Lab Test Results Explained – An overview of Risk Factors for each Biomarker

Your blood contains valuable information on your health across a range of functions in your body. However, results are often delivered in a way that is confusing and does not help the patient to understand lab test results. The section below gives a brief overview of the health categories and the risk factors associated with the biomarkers in each category. For more detail, register for our free trial where we explain blood test results with recommendations for each health category and each biomarker, helping you to understand your blood test results and make informed decisions to improve your health

Cardiovascular Health

The cardiovascular system, consisting of the heart and the blood vessels delivers nutrients and oxygen to all cells in the body [1]. A healthy cardiovascular system is key to providing the energy we need to allow our bodies to perform optimally.

Lipid Profile markers

A complete cholesterol test — also called a lipid panel or lipid profile measures the amount of cholesterol and triglycerides in your blood. A cholesterol test can help determine your risk for the build-up of plaques in your arteries, which can lead to narrowed or blocked arteries throughout your body (atherosclerosis) [2].

Cholesterol

Higher levels of LDL cholesterol are associated with an increased risk of coronary heart disease. Conversely, higher levels of HDL cholesterol in your blood are related to lower risk levels [31]. Coronary heart disease is a condition in which plaque builds up inside the coronary arteries. Plaque is made up of cholesterol, fat, calcium, and other substances found in the blood. When plaque builds up in the arteries, the condition is called atherosclerosis [6]. Genetic factors are highly correlated with the risk of heart disease, but you can still reduce your risk by making lifestyle changes to protect your heart [1].

Reference Ranges for Cholesterol:

Conversion Metric Optimal Borderline Risk
US Conventional Units mg/dl <=199 200-239 >=240
Standard International Units mmol/L <=5.2 5.3-6.2 >=6.3

Triglycerides

Although it’s unclear how, high triglycerides can contribute to hardening of the arteries or thickening of the artery walls (atherosclerosis) which increases the risk of stroke, heart attack and heart disease. Extremely high triglycerides (above 1000 mg/dL (11.29 mmol/L)) can also cause acute pancreatitis.

High triglycerides are often a sign of other conditions that increase the risk of heart disease and stroke as well, including obesity and metabolic syndrome — a cluster of conditions that includes too much fat around the waist, high blood pressure, high blood sugar and abnormal cholesterol levels.

Sometimes high triglycerides are a sign of poorly controlled type 2 diabetes, low levels of thyroid hormones (hypothyroidism), liver or kidney disease, or rare genetic conditions that affect how your body converts fat to energy. High triglycerides could also be a side effect of taking medications such as beta blockers, birth control pills, diuretics or steroids [8].

Reference Ranges for Triglycerides:

Conversion Metric Optimal Borderline Risk
US Conventional Units mg/dl <=99 100-129 >=130
Standard International Units mmol/L <=1.7 1.8-2.3 >=2.4

Apolipoprotein B (Apo B)

Apo B is associated with increased risk of developing heart disease and often outperforms LDL cholesterol as a marker for predicting risk. For example, patients with acceptable LDL cholesterol but elevated Apo B remain at higher risk of developing heart disease, conversely, patients with acceptably low Apo B but moderate LDL cholesterol elevations are at a comparably reduced risk for heart disease [11].

Reference Ranges for Apolipoprotein B:

Conversion Metric Optimal Borderline Risk
US Conventional Units mg/dl <=89 90-119 >=120
Standard International Units mmol/L <=2.3 2.4-3.1 >=3.2

Inflammation markers

Inflammation causes swelling and pain in the affected part of the body. While this is a normal immune system response and is important for healing, sometimes inflammation can become chronic. Long-term inflammation is linked to several diseases and conditions, such as rheumatoid arthritis and heart disease [25].

hs-CRP

Chronic inflammation, also known as low-grade or systemic inflammation is related to autoimmune disorders, such as rheumatoid arthritis, lupus and polymyalgia rheumatic, where the body’s immune system mistakenly initiates an inflammatory response even though there’s no apparent inflammation to fight off. Chronic inflammation plays a more obvious role in diseases such as asthma and the inflammatory bowel diseases ulcerative colitis and Crohn’s disease [16].

It is also thought that high CRP levels in your blood are associated with narrowed coronary arteries. A CRP test can’t tell your doctor where the inflammation is, so it’s possible that a high CRP level could mean there’s inflammation somewhere other than your heart [15].

Reference Ranges for hs-CRP:

Conversion Metric Optimal Borderline Risk
US Conventional Units mg/dl <=1.9 2-2.9 >=3
Standard International Units mmol/L <=1.9 2-2.9 >=3

Homocysteine

Elevated plasma homocysteine is associated with increased risk of cardiovascular disease, increased incidence of stroke, dementia and Alzheimer’s disease, bone fracture, and higher prevalence of chronic heart failure. It is also proven that elevated plasma homocysteine is a risk factor for preeclampsia and neural tube defects [20]. This multitude of relationships between elevated plasma homocysteine and disease points to the existence of a common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined [20].

