (3) The intracellular ferritin must have ‘dumped’ its unliganded iron somewhere, where it can participate in Haber–Weiss and Fenton reactions, creating hydroxyl radicals and consequent further cellular damage. (4) The serum ferritin protein is itself considered benign. (5) Yet the level of serum ferritin correlates with numerous inflammatory and degenerative diseases.” Kell D.B., Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6:748–773 [PubMed]
    2. “Ferritin – Adult men and non-menstruating women: 30 to 40 nanograms per milliliter (ng/mL) or 75 to 100 nanomoles per liter (nmol/L). The most commonly used threshold for iron deficiency in clinical studies is 12 to 15 ng/mL (30 to 37 nmol/L). You do not want to be below 20 ng/mL (50 nmol/L) or above 80 ng/mL (200 nmol/L). High iron during pregnancy is also problematic; having a level of 60 or 70 ng/mL (150 or 175 nmol/L) is associated with greater odds of poor pregnancy outcomes.” Mercola. January 09, 2019.
    3. “Optimal SF ranges for men and women are 25 – 75 ng/ml. Individuals with risk factors for diabetes, cardiovascular diseases, stoke, liver diseases and cancer face amplified risks proportional to the amount of stored body iron over and above the optimal range. Numerous medical research studies have demonstrated that serum ferritin above 100 ng/ml has been associated with decreased cardiovascular fitness and increased incidences of: atherosclerosis, type 2 diabetes, cancer gout and accelerated aging including osteoporosis and sarcopenia (muscle wasting) due to oxidative stress.” Iron Disorders Institute
    4. “In clinical practice, the use of a higher cutoff value for ferritin is recommended when screening for iron deficiency. Specifically, a cut-off of 40 ug/L improves diagnostic sensitivity in patients whose conditions are not complicated by infections or inflammation.” Knovich MA, Storey JA, Coffman LG, Torti SV, Torti FM. Ferritin for the clinician. Blood Rev. 2009;23(3):95–104. [PubMed]
    5. “…in women with serum ferritin levels categorised into three groups (low, < 40; middle, 40–80; high, > 80 μg/l) confirmed the assumption of a U-shaped relationship. Women with low or high serum ferritin levels tended to have a higher risk of CVD. Serum ferritin levels of about 60 μg/l appear to be optimal, whereas higher and lower levels were associated with an increasing risk of CVD and IHD.” Friedrich N, Milman N, Völzke H, Linneberg A, Jørgensen T. Is serum ferritin within the reference range a risk predictor of cardiovascular disease? A population-based, long-term study comprising 2874 subjects. Br J Nutr. 2009;102:594–600. [PubMed]
    6. “Among women, those in the lowest ferritin quartile (2-44ng/ml) had increased risk for all-cause mortality…” Kadoglou NPE, Biddulph JP, Rafnsson SB, Trivella M, Nihoyannopoulos P, Demakakos P. The association of ferritin with cardiovascular and all-cause mortality in community-dwellers: The English longitudinal study of ageing. PLoS One. 2017;12(6):e0178994. Published 2017 Jun 7. [PubMed]
    7. “…carotid atherosclerosis was positively associated with serum ferritin in individuals free from subclinical inflammation.” Ahluwalia N, Genoux A, Ferrieres J, et al. Iron status is associated with carotid atherosclerotic plaques in middle-aged adults. J Nutr. 2010;140(4):812–816. [PubMed]
    8. “Risk for all-cause mortality was found increased in men with hyperferritinemia (194-598ng/ml) and no history of major chronic diseases compared with the reference group…” Kadoglou NPE, Biddulph JP, Rafnsson SB, Trivella M, Nihoyannopoulos P, Demakakos P. The association of ferritin with cardiovascular and all-cause mortality in community-dwellers: The English longitudinal study of ageing. PLoS One. 2017;12(6):e0178994. Published 2017 Jun 7. [PubMed]
    9. “…men with serum ferritin greater than or equal to 200 micrograms/l had a 2.2-fold (95% CI, 1.2-4.0; p less than 0.01) risk factor-adjusted risk of acute myocardial infarction compared with men with a lower serum ferritin.” Salonen JT, Nyyssönen K, Korpela H, Tuomilehto J, Seppänen R, Salonen R. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation. 1992;86: 803–811. [PubMed]

Transferrin

    • Lab Min and Max: LabCorp – Transferrin
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 2 standard deviations from lab mean

See the Iron Science Library for an extensive list of studies related to iron, TIBC, % saturation, and ferritin.

Immune System – White Blood Cells (WBC) Reference Ranges

White Blood Cells (WBC)

A total white blood cell (WBC) count measures the sum of all the WBCs in the peripheral blood. WBCs fight infection; defend the body through a process called phagocytosis; and produce, transport, and distribute antibodies as part of the immune process. It is important to look at the WBC differential count (which counts the different varieties of WBCs: neutrophils, lymphocytes, etc.) to identify the source of an increased or decreased WBC count.

  • Decreased levels are associated with chronic bacterial or viral infections, immune insufficiency, and may be seen in people eating a raw food diet.
  • Increased levels are associated with acute bacterial or viral infections and may be seen in people who eat a diet of highly refined foods.
    • Lab Min and Max: “…a new reference range for total leukocyte count was accordingly estimated to be 3.11-8.83 x 109/L.” Revision in reference ranges of peripheral total leukocyte count and differential leukocyte percentages based on a normal serum C-reactive protein level. J Formos Med Assoc. 2007;106(8):608-616. [PubMed]
    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. “Populations eating diets centered around whole plant foods average about 5, whereas in the U.S., at the time, it was closer to 7 or 8. The reason we know it’s not genetic is if you take those living on traditional rural African diets, who are down around 4 or 5, and move them to Britain, they end up closer to 6, 7, or 8.” Greger M. What Is the Ideal White Blood Cell Count? NutritionFacts.org. Published June 30, 2017. [Video]
    2. “The white blood cell count is a “widely available and inexpensive measure of systemic inflammation.” At around age 85 in this study, half of women who started out with white counts under 5.6 were still alive, whereas 80% of those that started out over 7 were dead.” Greger M. What Does a Low White Blood Cell Count Mean? NutritionFacts.org. Published June 28, 2017. [Video]
    3. “High WBC within the reference range (8.65–10.05×109/L) was associated with significantly increased mortality compared to the middle quintile (6.25–7.25×109/L)… the second quintile (5.35–6.25×109/L) was associated with lowest risk… low values of white cell count outside the reference range (<2.95×109/L) were also associated with greater mortality [than all other quadrants].” Shah AD, Thornley S, Chung S‐C, Denaxas S, Jackson R, Hemingway H. White cell count in the normal range and short‐term and long‐term mortality: international comparisons of electronic health record cohorts in England and New Zealand. BMJ Open. 2017;7:e013100. [PubMed]
    4. “…never-smokers with WBC counts of 9,000-10,000 had a 3.2 fold elevated risk for CVD death compared with those with WBC counts of 4,000-4,900.” Tamakoshi K, Toyoshima H, Yatsuya H, Matsushita K, Okamura T, Hayakawa T, et al. White blood cell count and risk of all‐cause and cardiovascular mortality in nationwide sample of Japanese‐‐results from the NIPPON DATA90. Circ J. 2007;71(4):479–485. [PubMed]
    5. “Compared to persons with a WBC count < 6.1, persons with a WBC count > 7.6 were at increased risk of death from CHD…” Brown DW, Giles WH, Croft JB. White blood cell count: an independent predictor of coronary heart disease mortality among a national cohort. J Clin Epidemiol. 2001;54(3):316–322. [PubMed]
    6. Twig G, Afek A, Shamiss A, Derazne E, Tzur D, Gordon B, et al. White blood cell count and the risk for coronary artery disease in young adults. PLoS One. 2012;7: e47183.
    7. Ruggiero C, Metter EJ, Cherubini A, Maggio M, Sen R, Najjar SS, et al. White blood cell count and mortality in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol. 2007;49:1841–1850.
    8. Margolis KL, Manson JE, Greenland P, Rodabough RJ, Bray PF, Safford M, et al. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women’s Health Initiative Observational Study. Arch Intern Med. 2005;165: 500–508.
    9. Bloomer RJ, Kabir MM, Canale RE, et al. Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women. Lipids Health Dis. 2010;9:94.

Lab Min and Max for Absolute and % WBC Differentials

    • “…when a normal serum CRP level (< 0.1 mg/dL) is employed as the basis for revising reference ranges, there will be a lower total leukocyte count, mainly due to the lower neutrophil and monocyte counts.” Revision in reference ranges of peripheral total leukocyte count and differential leukocyte percentages based on a normal serum C-reactive protein level. J Formos Med Assoc. 2007;106(8):608-616. [PubMed]

Alarm and Optimal Min and Max for Absolute and % WBC Differentials

    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean

Lab and Alarm Min for Absolute and % Eosinophils

    1. Supported by this study of 2,065 patients admitted to the hospital for Clostridium difficile infection: Those with an undetectable eosinophil count (0.0 cells/μL) at admission had increased in-hospital mortality. Undetectable eosinophil counts were also associated with indicators of severe sepsis, such as admission to monitored care settings, the need for vasopressors, and emergency total colectomy. Kulaylat AS, Buonomo EL, Scully KW, et al. Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium difficile Infection. JAMA Surg. 2018;153(12):1127-1133. [PubMed]

Neutrophil/Lymphocyte Ratio (NLR)

    • Studies relating NLR to bacterial infections
    1. “The NLCR cut-off value of 6.2 exhibited a sensitivity value of 0.91 and a specificity value of 0.96 for bacterial infection. We assessed the potential use of the neutrophil to lymphocyte count ratio (NLCR) to discriminate between bacterial and viral infections. NLCR was evaluated in 45 patients with bacterial infections: 24 patients with viral infections and 18 healthy adults. The medians of NLCR were 11.73 in bacterial infections, 2.86 in viral infections and 1.86 in controls.” Holub M, Beran O, Kaspříková N, Chalupa P. Neutrophil to lymphocyte count ratio as a biomarker of bacterial infections. Cent. Eur. J. Med. 2012; 7(2): 258–61. [FullArticle]
    • Optimal Min and Max
    1. “The mean NLR across all ages in men and women was 1.63 (0.76) and 1.66 (0.82), respectively.” Lee JS, Kim NY, Na SH, Youn YH, Shin CS. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore). 2018;97(26). [PubMed]
    2. “NLR in different phases of BD [Bipolar Disorder] was significantly higher compared to the control group. NLR value was 2.23 ± 1.14 in the manic group, 2.07 ± 0.98 in the depressed group, 2.22 ± 1.21 in the euthymic group, and 1.52 ± 0.47 in the control group. NLR may be a trait inflammatory marker of BD independent of different episodes.” Ayhan MG, Cicek IE, Inanli I, Caliskan AM, Kirci Ercan S, Eren I. Neutrophil/lymphocyte and platelet/lymphocyte ratios in all mood states of bipolar disorder. Psychiatry and Clinical Psychopharmacology. 2017;27(3):278-282. [Full Article]
    3. “Patients in the low NLR tertile had a mean NLR of 1.5 ± 0.4, middle had a mean NLR of 2.6 ± 0.4, and high had a mean NLR of 6.0 ± 3.8. Significantly fewer patients in the low tertile had cognitive dysfunction than in the high tertile (6.9% vs 25.9%; P <.001) and middle tertile (6.9% vs 17.4%; P = .006)." Halazun HJ, Mergeche JL, Mallon KA, Connolly ES, Heyer EJ. Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid endarterectomy patients. J Vasc Surg. 2014;59(3):768-773. [PubMed]
    4. “High NLR at relapse was associated with poorer postprogression survival of follicular lymphoma (FL). The best cut-off values for LMR and NLR were 3.20 and 2.18, respectively.” Lee SF, Luque-Fernandez MA. Prognostic value of lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio in follicular lymphoma: a retrospective cohort study. BMJ Open. 2017;7(11):e017904. [PubMed]
    • Lab Min = Optimal Min – 0.5
    • Lab Max
    1. “Cut-off value of NLR above 2.54 and a value of MPV above 10.4 can predict the presence of atherosclerosis before coronary angiography.” Uysal HB, Dağlı B, Akgüllü C, et al. Blood count parameters can predict the severity of coronary artery disease. Korean J Intern Med. 2016;31(6):1093-1100. [PubMed]
    2. “Patients in the low NLR tertile had a mean NLR of 1.5 ± 0.4, middle had a mean NLR of 2.6 ± 0.4, and high had a mean NLR of 6.0 ± 3.8. Significantly fewer patients in the low tertile had cognitive dysfunction than in the high tertile (6.9% vs 25.9%; P <.001) and middle tertile (6.9% vs 17.4%; P = .006)." Halazun HJ, Mergeche JL, Mallon KA, Connolly ES, Heyer EJ. Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid endarterectomy patients. J Vasc Surg. 2014;59(3):768-773. [PubMed]
    • Alarm Min = Lab Min – 0.5
    • Alarm Max
    1. “The neutrophil-to-lymphocyte ratio has demonstrated to be a prognostic inflammatory marker in cardiovascular disease. The neutrophil-to-lymphocyte ratio appears to be a cost-efficient, non-invasive and independent potential marker of systemic endothelial dysfunction in asymptomatic subjects. Those with a neutrophil-to-lymphocyte ratio > 3 were at high risk.” Martínez-Urbistondo D, Beltrán A, Beloqui O, Huerta A. The neutrophil-to-lymphocyte ratio as a marker of systemic endothelial dysfunction in asymptomatic subjects. Nefrologia. 2016;36(4):397-403. [PubMed]
    2. “A NLR > 3.0 was an independent prognostic factor for OS [overall survival] for the entire cohort.” McNamara MG, Templeton AJ, Maganti M, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer. Eur J Cancer. 2014;50(9):1581-1589. [PubMed]
    3. “The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average.” Durmus E, Kivrak T, Gerin F, Sunbul M, Sari I, Erdogan O. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure. Arq Bras Cardiol. 2015;105(6):606-613. [PubMed]
    4. “NLR was elevated (> 3.3) in 26.6% of patients. Congestive cardiac failure and malignancy were two constant predictors of elevated NLR at >3.3 and > 4.5. There was a strong association between NLR and anesthesia risk scoring tools of ASA and RCRI.” Venkatraghavan L, Tan TP, Mehta J, Arekapudi A, Govindarajulu A, Siu E. Neutrophil Lymphocyte Ratio as a predictor of systemic inflammation – A cross-sectional study in a pre-admission setting. F1000Res. 2015;4:123. [PubMed]
    5. “The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001)." Bowen RC, Little NAB, Harmer JR, et al. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget. 2017;8(19):32171-32189. [PubMed]

Lymphocyte/Monocyte Ratio (LMR)

    • Optimal Min and Max
    • Lab Min and Max
    • Alarm Min and Max

Platelet/Lymphocyte Ratio (PLR)

    • Optimal Min and Max
    • Lab Min and Max
    • Alarm Min and Max

Coagulation (Platelets) Reference Ranges

Platelets

    • Lab Min and Max: The study below only included clinically assessed healthy or normal individuals (66,144) with platelet counts that fell within the range of 100 to 450 × 109/L and excluded those with possible hematological disease. This data set provides a healthier population than those typically used by laboratories. The 5th and 95th percentile range from this data set are used as the lab min and max in the software.
    1. “The aim of the current study was to evaluate the impacts of clinical and biochemical parameters on key hematological indices in healthy adults. Therefore, we only selected clinically assessed healthy or normal individuals for the current analysis. The purpose was to exclude subjects with possible hematological diseases and those with cytopenia resulting from non-hematological conditions (including, but not limited to, medication, toxic chemicals, viral infections, chronic inflammation, and immune disorders). We reasoned that inclusion of these individuals might inadvertently lead to biased estimation of potentially confounding factors on the variation in hemogram.” Wang M-C, Huang C-E, Lin M-H, et al. Impacts of demographic and laboratory parameters on key hematological indices in an adult population of southern Taiwan: A cohort study. PLoS ONE. 2018;13(8). [PubMed]

