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Total Protein
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Total Protein

The total protein blood test is an essential marker for assessing nutritional status and overall health; it can also inform the diagnosis and prognosis of various medical conditions. 

The total protein blood test measures the concentration of proteins in the blood, encompassing both albumin and globulin fractions; albumin and globulin are the first and second most prevalent proteins in the bloodstream.

Proteins are vital in human health, serving as building blocks for tissues, enzymes, hormones, and antibodies. Albumin maintains osmotic pressure, while globulins contribute to immune function and transport proteins.

Dietary sources of protein include both animal and plant-based foods such as meat, poultry, fish, dairy products, legumes, nuts, and seeds.  A balance of healthy protein sources is essential for overall health and wellness.

This article provides comprehensive insights into the definition, function, interpretation, and significance of total protein levels in the bloodstream, along with related factors such as dietary sources and natural ways to optimize levels.

Definition: What is the Total Protein Test?

The total protein blood test measures the amount of albumin and globulin present in the bloodstream.  Albumin and globulin are the two most abundant types of protein present in the human bloodstream.  

Albumin is a water-soluble protein, constituting about half of the total protein content in healthy human plasma (3.5 g/dL to 5 g/dL).  It is synthesized in the liver hepatocytes and swiftly enters the bloodstream. 

As the most abundant protein in the blood, albumin is a modulator of plasma oncotic pressure and a carrier for both endogenous and exogenous substances, including drugs. Serum albumin levels are utilized in clinical medicine as markers of an individual's nutritional status and liver function, offering insights into the body's ability to synthesize essential proteins and maintain overall homeostasis. 

Globulin proteins represent a diverse group of proteins found in the blood plasma and bodily fluids, playing essential roles in various physiological processes. Globulins are the second most abundant type of protein in the blood in humans, after albumin.  

Comprising several subclasses, including alpha, beta, and gamma globulins, they exhibit diverse structures and functions. 

Globulins are primarily synthesized in the liver and immune cells.  

Globulins are further characterized as alpha-1, alpha-2, beta, and gamma globulins.  

Alpha Globulins: 

Alpha globulins are a group of plasma proteins that include transport proteins such as alpha-1 antitrypsin, haptoglobin and ceruloplasmin.  They contain lipoproteins involved in lipid transport.  

Overall, alpha globulins contribute to immune function, enzyme regulation, and lipid transport in the body.

Beta Globulins: 

Beta globulins comprise a heterogeneous group of plasma proteins with diverse functions. These proteins include transferrin and complement proteins involved in the immune response against pathogens. 

Additionally, beta globulins encompass lipoproteins involved in lipid transport.  

Gamma Globulins: 

Gamma globulins, also known as immunoglobulins or antibodies, are key components of the immune system. These proteins include IgG, IgA, IgM, IgD, and IgE, each with distinct roles in humoral immunity.

Under normal conditions, all proteins in the body are synthesized from dietary proteins.  Malnutrition or severe digestive dysfunction may cause a decrease in protein levels which can have serious consequences for health.  

Function of Total Proteins: What Do Proteins Do in the Body?

Protein function is heavily determined by its structure.  Proteins are composed of various combinations of 20 common amino acids that act as structural components, enzymes, hormones, and more. 

Proteins exhibit four structural levels: primary, secondary, tertiary, and quaternary. Peptide bonds form between amino acids to create proteins, while disulfide bonds contribute to their stability.

Proteins facilitate transportation within cells, including secretory, lysosomal, and regulated pathways, each serving distinct functions such as constitutive secretion and lysosomal enzyme transport. Additionally, proteins play pivotal roles in biochemical reactions as enzymes, lowering the activation energy required for reactions to occur.

Amino Acids: The Building Blocks of Proteins

Amino acids, the building blocks of proteins, are categorized as non-essential, conditionally essential, or essential. Non-essential amino acids can be obtained from food or synthesized in the body. Conditionally essential amino acids are typically synthesized by healthy bodies but become essential under certain conditions. 

Essential amino acids must be obtained from the diet as the body cannot produce them. 

The Five Non-Essential Amino Acids

  • Alanine
  • Asparagine
  • Aspartic acid 
  • Glutamic acid 
  • Serine 

The Six Conditionally-Essential Amino Acids

  • Arginine
  • Cysteine 
  • Glutamine
  • Glycine
  • Proline
  • Tyrosine

The Nine Essential Amino Acids

  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Valine

Dietary Sources of Protein

Protein is available in animal- and plant-based foods.  A common misconception is that plant foods do not contain protein, or that they do not contain all 20 amino acids.  All plant foods contain all 20 amino acids, although in different proportions than animal foods.  [3.] 

