An enormous opportunity to spot and potentially prevent health problems early is lying right under our noses ... hidden clues in the results of standard blood tests like the Complete Blood Count (CBC) and Comprehensive Metabolic Panel (CMP).

These are the blood tests that conventional medical doctors order first and most often in most situations. These tests provide a broad overview of things like the immune system, liver and kidney function, and metabolic health. 

Most doctors interpret the results of these tests according to the standard "normal" reference ranges that are established by the lab performing the tests (most commonly LabCorp or Quest Diagnostics in the United States). The normal reference range for each blood marker is set to automatically include all values that occur within two "standard deviations" of the mean (average) value for that blood marker. Two standard deviations works out to be 95% of the entire range of values for each blood marker. This means that these "normal" reference ranges are based on the test results of 95% of the people using the lab for testing. 

Do you see a potential issue here?

Most of the population has. or is in the process of developing, one or more degenerative diseases. Yet their blood tests results are determining the top and bottom ends of the standard "normal" reference ranges for the blood marker values on your test results. And these standard "normal" reference ranges are constantly changing because the population is getting less and less healthy.

When blood test markers are interpreted according to standard "normal" reference ranges, early clues of illness are missed, and illnesses are diagnosed late in their development. If instead you would want to spot potential issues long before you have a disease, you would want your lab test results to be interpreted according to  "functional ranges" for blood markers instead of the standard reference ranges.

So it's up to you or a more functionally-oriented health practitioner to look for clues on your standard blood work about potential issues like these:

1. Hidden infections
2. Disease processes in the liver, kidneys, bones, and other tissues
3. Subclinical deficiencies in certain minerals and B vitamins
4. Elevated demand for glutathione (a sign of oxidative stress and/or toxicity) and/or problems with glutathione recycling

Hidden Infection Clues in the Complete Blood Count (CBC)

For hidden infections, you can look on your Comprehensive Blood Count (CBC) test at the total white blood cells (WBC) and some of the individual types of white blood cells, including neutrophils, lymphocytes, monocytes, and eosinophils.

Ideally, you would have a CBC with "differential", which means that it calculates the percentages of each type of white blood cell.

The functional range for WBCs is around 4,400 to 5,700. If your WBCs are higher than around 5,700 cells per microliter, your body is probably dealing with some kind of infection, typically a hidden and subtle one if you are not aware of it.

Sometimes the infection is something like Chlamydaphila pneumoniae infecting the endothelium of the blood vessels and gradually generating arterial disease and perhaps microvascular disease in the eyes that cause cataracts and glaucoma.

But mainstream doctors don't think anything is abnormal in your WBC count until it gets above 11,000 or 12,000. By that time, you could be in serious trouble.

If your percent neutrophils is much higher than 60% (say 70% or higher), that could suggest an infection, usually bacterial or fungal.

If your percent lymphocytes is much higher than 30% (say 40% or higher), that could suggest an ongoing infection with (or reactivation of) a virus such as long COVID (or Epstein Barr virus).

The ratio of neutrophils to lymphocytes (N:L ratio) is an even more sensitive way of looking for clues about hidden infections. If you divide neutrophils by lymphocytes and get a number of around 3 or higher, that probably indicates a bacterial or fungal infection.

One example of a hidden infection that could raise the N:L ratio is bacteria growing in the jawbone where a tooth (e.g. wisdom tooth) was extracted, or at the base of a root canal, or around an implant. These jawbone infections usually do not create any local symptoms because there are very nerves in the jawbone.

This is well-known in European Bioregulatory medicine but almost completely unknown to conventional medicine in the United States. Even functional medicine doctors in the United States usually do not have this issue on their radar, yet it is affecting the vast majority of their patients since up to 88% of tooth extractions (depending on the tooth's location in the mouth) and 90% of root canals are associated with jawbone cavitations (R).

If you divide neutrophils by lymphocytes and get a number of around 1.0 or lower, it could indicate a viral issue (e.g. long COVID or Epstein Barr).

If your MCV (mean corpuscular volume) is above 95 fL, this is could be due to low folate or B12, hypothyroidism, or liver disease. Slightly elevated MCV could be an early sign of a trend toward macrocytic anemia that can sometimes be seen before there is an appreciable drop in hemoglobin or hematocrit.

Full macrocytic anemia is diagnosed once MCV exceeds 100 fL and hemoglobin and hematocrit drop to 12 g/dL and 36% in women or 13 g/dL and 41% in males.

Organ Disease Clues Hidden in the Comprehensive Metabolic Panel (CMP)

The Comprehensive Metabolic Panel (CMP) provides clues about the health of your heart, liver, gallbladder, intestines, bones, and more.