Reference Ranges for Homocysteine:

Conversion Metric Optimal Risk
US Conventional Units mg/dl 0-13 >=14
Standard International Units mmol/L <0-13 >=14

Liver Health

The liver is one of the largest organs in the body and has many important metabolic functions. It converts the nutrients in our diets into substances that the body can use, stores these substances, and supplies cells with them when needed. It also takes up toxic substances and converts them into harmless substances or makes sure they are released from the body [29]. The health of your liver has a big bearing on your energy levels and immune function.

Liver function Test Markers

Liver function are used to help diagnose and monitor liver disease or damage. The tests measure the levels of certain enzymes and proteins in your blood.

Bilirubin

Your doctor will interpret your result for each biomarker in the context of the overall test and determine if your result Higher than normal levels of bilirubin may indicate different types of liver problems. Occasionally, higher bilirubin levels may indicate an increased rate of destruction of red blood cells (hemolysis) [33].

Sometimes the liver can’t process the bilirubin in the body. This can be due to an excess of bilirubin, an obstruction, or inflammation of the liver. When your body has too much bilirubin, your skin and the whites of your eyes will start to yellow. This condition is called jaundice, and in a newborn can be very serious and life-threatening if left untreated [34].

Reference Ranges for Bilirubin:

Conversion Metric Optimal Risk
US Conventional Units mg/dl 0-1.2 >=1.3
Standard International Units umol/L 0-21 >=22

Albumin

Your doctor will interpret your result for each biomarker in the context of the overall test and determine if your result warrants further investigation.

Low levels of Albumin in the Blood (hypoalbumenia) can be a sign of

  • Liver damage or disease
  • Renal (kidney) dysfunction
  • Certain heart conditions
  • Problems with your stomach – including inflammatory bowel disease can cause hypoalbuminemia
  • Poor nutrition – Lack of protein in the diet [35]

Reference Ranges for Albumin:

Conversion Metric Optimal Risk
US Conventional Units g/dl 3.5-5 <3.5 or >5
Standard International Units g/L 35-50 <35 or >50

Globulin

Your doctor will interpret your result for each biomarker in the context of the overall test and determine if your result warrants further investigation.

Low Globulin Levels can be a sign of several conditions, including renal disease, hepatic dysfunction, celiac disease and inflammatory bowel disease (IBD). It can also be a sign that proteins taken in by the digestive system are not being broken down or absorbed properly [36].

High globulin levels can be related to bone marrow disorders, autoimmunity diseases such as lupus or chronic inflammatory diseases such as Rheumatoid arthritis, ulcerative colitis, kidney disease or a chronic viral or bacterial infection [36].

Reference Ranges for Globulin:

Conversion Metric Optimal Risk
US Conventional Units g/dl 2-3.5 <2.0 or >3.5
Standard International Units g/L 20-35 <20 or >35

Total Protein

A low total protein level can suggest a liver disorder, a kidney disorder, or a disorder in which protein is not digested or absorbed properly. Low levels may be seen in malnutrition and with conditions that cause malabsorption, such as celiac disease or inflammatory bowel disease (IBD). A high total protein level may be seen with chronic inflammation or infection [37].

Reference Ranges for Total Protein:

Conversion Metric Optimal Risk
US Conventional Units g/dl 6-8 <6 or >8
Standard International Units g/dl 60-80 <60 or >80

A/G Ratio

  • A low A/G ratio may reflect overproduction of globulins, such as seen in multiple myeloma or autoimmune diseases, or underproduction of albumin, such as may occur with cirrhosis, or selective loss of albumin from the circulation, as may occur with kidney disease.
  • A high A/G ratio suggests underproduction of immunoglobulins as may be seen in some genetic deficiencies.
  • With a low total protein that is due to plasma expansion (dilution of the blood), the A/G ratio will typically be normal because both albumin and globulin will be diluted to the same extent [37].

Reference Ranges for A/G Ratio:

Conversion Ratio Optimal Risk
US Conventional Units Ratio 0.8-2 <.8 or >2
Standard International Units Ratio 0.8-2 <.8 or >2

Alkaline phosphatase (ALP)

  • Higher-than-normal levels of ALP may indicate liver damage or disease.
  • This test is often used to detect blocked bile ducts because ALP is especially high in the edges of cells that join to form bile ducts. If one or more of them are obstructed then blood levels of ALP will often be high.
  • Any condition that affects bone growth or causes increased activity of bone cells can affect ALP levels in the blood. Values from 10 to 25 times the upper limit of the reference interval are not unusual in these cases [37].

Reference Ranges for ALP:

Conversion Metric Optimal Borderline Risk
US Conventional Units U/L 30-129 130-149 <30 or >150
Standard International Units U/L 30-129 130-149 <30 or >150

Alanine transaminase (ALT)

In infectious hepatitis and other inflammatory conditions affecting the liver, ALT is characteristically as high as or higher than AST, and the ALT/AST ratio, which is normally <1, increases. ALT levels are usually elevated before clinical signs and symptoms of disease appear. Elevated ALT values are seen in parenchymal liver diseases characterized by a destruction of hepatocytes, where values are typically at least ten times above the normal range. Levels may reach values as high as one hundred times the upper reference limit, although twenty to fifty-fold elevations are most frequently encountered [41].