    • Alarm Min and Max = 3 standard deviations from lab mean
    • Optimal Min and Max = 1 standard deviation from lab mean
    1. “A close scrutiny of the 25% of the patients with the highest platelet counts showed that the 10% of the 487 men with the highest platelet counts (mean platelet count, 305 x 109/l) had an annual CHD mortality of 1.27%, and the remaining subjects of the fourth quartile had an annual CHD mortality of 0.93%.” Thaulow E, Erikssen J, Sandvik L, Stormorken H, Cohn PF. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation. 1991;84(2):613-617.  [PubMed]
      • Separate Reference Ranges for Males and Females: Multiple studies support using separate reference ranges for women and men, as women typically have higher platelet counts than men.
      1. In our study, men had, on average, 26.174 × 109/L fewer platelets than women. It is more comprehensible that female adults have more platelets than men. The total body iron storage is generally lower in women because of menstruation, and iron depletion is a well-known factor to stimulate platelet production.” Wang M-C, Huang C-E, Lin M-H, et al. Impacts of demographic and laboratory parameters on key hematological indices in an adult population of southern Taiwan: A cohort study. PLoS ONE. 2018;13(8). [PubMed]
      2. Women had higher platelet counts than men (239 vs. 207 x109/L, p<0.001).” Ittermann T, Feig MA, Petersmann A, et al. Mean platelet volume is more important than age for defining reference intervals of platelet counts. PLoS ONE. 2019;14(3):e0213658. [PubMed]
      3. “Even controlling for iron deficiency, women had higher platelet counts than men (275×103/microL; 95% CI, 271-279) versus 256×103/microL (95% CI, 251-260; p<0.001).” Segal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. Ann Epidemiol. 2006;16(2):123-130. [PubMed]
      • MPV-Adjusted Platelet Count Reference Ranges: It stands to reason that the larger the platelet size, the less one should have and conversely, the smaller the platelet size, the more one should have. This reasoning supports the study that showed MPV (mean platelet volume) has a big impact on the reference range for platelet count. LabSmarts uses the formula from the below study to calculate male and female platelet count lab min and max reference ranges and automatically adjust those ranges based on the client’s MPV size. If a value for MPV is not provided, the male and female reference ranges under the lab min and max section above will be used.
      1. “MPV and sex have a stronger association with platelet count than age. MPV should be considered to adjust platelet count reference intervals and needs to be respected as confounder for platelet counts in epidemiological studies and clinical practice.” Ittermann T, Feig MA, Petersmann A, et al. Mean platelet volume is more important than age for defining reference intervals of platelet counts. PLoS ONE. 2019;14(3):e0213658. [PubMed]

    Mean Platelet Volume (MPV)

      • Lab Min and Max: Demirin H, Ozhan H, Ucgun T, et al. Normal range of mean platelet volume in healthy subjects: Insight from a large epidemiologic study. Thromb Res. 2011;128(4):358-360. [PubMed]
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean

    Fibrinogen

      1. “Congenital hypofibrinogenemia, first reported in 1935, is defined as plasmafibrinogen levels below 150 mg/dl. Cai H, Liang M, Yang J, Zhang X. Congenital hypofibrinogenemia in pregnancy: a report of 11 cases. Blood Coagul Fibrinolysis. 2018;29(2):155-159. [PubMed]
      • Alarm Max
      1. “Levels of functionally normal fibrinogen increase in pregnancy to an average of 4.5 gram/liter (g/l) [450 mg/dL]compared to an average of 3 g/l in non-pregnant people. They may also increase in various forms of cancer, particularly gastric, lung, prostate, and ovarian cancers. In these cases, the hyperfibrinogenemia may contribute to the development of pathological thrombosis.” Fibrinogen. In: Wikipedia. ; 2019.
      • Optimal Min: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • Optimal Max
      1. The risk of stroke gradually increased with increasing fibrinogen levels. The risk of stroke was almost double when the fibrinogen level was > 340 mg/dL. Bots ML, Elwood PC, Salonen JT, et al. Level of fibrinogen and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe. J Epidemiol Community Health. 2002;56 Suppl 1:i14-18. [PubMed]
      2. “…an increased incidence of myocardial infarction or sudden death was associated with higher base-line concentrations of fibrinogen (mean ±SD, 3.28±0.74 g per liter [328 mg/dL] in patients who subsequently had coronary events, as compared with 3.00±0.71 g per liter in those who did not; P = 0.01)…” Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med. 1995;332(10):635-641. [PubMed]
      3. Of the patients whose fibrinogen levels fell within the two highest quartiles (>331 mg/dL), about 75% of men and 50% of women were diagnosed with clinical CAD. A previous history of heart attack in the group with CAD was also associated with significantly higher average levels of fibrinogen. Acevedo M, Foody JM, Pearce GL, Sprecher DL. Fibrinogen: associations with cardiovascular events in an outpatient clinic. Am Heart J. 2002;143(2):277-282. [PubMed]
      4. “The healthy range is 180–350 mg/dL.” Dr. Stephen Sinatra. Check Your Fibrinogen Level to Reduce Your Heart Risk. [Blog]

    D-Dimer

      1. Lab Max (age < 50) = 0.49 mg/L FEU (Fibrinogen Equivalent Units)
      2. Lab Max (age > 49) = age * 0.01 mg/L FEU (Fibrinogen Equivalent Units)
      • Lab Min and Max (pregnancy trimester):
      1. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
      • Alarm Max
      1. “D-dimer value on admission is an accurate biomarker for predicting mortality in patients with COVID-19. 1.5 μg/ml is the optimal cutoff value of admission D-dimer for predicting mortality in COVID-19 patients.” Poudel A, Poudel Y, Adhikari A, et al. D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS One. 2021;16(8):e0256744.[PubMed]
      • Optimal Max: Lab Max – 0.01
      1. The risk of stroke gradually increased with increasing fibrinogen levels. The risk of stroke was almost double when the fibrinogen level was > 340 mg/dL. Bots ML, Elwood PC, Salonen JT, et al. Level of fibrinogen and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe. J Epidemiol Community Health. 2002;56 Suppl 1:i14-18. [PubMed]
      2. “…an increased incidence of myocardial infarction or sudden death was associated with higher base-line concentrations of fibrinogen (mean ±SD, 3.28±0.74 g per liter [328 mg/dL] in patients who subsequently had coronary events, as compared with 3.00±0.71 g per liter in those who did not; P = 0.01)…” Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med. 1995;332(10):635-641. [PubMed]
      3. Of the patients whose fibrinogen levels fell within the two highest quartiles (>331 mg/dL), about 75% of men and 50% of women were diagnosed with clinical CAD. A previous history of heart attack in the group with CAD was also associated with significantly higher average levels of fibrinogen. Acevedo M, Foody JM, Pearce GL, Sprecher DL. Fibrinogen: associations with cardiovascular events in an outpatient clinic. Am Heart J. 2002;143(2):277-282. [PubMed]
      4. “The healthy range is 180–350 mg/dL.” Dr. Stephen Sinatra. Check Your Fibrinogen Level to Reduce Your Heart Risk. [Blog]

    Glucose Reference Ranges

    Glucose

      1. “Thus, the categories of Fasting plasma glucose (FPG) values are as follows: FPG <100 mg/dl (5.6 mmol/l) = normal fasting glucose; FPG 100–125 mg/dl (5.6–6.9 mmol/l) = IFG (impaired fasting glucose); FPG ≥126 mg/dl (7.0 mmol/l) = provisional diagnosis of diabetes (the diagnosis must be confirmed, as described below).” Association AD. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2008;31(Supplement 1):S55-S60. PubMed
      • Optimal Min
      1. “… patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) …” Wei M, Gibbons LW, Mitchell TL, Kampert JB, Stern MP, Blair SN. Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality. Circulation. 2000;101(17):2047-2052. [PubMed]
      2. This study showed a 1.2-fold increase in the risk of all-cause mortality among those with fasting blood glucose (FBG) <81 mg/dL. “… the multivariate-adjusted HRs … for subjects with low FPG concentrations (< 4.50 mmol/l [< 81 mg/dL]), 1.2 (1.0–1.4) for all-cause, 1.3 (1.0–1.8) for CVD, and 1.1 (0.9 –1.4) for non-CVD mortality.” DECODE Study Group, European Diabetes Epidemiology Group. Is the Current Definition for Diabetes Relevant to Mortality Risk From All Causes and Cardiovascular and Noncardiovascular Diseases? Diabetes Care. 2003;26(3):688-696. [PubMed]
      3. “We found that both low (<80 mg/dl) and high (>126 mg/dl) fasting glucose levels were significantly associated with increased risk of all-cause and cardiovascular diseases mortality …” Zhou L, Mai J-Z, Li Y, et al. Fasting glucose and its association with 20-year all-cause and cause-specific mortality in Chinese general population. Chronic Diseases and Translational Medicine. 2019;5(2):89-96. doi:10.1016/j.cdtm.2018.08.001
      • Optimal Max
      1. “The incidence of diabetes started to rise in those with FPG 5.0 mmol/l [90 mg/dL} …” Shaw JE, Zimmet PZ, Hodge AM, et al. Impaired fasting glucose: How low should it go? Diabetes Care. 2000;23(1):34-39. [PubMed]
      2. “This is the first study to show that patients with high-normal FPG … (91-100 mg/dL) … have increased arterial stiffness as measured by ba-PWV.” Shin JY, Lee HR, Lee DC. Increased arterial stiffness in healthy subjects with high-normal glucose levels and in subjects with pre-diabetes. Cardiovasc Diabetol. 2011;10:30. [PubMed]
      3. “… men in the highest glucose quartile (fasting blood glucose > 85 mg/dl) had a significantly higher mortality rate from cardiovascular diseases compared with those in the three lowest quartiles. … Fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.” Bjørnholt JV, Erikssen G, Aaser E, et al. Fasting blood glucose: An underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men. Diabetes Care. 1999;22(1):45-49.
      4. “… progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more …” Tirosh A, Shai I, Tekes-Manova D, et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med. 2005;353(14):1454-1462. [PubMed]

    Hemoglobin A1c (HbA1c)

      • Lab Min
      1. “An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality …” Carson AP, Fox CS, McGuire DK, et al. Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes. Circ Cardiovasc Qual Outcomes. 2010;3(6):661-667. [PubMed]
      2. “Nondiabetic adult/child: 4%-5.9%” Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
      1. “HbA(1c) <5.0% was associated with a significantly increased risk of all-cause mortality … and of cancer death …” Aggarwal V, Schneider ALC, Selvin E. Low hemoglobin A(1c) in nondiabetic adults: An elevated risk state? Diabetes Care. 2012;35(10):2055-2060. [PubMed]
      2. “Participants with glycated hemoglobin values in the lowest category (<5.0%) had a significantly higher risk of death from any cause as compared with those with glycated hemoglobin levels of 5.0 to less than 5.5% …” Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010;362(9):800-811. [PubMed]
      3. “HbA1c is a reliable risk factor of all-cause and cardiovascular mortality in both diabetics and non-diabetics. Our findings establish optimal HbA1c levels, for the lowest all-cause and cardiovascular mortality, ranging from 6.0% to 8.0% in people with diabetes and from 5.0% to 6.0% in those without diabetes.” Cavero-Redondo I, Peleteiro B, Álvarez-Bueno C, Rodriguez-Artalejo F, Martínez-Vizcaíno V. Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: A systematic review and meta-analysis. BMJ Open. 2017;7(7):e015949. [PubMed]
      • Optimal Max
      1. “A significantly elevated risk of CHD was observed among nondiabetic women and men with HbA1c levels of ≥5.5%.” Pai JK, Cahill LE, Hu FB, Rexrode KM, Manson JE, Rimm EB. Hemoglobin a1c is associated with increased risk of incident coronary heart disease among apparently healthy, nondiabetic men and women. J Am Heart Assoc. 2013;2(2):e000077. [PubMed]
      2. “… glycated hemoglobin values of 5.5% or higher were associated with a hazard ratio for coronary heart disease of 1.38 …” Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010;362(9):800-811. [PubMed]
      3. “A 5-year follow-up study of mortality among non-smoking insurance applicants based on hemoglobin A1c level found that the mortality risk increases for everyone in a consistent linear pattern above 5.9%, irrespective of age and gender.”  Dolan VF, Stout RL, Fulks M. Hemoblobin A1c and Mortality in Insurance Applicants: A 5-Year Follow-up Study. ON THE RISK Journal of The Academy of Life Underwriting. 2009;25(1):42-49. [Article]

    Insulin

      1. Individuals classified as “Not insulin resistant” had an insulin range of 2.6 – 10.8 (6.7 ± 4.1) μIU/mL. Abbasi F, Shiffman D, Tong CH, Devlin JJ, McPhaul MJ. Insulin Resistance Probability Scores for Apparently Healthy Individuals. J Endocr Soc. 2018;2(9):1050-1057. [PubMed]
      1. “The goal is to keep fasting insulin levels lower than 12 μIU/ml, although an ideal level is 5 μIU/ml.” Sinatra S, Simpson G. “Fire in the Heart”: New Developments in Diagnosis, Prevention & Treatment of Cardiovascular Disease. Chapter 4. [series online] 2004. [A4M]
      2. Your fasting insulin level can be determined by a simple, inexpensive blood test. A normal fasting blood insulin level is below 5, but ideally you’ll want it below 3. If your insulin level is higher than3 to 5.” The 7 Values That Really Impact Your Health. Mercola.com. Published April 27, 2012. [Article]

    C-peptide

      • Lab Min and Max: Quest Diagnostics – C-Peptide
      • Alarm Min: “Specifically a c-peptide level of less than 0.2 nmol/l (0.6 ng/mL) is associated with a diagnosis of type 1 diabetes mellitus (T1DM).” Leighton E, Sainsbury CA, Jones GC. A Practical Review of C-Peptide Testing in Diabetes. Diabetes Ther. 2017;8(3):475-487. [PubMed]
      • Alarm Max = 3 standard deviations from lab mean
      • Optimal Min: LabCorp – C-Peptide
      • Optimal Max
      1. “We found that women with high fasting C-peptide levels (values > 2.5 ng/mL) collected 3 years after diagnosis) had more than a two-fold increased risk of breast cancer death compared with women with low C-peptide levels [less than 1.7 ng/mL]. … among leaner women (those with a BMI < 25 kg/m), average C-peptide levels were significantly lower among women who were alive at follow-up (1.86 ng/mL, standard deviation [SD] = 0.70) than among those who had died (2.58 ng/mL, SD = 1.52). In contrast, average C-peptide levels were higher, less variable, and quite similar among women with a BMI more than 25 kg/m2 (2.59 ng/mL, SD = 1.20 and 2.57 ng/mL, SD = 1.10, for women alive and not alive at follow-up, respectively). Obesity is a strong predictor of insulin resistance and hyperinsulinemia, and we showed in our study that overweight and obese groups of women with breast cancer had higher C-peptide levels.” Irwin ML, Duggan C, Wang C-Y, et al. Fasting C-peptide levels and death resulting from all causes and breast cancer: The health, eating, activity, and lifestyle study. J Clin Oncol. 2011;29(1):47-53. [PubMed]
      2. Participants who had serum C-peptide levels between 1.33 – 2.09 ng/mL (0.44 – 0.692 nmol/L) had a 1.33, 1.62, and 1.52-fold increased risk of all-cause, cardiovascular-related, and coronary artery-disease related mortality compared with those who had low C-peptide levels < 1.33 ng/mL. “Our finding suggests that elevated C‐peptide levels may be a predictor of death.” Min J, Min K. Serum C-peptide levels and risk of death among adults without diabetes mellitus. CMAJ. 2013;185(9):E402-408. [PubMed]
      3. One statistically significant result was an adjusted HR for overall mortality of 1.57 for C-peptide in the range of 0.653 – 0.983 nmol/L (1.97 – 2.97 ng/mL). “C‐peptide predicted cardiovascular death even in subjects with normoglycemia and without metabolic syndrome. When compared with individuals in the lowest quartile of C‐peptide levels (≤0.418 nmol/L [1.26 ng/mL]), subjects in the highest C‐peptide quartile (≥0.984 nmol/L [2.97 ng/mL]) had a 60% increase in the adjusted hazards of cardiovascular death.” Patel N, Taveira TH, Choudhary G, Whitlatch H, Wu W-C. Fasting serum C-peptide levels predict cardiovascular and overall death in nondiabetic adults. J Am Heart Assoc. 2012;1(6):e003152. [PubMed]
      4. “The C-peptide range with an average of 2.08 ng/mL was associated with faster decline in global cognition and verbal memory compared to the range with an average of 1.09 ng/mL.” Okereke OI, Pollak MN, Hu FB, Hankinson SE, Selkoe DJ, Grodstein F. Plasma C-peptide levels and rates of cognitive decline in older, community-dwelling women without diabetes. Psychoneuroendocrinology. 2008;33(4):455-461. [PubMed]

    Fructosamine (Future Release)

    GlycoMark® (Future Release)

      • Lab Min and Max: LabCorp – GlycoMark®
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean

    Kidney Reference Ranges

    Blood Urea Nitrogen (BUN)

    BUN, or blood urea nitrogen, is used predominantly to measure kidney function. BUN reflects the ratio between the production and clearance of urea in the body. Urea is formed almost entirely by the liver from both protein metabolism and protein digestion. The amount of urea excreted as BUN varies with the amount of dietary protein intake.
    Increased levels are a sign of kidney dysfunction. An increased BUN level may be due to increased production of urea by the liver or decreased excretion by the kidney. Increased BUN levels are also associated with dehydration and hypochlorhydria.
    Decreased levels are associated with malabsorption and a diet low in protein.