When enzymes on the CMP like AST, ALT, alkaline phosphatase (ALP), and GGT are elevated, it can reveal that tissue damage is occurring in various organs. GGT is an enzyme that is not usually on the CMP but can easily be added as an additional marker, so request it from your doctor the next time they order a CMP for you.

The functional range on AST, ALT, and GGT is between 10 and 30 U/L, but disease processes can be occurring even when these are within the functional range. For example, enzymes often remain unaffected in the early stages of fatty liver disease.

And I would say that AST and/or ALT much above 20 (e.g. mid 20s or higher) probably suggests at least some degree of liver, biliary tree, and/or gallbladder congestion (cholestasis). The biliary tree is the network of canals within the liver that channel bile manufactured in the liver to the gallbladder, which temporarily stores and concentrates bile prior to secretion as part of the digestive process.

AST is present in highly metabolically active tissues such as skeletal muscle, liver, heart, kidneys, and lungs.

ALT is most highly present in the liver, and less so in the muscle, heart, and kidneys.

GGT is highest in the liver and biliary tree epithelial cells and lower in the kidneys, prostate, and pancreas.

The differences in distribution of AST, ALT, and GGT make elevations of AST more specific to heart problems, elevations of ALT more specific to liver problems, and elevations of GGT more specific to kidney, pancreas and/or biliary tree problems.

In other words ...

If AST is higher than ALT and GGT, this suggests cardiovascular problems.

If ALT is higher than AST and GGT, this suggests liver problems.

If GGT is higher than AST and ALT, this suggests kidney, pancreas, or biliary tree problems.

ALP (alkaline phosphatase) originates in the bone, liver, intestines, skin, and placenta.

The functional range of alkaline phosphatase (ALP) is around 70-90 U/L.

If ALP is above 100, an ALP "isozyme study" should be conducted to identify the ALP isozyme that is elevated, which indicates the type of tissue (bone, liver, intestines, skin, or placenta) that is generating the elevated ALP.

To summarize:

1. AST is most prevalent in the heart, ALT in the liver, and GGT in the kidneys, pancreas, and biliary tree.
2. If AST is higher than the others, consider heart problems.
3. If ALT is higher than the others, consider liver problems.
4. If GGT is higher than the others, consider kidney, pancreas, or biliary tree problems.
5. The functional ranges for AST, ALT, and GGT are 10-30 U/L, but disease can occur within these ranges (e.g. early stages of fatty liver disease).
6. I view ALT into the mid 20s as a possible sign of mild to moderate liver and bile stagnation (cholestasis).
7. ALP is most prevalent in bone, liver, intestines, skin, and placenta.
8. The functional range of ALP is around 70-90 U/L.
9. ALP above 100 should be followed up by an ALP "isozyme study" to determine which isozyme from which tissue is at issue.

Clues About Nutrient Status Hidden in Your CMP Test Results

The enzymes on the CMP can also shed light on the status of nutrients like vitamin D, zinc, magnesium, and vitamin B6.

ALP above 100 could be caused by excess vitamin D consumption.

ALP below 45 could indicate zinc or magnesium deficiency, or low thyroid or adrenal function.

AST, ALT, and GGT below 10 could indicate B6 deficiency.

Clues like these should be followed up with nutrient testing. Don't make decisions about supplements based solely on clues you might see in these markers from a CMP test.

A Clue in the CMP About the Status of Glutathione, the Body's "Master Antioxidant" and Detoxifying Agent

GGT can also shed light on the status of your body's "master antioxidant", glutathione. In addition to functioning as an antioxidant, glutathione gets used in "phase 2" detoxification processes to "conjugate" (bind to) many types of toxins (e.g. mold toxins) and toxicants (e.g. heavy metals) to facilitate their excretion from the body. This occurs mostly in the liver and kidneys.

In the process of performing its various roles, glutathione loses electrons and becomes "oxidized". "Oxidation" is the loss of electrons. Something that has lost electrons is called "oxidized".

"Reduction" is the process of an electron being added to something. Something that has gained electrons is called "reduced". The functional form of glutathione that can act as an antioxidant and as a conjugating agent in phase 2 detox processes is "reduced" glutathione.

GGT disassembles "oxidized" glutathione so that its constituent amino acids (cysteine, glutamic acid, and glycine) can be re-used to form glutathione again. Some people call GGT's disassembly of glutathione "recycling", but it's not the same type of recycling that is done by another enzyme called glutathione reductase (GSR) that adds electrons back to oxidized glutathione to make it "reduced" glutathione again.

