Biomarkers

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A biomarker, or biological marker, generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. [1] Some examples of biomarkers are serum cholesterol, fasting glucose, blood pressure, heart rate, body mass index (BMI), etc.

Biomarker Descriptions

Descriptions of various biomarkers and how they may be relevant to ApoE4 carriers.

VLDL, LDL, HDL and Lp(a) represented graphically

LDL-C

Low density lipoprotein cholesterol. ApoE4 is associated with high LDL. [2]

LDL-P

LDL particle number. Recent research indicates LDL-P is a more accurate predictor of cardiovascular disease. [3] [4] LDL-P can be measured with the #NMR LipoProfile test.

Below is a sortable table of biomarkers

Test Category Description
CARDIAC TROPONIN-1 Cardiac Function These proteins are released when the heart muscle has been damaged, such as occurs with a heart attack. The more damage there is to the heart, the greater the amount of troponin
NT-proBNP Cardiac Function NT-proBNP detects heart stress and damage, primarily used to help detect, diagnose, and evaluate the severity of heart failure.
Smc ENDOTHELIN Inflammation/Oxidation Endothelin is implicated in the pathogenesis of hypertension, coronary vasospasm, and heart failure
SMC INTERLEUKIN-6 (IL-6) Inflammation/Oxidation Active in inflammation, and in B cell maturation. It is produced in the body, wherever there is inflammation, either acute or chronic.
SMC- INTERLEUKIN-17A (IL-71A) Inflammation/Oxidation Most notable role of IL-17 is its involvement in inducing and mediating proinflammatory responses. IL-17 is commonly associated with allergic responses.
TNF-alpha Inflammation/Oxidation Primary role of TNF is in the regulation of immune cells. TNF stand for Tumor Necrosis Factor.
PLAC® Test for Lp-PLA 2 Inflammation/Oxidation Measures the function of Lp-PLA2 in the artery wall— a vascular-specific inflammatory marker critical in the formation of rupture-prone plaques.
hs-CRP Inflammation/Oxidation hsCRP is a protein that increases in the blood with inflammation. It is a useful test for determining risk of cardiovascular disease, heart attacks, and strokes.
HOMOCYSTEINE Inflammation/Oxidation Elevated levels of homocysteine in the blood appear to make for an elevated risk of cardiovascular (heart and vessel) disease. Homocysteine can damage blood vessels and also disrupt normal blood clotting mechanisms, increasing the risk of clots.
VITAMIN B12 Inflammation/Oxidation Vitamin B12, like the other B vitamins, is important for protein metabolism. It helps in the formation of red blood cells and in the maintenance of the central nervous system. Many people over age 50 lose the ability to absorb vitamin B12 from foods.
FOLATE Inflammation/Oxidation Folate and folic acid are forms of a water-soluble B vitamin. Folic acid is also of interest with respect to cognitive enhancement, cancer, psychiatric illnesses, and cardiovascular conditions.
URIC ACID Inflammation/Oxidation Used to detect high levels of this compound in the blood in order to help diagnose gout
Fibrinogen Inflammation/Oxidation A protein that is essential for blood clot formation
Lp-PLA2 Inflammation/Oxidation Lp-PLA2 is positively associated with coronary disease.
Myeloperoxidase Inflammation/Oxidation Also known as MPO. MPO is usually stored in a certain type of white blood cell. These cells release MPO when blood vessels are injured or become inflamed.
TOTAL CHOLESTEROL Lipid Management Total cholesterol score is calculated using the following equation: HDL + LDL + 20% of your triglyceride level
TRIGLYCERIDE Lipid Management Most common type of fat in the body. A high triglyceride level combined with low HDL cholesterol or high LDL cholesterol is associated with atherosclerosis, the buildup of fatty deposits in artery walls that increases the risk for heart attack and stroke.
HDL Lipid Management "Good Cholesterol" : higher levels are better.
HDL2b Lipid Management Only about half of the variability in coronary heart disease risk can be attributed to conventional risk factors (i.e. LDL, HDL and triglyceride levels). Other, more specific risk factors, enhance predictive power of cardiovascular disease in individuals. HDL2b is one of these specific risk factors that may be independent of other lipid-related risk factors.
LDL Lipid Management "Bad choleserol" : A low LDL cholesterol level is considered good for heart health.
sdLDL Lipid Management Small, dense form of your ‘bad’ LDL cholesterol: increased levels indicate build up of fatty materials in your arteries.
APO A-1 Lipid Management Levels of apo A-I tend to rise and fall with HDL(good) levels, and deficiencies in apo A-I correlate with an increased risk of developing cardiovascular disease.