Common sources of proteins include:

Animal Sources of Protein:

  • Chicken
  • Turkey
  • Beef
  • Pork
  • Lamb
  • Fish (such as salmon, tuna, and cod)
  • Shellfish (such as shrimp, crab, and lobster)
  • Eggs
  • Dairy products (such as milk, cheese, and yogurt)

Plant Sources of Protein:

  • Legumes (such as lentils, chickpeas, and black beans)
  • Soy products (such as tofu, tempeh, and edamame)
  • Quinoa
  • Seitan
  • Nuts (such as almonds, walnuts, and peanuts)
  • Seeds (such as chia seeds, flaxseeds, and pumpkin seeds)
  • Whole grains (such as brown rice, oats, and barley)
  • Spirulina
  • Leafy greens (such as spinach, kale, and broccoli)
  • Peas

Recommended Protein Intake 

The US Dietary Reference Intakes (DRIs), last updated in 2005, provide guidelines for protein intake, categorized into the Estimated Average Requirement (EAR) and Recommended Dietary Allowances (RDAs). The RDA is set to meet or exceed the requirements of 97.5% of the population, typically calculated as the EAR plus 2 standard deviations. 

For adults aged 18 and older, the EAR is 0.66 g/kg of body weight, while the RDA is 0.8 g/kg of body weight.  

In some situations, including growing children, physically active adults, and pregnant and lactating people, protein needs may be higher.  Alternatively, in some situations, for example in chronic kidney disease, protein requirements may be lower.  [10.] 

Lab Testing for Total Protein Levels

Knowing an individual’s protein status provides valuable insights into overall health status and aids in the detection and monitoring of various medical conditions.

Total Protein Blood Test: Procedure and Purpose

The total protein blood test is a routine diagnostic procedure that measures albumin levels in serum or plasma.  The total protein test is part of routine blood work called a comprehensive metabolic panel.  

Testing involves drawing a blood sample from a vein.  Fasting is typically required.

Increasingly, specialized testing companies are offering advanced protein testing to assess levels of specific amino acids in the bloodstream or urine, which may be beneficial for athletes, individuals wanting to optimize their health, as well as people struggling with metabolic or mental health concerns.  

Click here to explore examples of amino acid testing. 

Interpreting Total Protein Test Results

Reference Range for Total Protein Levels

It is important to consult individual labs for reference ranges used.  The reference range for total protein from one lab is given as 6.0-8.5 g/dL.  [1.]

Clinical Significance of High Levels of Total Protein  [1., 2., 7.]

Dehydration: dehydration reduces the volume of plasma and increases the concentration of proteins in the blood.

Chronic liver diseases: chronic active hepatitis and cirrhosis can lead to elevated total protein levels.

Neoplasms: neoplasms, particularly multiple myeloma and macroglobulinemia of Waldenström, can cause high total protein levels.

Tropical diseases: certain tropical diseases such as kala-azar and leprosy, as well as granulomatous diseases like sarcoidosis, may contribute to elevated protein levels.

Chronic infections or chronic inflammation: diseases including collagen diseases like systemic lupus erythematosus (SLE), can result in high total protein levels.

Some viral infections: Hepatitis B, Hepatitis C can cause elevations in protein levels.  

[9.]

Monoclonal Gammopathies and Multiple Myeloma: these can also cause elevated total protein levels.

Clinical Significance of Low Levels of Total Protein [1., 4., 6., 8.]

There can be many reasons for low protein levels in blood tests.  Major causes include: 

Liver disease: cirrhosis, hepatitis, liver failure, chronic alcoholism, and other liver conditions can impair protein synthesis, especially albumin, the most prevalent protein in the blood.

Overhydration: rapid overhydration can cause a temporary decrease in protein concentration.

Malnutrition: inadequate dietary protein intake or malabsorption disorders can lead to low protein levels.

Kidney disease: nephrotic syndrome, a condition where the kidneys leak protein into the urine, can decrease protein levels.

Gastrointestinal disorders: conditions such as Crohn's disease, celiac disease, and inflammatory bowel disease can interfere with protein absorption.

Protein-losing enteropathy: disorders affecting the gastrointestinal tract such as intestinal infections or lymphatic obstruction can cause protein loss.

Severe burns: extensive burns can lead to fluid loss and decreased protein levels, particularly albumin.

Proteinuria: excessive protein loss through the urine, often associated with kidney disease or certain medications, can result in low protein levels.

Acute infections or inflammation: conditions such as sepsis, burns, trauma, or chronic inflammatory diseases can cause a temporary decrease in protein due to increased demand or redistribution.

Congestive heart failure: fluid overload and dilutional effects can lead to decreased protein concentrations, especially albumin.

Excessive diuresis: overuse of diuretic medications can lead to increased excretion of protein.

Medications: certain drugs can affect albumin synthesis or metabolism.

Genetic disorders: rare genetic conditions affecting albumin production or metabolism can lead to low levels.  Additionally, Wilson’s disease can cause low albumin levels, affecting the total protein levels in the blood.  

Chronic illnesses: long-term diseases such as cancer, HIV/AIDS, thyroid disease, and autoimmune disorders can contribute to low albumin due to increased metabolic demands or inflammation.

Pregnancy: Albumin levels may decrease during pregnancy due to physiological changes and increased demand for nutrients.

Natural Ways to Optimize Protein Levels

Maintaining Healthy Protein Levels

Maintaining optimal protein levels is essential for overall health and well-being. To maintain optimal albumin levels, a multifaceted approach is often necessary. Firstly, treating the cause of low or high albumin levels is necessary and may warrant medical interventions.  