Reference Ranges for ALT:

Gender Conversion Metric Optimal Risk
Men US Conventional Units U/L <=41 >=42
Women US Conventional Units U/L <=33 >=34
Men Standard International U/L <=41 >=42
Women Standard International U/L <=33 >=34

Aspartate transaminase (AST)

Very high levels of AST (more than 10 times normal) are usually due to hepatitis or a viral infection. With acute hepatitis, AST levels usually stay high for about 1-2 months but can take as long as 3-6 months to return to normal. Levels of AST may also be markedly elevated (often over 100 times normal) as a result of exposure to drugs or other substances that are toxic to the liver as well as in conditions that cause decreased blood flow (ischemia) to the liver [43].

Reference Ranges for AST:

Conversion Metric Optimal Risk
US Conventional Units U/L 8-42 <8 or > 43
Standard International Units U/L 8-43 <8 or > 43

Kidney Health

The kidneys are two bean-shaped organs that extract waste from blood, balance body fluids, form urine, and aid in other important functions of the body.  They sit just below the rib cage either side of the spine, against the back muscles in the upper abdominal cavity [51].

Kidney function test markers

Kidney function tests look for the level of waste products, such as creatinine and urea, in your blood to assess how well your kidneys are working and assess the health of your kidneys.  As with liver function tests the combination of the tests are much more powerful that the individual tests in isolation and results for each marker are generally viewed in context of the overall test [51].

Creatinine

Increased creatinine levels in the blood can suggest kidney disease or other conditions that affect kidney function. These can include:

  • Damage to or swelling of blood vessels in the kidneys (glomerulonephritis) caused by, for example, infection or autoimmune diseases

  • Bacterial infection of the kidneys (pyelonephritis)

  • Death of cells in the kidneys’ small tubes (acute tubular necrosis) caused by, for example, drugs or toxins

  • Prostate disease, kidney stone, or other causes of urinary tract obstruction

  • Reduced blood flow to the kidney due to shock, dehydration, atherosclerosis, or complications of diabetes [53].

Low blood levels of creatinine are not common, but they are also not usually a cause for concern. They can be seen with conditions that result in decreased muscle mass [53].

Reference Ranges for Creatinine:

Gender Conversion Metric Optimal Risk
Men US Conventional Units mg/dl .67-.1.1 <.67 or>.1.18
Women US Conventional Units mg/dl .51-.95 <.51 or >.95
Men Standard International umol/L 59-104 <59 or >104
Women Standard International umol/L  45-84 <45 or >84

Estimated Glomular Filtration Rate (eGFR)

eGFR is considered the most effective way to measure changes in Kidney status and to identify Chronic kidney disease.   Chronic kidney disease can be seen with a variety of conditions, including diabetes and high blood pressure. Early detection of kidney dysfunction can help to minimize the damage. This is important as symptoms of kidney disease may not be noticeable until as much as 30-40% of kidney function is lost [55].

Reference Ranges for eGFR:

Conversion Metric Optimal Borderline Risk
US Conventional Units ml/min/1.73m2 >=90 60-89 <=59
Standard International ml/min/1.73m2  >=90 60-89 <=59

Blood Urea Nitrogen (BUN)

BUN concentrations may be elevated when there is excessive protein breakdown (catabolism), significantly increased protein in the diet, or gastrointestinal bleeding (because of the proteins present in the blood).

Increased BUN levels may suggest impaired kidney function. This may be due to acute or chronic kidney disease, damage, or failure. It may also be due to a condition that results in decreased blood flow to the kidneys, such as congestive heart disease, shock, stress, or severe burns, to conditions that cause obstruction of urine flow, or to dehydration.

Low BUN levels are not common and are not usually a cause for concern. They may be seen in severe liver disease, malnutrition, and sometimes when a person is overhydrated (too much fluid volume), but the BUN test is not usually used to diagnose or monitor these conditions.

If one kidney is fully functional, BUN concentrations may be normal even when significant dysfunction is present in the other kidney [58].

Reference Ranges for BUN:

Conversion Metric Optimal Risk
US Conventional Units mg/dl 7-22 <7 or >22
Standard International umol/L 2.5-7.9 <2.5 or >7.9

BUN:Creatinine Ratio

An increased ratio may be due to a condition that causes a decrease in the flow of blood to the kidneys, such as congestive het disease or dehydration. It may also be seen with increased protein, from gastrointestinal bleeding, or increased protein in the diet. The ratio may be decreased with liver disease (due to decrease in the formation of urea) and malnutrition [59].

Reference Ranges for BUN/Creatinine Ratio:

Conversion Ratio Optimal Risk
US Conventional Units Ratio 10-20 <10 or >20
Standard International Ratio 10-20 <10 or >20

Metabolic Health

Metabolism is the process by which your body converts what you eat and drink into energy. During this complex biochemical process, calories in food and drinks are combined with oxygen to release the energy your body needs to function [157]. Metabolic tests provide an overall picture of your body’s chemical balance and metabolism.

Glucose

Diabetes – There are a few different conditions that may disrupt the balance between glucose and the pancreatic hormones, resulting in high or low blood glucose. The most common cause is diabetes. Diabetes is a group of disorders associated with insufficient insulin production and/or a resistance to the effects of insulin. People with untreated diabetes are not able to process and use glucose normally. Those who are not able to produce any or enough insulin (and typically have diabetes autoantibodies) are diagnosed as having type 1 diabetes. Those who are resistant to insulin and may or may not be able to produce sufficient quantities of it may have prediabetes or type 2 diabetes [117].