      • Lab Min and Max: Adult: 10-20 mg/dL or 3.6-7.1 mmol/L (SI units). Elderly: may be slightly higher than those of adult. (Lax Min and Max increased by 1 mg/dL for adults > 60 years). Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean
      1. “… a BUN ≥ 30 mg/dL was associated with a nearly 2-fold increased risk of mortality…” Sullivan DH, Sullivan SC, Bopp MM, Roberson PK, Lensing SY. BUN as an Independent Predictor of Post-Hospital-Discharge Mortality among Older Veterans. J Nutr Health Aging. 2018;22(7):759-765. [PubMed]
      2. “Comparisons of hazard ratios when laboratory results were within the normal range demonstrated that blood albumin and blood urea nitrogen (BUN) were both negatively associated with mortality and alkaline phosphatase (AP) was positively associated with mortality.” Hu G, Duncan AW. Associations between selected laboratory tests and all-cause mortality. J Insur Med. 2013;43(4):208-220. [PubMed]
      3. Increased discharge serum urea (> 16 mg/dL) was a predictor of increased mortality in heart failure patients.  Gotsman I, Zwas D, Planer D, Admon D, Lotan C, Keren A. The significance of serum urea and renal function in patients with heart failure. Medicine (Baltimore). 2010;89(4):197-203. [PubMed]
      4. A steady increase in mortality was predicted for Medicare patients (aged > or = 65 years) who were hospitalized for myocardial infarction (n = 44,437) who had increased levels of BUN > 17 mg/dL(> 6.1 mmol/L), creatinine > 1.0 mg/dL (> 88.4 micromol/L), and eGFR < 100 mL/min per 1.73 m2 and in patients who experienced heart failure who had increased levels of BUN > 16 mg/dL (> 5.7 mmol/L), creatinine > 1.1 mg/dL (> 97.2 micromol/L), and a Mayo eGFR <=  90 mL/min per 1.73 m2. Smith GL, Shlipak MG, Havranek EP, et al. Serum urea nitrogen, creatinine, and estimators of renal function: mortality in older patients with cardiovascular disease. Arch Intern Med. 2006;166(10):1134-1142. [PubMed]

    Creatinine

    Creatinine is produced primarily from the contraction of muscles and is removed by the kidneys. A disorder of the kidney and/or urinary tract will reduce the excretion of creatinine and thus raise blood serum levels. Creatinine is traditionally used with BUN to assess for impaired renal function.
    Increased levels are associated with kidney dysfunction, kidney disease and a possible dysfunction in the prostate.
    Decreased levels are associated with muscle atrophy due to creatinine’s connection to muscle metabolism.

      • Lab Min and Max: Quest Diagnostics – Creatinine
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean
      1. A steady increase in mortality was predicted for Medicare patients (aged > or = 65 years) who were hospitalized for myocardial infarction (n = 44,437) who had increased levels of BUN > 17 mg/dL(> 6.1 mmol/L), creatinine > 1.0 mg/dL (> 88.4 micromol/L), and eGFR < 100 mL/min per 1.73 m2 and in patients who experienced heart failure who had increased levels of BUN > 16 mg/dL (> 5.7 mmol/L), creatinine > 1.1 mg/dL (> 97.2 micromol/L), and a Mayo eGFR <=  90 mL/min per 1.73 m2. Gotsman I, Zwas D, Planer D, Admon D, Lotan C, Keren A. The significance of serum urea and renal function in patients with heart failure. Medicine (Baltimore). 2010;89(4):197-203. [PubMed]
      2. “In our experience with athletes, we frequently observed high creatinine values, near or higher than 115 μmol/L (1.3 mg/dL).” Banfi G, Del Fabbro M. Serum creatinine values in elite athletes competing in 8 different sports: comparison with sedentary people. Clin Chem. 2006;52(2):330-331. [PubMed]

    eGFR

    An estimated glomerular filtration rate (eGFR) test is a blood test that’s used to figure out how well your kidneys are doing their job. The test measures the amount of creatinine in your blood and, using a formula, mathematically derives a number that estimates how well your kidneys are functioning. The formula uses your creatinine levels, age, sex, weight, and race to arrive at that number—your eGFR. Learn more here.

    BUN/Creatinine Ratio (BCR)

      1. “The ratio of BUN to creatinine is usually between 10:1 and 20:1.” LabCorp – BUN
      2. “…high BCR (> 20) patients had higher hospital mortality compared with low BCR (< 20) patients…” Uchino S, Bellomo R, Goldsmith D. The meaning of the blood urea nitrogen/creatinine ratio in acute kidney injury. Clin Kidney J. 2012;5(2):187-191. [PubMed]
      3. BUN/creatinine ratio increases with age, as a result of decreasing muscle mass. “… higher than normal range of BUN/creatinine ratio group was an independent predictor for all-cause death…” Matsue Y, van der Meer P, Damman K, et al. Blood urea nitrogen-to-creatinine ratio in the general population and in patients with acute heart failure. Heart. 2017;103(6):407-413. [PubMed]

    Uric Acid

      1. “Our primary definition of hyperuricemia was a serum urate level of >7.0 mg/dl for men and >5.7 mg/dl for women.” Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-3141. [PubMed]
      2. “High serum levels of UA, or hyperuricemia, is defined as a metabolic pathology with a blood UA concentration greater than 7.0 mg/dL in men and 6.0 mg/dL in women..” Fang P, Li X, Luo JJ, Wang H, Yang X-F. A Double-edged Sword: Uric Acid and Neurological Disorders. Brain Disord Ther. 2013;2(2):109. [PubMed]
      1. “An elevated level of uric acid [>8.8 mg/dL] was associated with one-year mortality…” Novack V, Pencina M, Zahger D, et al. Routine laboratory results and thirty day and one-year mortality risk following hospitalization with acute decompensated heart failure. PLoS ONE. 2010;5(8):e12184. [PubMed]
      • Optimal Min
      1. “Serum UA levels (mean ± standard error) were significantly lower in PD (4.7 ± 1.2 mg/dl), MSA (4.6 ± 1.2 mg/dl) and PSP (4.0 ± 1.2 mg/dl) patients compared with the controls (5.5 ± 1.2 mg/dl) after adjusting for age, gender, and BMI (Table 3).” From table 3 in this study, we’re using the value for the lower range of PD for men (3.8 mg/dL) and women (3.2 mg/dL) as the optimal min values. Sakuta H, Suzuki K, Miyamoto T, et al. Serum uric acid levels in Parkinson’s disease and related disorders. Brain Behav. 2017;7(1):e00598. [PubMed]
      2. “The UA level was lower in the ALS patients (4.50±1.17 mg/dL, mean±SD [3.33 – 5.67 mg/dL]) than in the controls (5.51±1.22 mg/dL; p<0.001). Among the ALS patients, the level of UA acid was inversely correlated with the rate of disease progression.” Oh SI, Baek S, Park JS, Piao L, Oh KW, Kim SH. Prognostic Role of Serum Levels of Uric Acid in Amyotrophic Lateral Sclerosis. J Clin Neurol. 2015;11(4):376-382. [PubMed]
      3. “The elevated serum UA was associated with a higher BMD [bone mineral density] and a greater muscle mass in a middle-aged and elderly Chinese population… Compared with participants in lowest quartile of UA [3.7 – 4.94 mg/dL], those participants in highest quartile [6.57 – 8.6 mg/dL] showed a 2.3%(whole body), 4.1%(lumbar spine), 2.4%(total hip), and 2.0% (femoral neck) greater BMDs.” Dong X-W, Tian H-Y, He J, Wang C, Qiu R, Chen Y-M. Elevated Serum Uric Acid Is Associated with Greater Bone Mineral Density and Skeletal Muscle Mass in Middle-Aged and Older Adults. PLoS ONE. 2016;11(5):e0154692. [PubMed]
      • Optimal Max
      1. Although this study demonstrated that serum uric acid (UA) levels are positively associated with HGS [handgrip strength] after adjusting for potential confounders in Japanese adult women aged 60–90 years, there is a more important finding that we are using to support the male and female optimal max values. A positive correlation was shown between serum UA and chronic kidney disease in both males and females going from quartile 1 to quartile 4. The mid-range of quartile 2 for both males (5.5 mg/dL) and females (4.4 mg/dL) are being used as the optimal max values for these genders. Kawamoto R, Ninomiya D, Kasai Y, et al. Serum Uric Acid Is Positively Associated with Handgrip Strength among Japanese Community-Dwelling Elderly Women. PLoS ONE. 2016;11(4):e0151044. [PubMed]
      2. This study found that there was a gradual increase in risk of AMI, stroke and CHF by increasing levels of UA. We are using the upper limit of the 2nd uric acid quartile for men (5.4 mg/dL) and women (4.1 mg/dL) to support our optimal max values. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417 734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med. 2009;266(6):558-570. [PubMed]
      3. “Increasing UA levels, even in subjects with normouricemia and without diabetes, were associated with increasing prevalence of cardiovascular risk factors, suggesting that clinically dichotomous definition of hyperuricemia may be inadequate and high-normal value of UA may warn of metabolic disorders.” Upper limit of normal reference range used in this study was 7 mg/dL for men and 6 mg/dL for women.” Jin YL, Zhu T, Xu L, et al. Uric acid levels, even in the normal range, are associated with increased cardiovascular risk: the Guangzhou Biobank Cohort Study. Int J Cardiol. 2013;168(3):2238-2241. [PubMed]

    Nutrients Reference Ranges

    Calcium (Ca)

      1. “We found that men less than 50 yr of age at screening (n = 21,131) with S-Ca greater than 2.45 mmol/L exhibited a 20% increased mortality rate compared with those with lower S-Ca values [2.31-2.45]…” Leifsson BG, Ahrén B. Serum calcium and survival in a large health screening program. J Clin Endocrinol Metab. 1996;81(6):2149-2153. [PubMed]
        • Optimal Min: 2.31 mmol/L = 9.3 mg/dL
        • Optimal Max: 2.45 mmol/L = 9.8 mg/dL

    Calcium, Corrected

      • In serum, calcium exists in three forms: (1) bound to proteins, predominantly albumin (40–50%), (2) bound to anions such as bicarbonate, citrate, lactate or phosphate (5–10%), and (3) in a free ionized form known as ionized calcium (Ca2+; 45–50%).
      • The calcium tested on the Comprehensive Metabolic Panel (CMP) is a measurement of the total serum calcium, both bound and free (ionized).
      • Because the majority of total calcium is bound to albumin, decreased albumin levels will cause decreased calcium levels.
      • The following formula is used to correct calcium when albumin levels are below the albumin Optimal Min of 4.5:
      1. (0.8 mg/dL x [4.5 – observed albumin] ) + observed calcium
      2. Values for observed albumin and observed calcium come from the CMP test.
      3. 4.5 represents the Optimal Min for albumin based on the research studies below.
      4. Parent X, Spielmann C, Hanser A-M. [“Corrected” calcium: calcium status underestimation in non-hypoalbuminemic patients and in hypercalcemic patients]. Ann Biol Clin (Paris). 2009;67(4):411-418. [PubMed]
      5. https://www.mdcalc.com/calcium-correction-hypoalbuminemia#evidence

    Calcium, Ionized (Future Release)

      • Ionized calcium (Ca2+) is the biologically active form of calcium, and its measurement has been suggested to be a better reference test for calcium status than the calcium bound to albumin. Therefore, it’s important to know this value when assessing a person’s true blood calcium status. The following formula from the below research study is used to determine ionized calcium:
      1. Equation 3: Ca2+ = 1.631 × CaTot0.5 – 0.144 × Alb0.75 + 0.317
      2. units: Ca2+ in mg/dl, CaTot in mg/l, Alb in g/dl)
      3. CaTot is the calcium value on the CMP test.
      4. Mateu-de Antonio J. New Predictive Equations for Serum Ionized Calcium in Hospitalized Patients. Med Princ Pract. 2016;25(3):219-226. [PubMed]

    Phosphorus

      1. “Elderly: values slightly lower than adult.” Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
      2. Adjusting the range downward for females > 64 years based on adjustments done by Quest Diagnostics – Phosphate (as Phosphorus)
      • Alarm Min and Max (male and female of all ages) = 3 standard deviations from lab mean
      • Optimal Min (male and female of all ages) = 1 standard deviation from lab mean
      • Optimal Max (male of all ages and female > 64)
      1. “Age, MetS, and phosphorus levels are significantly associated with ED [erectile dysfunction]. We found that, in clinically stable middle-aged men, serum phosphorus was strongly associated with ED. [Mild to moderate levels of ED were seen in the group with a mean phosphorus of 3.5 mg/dL.] And, recommended serum phosphorus levels could be different for males than for females. Given this finding, handling of phosphorus in men may have a particular meaning of reducing the risk of ED.” Min SK, Choi K, Kim SK, Lee GI, Cho I-C. Phosphorus as predictive factor for erectile dysfunction in middle aged men: A cross sectional study in Korea. Investig Clin Urol. 2016;57(6):442-448. [PubMed]
      • Optimal Max (female < 65)
      1. “The risk of coronary calcification was significantly higher in individuals with a serum phosphorus concentration >3.9 mg/dL than in those with a serum phosphorus concentration <3.3 mg/dL.It suggested that even a relatively higher concentration of serum phosphorus within the normal range could be a risk factor for cardiovascular disease.” Park KS, Chang JW, Kim TY, et al. Lower concentrations of serum phosphorus within the normal range could be associated with less calcification of the coronary artery in Koreans with normal renal function. Am J Clin Nutr. 2011;94(6):1465-1470. [PubMed]
      2. “There was a strong, positive association between the highest quartile of serum phosphorus (3.7 to 5.0 mg/dL) and high ABPI [ankle brachial pressure index] when compared to the reference group (3.1 to 3.4 mg/dL) after adjustment…” Kendrick J, Ix JH, Targher G, Smits G, Chonchol M. Relation of serum phosphorus levels to ankle brachial pressure index (from the Third National Health and Nutrition Examination Survey). Am J Cardiol. 2010;106(4):564-568. [PubMed]
      3. “Individuals with a serum phosphorus concentration >3.5 mg/dL had a higher incidence of cardiovascular events than did those with a serum phosphorus concentration <2.8 mg/dL.” Dhingra R, Sullivan LM, Fox CS, et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007;167(9):879-885. [PubMed]
      4. “Those with a serum phosphorus concentration >3.9 mg/dL had a higher level of coronary calcification than did those with a serum phosphorus concentration <3.3 mg/dL.” Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA. Serum phosphorus levels associate with coronary atherosclerosis in young adults. J Am Soc Nephrol. 2009;20(2):397-404. [PubMed]

    Calcium/Phosphorus Ratio (Future Release)