Additionally, dietary interventions, appropriate hydration, and healthy digestion are essential.

How to Raise Protein Levels

Consuming a well-balanced diet rich in protein is recommended. Foods high in protein include lean meats, poultry, fish, eggs, dairy products, legumes, nuts, and seeds. Additionally, incorporating foods rich in essential amino acids such as lysine and methionine, can support albumin synthesis in the body.

Individuals who are struggling to meet their dietary protein needs may consider supplementing with a high-quality protein powder.  

In some cases, medical treatments are necessary to increase albumin levels. Healthcare providers may prescribe albumin infusions or administer medications to address underlying medical conditions contributing to hypoalbuminemia, such as liver or kidney disease.

How to Lower Protein Levels

Maintaining adequate hydration is important for supporting albumin blood concentration and maintaining blood volume. Encouraging patients to drink sufficient fluids, such as water, herbal teas, and electrolyte-rich beverages, can help prevent dehydration and support overall health.

Order Total Protein Testing

Click here to compare testing options and order total protein testing as part of a comprehensive metabolic panel.  

Click here to explore examples of amino acid testing. 

What's 
Total Protein
?
Total Protein is a way to measure all the proteins in your blood, which are the building blocks of your body. These proteins, made up of amino acids, have many important jobs. They help fix and build tissues, create antibodies to fight infections, control enzymes and hormones, and keep the right balance of fluids in your body. There are two main types of proteins: albumin and globulin. Albumin stops fluid from leaking out of blood vessels, while globulins are crucial for your immune system and blood clotting processes. In short, Total Protein gives an overview of your overall nutrition and the health of your liver and kidneys, which are in charge of making and managing proteins.
If Your Levels Are High
Elevated Total Protein levels might mean that your body is making more proteins than usual. This can happen for various reasons, such as not having enough water in your body, which makes the proteins in your blood more concentrated. It could also be a reaction to certain medications or a sign that your body is trying to fight off an infection or inflammation since proteins are important for your immune system. Sometimes, it could mean that your liver or kidneys, which help control protein levels, are working harder than they should be. Keep in mind that these are just some possible reasons for high Total Protein levels, and other factors might also be involved.
Symptoms of High Levels
Symptoms of high levels of Total Protein may not be easily noticeable as they can be quite general. However, they could include fatigue, loss of appetite, weight loss, or swelling in your hands, feet, or abdomen due to fluid retention.
If Your Levels are Low
Low Total Protein levels might mean that your body isn't getting enough protein from your diet, or it's having trouble absorbing and digesting proteins properly. Certain medications, like those for heartburn or acid reflux, could also affect how well your body processes proteins. Low levels could also point to issues with your liver or kidneys, since they're responsible for making and managing proteins in your body. Conditions like liver disease or kidney disorders might be causing these low protein levels. It's worth noting that drinking too much alcohol can also impact your liver's ability to function properly, which could affect your protein levels.
Symptoms of Low Levels
Symptoms of low levels of Total Protein might include fatigue, weight loss, muscle weakness, and frequent infections due to a weakened immune system.

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See References

[1.] 001073: Protein, Total | Labcorp. www.labcorp.com. Accessed April 9, 2024. https://www.labcorp.com/tests/001073/protein-total

[2.] DynaMedex. www.dynamedex.com. Accessed April 9, 2024. https://www.dynamedex.com/lab-monograph/serum-total-protein-measurement#GUID-07323C49-6593-4CE6-8038-F5347786F6BB

[3.] Gardner CD, Hartle JC, Garrett RD, Offringa LC, Wasserman AS. Maximizing the intersection of human health and the health of the environment with regard to the amount and type of protein produced and consumed in the United States. Nutrition Reviews. 2019;77(4):197-215. doi:https://doi.org/10.1093/nutrit/nuy073 

[4.] Gounden V, Vashisht R, Jialal I. Hypoalbuminemia. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526080/

[5.] LaPelusa A, Kaushik R. Physiology, Proteins. [Updated 2022 Nov 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555990/ 

[6.] Małgorzata Godala, Ewelina Gaszyńska, Walczak K, Małecka-Wojciesko E. Evaluation of Albumin, Transferrin and Transthyretin in Inflammatory Bowel Disease Patients as Disease Activity and Nutritional Status Biomarkers. Nutrients. 2023;15(15):3479-3479. doi:https://doi.org/10.3390/nu15153479   

[7.] Mayo Clinic Staff. High blood protein Causes. Mayo Clinic. Published 2018. https://www.mayoclinic.org/symptoms/high-blood-protein/basics/causes/sym-20050599 

[8.] Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enteral Nutr. 2019 Feb;43(2):181-193. doi: 10.1002/jpen.1451. Epub 2018 Oct 4. PMID: 30288759; PMCID: PMC7379941. 

[9.] TOMASI, T., TISDALE, W. Serum Gamma-globulins in Acute and Chronic Liver Diseases. Nature 201, 834–835 (1964). https://doi.org/10.1038/201834a0

[10.] Wu G. Dietary Protein Intake and Human Health. Food & Function. 2016;7(3):1251-1265. doi:https://doi.org/10.1039/c5fo01530h

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