Gestational Diabetes – Some women may develop gestational diabetes, which is hyperglycemia that occurs only during pregnancy. If untreated, this can cause these mothers to give birth to large babies who may have low glucose levels. Women who have had gestational diabetes may or may not go on to develop diabetes [117].

Chronically high blood glucose levels can cause progressive damage to body organs such as the kidneys, eyes, heart and blood vessels, and nerves. Chronic low blood sugar can lead to nerve damage [117].

Reference Ranges for Glucose:

Conversion Units Optimal Borderline Risk
US Conventional Units mg/dl 70-99 50-69 or 100-129 <50 or > 129
Standard International Units mmol/L 3.9-5.6 2.8-3.8 or 5.7-7.2 <2.8 or >7.3

Hemoglobin A1c (HbA1c)

See Glucose for Risk factors associated with HbA1c.

Reference Ranges for HbA1c:

Conversion Units Optimal Borderline Risk
US Conventional Units % 4-5.6 5.7-6.4 <4 or >6.4
Standard International Units % 4-5.6 5.7-6.4 <4 or >6.4

Cortisol

The body’s stress-response system is usually self-limiting. Once a perceived threat has passed, hormone levels return to normal. As adrenaline and cortisol levels drop, your heart rate and blood pressure return to baseline levels, and other systems resume their regular activities.

But when stressors are always present and you constantly feel under attack, that fight-or-flight reaction stays turned on.

The long-term activation of the stress-response system — and the subsequent overexposure to cortisol and other stress hormones — can disrupt almost all your body’s processes. This puts you at increased risk of numerous health problems, including:

  • Anxiety
  • Depression
  • Digestive problems
  • Headaches
  • Heart disease
  • Sleep problems
  • Weight gain
  • Memory and concentration impairment [126]

Reference Ranges for Cortisol:

Conversion Units Optimal Risk
US Conventional Units mg/dl 7-22 <7 or >22
Standard International Units ug/dl 138-429 <138 or >429

Thyroid Stimulating Hormone (TSH)

Overactive Thyroid – If the thyroid releases inappropriately large amounts of T4 and T3, the affected person may experience symptoms associated with hyperthyroidism, such as rapid heart rate, weight loss, nervousness, hand tremors, irritated eyes, and difficulty sleeping. Graves disease is the most common cause of hyperthyroidism. It is a chronic autoimmune disorder in which the affected person’s immune system produces antibodies that act like TSH, leading to the production of excessive amounts of thyroid hormone. In response, the pituitary may produce less TSH, usually leading to a low level in the blood [132].

Underactive Thyroid – If there is decreased production of thyroid hormones by the thyroid (hypothyroidism), the person may experience symptoms such as weight gain, dry skin, constipation, cold intolerance, and fatigue. Hashimoto thyroiditis is the most common cause of hypothyroidism. It is a chronic autoimmune condition in which the immune response causes inflammation and damage to the thyroid as well as the production of autoantibodies. With Hashimoto thyroiditis, the thyroid produces low levels of thyroid hormone. The pituitary may produce more TSH, usually resulting in a high level in the blood [132].

However, the level of TSH does not always predict or reflect thyroid hormone levels. Some people produce an abnormal form of TSH that does not function properly. They often have hypothyroidism despite having normal or even mildly elevated TSH levels. In a variety of thyroid diseases, thyroid hormone levels may be high or low, regardless of the amount of TSH present in the blood [132].

Reference Ranges for TSH:

Conversion Units Optimal Borderline Risk
US Conventional Units mU/L 0.3-4.2 4.3-5 <0.3 or >5
Standard International Units mU/L 0.3-4.2 4.3-5 <0.3 or >5

Testosterone (Total)

In adult males, low testosterone may alter certain masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include:

  • Erectile dysfunction
  • Infertility
  • Decrease in beard and body hair growth
  • Decrease in muscle mass
  • Development of breast tissue (gynecomastia)
  • Loss of bone mass (osteoporosis) [135]

Low testosterone can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include:

  • Fatigue
  • Decreased sex drive
  • Difficulty concentrating
  • Hot flashes [135]

In females, testosterone testing may be done when a woman has irregular or no menstrual periods (amenorrhea) or is having difficulty getting pregnant, Testosterone levels can rise because conditions such as polycystic ovarian syndrome (PCOS) [134].

Thyroid problems, depression, excessive alcohol use and conditions such as obstructive sleep apnea can all affect testosterone levels in men and women.