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Magnesium, RBC

      1. “Levels for a lab test, Magnesium, RBC, in a population that is already 80% deficient in magnesium are not “normal” and not “optimal.” In The Magnesium Miracle, I point this out in detail. I say that if the range in the labs is 4.2-6.8mg/dL, you want to be at least 6.0-6.5mg/dL up in the 80th percentile.” Dr. Carolyn Dean, author of The Magnesium Miracle. Dr. Carolyn Dean MD ND. Published May 31, 2014. Accessed March 10, 2021. [Website]
      2. “The level that most functional medicine experts recommend for optimal function is 6-7.2 mg/dL.” Magnesium the Magnificent! The Most Powerful Mineral? – Nexus Health Partnership. Accessed March 10, 2021. [Website]
      3. “Red blood cell (RBC) magnesium is the most precise way to assess intracellular magnesium status, and free RBC magnesium has been shown to be inversely related with hypertension (Resnick 1984; Geiger 2012; Rosanoff 2005; Volpe 2013).” Reference Range: 4.2-6.8 mg/dL. LE’s Optimal Range: >6.0 mg/dL. Lab Testing: Introduction – Life Extension. Accessed March 10, 2021. [Website]
      4. “If your results fall below 6.0 mg/dl, you’ll want to supplement. Magnesium Deficiency Signs, Symptoms and How to Fix It. Bulletproof. Published February 5, 2020. Accessed March 10, 2021. [Website]

    Magnesium, serum

      1. “Magnesium below 2.05 mg/dL detected PEI [pancreatic exocrine insufficiency]…” Lindkvist B, Domínguez-Muñoz JE, Luaces-Regueira M, Castiñeiras-Alvariño M, Nieto-Garcia L, Iglesias-Garcia J. Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis. Pancreatology. 2012;12(4):305-310. [PubMed]
      2. “In conclusion, metabolic unit balance and depletion and repletion experiments indicate that serum magnesium concentrations <0.82 mmol/L (2.0 mg/dL)… strongly suggests that an individual is magnesium deficient, thus potentially increasing the risk for some chronic diseases. Based on the review of literature presented herein, we propose adopting an evidenced-based reference interval for STMC ≥0.85 mmol/L [2.07 mg/dL] Costello RB, Elin RJ, Rosanoff A, et al. Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come. Adv Nutr. 2016;7(6):977-993. [PubMed]
      • Optimal Max
      1. The upper limit of the proposed reference range from this study is 0.955 mmol/L [2.3 mg/dL]. Costello RB, Elin RJ, Rosanoff A, et al. Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come. Adv Nutr. 2016;7(6):977-993. [PubMed]

    Vitamin B12 (Cobalamin)

      1. “Patients with low Cbl levels (< 74 pmol/L [100 pg/mL]) usually have Cbl deficiency.” Snow CF. Laboratory Diagnosis of Vitamin B12 and Folate Deficiency: A Guide for the Primary Care Physician. Arch Intern Med. 1999;159(12):1289-1298. [PubMed]
      2. “For serum vitamin B12 below 149 pg/mL, no further testing is needed to confirm a vitamin B12 deficiency.” Prousky J. Understanding the serum vitamin B12 level and its implications for treating neuropsychiatric conditions: An orthomolecular perspective. J Orthomol Med. 2010;25:77-88. [Townsend Letter] [Research Gate – PDF]

    Vitamin D 25-Hydroxy (25-OH)

      1. “Serum 25OHD levels above 150 ng/ml are considered as VDI [Vitamin D Intoxication].” Ozkan B, Hatun S, Bereket A. Vitamin D intoxication. Turk J Pediatr. 2012;54(2):93-98. [PubMed]
      • Optimal Min and Max
      1. “To ward off infection and prevent chronic diseases, the level you’re aiming for is between 60 and 80 ng/mL, with 40 ng/mL being the low cutoff point for sufficiency to prevent a wide range of diseases, including cancer.Vitamin D Protects Against Infections. Mercola.com. Published January 14, 2020.
      2. “A few years back, the recommended level was between 40 to 60 nanograms per milliliter (ng/ml), but more recently the optimal vitamin D level has been raised to 50-70 ng/ml, and when treating cancer or heart disease, as high as 70-100 ng/ml.” Get Your Vitamin D Levels to a Healthy Range. Mercola.com. Published November 21, 2011.
      3. “Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ≥60 ng/ml being most protective.” McDonnell SL, Baggerly CA, French CB, et al. Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort. PLOS ONE. 2018;13(6):e0199265. [PubMed]
      4. “Research has demonstrated many health benefits of higher vitamin D levels. What do scientists say is the target amount? 48 world-wide vitamin D researchers agree it is 40-60 ng/ml (100-150 nmol/L).” Are You Vitamin D Deficient? GrassrootsHealth.
      5. “Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml.” McDonnell SL, Baggerly C, French CB, et al. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. PLOS ONE. 2016;11(4):e0152441. [PubMed]
      6. “Optimal vitamin D status, defined by estimated maximum PTH suppression, does not occur until at least 25OHD levels ≥40 ng/ml.” Ginde AA, Wolfe P, Camargo CA, Schwartz RS. Defining vitamin D status by secondary hyperparathyroidism in the U.S. population. J Endocrinol Invest. 2012;35(1):42-48. [PubMed]

    Vitamin D, 1,25-Dihydroxy (OH)2

      • Lab Min and Max: Vitamin D, 1,25-Dihydroxy
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min = Lab Min + 1.0
      • Optimal Max = Lab Max – 1.0

    Ceruloplasmin (Copper) – Future Release

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Electrolytes Reference Ranges

    Sodium (Na)

      1. “Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L) showed significantly increased risk of major CVD events and total mortality compared to men within the upper normal range (139-143 mEq/L).” Wannamethee SG, Shaper AG, Lennon L, Papacosta O, Whincup P. Mild hyponatremia, hypernatremia and incident cardiovascular disease and mortality in older men: A population-based cohort study. Nutr Metab Cardiovasc Dis. 2016;26(1):12-19. [PubMed]
      • Optimal Max
      1. “We found mortality risks below the population average within these proposed DLs [decision-limits]: potassium 3.4-4.3 mmol/L; sodium 136-142 mmol/L; chloride 100-108 mmol/L; creatinine 0.6-1.1 mg/dL; blood urea nitrogen (BUN) 5-20 mg/dL. The DLs correspond roughly to the usually-quoted RIs, with a notable narrowing for electrolytes. Potassium and sodium have reduced upper limits, avoiding a “high-normal” area where the odds ratio rises 2 to 3 times the population average.” Solinger AB, Rothman SI. Risks of mortality associated with common laboratory tests: a novel, simple and meaningful way to set decision limits from data available in the Electronic Medical Record. Clin Chem Lab Med. 2013;51(9):1803-1813. [PubMed]

    Potassium (K)

      • Lab Min and Max: Labcorp – Potassium
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max
      1. “Compared with the 4.0–4.4 mEq/L category, those with serum potassium between 4.5 and 4.9 mEq/L were at a significantly higher risk of cancer…” Hughes-Austin JM, Rifkin DE, Beben T, et al. The Relation of Serum Potassium Concentration with Cardiovascular Events and Mortality in Community-Living Individuals. Clin J Am Soc Nephrol. 2017;12(2):245-252. [PubMed]
      2. “[compared with a reference range of 3.8-4.4 mEq/L] …increased cardiovascular mortality among subjects with moderately increased serum potassium [4.5-5.4 mmol/L] was most prominent…” Fang J, Madhavan S, Cohen H, Alderman MH. Serum potassium and cardiovascular mortality. J Gen Intern Med. 2000;15(12):885-890. [PubMed]

    Na/K Ratio (Future Release)

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Chloride (Cl)

      • Lab Min and Max: Quest Diagnostics – Chloride
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Max = 1 standard deviation from lab mean
      • Optimal Min
      1. “The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L)…” Ferreira JP, Girerd N, Duarte K, et al. Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative. Circ Heart Fail. 2017;10(2). [PubMed]
      2. “The risk ratio for CVD mortality associated with a low serum chloride level [< or =100 mmol/l] was comparable to or higher than those observed for well-established CVD risk factors.” De Bacquer D, De Backer G, De Buyzere M, Kornitzer M. Is low serum chloride level a risk factor for cardiovascular mortality? J Cardiovasc Risk. 1998;5(3):177-184. [PubMed]
      3. “Serum Cl− <100 mmol/L was found to be a strong predictor (RR 1.77; 95 % CI 1.22–2.5), in multivariate analysis, of total, cardiovascular, and non-cardiovascular mortality independent of other classic risk factors…” McCallum L, Lip S, Padmanabhan S. The hidden hand of chloride in hypertension. Pflugers Arch. 2015;467(3):595-603. [PubMed]
      4. “Low, not high Serum Cl- (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders.” McCallum L, Jeemon P, Hastie CE, et al. Serum chloride is an independent predictor of mortality in hypertensive patients. Hypertension. 2013;62(5):836-843. [PubMed]

    Carbon Dioxide (CO2)

      • Lab Min and Max: Quest Diagnostics – Carbon Dioxide. LabSmarts uses the high altitude range defined here for clients living at elevations above 3,281 feet (1,000 meters).
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean
      1. “In generally healthy older individuals, low serum bicarbonate [< 23.0 mEq/L (low)] associated with higher mortality independent of systemic pH and potential confounders. This association seemed to be present regardless of whether the cause of low bicarbonate was metabolic acidosis or respiratory alkalosis. Metabolic alkalosis also associated with higher mortality.” Farwell WR, Taylor EN. Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey. CMAJ. 2010;182(2):137-141. [PubMed]
      2. “Compared with participants in the highest quartile of bicarbonate level [> 25 mmol/L], those in the lowest quartile [< 23 mmol/L] had a leukocyte count that was 0.7 × 109/L higher and a C-reactive protein level that was 4.0 nmol/L higher (p ≤ 0.02).” Raphael KL, Murphy RA, Shlipak MG, et al. Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study. Clin J Am Soc Nephrol. 2016;11(2):308-316. [PubMed]
      3. “Compared with participants with bicarbonate levels ≥23 mEq/L, those with bicarbonate levels<23 mEq/L had higher body mass index and serum albumin levels; were more likely to have low socioeconomic status, a diagnosis of diabetes mellitus, or glomerular filtration rate <60 mL/min/1.73 m(2); and were less likely to use diuretics. Serum bicarbonate level <23 mEq/L compared with ≥23 mEq/L was associated with low gait speed…” Abramowitz MK, Hostetter TH, Melamed ML. Association of serum bicarbonate levels with gait speed and quadriceps strength in older adults. Am J Kidney Dis. 2011;58(1):29-38. [PubMed]
      4. “Low fitness was most prevalent among those in the lowest quartile of serum bicarbonate [< 24 mEq/L] or highest quartile of anion gap [> 11.9 mEq/L].” Abramowitz MK, Hostetter TH, Melamed ML. Lower serum bicarbonate and a higher anion gap are associated with lower cardiorespiratory fitness in young adults. Kidney Int. 2012;81(10):1033-1042. [PubMed]
      5. “…women with plasma bicarbonate above the median level [> 22.4 mmol/L] had lower odds of diabetes… compared with women below the median level.” Mandel EI, Curhan GC, Hu FB, Taylor EN. Plasma bicarbonate and risk of type 2 diabetes mellitus. CMAJ. 2012;184(13):E719-725. [PubMed]
      6. “…both persons with bicarbonate < 23.0 and > 28.0 mmol/L had more rapid longitudinal decline in eGFR than those in intermediate categories…” Goldenstein L, Driver TH, Fried LF, et al. Serum bicarbonate concentrations and kidney disease progression in community-living elders: the Health, Aging, and Body Composition (Health ABC) Study. Am J Kidney Dis. 2014;64(4):542-549. [PubMed]

    Anion Gap

      • The serum anion gap is useful in determining the likelihood of an acid-base imbalance.
      • The anion gap represents the difference between the unmeasured anions and the unmeasured cations and is estimated using one of these two formulas (the first more commonly used):
      1. Anion Gap = Na+ – (Cl _ + HCO3_ )
      2. Anion Gap w/ K = (Na+ + K+) – (Cl _ + HCO3_ )
      3. HCO3_  is bicarbonate and is represented as CO2 on most blood test results in the U.S.
      • “Since normal serum potassium concentration is quantitatively a minor component of serum electrolytes, the fluctuation in its concentration affects the overall result very little, and hence the first of the two equations is more commonly used to estimate the anion gap.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • LabSmarts calculates a value for both equations and plots them on separate bar graphs having their own set of research-backed reference ranges.

    Anion Gap Adjusted for Low Albumin

      • Low albumin will cause a falsely low anion gap. LabSmarts uses the formula below to correct the anion gap when albumin is below optimal min:
      1. adjusted anion gap = observed anion gap + 0.25 x ([normal albumin]-[observed albumin]) where normal albumin = optimal min value of 4.5
      2. This adjustment returns the anion gap to the familiar scale of values that apply when albumin concentration is normal.
      3. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26(11):1807-1810. [PubMed]

    Anion Gap Reference Ranges

      • Lab Min
      1. “The reference range for the anion gap has shifted downward (to 3 to 11 mmol/L in one of our laboratories).” Winter SD, Pearson JR, Gabow PA, Schultz AL, Lepoff RB. The fall of the serum anion gap. Arch Intern Med. 1990;150(2):311-313. [PubMed]
      2. “At present, the reference range of anion gap has been lowered from 8-16 to 3-11 mmol/l because of the changes in technique for measuring electrolyte.” Lolekha PH, Vanavanan S, Lolekha S. Update on value of the anion gap in clinical diagnosis and laboratory evaluation. Clin Chim Acta. 2001;307(1-2):33-36. [PubMed]
      3. “The new method that uses measurement by ion-selective electrodes has caused a shift of the anion gap from 12±4 mEq/L down to 6±3 [3-9] mEq/L.” Lee S, Kang KP, Kang SK. Clinical usefulness of the serum anion gap. Electrolyte Blood Press. 2006;4(1):44-46. [PubMed]
      • Lab Max
      1. CMAMA – Clinical: Comprehensive Metabolic Panel, Serum. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/113631. Accessed October 11, 2019.
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min = 1 standard deviation from lab mean
      • Optimal Max = 1 standard deviation from lab mean
      1. “Compared with participants in the lowest quartile of anion gap [< 10 mmol/L], those in the highest quartile [> 13 mmol/L] had a leukocyte count that was 1.0 × 09/L higher and a C-reactive protein level that was 10.9 nmol/L higher (p < 0.01).” Farwell WR, Taylor EN. Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey. CMAJ. 2010;182(2):137-141. [PubMed]
      2. “In the U.S., the anion gap is [Na] – ([Cl] + [HCO3]) and the normal range is 8-12; in many other countries (e.g., Europe, Australia) the anion gap is calculated as ([Na] + [K]) – ([Cl]+[HCO3]).  The addition of the cation [K] in the equation means that these anion gaps would be slightly lower than those in the U.S.” Gamblegrams. Renal Fellow Network. https://www.renalfellow.org/2008/12/03/gamblegrams. Published December 3, 2008. Accessed October 7, 2019.
      3. “The normal anion gap varies with different assays, but is typically 4 to 12mmol/L (if measured by ion selective electrode; 8 to 16 if measured by older technique of flame photometry).” Anion Gap • LITFL Medical Blog • CCC Acid-Base. Life in the Fast Lane • LITFL • Medical Blog. January 2019. https://litfl.com/anion-gap. Accessed October 7, 2019.
      4. “Low fitness was most prevalent among those in the lowest quartile of serum bicarbonate [< 24 mEq/L] or highest quartile of anion gap [> 11.9 mEq/L].” Abramowitz MK, Hostetter TH, Melamed ML. Lower serum bicarbonate and a higher anion gap are associated with lower cardiorespiratory fitness in young adults. Kidney Int. 2012;81(10):1033-1042. [PubMed]

    Anion Gap w/ K Reference Ranges

      • Anion Gap with Potassium  = (Na + K) – (Cl + CO2)
      • Lab Min and Max = 4 + lab min and max of anion gap w/o K
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean

    Osmolarity (Future Release)