APO B Lipid Management ApoB is a count of actual LDL particles. Concentrations of apo B tend to mirror those of LDL-C. Associated with an increased risk of cardiovascular disease (CVD).
Lp(a) Lipid Management Lipoprotein(a) A particle similar to LDL; your level of Lp(a) is determined by your genes. You want a low amount.
Apo B ratio to ApoA-1 Lipid Management ApoB/ApoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. This ratio is considered better than LDL-C in predicting cardiovascular risk.
LDL-C Lipid Management Low density lipoprotein cholesterol
LDL-P Lipid Management LDL particle number. Recent research indicates LDL-P is a more accurate predictor of cardiovascular disease.
HDL-P Lipid Management Total HDL particle number concentration as a predictor of cardiovascular disease
ox-LDL Lipid Management Oxidized LDL is LDL cholesterol (the “bad” cholesterol) that has been modified by oxidation. Oxidized LDL triggers inflammation leading to the formation of plaque in the arteries.
GLUCOSE Diabetes & Weight Management Measures the amount of a sugar called glucose in a sample of blood
INSULIN Diabetes & Weight Management Regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to skeletal muscles and fat tissue and causes fat to be stored rather than used for energy.
HEMOGLOBIN A1c Diabetes & Weight Management Average of blood sugar control over the past 2 to 3 months. To use an analogy, the glucose measurement is like a snapshot, HbA1c is like movie.
CORTISOL A.M. Diabetes & Weight Management Known as the “stress hormone,” cortisol has many functions. It helps the body use sugar (glucose) and fat for energy (metabolism), and it helps the body manage stress. Cortisol levels rise during the early morning hours and are highest about 7 a.m. Cortisol level may show problems with the adrenal glands or pituitary gland.
ADIPONECTIN Diabetes & Weight Management Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation.
LEPTIN Diabetes & Weight Management Known as the "satiety hormone," leptin is made by fat cells to help regulate energy balance by inhibiting hunger. Leptin level is decreased by increases in testosterone levels and increased by increases in estrogen levels. Leptin level is reduced by physical exercise training.
FERRITIN Diabetes & Weight Management Protein found inside cells that stores iron so your body can use it later. A ferritin test indirectly measures the amount of iron in your blood.
CALCIUM Calcium, Bone & Mineral Health Calcium has many important jobs. The body stores more than 99 percent of its calcium in the bones and teeth to help make and keep them strong. The rest is throughout the body in blood, muscle, and the fluid between cells. Your body needs calcium to help muscles and blood vessels contract and expand, to secrete hormones and enzymes, and to send messages through the nervous system.
PARATHYROID HORMONE Calcium, Bone & Mineral Health Parathyroid hormone (PTH) is released by the parathyroid glands. PTH controls calcium, phosphorus, and vitamin D levels in the blood.
VITAMIN D Calcium, Bone & Mineral Health A fat-soluble vitamin that is naturally present in very few foods. It is also produced when sunlight strikes the skin and triggers vitamin D synthesis. Vitamin D promotes calcium absorption in the gut, enables normal mineralization of bone, prevents hypocalcemic tetany, and is needed for bone growth and bone remodeling. It helps protect older adults from osteoporosis. Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation.
PHOSPHOROUS, INORGANIC Calcium, Bone & Mineral Health Phosphorus that may be measured in the blood as phosphate ions. Increased concentration may indicate bone, kidney, or glandular disease; decreased concentration may be associated with alcoholism, vitamin deficiency, and other problems.
MAGNESIUM Calcium, Bone & Mineral Health Magnesium is a mineral that's crucial to the body's function. Magnesium helps keep blood pressure normal, bones strong, and the heart rhythm steady.
Osteocalcin Calcium, Bone & Mineral Health As osteocalcin is produced by osteoblasts; it is often used as a marker for the bone formation process
B-Crosslaps (B-CTx) Calcium, Bone & Mineral Health An aid in monitoring antiresorptive therapies (eg, bisphosphonates and hormone replacement therapy) in postmenopausal women treated for osteoporosis and individuals diagnosed with osteopenia. An adjunct in the diagnosis of medical conditions associated with increased bone turnover.
SODIUM Renal (kidney function) The sodium blood test measures the amount of sodium in the blood. Sodium is a substance that the body needs to work properly. Your blood sodium level represents a balance between the sodium and water in the food and drinks you consume and the amount in your urine. A small amount is lost through stool and sweat.