Reference Ranges for Testosterone (Total):

Gender Conversion Units Optimal Risk
Men US Conventional Units ng/dl 240-1200 <240 or >1200
Women US Conventional Units ng/dl 8-75 <8 or >75
Men Standard International Units nmol/L 8.3-41.6 8.3-41.6
Women Standard International Units nmol/L .27-2.6 <.27 or >2.6


Sex Hormone Binding Globulin (SHBG)

Males – A high SHBG level in relation to the amount of testosterone means that less free testosterone is available to the tissues than is indicated by the total testosterone test and therefore symptoms of low testosterone may occur

Low testosterone may alter certain masculine physical characteristics and impair normal reproductive function. Signs and symptoms may include:

  • Erectile dysfunction
  • Infertility
  • Decrease in beard and body hair growth
  • Decrease in muscle mass
  • Development of breast tissue (gynecomastia)
  • Loss of bone mass (osteoporosis) [135]

Low testosterone can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include:

  • Fatigue
  • Decreased sex drive
  • Difficulty concentrating
  • Hot flashes [135]

Females – SHBG has a higher affinity for the androgens testosterone and DHT and so, in the setting of low SHBG, women may have signs and symptoms related to excess testosterone

High testosterone can result in irregular or no menstrual periods (amenorrhea) or difficulty getting pregnant,

Reference Ranges for SHBG:

Gender Conversion Units Optimal Risk
Men US Conventional Units nmol/L 10-57 <10 or >57
Women US Conventional Units nmol/L 18-144 <18 or >144
Men Standard International Units nmol/L 10-57 <10 or >57
Women Standard International Units nmol/L 18-144 <18 or >144

Estradiol (E2)

Metabolic Conditions – Increased or decreased levels of estrogens are seen in many metabolic conditions. However, care must be used in the interpretation of results because the levels vary on a day-to-day basis and throughout a woman’s menstrual cycle. Therefore it is important to look at trends over time in conjunction with the menstrual cycle or pregnancy rather than evaluating single test results [145].

Weight Gain – Sex hormones, such as estrogen, influence the amount of fat in the body. Estrogen regulates glucose and lipid metabolism. If your estrogen levels are low, it can result in weight gain. Being overweight can increase your risk of obesity, diabetes, and cardiovascular disease.

Mood – Depression and anxiety disorders are twice as common in women as in men, but the reason for this gender difference is unclear. Research from Harvard suggests that women are most at risk for symptoms when their estrogen is low [146].

In males gynecomastia or other signs of feminization may be due to an absolute or relative (in relation to androgens) surplus of estrogens. Gynecomastia is common during puberty in boys.

Reference Ranges for Estradiol:

Gender Conversion Units Optimal Risk
Men US Conventional Units pg/ml 10-40 <10 or >40
Women US Conventional Units pg/ml 37-147 <37 or >147
Men Standard International Units pmol/L 8.3-41.6 8.3-41.6
Women Standard International Units pmol/L 55-1285 <55 or >1285

Vitamins and Minerals

Vitamins and minerals are considered essential nutrients because acting in concert, they perform hundreds of roles in the body. They help strengthen bones, heal wounds, and bolster your immune system. They also convert food into energy, and repair cellular damage [65].

Vitamins

Vitamins are organic substances (made by plants or animals). There are two types of vitamins: fat-soluble and water-soluble. Fat-soluble vitamins (A,D,E & K) are found mainly in fatty foods and animal products, such as vegetable oils, dairy foods, eggs, liver, oily fish and butter. Unlike fat soluble vitamins, water soluble vitamins (B & C) are not stored in the body and therefore need to be eaten more frequently. Water soluble vitamins are found in a wide range of foods including fruits, vegetables and grains [66].

Vitamin D

Osteoporosis is most often associated with inadequate calcium intakes, but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption [72].

Rickets and osteomalacia are extreme examples of the effects of vitamin D deficiency.

A growing body of research suggests that vitamin D might play some role in the prevention and treatment of type 1 [73] and type 2 diabetes [74], hypertension [75], glucose intolerance [76], multiple sclerosis [77], and other medical conditions [78,79].

Vitamin D toxicity due to excess Vitamin D is rare, but can cause non-specific symptoms such as anorexia, weight loss, polyuria, and heart arrhythmias [67]. More seriously, it can also raise blood levels of calcium which leads to vascular and tissue calcification, with subsequent damage to the heart, blood vessels, and kidneys [68].

Reference Ranges for Vitamin D:

Conversion Units Optimal Borderline Risk
US Conventional Units ng/dl 30-99 20-30 <19 or >100
Standard International Units nmol/L 74-249 54-74 <54 or >249

Folate & RBC Folate

Cardiovascular disease – An elevated homocysteine level has been associated with an increased risk of cardiovascular disease. Folate and other B vitamins are involved in homocysteine metabolism and researchers have hypothesized that they reduce cardiovascular disease risk by lowering homocysteine levels [84].
Dementia, cognitive function, and Alzheimer’s disease – Most observational studies show positive associations between elevated homocysteine levels and the incidence of both Alzheimer’s disease and dementia. Some, but not all, observational studies have also found correlations between low serum folate concentrations and both poor cognitive function and higher risk of dementia and Alzheimer’s disease [84].
Depression – Low folate status has been linked to depression and poor response to antidepressants. In an ethnically diverse population study in the United States, folate concentrations were significantly lower in individuals with major depression than in those who had never been depressed. Results from a study of men and women with major depressive disorder showed that only 1 of 14 subjects with low serum folate levels responded to antidepressant treatment compared with almost 1 in 2 subjects with normal folate levels [84].
Cancer – Several epidemiological studies have suggested an inverse association between folate status and the risk of colorectal, lung, pancreatic, esophageal, stomach, cervical, ovarian, breast, and other cancers [84]. However, research has not established the precise nature of folate’s effect on carcinogenesis.