      • Osmolarity (mOsm/L) is calculated using the Smithline-Gardner formula: 2 x Sodium (mmol/L) + Glucose (mg/dL)/18 + BUN (mg/dL)/2.8
      1. Choy KW, Wijeratne N, Lu ZX, Doery JC. Harmonisation of Osmolal Gap – Can We Use a Common Formula?. Clin Biochem Rev. 2016;37(3):113–119. [PubMed]
      2. Video explaining this formula.
      3. Article explaining why medicine uses osmolarity instead of osmolality.
      4. Video explaining the difference between tonicity and osmolarity.
      • Lab Min and Max
      1. This website has an extensive collection of graphics from multiple sources showing different standard (lab) reference ranges. The most widely used range is 285 – 295 mOsm/kg (mOsm/L).
      2. “Normal findings: Adult/elderly: 285-295 mOsm/kg.” Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
      3. “ADH secretion is maximally stimulated at a serum osmolality greater than 295 mOsm/kg</span. and is suppressed when the osmolality falls below 284 mOsm/kg.” McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max
      1. “Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD.” Kuwabara M, Hisatome I, Roncal-Jimenez CA, et al. Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study [published correction appears in PLoS One. 2018 May 17;13(5):e0197941] PLoS One. 2017;12(1):e0169137. Published 2017 Jan 12. [PubMed]

    Proteins Reference Ranges

    Protein, Total

    Albumin

      1. “This translates into 150% risk thresholds at approximately 3.8 mg/dL for all females and for males 70+, and 4.1 mg/dL for males ages 20 to 69. Fulks M, Stout RL, Dolan VF. Albumin and all-cause mortality risk in insurance applicants. J Insur Med. 2010;42(1):11-17. [PubMed]
      2. “Comparisons of hazard ratios when laboratory results were within the normal range demonstrated that blood albumin and blood urea nitrogen (BUN) were both negatively associated with mortality …” Hu G, Duncan AW. Associations between selected laboratory tests and all-cause mortality. J Insur Med. 2013;43(4):208-220. [PubMed]
      3. “For albumin, the comparable low values [that identified substantially increased mortality risk] were ≤ 3.9 g/dL for women and ≤ 4.1 g/dL for men.” Fulks M, Stout RL. Low Cholesterol and Low Albumin Levels: Alerts to Hidden Mortality Risk. ON THE RISK Journal of The Academy of Life Underwriting. 2015;31(4):65-69. [Article] [Full Issue]
      4. Mortality rate increased as albumin dropped below 4.5 g/dL. Novack V, Pencina M, Zahger D, et al. Routine laboratory results and thirty day and one-year mortality risk following hospitalization with acute decompensated heart failure. PLoS ONE. 2010;5(8):e12184. [PubMed]
      5. In 1,726 systolic HF patients (age 52 +/- 13 years), one-year survival was 66% in patients with and 83% in those without hypoalbuminemia (<= 3.4 g/dL). Mean albumin was 3.8 +/- 0.6 g/dL, and 25% of patients had hypoalbuminemia. Horwich TB, Kalantar-Zadeh K, MacLellan RW, Fonarow GC. Albumin levels predict survival in patients with systolic heart failure. Am Heart J. 2008;155(5):883-889. [PubMed]
      6. “The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter.” Owen WF, Lew NL, Liu Y, Lowrie EG, Lazarus JM. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med. 1993;329(14):1001-1006. [PubMed]
      7. “Of the laboratory variables, low serum albumin less than 40 g/L (less than 4.0 g/dL) was most highly associated with death probability. Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis. 1990;15(5):458-482. [PubMed]
      8. In data from 2,091 individuals aged 23-87 who underwent a general health examination, compared to the middle tertile (4.4-4.5g/dl), the lowest tertile (3.3-4.3g/dl) was associated with increased prevalence of inflammation. Kadono M, Hasegawa G, Shigeta M, et al. Serum albumin levels predict vascular dysfunction with paradoxical pathogenesis in healthy individuals. Atherosclerosis. 2010;209(1):266-270. [PubMed]

    Globulin

      1. “… relative mortality was found to increase gradually for globulin values > 3.2 g/dL. Values > 4.0 were associated with a mortality risk that was approximately doubled. There is also a small increased risk for globulin values < 1.9 g/dL.” Fulks M, Stout RL, Dolan VF. Serum globulin predicts all-cause mortality for life insurance applicants. J Insur Med. 2014;44(2):93-98. [PubMed]
      2. “Our data shows that in fully adjusted models, lower cut points, ranging from 3.1 to 3.7 g/dl, are associated with an increased risk of death… . The gamma gap [difference between total serum protein and albumin which is the same thing as globulin] is an independent risk factor for all-cause mortality at values as low as 3.1 g/dl (in contrast to the traditional definition of 4.0 g/dl), and is strongly associated with death from pulmonary causes.” Juraschek SP, Moliterno AR, Checkley W, Miller ER. The Gamma Gap and All-Cause Mortality. PLoS ONE. 2015;10(12):e0143494. [PubMed]
      3. Serum globulin for lung cancer group was 2.052± 0.233 gm/dL (1.819 – 2.285 gm/dL) compared to control group of 2.873± 0.208 gm/dL. Samanta S, Sharma A, Das B, Mallick AK, Kumar A. Significance of Total Protein, Albumin, Globulin, Serum Effusion Albumin Gradient and LDH in the Differential Diagnosis of Pleural Effusion Secondary to Tuberculosis and Cancer. J Clin Diagn Res. 2016;10(8):BC14-18. [PubMed]
      4. In conclusion, the gamma gap is an independent prognostic factor for long-term mortality in nonagenarians and centenarians. A value greater than or equal to 3.1 g/dl may define an elevated gamma gap, but further studies are required. Yang M, Xie L, Liu X, Hao Q, Jiang J, Dong B. The gamma gap predicts 4-year all-cause mortality among nonagenarians and centenarians. Sci Rep. 2018;8(1):1046. [PubMed]

    A/G Ratio (Albumin/Globulin Ratio, AGR)

      1. “Results of multivariate analysis showed that low preoperative AGR (<1.36) was an independent risk factor for poorer overall survival in GC [gastric cancer] patients.” Xue F, Lin F, Yin M, et al. Preoperative albumin/globulin ratio is a potential prognosis predicting biomarker in patients with resectable gastric cancer. Turk J Gastroenterol. 2017;28(6):439-445. [PubMed]
      2. “Patients with lower AGR (<1.29) were estimated to have 1.35 times higher risk of death than those with higher AGR (≥1.29).” Zhou T, He X, Fang W, et al. Pretreatment Albumin/Globulin Ratio Predicts the Prognosis for Small-Cell Lung Cancer. Medicine (Baltimore). 2016;95(12). [PubMed]
      3. “… patients with a lower AGR level [<1.66] showed significantly shorter overall survival than patients with a higher AGR level [≥1.66] … and … patients with a lower AGR tended to suffer inflammatory disease and hyperfibrinogenemia compared with the higher group. ≥1.29).”Li X-H, Gu W-S, Wang X-P, et al. Low Preoperative albumin-to-globulin ratio Predict Poor Survival and Negatively Correlated with Fibrinogen in Resectable Esophageal Squamous Cell Carcinoma J Cancer. 2017;8(10):1833-1842. [PubMed]

    Liver / Biliary Reference Ranges

    Bile Acids, Total

      • Lab Min: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • Alarm Min and Max: Quest Diagnostics – Bile Acids, Total
      • Optimal Min and Max = 1 standard deviation from lab mean
      • Lab Max
      1. LabCorp – Bile Acids
      2. Mild OC [Obstetric Cholestasis] is defined as SBA levels of 10 – 39 μmol/l. Egan N, Bartels A, Khashan AS, Broadhurst DI, Joyce C, O’Mullane J, et al. Reference standard for serum bile acids in pregnancy. BJOG. 2012;119: 493–498. [PubMed]

    Bilirubin, Total

      • Lab Min and Max –  Separate Reference Ranges for Gender and Race
      1. “Common usage prescribes a single normal range for serum bilirubin levels. However, we have not only confirmed that men have higher levels than women but have discovered significant racial differences as well. Among 1,538 healthy Americans, blacks had lower mean bilirubin levels than whites of European origin, Latin Americans, and Asians. These racial differences, which were more pronounced among women than men, were maintained in pernicious anemia.” Carmel R, Wong ET, Weiner JM, Johnson CS. Racial differences in serum total bilirubin levels in health and in disease (pernicious anemia). JAMA. 1985;253(23):3416-3418. [PubMed]
      2. “Mean serum bilirubin concentrations in the men significantly exceeded values in the women over all age groups examined.” Rosenthal P, Pincus M, Fink D. Sex- and age-related differences in bilirubin concentrations in serum. Clin Chem. 1984;30(8):1380-1382. [PubMed]
      3. “Serum bilirubin levels vary significantly with gender, race, and smoking status. The mean serum total bilirubin in the adult population is 0.62 +/- 0.003 mg/dL (SEM), with a 97.5% cut-off of 1.4 mg/dL. Serum bilirubin levels are significantly higher in men (0.72 +/- 0.004) than in women (0.52 +/- 0.003 mg/dL) and are lower in non-Hispanic blacks (0.55 +/- 0.005 mg/dL) compared with non-Hispanic whites (0.63 +/- 0.004 mg/dL) and Mexican Americans (0.61 +/- 0.005 mg/dL).” Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: Gender effect and inverse correlation with colorectal cancer. Hepatology. 2004;40(4):827-835. [PubMed]
      1. “Males had higher TBili levels while females tended to have levels less than 11 micromoles per liter [0.64 mg/dL].” Fischman D, Valluri A, Gorrepati VS, Murphy ME, Peters I, Cheriyath P. Bilirubin as a Protective Factor for Rheumatoid Arthritis: An NHANES Study of 2003 – 2006 Data. J Clin Med Res. 010;2(6):256-260. [PubMed]
      • Alarm Min = 0.1 mg/dL
      1. “In this nationally representative sample of older adults [≥ 60 years], the association of total bilirubin levels with total mortality was the highest among those with a level between 0.1 and 0.4 mg/dl.” Ong K-L, Allison MA, Cheung BMY, Wu BJ, Barter PJ, Rye K-A. The relationship between total bilirubin levels and total mortality in older adults: The United States National Health and Nutrition Examination Survey (NHANES) 1999-2004. PLoS ONE. 2014;9(4):e94479. [PubMed]
      • Alarm Max = 3 standard deviations from lab mean
      • Optimal Min = 1 standard deviation from lab mean supported by these studies (varies based on gender and ethnicity)
      1. In a study of over 1.9 million insurance applicants… “Low values of bilirubin are associated with increased cardiovascular and mortality risk. Relative mortality increased as bilirubin decreased below bilirubin levels seen for the middle 50% of the population [< 0.45 mg/dL for females < 60 years, < 0.65 for males < 60 years, < 0.55 for all 60+].” Fulks M, Stout RL, Dolan VF. Mortality associated with bilirubin levels in insurance applicants. J Insur Med. 2009;41(1):49-53. [PubMed]
      2. “In this nationally representative sample of older adults [≥ 60 years], the association of total bilirubin levels with total mortality was the highest among those with a level between 0.1 and 0.4 mg/dl.” Ong K-L, Allison MA, Cheung BMY, Wu BJ, Barter PJ, Rye K-A. The relationship between total bilirubin levels and total mortality in older adults: The United States National Health and Nutrition Examination Survey (NHANES) 1999-2004. PLoS ONE. 2014;9(4):e94479. [PubMed]
      3. In a study from China of 71 patients newly diagnosed with CD who did not receive any treatment on admission, 13 patients with severe chronic kidney disease had a total bilirubin level  between 0.27 and 0.38 mg/dL. Su Q, Li X, Mo W, Yang Z. Low serum bilirubin, albumin, and uric acid levels in patients with Crohn’s disease. Medicine (Baltimore). 2019;98(19):e15664. [PubMed]
      4. “The serum T-bil level [≤ 0.45 mg/dL], is negatively associated with cerebral atherosclerosis, especially extracranial atherosclerosis, but not with SVD (cerebral small vessel disease).” Kim J, Yoon S-J, Woo M-H, et al. Differential impact of serum total bilirubin level on cerebral atherosclerosis and cerebral small vessel disease. PLoS ONE. 2017;12(3):e0173736. [PubMed]
      5. “… lower levels of bilirubin are perhaps not the causal factor for CAD but may indicate patients at an increased risk of developing CAD.” Gupta N, Singh T, Chaudhary R, et al. Bilirubin in coronary artery disease: Cytotoxic or protective? World J Gastrointest Pharmacol Ther. 2016;7(4):469-476. [PubMed]
      6. “… total bilirubin value < 0.55 mg/dl was identified as an effective cutoff value for predicting severe carotid atherosclerosis.” Tatami Y, Suzuki S, Ishii H, et al. Impact of serum bilirubin levels on carotid atherosclerosis in patients with coronary artery disease. IJC Metabolic & Endocrine. 2014;5:24-27. [ScienceDirect]
      7. “Total bilirubin concentrations in serum are negatively associated with HbA1c levels after adjustment for sex, age, and other confounding factors in type 2 diabetes patients. Total bilirubin level of ≥ 0.8 mg/dL was significantly associated with an HbA1c value of < 6.5% (OR 0.4, 95% CI, 0.2-0.8) as compared with a total bilirubin level of ≤ 0.4 mg/dL.” Choi S-W, Lee Y-H, Kweon S-S, et al. Association between total bilirubin and hemoglobin A1c in Korean type 2 diabetic patients. J Korean Med Sci. 2012;27(10):1196-1201. [PubMed]
      • Optimal Max
      1. “In this nationally representative sample of older adults [≥ 60 years] there was a tendency for a total bilirubin level of ≥0.8 mg/dl to be associated with a higher mortality risk, compared to a level of 0.5–0.7 mg/dl in the present study, especially in non-Hispanic Whites and never smokers.” Ong K-L, Allison MA, Cheung BMY, Wu BJ, Barter PJ, Rye K-A. The relationship between total bilirubin levels and total mortality in older adults: The United States National Health and Nutrition Examination Survey (NHANES) 1999-2004. PLoS ONE. 2014;9(4):e94479. [PubMed]

    Bilirubin, Direct

      • Lab Min and Max: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • Alarm Max = 3 standard deviations from lab mean
      • Alarm Min = Lab Min = Optimal Min
      • Optimal Max: Quest Diagnostics – Bilirubin, Fractionated

    Bilirubin, Indirect

      • Lab Min and Max: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min = Lab Min
      • Optimal Max = 1 standard deviation from lab mean
      1. “With hemolysis or severe ineffective erythropoiesis, indirect bilirubin increases to 0.8 – 3 mg/dL.” Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in Clinical Practice. 5th ed. New York: McGraw-Hill Medical; 2010.