POTASSIUM Renal (kidney function) Potassium (K+) helps nerves and muscles communicate. It also helps move nutrients into cells and waste products out of cells. You may have this test to diagnose or monitor kidney disease. Potassium is important to heart function.
CHLORIDE Renal (kidney function) Chloride is a type of electrolyte. It works with other electrolytes such as potassium, sodium, and carbon dioxide (CO2). These substances help keep the proper balance of body fluids and maintain the body's acid-base balance.
CARBON DIOXIDE Renal (kidney function) CO2 blood test is a measure of your blood bicarbonate level. The CO2 test is most often done as part of an electrolyte or basic metabolic panel. Changes in your CO2 level may suggest that you are losing or retaining fluid. This may cause an imbalance in your body's electrolytes. If you are in ketosis, they will likely measure as “red” or low but that’s normal because of the ketotic state.
BUN Renal (kidney function) BUN stands for blood urea nitrogen. Urea nitrogen is what forms when protein breaks down. The BUN test is often done to check kidney function.
CREATININE Renal (kidney function) Reflects how well your kidneys work. Creatinine is a chemical waste product of creatine. It varies according to a person's size and muscle mass.
CYSTATIN C Renal (kidney function) To screen for and monitor kidney dysfunction. An high level of cystatin C in the blood corresponds to a decreased glomerular filtration rate (GFR) and hence to kidney dysfunction. Increased levels of cystatin C may also indicate an increased risk of heart disease, heart failure, stroke, and mortality.
eGFR Renal (kidney function) eGFR is used to screen for and detect early kidney damage and to monitor kidney status.
eGFR (AFRICAN-AMERICAN) Renal (kidney function) For African Americans. eGFR is used to screen for and detect early kidney damage and to monitor kidney status.
ALT Hepatic (liver) The alanine aminotransferase (ALT) test is typically used to detect liver injury.
AST Hepatic (liver) The blood test for aspartate aminotransferase (AST) is usually used to detect liver damage.
Gamma GT Hepatic (liver) Gamma-glutamyl transferase (GGT) test may be used to determine the cause of elevated alkaline phosphatase (ALP). Both ALP and GGT are elevated in disease of the bile ducts and in some liver diseases, but only ALP will be elevated in bone disease. Therefore, if the GGT level is normal in a person with a high ALP, the cause of the elevated ALP is most likely bone disease. GGT test is sometimes used to help detect liver disease and bile duct obstructions.
ALKALINE PHOSPHATASE Hepatic (liver) Alkaline phosphatase (ALP) is a protein found in all body tissues. Tissues with higher amounts of ALP include the liver, bile ducts, and bone. Used to diagnose liver or bone disease.
BILIRUBIN, TOTAL Hepatic (liver) Bilirubin test is used to detect an increased level in the blood. It may be used to help determine the cause of jaundice and/or help diagnose conditions such as liver disease, hemolytic anemia, and blockage of the bile ducts.
BILIRUBIN, DIRECT Hepatic (liver) The laboratory can use a second chemical test to detect water-soluble forms of bilirubin, called "direct" bilirubin. The direct bilirubin test provides an estimate of the amount of conjugated bilirubin present.
TOTAL PROTEIN Hepatic (liver) The total protein test measures the total amount of two classes of proteins found in the fluid portion of your blood. These are albumin and globulin. Albumin helps prevent fluid from leaking out of blood vessels. Globulins are an important part of your immune system. This test is often done to diagnose nutritional problems, kidney disease, or liver disease.
ALBUMIN Hepatic (liver) Albumin is a protein made by the liver. A serum albumin test measures the amount of this protein in the clear liquid portion of the blood. Albumin helps move many small molecules through the blood, including bilirubin, calcium, progesterone, and medicines. It plays an important role in keeping the fluid from the blood from leaking out into the tissues. This test can help determine if a patient has liver disease or kidney disease, or if the body is not absorbing enough protein.
TSH Thyroid Thyroid-stimulating hormone (TSH) test is often the test of choice for evaluating thyroid function and/or symptoms of a thyroid disorder, including hyperthyroidism or hypothyroidism.
T4 Thyroid T4 (thyroxine) is the main hormone produced by the thyroid gland.
FREE T4 Thyroid Free thyroxine (free T4) tests are used to help evaluate thyroid function and diagnose thyroid diseases.
T3 Thyroid Triiodothyronine (T3) is a thyroid hormone. It plays an important role in the body's control of metabolism.
FREE T3 Thyroid A free or total triiodothyronine (free T3 or total T3) test is used to assess thyroid function.
Asymmetric