Neural tube defects (NTD’s) – NTDs result in malformations of the spine (spina bifida), skull, and brain (anencephaly). They are the most common major congenital malformations of the central nervous system and result from a failure of the neural tube to close at either the upper or lower end during days 21 to 28 after conception. The incidence of NTDs varies from 0.5 to 4.0 per 1,000 births in North America. Rates of spina bifida and anencephaly (the two most common types of NTDs) are highest among Hispanic women and lowest among African American and Asian women [84].

Due to its role in the synthesis of DNA and other critical cell components, folate is especially important during phases of rapid cell growth [84].

Vitamin B12

Cardiovascular disease – An elevated homocysteine level has been associated with an increased risk of cardiovascular disease. B12 along with B9 and B9 are involved in homocysteine metabolism and researchers have hypothesized that they reduce cardiovascular disease risk by lowering homocysteine levels. However, researchers do not know whether high homocysteine levels actually cause heart disease or if it is merely a marker for it [90].
Fatigue – Fatigue is one of the most widely reported symptoms of a vitamin B12 deficiency. Studies suggest that people with chronic fatigue syndrome might benefit from B12 injections [91]
Pernicious anemia – Pernicious anemia is a type of anemia that happens when stomach cells are not able to make intrinsic factor. Without intrinsic factor, your body cannot absorb vitamin B12 [91].

Reference Ranges for Vitamin B12:

Conversion Units Optimal Borderline Risk
US Conventional Units pg/ml 400-914 150-399 <150 or >914
Standard International Units pmol/L 295-675 111-674 <111 or >674

Ferritin

If a ferritin test reveals that your blood ferritin level is lower than normal, it indicates your body’s iron stores are low and you have iron deficiency. Iron deficiency is the most common nutritional deficiency and the leading cause of anemia in the world.

If a ferritin test shows higher than normal levels, it could indicate that you have a hereditary condition which causes your body to store too much iron [93]. However it is important to remember that elevated ferritin does not equal iron overload and there are many patients with elevated ferritin caused by inflammation [96]. High ferritin can also be a marker for liver disease, rheumatoid arthritis or hyperthyroidism [96].

Reference Ranges for Ferritin:

Gender Conversion Units Optimal Risk
Men US Conventional Units ug/L or mcg/L 23-400 <23 or >400
Women US Conventional Units ug/L or mcg/L 13-150 <13 or >150
Men Standard International Units ug/L or mcg/L 23-400 <23 or >400
Women Standard International Units ug/L or mcg/L 13-150 <13 or >150

Iron

Iron deficiency is the most common nutritional deficiency and the leading cause of anemia in the world. In the USA, despite food fortification, iron deficiency is on the rise in certain populations [99].

A low iron (serum) result with a high transferrin or total iron binding capacity is usually due to iron deficiency. Iron deficiency is usually due to long-term or heavy bleeding. However, it can also be due to increased iron requirements (in pregnancy), rapid growth (in children), poor diet, and problems with absorption (stomach or intestinal disease). If the iron-deficiency anemia is severe, shortness of breath, dizziness, chest pain, headaches, and leg pains may occur [99].

Iron overload is an excess iron in vital organs. Iron overload may increase the risk for liver disease (cirrhosis, cancer), heart disease, diabetes, osteoarthritis, osteoporosis, metabolic syndrome or hypothyroidism [99]. Iron overload can be inherited (genetic) or acquired by receiving numerous blood transfusions, getting iron shots or injections, or consuming high levels of supplemental iron. Some of the genetic disorders that result in iron overload include are hereditary hemochromatosis (all types), African iron overload, sickle cell disease, thalassemia, X-linked sideroblastic anemia, enzyme deficiencies (pyruvate kinase; glucose-6-phosphate dehydrogenase) and very rare protein transport disorders aceruloplasminemia and atransferrinemia [99].

Anemia of chronic disease – Some chronic diseases, like rheumatoid arthritis, inflammatory bowel disease, and some types of cancer—can interfere with the body’s ability to use its stored iron. Taking more iron from foods or supplements usually does not reduce the resulting anemia of chronic disease because iron is diverted from the blood circulation to storage sites. The main therapy for anemia of chronic disease is treatment of the underlying disease [100].

RBC Magnesium

Because of the number of functions that magnesium is involved in, being deficient in this mineral can have a number of implications for your health:

Heart Disease – Studies have found that higher serum levels of magnesium were significantly associated with a lower risk of cardiovascular disease, and higher dietary magnesium intakes (up to approximately 250 mg/day) were associated with a significantly lower risk of ischemic heart disease which is caused by a reduced blood supply to the heart muscle [104].

Type 2 diabetes – Diets with higher amounts of magnesium are associated with a significantly lower risk of diabetes, possibly because of the important role of magnesium in glucose metabolism. Magnesium deficiency may worsen insulin resistance, a condition that often precedes diabetes, or it might be a consequence of insulin resistance. Diabetes leads to increased urinary losses of magnesium, and the subsequent magnesium inadequacy may impair insulin secretion and action, thereby worsening diabetes control [104].