    Alkaline Phosphatase (ALP)

      1. Reference supporting the use of a higher reference range for woman > 50 years of age: “After menopause, the bone isoenzyme increases slightly in women, causing a rise in reference limits after 50 years of age.” Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in Clinical Practice. 5th ed. New York: McGraw-Hill Medical; 2010.
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min and Max = 1 standard deviation from lab mean
      1. “In the present study, we found a graded, independent association between baseline AlkP level and adverse clinical outcomes in people free of kidney failure, both in those with established vascular disease and in a representative sample of the general population. Most of these people (≈91%) had AlkP levels within the range that is considered normal, and results were consistent among people without evidence of non–dialysis-dependent kidney disease (estimated GFR ≥60). As was observed in the CARE data set, higher levels of AlkP and serum phosphate were associated with an increased risk for both all-cause and cardiovascular death. For example, the HRs for all-cause and cardiovascular death among participants with higher levels of both AlkP and phosphate (ie, ≥77.4 IU/L and 3.5 mg/dL, respectively) were 1.41 and 1.58, respectively, compared with those with neither characteristic.” Tonelli M, Curhan G, Pfeffer M, et al. Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. Circulation. 2009;120(18):1784-1792. [PubMed]
      2. “Higher levels of serum AlkPhos and phosphate were associated with increased mortality and cardiovascular-related hospitalization in an inner-city clinic population. Comparing patients in the highest (≥104 U/L) versus lowest quartile of AlkPhos (≤66 U/L), the adjusted hazard ratio (HR) for mortality was 1.65 (P trend across quartiles <0.001) [and for the 3rd highest quartile of AlkPhos (83 to 103 U/L), the HR was 1.3]. Furthermore, excluding patients with any history of a liver test abnormality or baseline serum AlkPhos >115 U/L (n included in analysis = 7685), the multivariable adjusted HR for the highest quartile (92 to 115 U/L) was 1.37 (95% CI 1.09 to 1.73) compared with the lowest quartile (≤63 U/L).” Abramowitz M, Muntner P, Coco M, et al. Serum alkaline phosphatase and phosphate and risk of mortality and hospitalization. Clin J Am Soc Nephrol. 2010;5(6):1064-1071. [PubMed]
      3. “Comparisons of hazard ratios when laboratory results were within the normal range demonstrated that blood albumin and blood urea nitrogen (BUN) were both negatively associated with mortality and alkaline phosphatase (AP) was positively associated with mortality.” Hu G, Duncan AW. Associations between selected laboratory tests and all-cause mortality. J Insur Med. 2013;43(4):208-220. [PubMed]
      4. “What is clear is the extent of mortality risk associated with even modestly higher values of AP, even among those under age 60.” Fulks M, Stout RL, Dolan VF. Using liver enzymes as screening tests to predict mortality risk. J Insur Med. 2008;40(3-4):191-203. [PubMed]
      • Future Feature – Separate Reference Ranges for Race and Pregnancy.
      1. Reference limits for ALP are 15% higher in African American men and 10% higher in African American women. Manolio TA, Burke GL, Savage PJ, Jacobs DR Jr, Sidney S, Wagenknecht LE. Sex- and race-related differences in liver-associated serum chemistry tests in young adults in the CARDIA study. Clin Chem. 1992;38(9):1853. [PubMed]
      2. Pregnancy causes a two- to threefold increase in ALP, mainly due to the placental isoenzyme, but also because of an increase in bone isoenzyme. Valenzuela GJ, Munson LA, Tarbaux NM, Farley JR. Time-dependent changes in bone, placental, intestinal, and hepatic alkaline phosphatase activities in serum during human pregnancy. Clin Chem. 1987;33(10):1801-1806. [PubMed]

    AST (SGOT)

      1. “Females tend to have slightly lower values than males. Elderly values slightly higher than adult values.” Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
      • Alarm Min and Max = 3 standard deviations from lab mean
      • Optimal Min Based on Deficient B6 Status
      1. “A positive correlation was noted between plasma (p) PLP [pyridoxal-5′-phosphate, B6] and low AST and ALT. Prior to [B6] supplementation (Day 0), 17 (33%) patients had deficient pPLP levels (Group 1), the remainder (35 patients) had normal pPLP values (Group 2). The mean pAST (9.2 +/- 0.3 vs 13.4 +/- 0.7 U/l) and pALT (8.6 +/- 0.6 vs 11.4 +/- 0.9 U/l) were markedly lower in Group 1 than those in Group 2, respectively. The administration of vitamin B6 resulted in a significant increase in pPLP in both groups (Day 35)…” Ono K, Ono T, Matsumata T. The pathogenesis of decreased aspartate aminotransferase and alanine aminotransferase activity in the plasma of hemodialysis patients: the role of vitamin B6 deficiency. [PubMed]
      • Optimal Max = 1 standard deviation from lab mean (supported by the below studies)
      1. “AST has a ‘U’’ shaped mortality curve, ie, elevated relative risk at both low and high values.” [Optimal ranges of AST where mortality was 100% or less when only AST was elevated were: 13-19 U/L (females < 60 years of age), 22-30 U/L (males < 60), and 20-33 U/L (both genders 60+). Fulks M, Stout RL, Dolan VF. Using liver enzymes as screening tests to predict mortality risk. J Insur Med. 2008;40(3-4):191-203. [PubMed]
      2. “Similarly, compared with the fourth decile of baseline AST levels (21 U/L), the risk of all-cause mortality was also higher in both the higher and lower baseline AST deciles (10th decile ≥38 U/L: HR=1.70, 95% CI 1.59 to 1.81; 1st decile, ≤16 U/L: HR=1.15, 95% CI 1.07 to 1.24).” [HR=1.20 for 9th decile 32-37 U/L, 95% CI 1.12 to 1.28.] Kim K-N, Joo J, Sung HK, Kim CH, Kim H, Kwon YJ. Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population: a large-scale national health screening cohort study. BMJ Open. 2019;9(5). [PubMed]

    ALT (SGPT)

      1. “Compared with the fourth decile of baseline ALT levels (17–18 U/L), the risk of all-cause mortality was higher in both the higher and lower baseline ALT deciles (10th decile, ≥43 U/L: HR=1.53, 95% CI 1.44 to 1.62; 1st decile, ≤12 U/L: HR=1.16, 95% CI 1.10 to 1.23).” Kim K-N, Joo J, Sung HK, Kim CH, Kim H, Kwon YJ. Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population: a large-scale national health screening cohort study. BMJ Open. 2019;9(5). [PubMed]
      2. “Maximum correct classification was achieved at ALT = 29 IU/L for men (88% sensitivity, 83% specificity) and 22 IU/L (89% sensitivity, 82% specificity) for women.” Ruhl CE, Everhart JE. Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology. 2012;55(2):447-454. [PubMed]
      3. “… the relative mortality risk [of ALT] increases at low values but remains flat from the middle 50% band and higher.” [Optimal ranges of ALT where mortality was 100% or less when only ALT was elevated were: 15-36 U/L (females < 60 years of age), >26 U/L (males < 60), and >19 U/L (both genders 60+). Fulks M, Stout RL, Dolan VF. Using liver enzymes as screening tests to predict mortality risk. J Insur Med. 2008;40(3-4):191-203. [PubMed]
      4. “A total of 1309 subjects, with the mean age of 61.5 ± 7.5 years were included. UNL [upper normal limit] of ALT was 18.8 U/L and 21.4 U/L in women and men, respectively.” Kabir A, Pourshams A, Khoshnia M, Malekzadeh F. Normal limit for serum alanine aminotransferase level and distribution of metabolic factors in old population of kalaleh, iran. Hepat Mon. 2013;13(10):e10640. [PubMed]
      5. “The new ULN [upper limit of normal] of serum ALT level defined as the 95% percentile in the healthy population were 21 IU/L and 17 IU/L for men and women respectively.” Wu W-C, Wu C-Y, Wang Y-J, et al. Updated thresholds for serum alanine aminotransferase level in a large-scale population study composed of 34 346 subjects. Aliment Pharmacol Ther. 2012;36(6):560-568.  [PubMed]
      6. “Those with high-normal ALT [19–40 IU/L in women and 31–40 IU/L in men] or elevated ALT [> 40 IU/L] had a higher triglyceride, VLDL-P, ApoB:ApoA ratio, LDL-C, % sdLDL, sdLDL-C and sdLDL-P (P<.001 for all) compared to those with low normal ALT (Table 1).” Siddiqui MS, Sterling RK, Luketic VA, et al. Association between high-normal levels of alanine aminotransferase and risk factors for atherogenesis. Gastroenterology. 2013;145(6):1271-1279.e1-3. [PubMed]
      7. “ALT was categorized as deciles 1, 2, 3, 4–9, and 10, with decile cutpoints of 16, 18, 20, and 46 IU/L for men and 12, 14, 15, and 31 IU/L for women. … all cause mortality was increased among participants with ALT levels in deciles 1, 2, 3, and 10, as compared with deciles 4–9 (P < 0.05). … the ALT distribution at both tails was small: 2% with ALT ≤5 IU/L and 6% with ALT >35 IU/L. Ruhl CE, Everhart JE. The association of low serum alanine aminotransferase activity with mortality in the US population. Am J Epidemiol. 2013;178(12):1702-1711. [PubMed]
      8. “A positive correlation was noted between plasma (p) PLP [pyridoxal-5′-phosphate, B6] and low AST and ALT. Prior to [B6] supplementation (Day 0), 17 (33%) patients had deficient pPLP levels (Group 1), the remainder (35 patients) had normal pPLP values (Group 2). The mean pAST (9.2 +/- 0.3 vs 13.4 +/- 0.7 U/l) and pALT (8.6 +/- 0.6 vs 11.4 +/- 0.9 U/l) were markedly lower in Group 1 than those in Group 2, respectively. The administration of vitamin B6 resulted in a significant increase in pPLP in both groups (Day 35)…” Ono K, Ono T, Matsumata T. The pathogenesis of decreased aspartate aminotransferase and alanine aminotransferase activity in the plasma of hemodialysis patients: the role of vitamin B6 deficiency. [PubMed]

    Gamma Glutamyl Transferase (GGT)

      1. In this review of the Framingham Offspring Study, morbidity and mortality were two-fold greater in those with baseline GGT levels above 16 U/L for men and 9 U/L for women. Koenig G, Seneff S. Gamma-glutamyltransferase: a predictive biomarker of cellular antioxidant inadequacy and disease risk. Dis Markers. 2015;2015(818570):1-18. [PubMed]
      2. “GGTP should be in the teens, even below 10 if you’re a woman.” Mercola, J. Dr. Mercola and Gerry Koenig on Serum Ferritin and GGT (Full Interview). @ time 47:41 in this video or see PDF transcript of this video
      3. “The ideal level of GGT is below 16 units per liter (U/L) for men and below 9 U/L for women. Above 25 U/L for men and 18 U/L for women, your risk of chronic disease increases significantly.” Mercola DJ. Iron Overload Destroys Mitochondria and Sabotages Health. Dr. Mercola’s Censored Library (Private Membership). Published December 1, 2021. https://takecontrol.substack.com/p/iron-overload-destroys-mitochondria
      4. “GGT — Below 16 units per liter (U/L) for men and below 9 U/L for women. Above 25 U/L for men and 18 U/L for women, your risk of chronic disease increases significantly.” Mercola DJ. Nearly Half of This Age Group Have Cardiovascular Disease. Dr. Mercola’s Censored Library (Private Membership). Published April 12, 2022. https://takecontrol.substack.com/p/cardiovascular-disease-risk-factors
      5. In a cross-sectional study of 14,439 Korean subjects without CAD, coronary artery calcification (CAC) was lowest in men with GGT of 21 U/L or less and women with a GGT of 10 U/L or less. Lee W, Ryoo JH, Suh BS, Lee J, Kim J. Association of coronary artery calcification and serum gamma-glutamyl transferase in Korean. Atherosclerosis. 2013;226(1):269-274. [PubMed]
      6. “… GGT above the reference category ( GGT > or = 9 U/L in women, > or = 14 U/L in men) was significantly (P <0.001) associated with all-cause, cancer, hepatobiliary, and vascular mortalities.” Kazemi-Shirazi L, Endler G, Winkler S, Schickbauer T, Wagner O, Marsik C. Gamma glutamyltransferase and long-term survival: is it just the liver? Clin Chem. 2007;53(5):940–946. [PubMed]
      7. “In ROC curve analysis, the optimal cut-off value for GGT to discriminate IGT [impaired glucose tolerance] from normal condition was 20.5 IU with the sensitivity of 71.6% and the specificity of 66.1%. The best cutoff value for GGT to discriminate MS [metabolic syndrome] from normal condition was also 16.5 IU with the sensitivity and specificity of 78.4% and 78.4%, respectively.”
      • Lab Max (women = 18, men = 25)
      1. “The ideal level of GGT is below 16 units per liter (U/L) for men and below 9 U/L for women. Above 25 U/L for men and 18 U/L for women, your risk of chronic disease increases significantly.” Mercola DJ. Iron Overload Destroys Mitochondria and Sabotages Health. Dr. Mercola’s Censored Library (Private Membership). Published December 1, 2021. https://takecontrol.substack.com/p/iron-overload-destroys-mitochondria
      2. “GGT — Below 16 units per liter (U/L) for men and below 9 U/L for women. Above 25 U/L for men and 18 U/L for women, your risk of chronic disease increases significantly.” Mercola DJ. Nearly Half of This Age Group Have Cardiovascular Disease. Dr. Mercola’s Censored Library (Private Membership). Published April 12, 2022. https://takecontrol.substack.com/p/cardiovascular-disease-risk-factors
      3. “GGT and alkaline phosphatase are significant predictors of mortality risk for all values. Until now, both the risk presented by GGT values even mildly higher than those in the middle 50% range and the reduced mortality risk for lower GGT values have not been fully appreciated.” [The middle 50% range is 18 for women < 60, 30 for men < 60, and 25 for all 60+]. Fulks M, Stout RL, Dolan VF. Using liver enzymes as screening tests to predict mortality risk. J Insur Med 2008;40(3-4):191–203. [PubMed]
      4. “GGT, even at physiologic high levels, predicted mortality, especially cardiovascular mortality and cancer mortality.” Long Y, Zeng F, Shi J, Tian H, Chen T. Gamma‐glutamyltransferase predicts increased risk of mortality: a systematic review and meta‐analysis of prospective observational studies. Free Radic Res. 2014;48(6):716–728. [PubMed]
      5. “…serum GGT activity, even high normal values within the reference range, is associated with an increased risk of major vascular and non‐vascular outcomes…” Targher G. Elevated serum gamma‐glutamyltransferase activity is associated with increased risk of mortality, incident type 2 diabetes, cardiovascular events, chronic kidney disease and cancer ‐ a narrative review. Clin Chem Lab Med. 2010;48: 147–157. [PubMed]
      6. Kengne AP, Czernichow S, Stamatakis E, Hamer M, Batty GD. Gamma‐glutamyltransferase and risk of cardiovascular disease mortality in people with and without diabetes: pooling of three British Health Surveys. J Hepatol. 2012;57(5):1083–1089. [PubMed]
      7. Ruttmann E, Brant LJ, Concin H, et al. Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation. 2005;112(14):2130–2137. [PubMed]
      8. Lee DS, Evans JC, Robins SJ, et al. Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality Risk. Arterioscler Thromb Vasc Biol. 2007;27(1):127–133. [PubMed]

    Lactate Dehydrogenase (LDH, LD)

      1. “Higher serum LDH level had lower cumulative survival in those with MetS. For all-cause mortality in participants with MetS, multivariable adjusted HRs were 1.006 (95% CI 0.837 to 1.210; p=0.947) for serum LDH of 149-176 U/L compared with 65-149 U/L, and 1.273 (95% CI 1.049 to 1.547; p=0.015) for serum LDH of 176-668 U/L compared with 65-149 U/L.” Wu L-W, Kao T-W, Lin C-M, et al. Examining the association between serum lactic dehydrogenase and all-cause mortality in patients with metabolic syndrome: a retrospective observational study. BMJ Open. 2016;6(5):e011186. [PubMed]

    AST/ALT Ratio (Future Release)