Dimethylarginine

Endothelial Function (associated w cardiovascular events) Chemical found in blood plasma. Raised levels of ADMA seem to be associated with adverse human health consequences for cardiovascular disease, metabolic diseases, and also a wide range of diseases of the elderly. ADMA's role has been linked with elevated levels of homocysteine.
Symmetric

Dimethylarginine

Endothelial Function (associated w cardiovascular events) A renal-function biomarker used to diagnose chronic kidney disease.
L-arginine Endothelial Function (associated w cardiovascular events) Arginine, also known as L-arginine, is involved in a number of different functions in the body: wound healing, helping kidneys remove waste products, maintaining immune and hormone functions, dilating and relaxing the arteries.
Asymmetric

Dimethylarginine/ Arginine Ratio

Endothelial Function (associated w cardiovascular events Example
Galectin-3 Myocardial Structure/Stress/Function Lab uses this is as a marker of myocardial strain. Dr Gundry uses this as a way of detecting gut dysbiosis, citing two papers in human trials giving people with elevated Galectin-3s a supplement called Modified Citrus Pectin.
NT-proBNP Myocardial Structure/Stress/Function Primarily used to help detect, diagnose, and evaluate the severity of heart failure
Factor V Leiden (G1691A)§

rs6025

Coagulation Genetics Increased risk for the venous thromboembolism (VTE), i.e. blood clots in the vein
Prothrombin Mutation (G20210A)§

rs1799963

Coagulation Genetics Increases the risk of blood clots
MTHFR (C677T)§

rs1801133 (Methylenetetrahydrofolate Reductase)

Coagulation Genetics Associated with poor methylation and enzyme production
MTHFR (A1298C)§

rs1801131

Coagulation Genetics Associated with poor methylation and enzyme production
Free Fatty Acid Metabolic Elevated free fatty acids have been associated with the metabolic syndrome and increased risk for the development of type 2 diabetes. However, if you're in ketosis, you’re burning free fatty acids, which will produce a high measured level
Fructosamine Metabolic Looks at two weeks of how many sugars, particularly fruit sugars, you are eating
Dehydroepiandrosterone sulfate Hormones DHEA, a weak male hormone (androgen) produced by the adrenal glands in both men and women.
Estradiol Hormones Estrogen
FSH Hormones Follicle-stimulating hormone
LH Hormones Luteinizing Hormone. In women, LH helps regulate the menstrual cycle and egg production (ovulation)
Progesterone Hormones Involved in the menstrual cycle, pregnancy, and embryogenesis of humans
Testosterone Hormones Primary male sex hormone
Insulin-like Growth Factor 1 (IGF1) Hormones Correlated to greater longevity, the lower the number the better. Sensitive to sugars and animal protein
Human Sex Hormone Binding Globulin Hormones Used to help evaluate men for low testosterone and women for excess testosterone production
Free Testosterone (calculated) Hormones The amount of unattached, or "free," testosterone in your blood
Pregnenolone Hormones Pregnenolone belongs to the group of neurosteroids that are found in high concentrations in certain areas of the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization
HS-Omega-3 Index®

(RBC EPA+DHA)