Osteoporosis – Magnesium is involved in bone formation and influences the activities of osteoblasts and osteoclasts. Several population-based studies have found positive associations between magnesium intake and bone mineral density in both men and women. Other research has found that women with osteoporosis have lower serum magnesium levels [104].
Migraine headaches – People who experience migraine headaches have lower levels of serum and tissue magnesium than those who do not. However, research on the use of magnesium supplements to prevent or reduce symptoms of migraine headaches is limited. Three of four small, short-term, placebo-controlled trials found modest reductions in the frequency of migraines in patients given up to 600 mg/day magnesium [104].

Reference Ranges for RBC Magnesium:

Conversion Units Optimal Risk
US Conventional Units mg/dl 4.2-6.6 <4.2 or >6.8
Standard International Units mmol/L 1.7-2.8 <1.7 or >2.8

Electrolytes (Potassium / sodium / chloride / CO2 / Magnesium / Calcium)

If we do not consume the necessary levels of electrolytes there can be health consequences. The most common imbalances are hypernatremia and hyponatremia (too much or too little sodium), and hyperkalemia and hypokalemia, (excessive and insufficient levels of potassium) [113].

An electrolyte imbalance can be manifested in several ways. The symptoms will depend on which electrolyte is out of balance, and whether that level is too high or too low.

An imbalance may produce one or more of the following symptoms:

  • Irregular heartbeat
  • Weakness
  • Bone disorders
  • Twitching
  • Blood pressure changes [113].

Blood

Blood consists of three types of cells suspended in fluid called plasma: white blood cells (WBCs), red blood cells (RBCs), and platelets (PLTs).

Complete Blood Count markers

The complete blood count (CBC) is a test that evaluates the cells that circulate in blood. Many conditions will result in an increases or decreases in the cell populations in your blood, meaning it is a good marker to look for potential issues, however further tests are usually required to look for specific conditions and underlying causes [151].

Red Cell Count

The typical lifespan of an RBC is 120 days; thus the bone marrow must continually produce new RBCs to replace those that age and degrade or are lost through bleeding. There are a number of conditions that can affect the production of new RBCs and/or their lifespan, in addition to those conditions that may result in significant bleeding. These conditions may lead to a rise or drop in the RBC count.

Changes in the RBC count usually mirror changes in the hematocrit and hemoglobin level. When the values of the RBC count, hematocrit, and hemoglobin decrease below the established reference interval, the person is said to be anemic. When the RBC and hemoglobin values increase above the normal range, the person is said to be polycythemic.

If the liquid component of the blood (plasma) is decreased, as in dehydration, the red blood cell count increases. This is due to the red blood cells becoming more concentrated. The actual number of red blood cells stays the same.

Too few RBCs can affect the amount of oxygen reaching the tissues, while too many RBCs can cause decreased blood flow and related problems.

While an RBC count can be used to detect a problem with red blood cell production and/or lifespan, it cannot determine the underlying cause [148].

Reference Ranges for Red Cell Count:

Gender Conversion Units Optimal Risk
Men US Conventional Units x10E6/uL = x10^12/L 4.3-5.72 <4.3 or >5.72
Women US Conventional Units x10E6/uL = x10^12/L 4.3-5.72 <4.3 or >5.72
Men Standard International Units x10E6/uL = x10^12/L 4.3-5.72 <4.3 or >5.72
Women Standard International Units x10E6/uL = x10^12/L 3.9-5.03 <3.9 or >5.03

Hemoglobin

Several diseases and conditions can affect RBCs and consequently the level of haemoglobin and haematocrit in the blood.

In general, the hemoglobin level and hematocrit rise when the number of red blood cells increases. The hemoglobin level and hematocrit fall to less than normal when there is a drop in production of RBCs by the bone marrow, an increase in the destruction of RBCs, or if blood is lost due to bleeding. A drop in the RBC count, hemoglobin and hematocrit can result in anemia, a condition in which tissues and organs in the body do not get enough oxygen, causing fatigue and weakness. If too many RBCs are produced, polycythemia results and the blood can become thickened, causing sluggish blood flow and related problems [148].

Reference Ranges for Hemoglobin:

Conversion Units Optimal Risk
US Conventional Units g/dl 13-17.5 <13 or >17.5
Standard International Units g/dl 13-17.5 <13 or >17.5

Hematocrit (HCT)

Several diseases and conditions can affect RBCs and consequently the level of haemoglobin in the blood and haematocrit.

In general, the hemoglobin level and hematocrit rise when the number of red blood cells increases. The hemoglobin level and hematocrit fall to less than normal when there is a drop in production of RBCs by the bone marrow, an increase in the destruction of RBCs, or if blood is lost due to bleeding. A drop in the RBC count, hemoglobin and hematocrit can result in anemia, a condition in which tissues and organs in the body do not get enough oxygen, causing fatigue and weakness. If too many RBCs are produced, polycythemia results and the blood can become thickened, causing sluggish blood flow and related problems [148].