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Lipids Reference Ranges

    Cholesterol, Total

      • Optimal Min and Max
      1. Total cholesterol level: 180–240 mg/dL. Dr. Stephen Sinatra. What Do Your Cholesterol Levels Mean?
      2. In a study of 12.8 M Korean adults… “TC levels associated with lowest mortality were 210-249 mg/dL, except for men aged 18-34 years (180-219 mg/dL) and women aged 18-34 years (160-199 mg/dL) and 35-44 years (180-219 mg/dL). The inverse associations for TC < 200 mg/dL were stronger than the positive associations in the upper range.” Yi S-W, Yi J-J, Ohrr H. Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults. Sci Rep. 2019;9(1):1596. [PubMed]
      • Lab Max = 2 standard deviations from optimal mean
      1. In a study of 52K Norwegians, ages 20-74… “the association with IHD (ischemic heart disease) was not linear but seemed to follow a “U-shaped” curve, with the highest mortality <5 mmol/l (193 mg/dl) and >= 7 mmol/l (271 mg/dl).” Petursson H, Sigurdsson JA, Bengtsson C, Nilsen TIL, Getz L. Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. J Eval Clin Pract. 2012;18(1):159-168. [PubMed]
      • Alarm Max  = 3 standard deviations from optimal mean
      • Lab Min
      1. “Among older hospitalized adults [65 years or older], low serum cholesterol levels (< 160 mg/dL) appear to be an independent predictor of short-term mortality. Mortality was inversely related to cholesterol levels (<160 mg/dL: 5.2% [110/2115]; 160-199 mg/dL: 2.2% [49/2210]; 200-239 mg/dL: 1.6% [27/1719]; and >or=240 mg/dL: 1.7% [16/940]; P for linear trend <0.001).” Onder G, Landi F, Volpato S, et al. Serum cholesterol levels and in-hospital mortality in the elderly. Am J Med. 2003;115(4):265-271. [PubMed]
      2. In a study of over 51K adults over 30 years old, mean age of 62.6 years (47.6% men) free of cardiovascular disease (2008-2012) but diagnosed with hypertension, dyslipidemia, or diabetes mellitus… “Total cholesterol has a U-shape risk curve where values < 160 and > 263 mg/dL showed increased risk for coronary heart disease.” Orozco-Beltran D, Gil-Guillen VF, Redon J, et al. Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study. PLoS ONE. 2017;12(10):e0186196. [PubMed]
      3. This is a 12-year follow-up cohort study with 800 people (60-85 years old). There was a positive association [with mortality] only with TC <170 mg/dL. The data showed higher mortality among older adults with low TC. Cabrera MAS, de Andrade SM, Dip RM. Lipids and all-cause mortality among older adults: a 12-year follow-up study. Scientific World Journal. 2012;2012:930139. [PubMed]
      4. “TC and LDL and was limited to applicants with TC >160 mg/dL and LDL >100 mg/dL. The reason for those limits is apparent from Figures 1–4 where it can be seen that low TC values are also associated with increasing mortality risk. Not surprisingly, the same is true for low LDL values.” Fulks M, Stout RL, Dolan VF. Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants.J Insur Med.. 2009;41(4):244-253. [PubMed]
      • Alarm Min
      1. “Total cholesterol (TC) ≤130 mg/dL for women and ≤140 mg/dL for men was present in a small percentage of life insurance applicants and identified substantially increased mortality risk.” Fulks M, Stout RL. Low Cholesterol and Low Albumin Levels: Alerts to Hidden Mortality Risk. ON THE RISK Journal of The Academy of Life Underwriting. 2015;31(4):65-69. [Article] [Full Issue]

    HDL Cholesterol

    Triglycerides

      • Lab Min and Max = 2 standard deviations from optimal mean
      • Alarm Min and Max  = 3 standard deviations from optimal mean
      • Optimal Min and Max
      1. Triglycerides level: 50–100 mg/dL. Dr. Stephen Sinatra. What Do Your Cholesterol Levels Mean?
      2. “Data in this study seem to indicate that low TG value may be a precocious marker of autoimmunity or immune system hyperreactivity. Concerning chronic autoimmune thyroiditis, the lean and obese patients had a reduced TG level (-69% [43 mg/dL] and -52% [77 mg/dL], respectively) compared with TG value of the lean and obese control subjects without autoimmune disease [142 mg/dL and 160 mg/dL].” Iannello S, Cavaleri A, Milazzo P, Cantarella S, Belfiore F. Low fasting serum triglyceride level as a precocious marker of autoimmune disorders. MedGenMed. 2003;5(3):20. [PubMed]

    LDL Cholesterol

      • Lab Min and Max = 2 standard deviations from optimal mean
      • Alarm Min and Max  = 3 standard deviations from optimal mean
      • Optimal Min and Max: LDL cholesterol level: 80–130 mg/dL. Dr. Stephen Sinatra. What Do Your Cholesterol Levels Mean?
      1. “LDL-C levels <70 mg/dL and low triglyceride levels were associated with increased risk of hemorrhagic stroke among women.” Rist PM, Buring JE, Ridker PM, Kase CS, Kurth T, Rexrode KM. Lipid levels and the risk of hemorrhagic stroke among women. Neurology. 2019;92(19):e2286-e2294. [PubMed]
      2. “High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.” Ravnskov U, Diamond DM, Hama R, et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open. 2016;6(6):e010401. [PubMed]
      3. “A population-based register study in the period 1999-2007 including 118,160 subjects aged 50 + without statin use at baseline. All-cause mortality was lower in the groups with TC [>190 mg/dL] or LDL-C [>115 mg/dL] above the recommended levels.” Bathum L, Depont Christensen R, Engers Pedersen L, Lyngsie Pedersen P, Larsen J, Nexøe J. Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease: a population-based register study. Scand J Prim Health Care. 2013;31(3):172-180. [PubMed]
      4. “TC and LDL and was limited to applicants with TC >160 mg/dL and LDL >100 mg/dL. The reason for those limits is apparent from Figures 1–4 where it can be seen that low TC values are also associated with increasing mortality risk. Not surprisingly, the same is true for low LDL values.” Fulks M, Stout RL, Dolan VF. Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants.J Insur Med.. 2009;41(4):244-253. [PubMed]

    VLDL Cholesterol (Future Release)

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Non-HDL Cholesterol (Future Release)

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Cholesterol/HDL Ratio

      • Lab Min and Max
      • Alarm Min and Max
      • Optimal Min and Max

    Triglycerides/HDL Ratio

      • “Those with the highest ratio of triglycerides to HDL had 16 times the risk of heart attack as those with the lowest ratio of triglycerides to HDL. Triglycerides/HDL ratio was the strongest predictor of a heart attack, even more accurate than the LDL/HDL and total cholesterol/HDL ratios. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96(8):2520-2525. [PubMed]
      • Alarm Min = Lab Min = Optimal Min = 0
      • Optimal Max
      1. “If you have a ratio of around 2, you should be happy, indeed, regardless of your cholesterol levels.” Bowden, J. and Sinatra, S., 2012. The Great Cholesterol Myth. Beverly, MA: Fair Winds Press. p. 44. [Amazon]
      2. “Divide your triglyceride number by your HDL. This ratio should ideally be below 2.” The 7 Values That Really Impact Your Health. Mercola.com. Published April 27, 2012. Accessed May 13, 2020. [Article]
      3. “A much better indicator of your overall risk for heart disease is the triglycerides to HDL ratio. If, for example, your triglycerides are 100 and your HDL is 50 your ratio is 2. If, however, your triglycerides are 150 and your HDL is 30, your ratio is 5. A ratio of 2 or under is excellent. A ratio of 4 is considered high, with increased risk.” By Jonny Bowden, PhD, CNS and Stephen Sinatra, MD, FACN. Cholesterol Facts vs. Myths. doctoroz.com. Accessed July 10, 2020. [Article]
      • Lab Max
      1. “A ratio of 4 is considered high, with increased risk.” By Jonny Bowden, PhD, CNS and Stephen Sinatra, MD, FACN. Cholesterol Facts vs. Myths. doctoroz.com. Accessed July 10, 2020. [Article]
      • Alarm Max
      1. “A ratio of 5, however, is problematic.” Bowden, J. and Sinatra, S., 2012. The Great Cholesterol Myth. Beverly, MA: Fair Winds Press. p. 44. [Amazon]

    Lipoprotein(a)

      • Lab Max
      1. “Studies indicate that about one in five individuals have plasma levels above 50 mg/dL (80th percentile), and about one in four have plasma levels above 32 mg/dL (75th percentile). Lp(a) levels less than 30 mg/dL are considered normal.” Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412-423. [PubMed]
      2. “Plasma levels above 30 mg/dL are reported to be associated with a two to threefold increased risk for coronary artery disease.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
      • Alarm Max
      1. “The Copenhagen City Heart Study found that individuals with plasma Lp(a) levels above 50 mg/L had 2 to 3 – fold increase risk for heart attack (myocardial infarction).” Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331-2339. [PubMed]
      2. “We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.” Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844-2853. [PubMed]
      • Optimal Min and Max
      1. “Here’s how Lp(a) lelevls are looked at in terms of risk:
        1. Desirable: < 14 mg/dL (< 35 nmol/l)
        2. Borderline risk: 14 – 30 mg/dL (35 – 75 nmol/l)
        3. High risk: 31 – 50 mg/dL (75 – 125 nmol/l)
        4. Very high risk: > 50 mg/dL (> 125 nmol/l)
        5. Sigurdsson AF, MD, PhD. Lipoprotein(a). Doc’s Opinion. Published June 22, 2021. [Article]
      2. “Plasma concentrations greater than 20 mg/dL have been reported to increase the risk of CAD, cardiovascular accident, and peripheral arterial disease.” Kullo IJ, Gau GT, Tajik AJ. Novel risk factors for atherosclerosis. Mayo Clin Proc. 2000;75(4):369-380. [PubMed]
      • 5 mg/dL is added to all ranges above to account for the normal increased levels in African Americans when this ethnicity is selected.
      1. “Racial differences have been noted with respect to the concentration of Lp(a) with the highest levels in African Americans, followed by slightly higher levels in Hispanics, and the lowest levels in non- Hispanic Caucasians, Chinese and Japanese.” Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844-2853. [PubMed]
      2. “Lp[a] concentrations were higher in blacks than whites.” Marcovina SM, Albers JJ, Wijsman E, Zhang Z, Chapman NH, Kennedy H. Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans. J Lipid Res. 1996;37(12):2569-2585. [PubMed]
      3. “Lp(a) is higher among African Americans, compared with whites and Hispanics.” Matthews KA, Sowers MF, Derby CA, et al. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women’s Health Across the Nation (SWAN). Am Heart J. 2005;149(6):1066-1073. [PubMed]

    Inflammation / Oxidative Stress Reference Ranges

    Fibrinogen

      1. “Congenital hypofibrinogenemia, first reported in 1935, is defined as plasmafibrinogen levels below 150 mg/dl. Cai H, Liang M, Yang J, Zhang X. Congenital hypofibrinogenemia in pregnancy: a report of 11 cases. Blood Coagul Fibrinolysis. 2018;29(2):155-159. [PubMed]
      • Alarm Max
      1. “Levels of functionally normal fibrinogen increase in pregnancy to an average of 4.5 gram/liter (g/l) [450 mg/dL]compared to an average of 3 g/l in non-pregnant people. They may also increase in various forms of cancer, particularly gastric, lung, prostate, and ovarian cancers. In these cases, the hyperfibrinogenemia may contribute to the development of pathological thrombosis.” Fibrinogen. In: Wikipedia. ; 2019.
      • Optimal Min: McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
      • Optimal Max
      1. The risk of stroke gradually increased with increasing fibrinogen levels. The risk of stroke was almost double when the fibrinogen level was > 340 mg/dL. Bots ML, Elwood PC, Salonen JT, et al. Level of fibrinogen and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe. J Epidemiol Community Health. 2002;56 Suppl 1:i14-18. [PubMed]
      2. “…an increased incidence of myocardial infarction or sudden death was associated with higher base-line concentrations of fibrinogen (mean ±SD, 3.28±0.74 g per liter [328 mg/dL] in patients who subsequently had coronary events, as compared with 3.00±0.71 g per liter in those who did not; P = 0.01)…” Thompson SG, Kienast J, Pyke SD, Haverkate F, van de Loo JC. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med. 1995;332(10):635-641. [PubMed]
      3. Of the patients whose fibrinogen levels fell within the two highest quartiles (>331 mg/dL), about 75% of men and 50% of women were diagnosed with clinical CAD. A previous history of heart attack in the group with CAD was also associated with significantly higher average levels of fibrinogen. Acevedo M, Foody JM, Pearce GL, Sprecher DL. Fibrinogen: associations with cardiovascular events in an outpatient clinic. Am Heart J. 2002;143(2):277-282. [PubMed]
      4. “The healthy range is 180–350 mg/dL.” Dr. Stephen Sinatra. Check Your Fibrinogen Level to Reduce Your Heart Risk. [Blog]

    Homocysteine

      1. “Elevated plasma total homocysteine is an independent risk factor for atherosclerotic vascular disease. Risk rises continuously across the spectrum of homocysteine concentrations and may become appreciable at levels greater than 10 mumol/l.Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol. 1999;10(5):417-428. [PubMed]
      2. “The proportion of cases with homocysteine ≥11.0 μmol/L was 2-fold higher in cases than in control subjects for total stroke and stroke subtypes other than subarachnoid hemorrhage.” Iso H, Moriyama Y, Sato S, et al. Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese. Circulation. 2004;109(22):2766-2772.[PubMed]
      3. “Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Levels of homocyst(e)ine were higher in cases than in controls (11.1 +/- 4.0 [SD] vs 10.5 +/- 2.8 nmol/mL; P = .03).” Stampfer MJ, Malinow MR, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992;268(7):877-881. [PubMed]
      4. “In an analysis in which the patients with homocysteine levels below 9 μmol per liter were used as the reference group, the mortality ratios were 1.9 for patients with homocysteine levels of 9.0 to 14.9 μmol per liter, 2.8 for those with levels of 15.0 to 19.9 μmol per liter, and 4.5 for those with levels of 20.0 μmol per liter or higher (P for trend = 0.02). When death due to cardiovascular disease (which occurred in 50 patients) was used as the end point in the analysis, the relation between homocysteine levels and mortality was slightly strengthened..” Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease. New England Journal of Medicine. 1997;337(22):1631-1633. [PubMed]

      hs-CRP

          • Optimal Max = 0.9 – Jellinger PS et al. Endocr Pract. 2017;23(Suppl 2):1-87.
          • Lab Max = 3.0
          • Alarm Max = 10.0
          • Values used in LabSmarts to define all ranges for hs-CRP are from Quest Diagnostics using the table below. Quest Diagnostics – hs-CRP

        Erythrocyte Sedimentation Rate (ESR)

        hs-CRP

        Erythrocyte Sedimentation Rate (ESR)

        Thyroid Reference Ranges

        Assessing Thyroid Physiology

          • There are 5 areas of thyroid physiology that can be dysfunctional: Signaling, Production, Transport, Conversion, and Utilization
          1. Signaling – the hypothalamus sends thyrotropin-releasing hormone (TRH) to the pituitary to signal it to release thyrotropin, also known as thyroid-stimulating hormone (TSH). TSH signals the thyroid to produce roughly 93% T4 and 7% T3.
            1. The hypothalamus is modulated by serotonin and dopamine. Low TSH could be caused by low TRH which could be caused by low serotonin or dopamine.
            2. Issues with the pituitary itself, such as a tumor, could cause decreased levels of TSH.
            3. Increased levels of cytokines, prolactin, and cortisol can have a negative impact on the hypothalamus and the pituitary, resulting in a decreased production of TRH and TSH.
          2. Production – there are two main reasons for a lower production of thyroid hormones by the thyroid:
            1. Thyroid destruction as a result of antibodies (TPO Ab, Tg Ab, TR Ab, and TSI)
            2. Insufficient co-factors (progesterone, Se, Cu, Mg, B3, B5, P5P, Zn, iodine, and tyrosine)
          3. Transport – T4 and T3 made in the thyroid are transported in the blood by thyroid-binding proteins, mainly thyroid-binding globulin (TBG), to the tissues for conversion. Improper attachment or detachment can impact free hormone levels.
            1. Excess levels of estrogen can cause increased levels of thyroid binding globulin (TBG) resulting in decreased levels of free T3 and free T4.
            2. Excess levels of testosterone can cause decreased levels of TBG resulting in increased levels of free T3 and free T4.
          4. Conversion – T4 to T3 conversion happens mainly in the liver and and some in the gut.
            1. The conversion in the liver is performed by the 5′-deiodinase enzyme. Iron is needed to make this enzyme and serotonin, dopamine, and selenium are needed for proper enzyme activity.
            2. The T3 sulfate (T3S0 and triiodothyroacetic acid (T3AC) created during this conversion in the liver is inactive until they circulate to the gut and are acted upon by intestinal sulfatase to become active T3. Sulfatase activity is depending upon healthy gut microflora.
          5. Utilization – active (or free) T3 binds to the thyroid receptors of the target cells so they can utilize these hormones to promote mitochondrial activity. There are things that can cause issues with the free T3 binding to these thyroid receptor sites.
            1. Thyroid receptor resistance can be caused by increased levels of cytokines, cortisol, and homocysteine or decreased levels of vitamin A.