Omega-3 RBC - Red Blood Count (so covers a period of time, does not reflect last night's meal) of the two main components in fish oil - EPA + DHA. “Good” level per lab is over 8, Dr Gundry prefers his ApoE4s to be 10 – 12.
Ferritin Anemia Usually reflects a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of anemia of chronic disease where ferritin is elevated in its capacity as an inflammatory acute phase protein and not as a marker for iron overload.
Iron Anemia Body's current level of iron.
UIBC Anemia Unsaturated Iron Binding Capacity (UIBC). Transferrin is the main protein in the blood that binds to iron and transports it throughout the body. The amount of transferrin that is available to bind to and transport iron is reflected in measurements of the total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), or transferrin saturation.
TIBC Anemia Total Iron Binding Capacity (TIBC). Used along with a serum iron test to evaluate iron deficiency or iron overload
Transferrin Anemia Measures the amount of the protein transferrin in your blood. The liver makes transferrin. It creates much more when your body's stores of iron run low. Nearly all the iron in your body is normally attached to transferrin.
Transferrin Saturation Anemia Checks how many places on your transferrin that can hold iron are actually doing so. A more useful indicator of iron status than just iron or TIBC alone.
HOMA-IR Diabetes & Weight Management Short for Homeostatic Model Assessment of Insulin Resistance, commonly referred to in medical literature. Used to quantify insulin resistance and beta-cell function. It is calculated by taking the fasting glucose times fasting insulin divided by 405. (FG x FI/405) Desired range: 1.0 or lower. Over 2.5 is insulin resistance.
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Tests

Many tests can be ordered through a primary doctor and health insurance. Another option is to order them directly from a major national lab, like LabCorp, through DirectLabs.com or PrivateMDLabs.com.

NMR LipoProfile

Nuclear Magnetic Resonance lipoprotein profile. A LipoScience proprietary test that measures cholesterol particle numbers (e.g. LDL-P) and size, in addition to the standard lipid profile. e.g. MDLabTests NMR Lipoprofile

Peter Attia explains with his customary thoroughness and lucidity why the LDL-P from this test is valuable.

ApoE4-Community Test Results

If you would like to view or update the spreadsheet without causing your own personal Google account to be visible to other users of the spreadsheet, you can do so by opening the link in a private browsing window. The feature is called "incognito", "Private", and "InPrivate" in Chrome, Firefox, and Internet Explorer, respectively. In Chrome and Firefox, for convenience you can right-click on the link and open it directly in the private browsing window.

The Community Test Results are a Google Sheet that anyone can edit. The columns are intended to be narrow to view as much data as possible at one time - this means column titles are abbreviated.

Google Spreadsheet example to insert row sorted by LDL-P:

  1. left-click left-most row number with LDL-P just larger than new LDL-P number (the entire row will be highlighted)
  2. right-click Insert 1 above
  3. TC/H and TG/H are equations - select those cells above or below new ones, <Ctrl>-c to copy equation, select new cell and <Ctrl>-v to paste

Google Spreadsheet example for web link:

  1. right-click forum topic or reply link, select Copy shortcut
  2. in the following hyperlink example, select first field between double-quotes, right-click past, edit second field between quotes with desired display text
    =hyperlink("apoe4.info/forums/viewtopic.php?f=5&t=259";"MarkES NMR Results")
  3. select newly created hyperlink starting from = and ending in ), right-click copy, select spreadsheet cell location and keyboard <Ctrl>-v to paste

The Google Spreadsheet that was once visible on this webpage used the Google Spreadsheet Widget. The feature no longer works, but we're saving the widget code here ...

Actual test results of ApoE4 carriers. Spreadsheet is intended to be sorted by LDL-P.

{{#widget:Google Spreadsheet |key=1Zj39xxOV0mXb8_-RVpEag2Nniy3CWRbVBrDmpQ2nd8g |width=100% |height=700 }}

... and the instructions here until we figure out what happened:

The following items need to be done one time and are listed here as instruction for any new spreadsheets that may want to use this same method.

  • Publish Google spreadsheet - the Google spreadsheet must be published to the web (File->Publish to the web..., click start publishing).
  • Copy link key - the key value to use in the widget is shown in the File->Publish "Get a link to the published data" link.
  • Optionally share doc to be public on the web - File->Share... who has access - public on the web