Reference Ranges for Hematocrit:

Conversion Units Optimal Risk
US Conventional Units % 38.8-50 <38.8 or >50
Standard International Units % 38.8-50 <38.8 or >50

Red blood cell indices (MCV / MCH / MCHC / RDW)

Below are some of the types of anemia indicated by results for the different indices:

MCV below normal – Microcytic anemia (may be due to low iron levels, lead poisoning, or thalassemia).

MCV normal – Normocytic anemia (may be due to sudden blood loss, long-term diseases, kidney failure, aplastic anemia, or man-made heart valves).

MCV above normal – Macrocytic anemia (may be due to low folate or B12 levels, or chemotherapy).

MCH below normal – Hypochromic anemia (often due to low iron levels).

MCH normal – Normochromic anemia (may be due to sudden blood loss, long-term diseases, kidney failure, aplastic anemia, or man-made heart valves).

MCH above normal – Hyperchromic anemia (may be due to low folate or B12 levels, or chemotherapy) [152].

Generally, a low MCV and a low MCHC will be found together. Anemias in which both MCV and MCHC are low are called microcytic, hypochromic anemia [153].

White Cell Count

A WBC count can indicate that there is a disease or condition affecting white blood cells, but it cannot determine the underlying cause. In addition to infections and inflammation, there are a number of conditions that can affect the production of WBCs by the bone marrow or the survival of WBCs in the blood,

Some diseases trigger a response by the immune system and cause an increase in the number of WBCs. Other conditions affect the production of WBCs by the bone marrow or the survival of WBCs in the circulation, resulting in either an increase or decrease in the number of circulating WBCs [155].

There are five types of WBCs, and these are generally measured in isolation as well as part of the white blood cell analysis: Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.

Reference Ranges for White Cell Count:

Conversion Units Optimal Risk
US Conventional Units x10E6/uL = x10^9/L 3.5-10.5 <3.5 or >10.5
Standard International Units x10E6/uL = x10^9/L 3.5-10.5 <3.5 or >10.5

Platelet Count

Platelets survive in the circulation about 8 to 10 days, and the bone marrow must continually produce new platelets to replace those that degrade, are used up, and/or are lost through bleeding. Determining the number of platelets in blood with a platelet count can help diagnose a range of disorders having to do with too few or too many platelets.

An excess of platelets can cause excessive clotting or sometimes bleeding if the platelets are not functioning properly.

Reference Ranges for Platelet:

Conversion Units Optimal Risk
US Conventional Units x10E6/uL = x10^9/L 150-450 <150 or >450
Standard International Units x10E6/uL = x10^9/L 150-450 <150 or >450

Bone Health

Bones play many roles in the body — providing structure, protecting organs, anchoring muscles and storing calcium. While it’s important to build strong and healthy bones during childhood and adolescence, you can take steps during adulthood to protect bone health, too [116]. Maintaining healthy levels of calcium, vitamin D are both key to maintaining healthy bones.

Vitamin D – See Vitamins & Minerals section above

Calcium

Bone health and osteoporosis – When calcium intake is low or ingested calcium is poorly absorbed, bone breakdown occurs as the body uses its stored calcium to maintain normal biological functions. Bone loss also occurs as part of the normal aging process, particularly in postmenopausal women due to decreased amounts of estrogen. Many factors increase the risk of developing osteoporosis, including being female, thin, inactive, or of advanced age; smoking cigarettes; drinking excessive amounts of alcohol; and having a family history of osteoporosis [106].
Blood pressure and hypertension – Several clinical trials have demonstrated a relationship between increased calcium intakes and both lower blood pressure and risk of hypertension [98-100]. In hypertensive subjects, calcium supplementation appears to lower systolic blood pressure by 2–4 mmHg, whereas calcium appears to have no significant effect on blood pressure where it is already in the normal range [106].
Preeclampsia – Preeclampsia is a serious medical condition in which a pregnant woman develops hypertension and proteinuria, usually after 20 weeks’ gestation. It is a leading cause of maternal and neonatal morbidity and mortality, affecting about 5–8% of pregnancies in the United States and up to 14% of pregnancies worldwide. Studies suggest that calcium supplementation during pregnancy reduces the risk of preeclampsia [106].
Weight management – Several studies have linked higher calcium intakes to lower body weight or less weight gain over time. Two explanations have been proposed. First, high calcium intakes might reduce calcium concentrations in fat cells by decreasing the production of parathyroid hormone and the active form of vitamin D. Decreased intracellular calcium concentrations in turn increase fat breakdown and discourage fat accumulation in these cells. Secondly, calcium from food or supplements might bind to small amounts of dietary fat in the digestive tract and prevent its absorption. Dairy products, in particular, might contain additional components that have even greater effects on body weight than their calcium content alone would suggest [106].
Health Risks from Excessive Calcium – Excessively high levels of calcium in the blood known as hypercalcemia can cause renal insufficiency, vascular and soft tissue calcification, hypercalciuria (high levels of calcium in the urine) and kidney stones [106].

Reference Ranges for Calcium:

Conversion Units Optimal Risk
US Conventional Units mmol/L or mEq/L 2.2-2.6 <2.2 or >2.6
Standard International Units mmol/L or mEq/L 2.2-2.6 <2.2 or >2.6

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