        TSH (Thyroid Stimulating Hormone)

          • TSH has moderate intraindividual variability (within a client) but a lot more interindividual variability (between clients). The variation between client can be as high as 32%; consequently there is a wide population-based reference interval for TSH. Since the intraindividual variation is considerably less, comparing a specific client’s current TSH level with any past level may be more illuminating than comparing their current TSH level to the reference interval. When comparing two tests for the same client, a difference of 0.7 mIU/L or greater is considered significant. Browning MC, Ford RP, Callaghan SJ, Fraser CG. Intra- and interindividual biological variation of five analytes used in assessing thyroid function: implications for necessary standards of performance and the interpretation of results. Clin Chem. 1986;32(6):962-966. [PubMed]
          • Lab Min and Max (including different ranges for each trimester of pregnancy): Quest Diagnostics – TSH
          1. If the trimester is unknown, LabSmarts will use the Quest ranges for the third trimester.
          2. “The range of thyrotropin (TSH), under the impact of placental human chorionic gonadotropin (hCG), is decreased throughout pregnancy with the lower normal TSH level in the first trimester being poorly defined and an upper limit of 2.5 mIU/L. If trimester-specific reference ranges for TSH are not available in the laboratory, the following reference ranges are recommended: first trimester, 0.1–2.5 mIU/L; second trimester, 0.2–3.0 mIU/L; third trimester, 0.3–3.0 mIU/L.” Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125. [PubMed]
          • Alarm Min and Max = 3 standard deviations from lab mean
          • Optimal Min and Max (pregnant women) = 1 standard deviations from lab mean
          • Optimal Min and Max (men and non-pregnant women)
          1. Datis Kharrazian. Mastering The ThyroidTM | Apex SeminarsTM
          2. “We will probably never have an absolute cutoff value for TSH distinguishing normal from abnormal, but recognition that the mean of normal TSH values is only between 1.18 and 1.40 mU/liter (7) and that more than 95% of the normal population will have a TSH level less than 2.5 mU/liter (10) clearly imply that anyone with a higher value should be carefully assessed for early thyroid failure.” Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005;90(9):5483-5488. [PubMed]
          3. “Most labs have a range somewhere between 0.4 and 6 mIU/L, but many researchers have called for the upper limit to be decreased to between 2.5 and 3 mIU/L. One reason for this is that levels above 2.5 mIU/L have been linked to an increased risk for developing an under-active thyroid (hypothyroidism) and even mortality [1, 2, 3, 4, 5].” Optimal vs. Normal Lab Ranges For Blood Tests. SelfDecode Labs. Published December 1, 2019. [Article]
          4. “I have found that I, as well as many other thyroid patients, feel best when my TSH is between 0.5 and 2 μIU/mL. Some integrative professionals will go as far as to say that people should have a TSH of right around 1 μIU/mL or below 1 μIU/mL, to feel their best.” Top 10 Thyroid Tests and How to Interpret Them. Dr. Izabella Wentz, PharmD. Published September 30, 2020. [Article]
          5. “The risk [of hypothyroidism] increased gradually from TSH of 0.50-1.4 mU/liter to a TSH of 4.0-4.5 mU/liter.” Åsvold BO, Vatten LJ, Midthjell K, Bjøro T. Serum TSH within the reference range as a predictor of future hypothyroidism and hyperthyroidism: 11-year follow-up of the HUNT Study in Norway.” J Clin Endocrinol Metab. 2012;97(1):93-99. [PubMed]
          6. “Optimal cutoffs for predicting hypothyroidism were baseline TSH above 2.5 mU/liter. Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O’Leary P. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques. J Clin Endocrinol Metab. 2010;95(3):1095-1104. [PubMed]

        T4 (Thyroxine), Total

          • Lab Min and Max (including different ranges for male and female): Quest Diagnostics – T4 (Thyroxine), Total
          • Alarm Min and Max = 3 standard deviations from lab mean
          • Optimal Min = 1 standard deviation from lab mean
          • Optimal Max = Lab Max – 0.1

        T4, Free

        T3 (Triiodothyronine), Total

        T3, Free

        Reverse T3 (RT3)

          • Lab Min and Max: Quest Diagnostics – T3 Reverse
          • Alarm Min and Max = 3 standard deviations from lab mean
          • Optimal Min = Lab Min + 1
          • Optimal Max = Lab Max – 1

        Thyroid Peroxidase Antibodies (TPO Ab)

        Thyroglobulin Antibodies (Tg Ab)

        Thyroxine Binding Globulin (TBG)

        T3 Uptake

          • Lab Min and Max: Quest Diagnostics – T3 Uptake
          • Alarm Min and Max = 3 standard deviations from lab mean
          • Optimal Min = Lab Min + 1
          • Optimal Max = Lab Max – 1

        Free Thyroxine (T4) Index (FTI, T7)

        Hormones Reference Ranges

        Cortisol, AM

          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Mean
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range should be above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Cortisol, PM

          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Mean
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range should be above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        DHEA-S (Dehydroepiandrosterone Sulfate)

          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Mean
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range should be above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Dihydrotestosterone (DHT)

          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min and Max
          1. “LE’s Optimal Range for Men: 30-50 ng/dL.” Lab Testing: Introduction – Life Extension. Dihydrotestosterone (DHT) (serum or plasma, frozen).

        Estradiol (E2)

          • Reference ranges adjusted automatically for the following criteria:
          1. Male and female children up to 10 years of age
          2. Adult males
          3. Postmenopausal females
          4. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          5. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          • Lab Min and Max: LabCorp – Estradiol
          • Alarm Max = Lab Max + Lab Max * 0.3
          • Alarm Min = Lab Min – Lab Min * 0.3
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Mean
          1. “The patient’s value should be considered increased if it’s greater than the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Estriol (E3)

          • Reference ranges adjusted automatically for the following criteria:
          1. Males of all ages
          2. Postmenopausal females
          3. Premenopausal females
          4. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for all trimesters (except Lab Min for trimester 3) from: Quest Diagnostics – Estriol, Serum
            2. Lab Min for trimester 3 from: LabCorp – Estriol
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.01
          • Optimal Max = Lab Mean
          1. “The patient’s value should be considered increased if it’s greater than the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Estrogens, Total

          • Reference ranges adjusted automatically for the following criteria:
          1. Male and female children up to 10 years of age
          2. Adult males
          3. Postmenopausal females
          4. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          5. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Mean
          1. “The patient’s value should be considered increased if it’s greater than the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Estrone (E1)

          • Reference ranges adjusted automatically for the following criteria:
          1. Male children ages: 1-9, 10-11, 12-14, 15-17
          2. Female children ages: 1-9, 10
          3. Adult males
          4. Postmenopausal females
          5. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          6. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab range for trimesters 1 and 2 from: LabCorp – Estrone
            2. Lab range for trimester 3 from: Schock H, Zeleniuch-Jacquotte A, Lundin E, et al. Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study. BMC Pregnancy Childbirth. 2016;16(1):146. [PubMed]
          • Lab Min and Max: LabCorp – Estrone
          • Alarm Max = Lab Max + Lab Max * 0.3
          • Alarm Min = Lab Min – Lab Min * 0.3
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Mean
          1. “The patient’s value should be considered increased if it’s greater than the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Follicle-stimulating Hormone (FSH)

          • Reference ranges adjusted automatically for the following criteria:
          1. Male children ages: 1-4, 5-9, 10-12, 13-16
          2. Female children ages: 1-10
          3. Adult males
          4. Postmenopausal females
          5. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          6. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for all 3 trimesters from: “The normal range of FSH in pregnancy is between 3-10mIU/ml. However, in the initial stages of pregnancy, it will be at 2mIU/ml.” FSH (Follicle Stimulating Hormone) Levels in Pregnancy. Parenting.FirstCry.com. [Article]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range: use lab range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min and Max for adult males
          1. “Normal FSH values for fertility are typically reported between 1-11.1mIU/mL, several recent studies suggest a tighter range of 2-7mIU/mL as more indicative of predicting normal sperm production in men.” SDx S. Understanding Blood Test Results: Normal FSH levels in men. Don’t Cook Your Balls. Published March 25, 2016. [Article]

        Human Chorionic Gonadatropin (hCG)

          • Reference ranges adjusted automatically for the following criteria:
          1. Males
          2. Postmenopausal females
          3. Premenopausal females
          4. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for all trimesters from: Edelstam G, Karlsson C, Westgren M, Löwbeer C, Swahn ML. Human chorionic gonadatropin (hCG) during third trimester pregnancy. Scand J Clin Lab Invest. 2007;67(5):519-525. doi:10.1080/00365510601187765
            2. Gnoth C, Johnson S. Strips of Hope: Accuracy of Home Pregnancy Tests and New Developments. Geburtshilfe Frauenheilkd. 2014;74(7):661-669. [PubMed]
            3. Normal hCG Levels in Early Pregnancy. babyMed.com. Published February 24, 2018. [Article]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Max – 0.1

        Luteinizing Hormone (LH)

          • Reference ranges adjusted automatically for the following criteria:
          1. Male children ranges vary using these age groups from LabCorp: 0-4, 5-9, 10-12, 13-16
          2. Female children ranges vary using these age groups from LabCorp: 0-4, 5-9, 10
          3. Adult males
          4. Postmenopausal females
          5. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          6. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for all 3 trimesters from: “Pregnancy: <1.5 IU/L.” What is LH? Luteinizing Hormone Function, Levels, & Testing. Mira Fertility Tracker. Published December 23, 2021. [Article]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range: use lab range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Pregnenolone, LC/MS

          • Reference ranges adjusted automatically for the following criteria:
          1. Ages: 1, 2-6, 7-9, 10-12, 13-17, 18+
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Mean
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range should be above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Progesterone

          • Reference ranges adjusted automatically for the following criteria:
          1. Males of all ages
          2. Female children up to 10 years of age
          3. Postmenopausal females
          4. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          5. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Mean
          1. “If the lab value is below the midline of the range provided, consider it decreased.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        17-Hydroxyprogesterone (17-OHP)

          • Reference ranges adjusted automatically for the following criteria:
          1. Male and female children up to 10 years of age, ranges adjusted at each age: 1, 2, 3, 4, 5, 6, 7, 8 , 9, 10
          2. Males ages: 11, 12, 13, 14, 15, 16, 17, 18-30, 31-40, 41-50, 51+
          3. Postmenopausal females
          4. Premenopausal females in one of these menstrual phases starting at age 11: follicular, ovulation, luteal, and none (none uses the female child ranges)
          5. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Mean
          1. “If the lab value is below the midline of the range provided, consider it decreased.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Prolactin

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-17, 18+
          2. Premenopausal females ages: 1-17, 18+
          3. Postmenopausal females
          4. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 0.1
          • Optimal Max = Lab Max – 0.1
          1. “Optimal range: use lab range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Prolactin, Lactating: Normal prolactin levels in breastfeeding mothers. KellyMom.com. Published August 19, 2011. [Article]

        Sex Hormone Binding Globulin (SHBG)

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-9, 10-13, 14-17, 18-55, 56+
          2. Premenopausal females ages: 1-9, 10-13, 14-17, 18-55, 56+
          3. Postmenopausal females
          4. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min = Lab Min + 1
          • Optimal Max = Lab Max – 1
          1. “Optimal range: use lab range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Testosterone, Bioavailable (Free + Weakly Bound)

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-69, 70+
          2. Females
          3. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Kerlan V, Nahoul K, Le Martelot MT, Bercovici JP. Longitudinal study of maternal plasma bioavailable testosterone and androstanediol glucuronide levels during pregnancy. Clin Endocrinol (Oxf). 1994;40(2):263-267.[PubMed]
          1. “Non-SHBG-bound testosterone (assayed, ng/dl) for normal (non-Hirsute) women: 3.73 ± 1.71 (2.02 – 5.44).” Cumming DC, Wall SR. Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism. J Clin Endocrinol Metab. 1985;61(5):873-876. [PubMed]
          • Alarm Max = Lab Max + Lab Max * 0.3
          • Alarm Min = Lab Min – Lab Min * 0.3
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min (males) = Lab Mean
          • Optimal Max (males) = Lab Max – 0.1
          1. “Optimum range: Above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Testosterone, Bioavailable (Free + Weakly Bound) %

          • Reference ranges adjusted automatically for the following criteria:
          1. Males
          2. Females
          3. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Using the % increase in pregnancy trimester ranges over the non-pregnant ranges from above ng/dL values.
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min (males) = Lab Mean
          • Optimal Max (males) = Lab Max – 1
          1. “Optimum range: Above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Testosterone, Free, Calculated

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-5, 6-7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18-30, 31-40, 41-50, 51-60, 61-70, 71-80, 80+
          2. Females ages: 1-5, 6-12, 13-17, 18-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81+
          3. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. “The level of free testosterone was significantly (P < 0.01) higher in the period from week 28 to term (mean 3.04 plus or minus 0.24 ng/dl, n = 22) than in the period before week 28 (mean 1.15 plus or minus 0.09, n = 17).” Bammann BL, Coulam CB, Jiang NS. Total and free testosterone during pregnancy. Am J Obstet Gynecol. 1980;137(3):293-298. [PubMed]
          • Lab Min and Max (males ages 1-17 and females of all ages): LabCorp – Testosterone Free, Profile II
          • Lab Max (males ages 18+): Quest Diagnostics – Free Testosterone
          • Lab Min (males ages 18+):
            1. “72 pg/mL for <= 45 yo with 60% prevalence in men with CHF.” Jankowska EA, Biel B, Majda J, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006;114(17):1829-1837. [PubMed]
          • Alarm Max = Lab Max + Lab Max * 0.3
          • Alarm Min = Lab Min – Lab Min * 0.3
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min (males) = Lab Mean
          • Optimal Max (males) = Lab Max – 1
          1. “Optimum range: Above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Testosterone, Free, Direct

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-29, 30-39, 40-49, 50-59, 60+
          2. Females
          3. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. “The level of free testosterone was significantly (P < 0.01) higher in the period from week 28 to term (mean 3.04 plus or minus 0.24 ng/dl, n = 22) than in the period before week 28 (mean 1.15 plus or minus 0.09, n = 17).” Bammann BL, Coulam CB, Jiang NS. Total and free testosterone during pregnancy. Am J Obstet Gynecol. 1980;137(3):293-298. [PubMed]
          • Lab Min and Max for males and Lab Max for females: LabCorp – Testosterone, Free, Direct
          • Lab Min (females)
            1. “Non-frail mean is 1.16 pg/mL.” Cappola AR, Xue QL, Fried LP. Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women’s Health and Aging studies. J Gerontol A Biol Sci Med Sci. 2009;64(2):243-248. [PubMed]
          • Alarm Max = Lab Max + Lab Max * 0.3
          • Alarm Min (males) = Lab Min – Lab Min * 0.3
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Alarm Min (females)
            1. “Deficiency defined as < 0.7 pg/mL.” Cappola AR, Xue QL, Fried LP. Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women’s Health and Aging studies. J Gerontol A Biol Sci Med Sci. 2009;64(2):243-248. [PubMed]
          • Optimal Min (males) = Lab Mean
          • Optimal Max (males) = Lab Max – 1
          1. “Optimum range: Above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Testosterone, Total

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-8, 9-10, 11, 12, 13-15, 16-19, 20+
          2. Females ages: 1, 2-5, 6-8, 9-10, 11-12, 13-17, 18-30, 31-40, 41-60, 61-80, 81+
          3. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min (males) = Lab Mean
          • Optimal Max (males) = Lab Max – 1
          1. “Optimum range: Above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.

        Testosterone, Total, LC/MS-MS

          • Reference ranges adjusted automatically for the following criteria:
          1. Males ages: 1-10, 11-17, 18+
          2. Females ages: 1-5, 6-7, 8-10, 11-17, 18+
          3. Trimester of pregnancy (if unknown is selected, ranges for trimester 1 are used)
            1. Lab ranges for each trimester from: Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. [PubMed]
          1. “Possible Panic Range: Any value 30 percent above or below the reference range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.
          • Optimal Min (males) = Lab Mean
          • Optimal Max (males) = Lab Max – 1
          1. “Optimum range: Above the midline of the laboratory range.” Eidenier, HO. Balancing Body Chemistry with Nutrition “More Than Just a Bunch of Numbers — Making Sense of Blood Chemistry Results.” 11th ed. Phoenix, AZ: Balancing Body Chemistry with Nutrition LLC; 2018.