Glutathione that lost an electron and thereby became "oxidized" can be "reduced" back to "reduced" glutathione by the glutathione reductase (GSR) enzyme. Recycling of oxidized glutathione back to reduced glutathione by GSR just requires adding electrons and does not require completely disassembling glutathione like GGT does.

But if GSR isn't keeping up with the job of reducing oxidized glutathione back to reduced glutathione, this increases demand on GGT to disassemble glutathione so that its amino acids can be reassembled back into reduced glutathione. This increased demand on GGT raises production of GGT to handle the extra work load, so GGT ends up being higher on blood tests.

According to a study published in 2016, "Increased GGT activity is a marker of antioxidant inadequacy and increased oxidative stress. Ample evidence suggests that elevated GGT activity is associated with increased risk of cardiovascular disease (CVD) such as coronary heart disease (CHD), stroke, arterial hypertension, heart failure, cardiac arrhythmias and all-cause and CVD-related mortality." (R)

From a functional perspective, if GGT is above 17 on a blood test, oxidative stress and/or toxicity is causing glutathione to be oxidized or otherwise damaged at a higher than healthy rate. Or, glutathione reductase (GSR) might be operating in an inefficient manner, requiring GGT to take up the slack.

There are three main reasons that the GSR enzyme could be operating inefficiently. First, the GSR gene that codes for the GSR enzyme is often affected by genetic polymorphisms (SNPs) that reduce its function. I often see this when I analyze the DNA of people who have had long term health challenges, which are often associated with genetic impairments in detoxification processes.

Second, in order to do its job, the GSR enzyme requires a cofactor derived from vitamin B2 (riboflavin). So B2 deficiency could slow down GSR and raise GGT. 

Third, GSR also needs electrons from NADPH, the main electron donor in the body. But NADPH often gets depleted by various disease processes, impairing GSR's ability to recycle oxidized glutathione. NADPH gets depleted by a wide variety of factors, some of which include the following:

• Chronic infections (e.g. Lyme disease, viruses)
• Chronic inflammation (mediated by histamine, NF-kB, interleukin-6, TNF-alpha)
• Lipopolysaccharide (LPS) entering the bloodstream as a result of intestinal dysbiosis and hyperpermeability
• Mercury
• Mycotoxins
• Airborne particular matter
• Sulfite
• Oxalate
• Stress
• High levels of dopamine
• Elevated homocysteine
• High blood pressure mediated by elevated aldosterone
• Deficiencies of thiamine (vitamin B1) and/or magnesium

To summarize, oxidative stress and toxicity increase the demand for glutathione, and individual genetics, riboflavin deficiency, or NADPH deficiency caused by a wide range of other factors slow down the recycling of oxidized glutathione by GSR, all of which can elevate GGT as a signal of these potential issues. 

Catching Insulin Resistance and Metabolic Disease Earlier with a Few Additional Blood Markers

Aside from missing clues  hidden in standard blood work, opportunities to catch disease processes early on are also missed when a few additional blood markers are not ordered that could be included every time a CMP is ordered. 

Metabolic disease (i.e. insulin resistance and diabetes), which is one of the main causes of heart disease, Alzheimer's disease, and other neurodegenerative diseases, can be developing long before you have elevated fasting glucose on a CMP. And this can be spotted by simply ordering a few additional markers like hemoglobin A1C (HbA1C), fasting insulin, and/or C-peptide.

HbA1C measures the degree of "glycation" (attachment of sugars) to hemoglobin in your red blood cells, which is an indirect measure of the average level of blood glucose over the lifespan of red blood cells, which is usually 90 days. Fortunately, many conventional doctors are beginning to order this blood marker.

However, although HbA1C is a better tool than fasting glucose for screening for insulin resistance, people are likely to have developed significant insulin resistance and pancreatic beta-cell dysfunction by the time HbA1C rises significantly (R, R). 

Early in the process of the development of insulin resistance, pancreatic beta cells increase production of insulin, so fasting insulin levels could identify insulin resistance long before plasma glucose and HbA1c levels rise. This makes fasting insulin a more sensitive marker of insulin resistance than fasting glucose or HbA1C. 

However, fasting insulin is not a perfect indicator of insulin production because after the pancreas releases insulin, the liver clears much of it from the bloodstream on the first pass through the liver. So insulin is not the most reliable indicator of insulin secretion by the pancreas. 

C-peptide is a more reliable indicator of insulin secretion because it is not cleared by the liver. And C-peptide has a longer half-life than insulin (30 minutes for C-peptide versus 4 minutes for insulin). However, reference ranges may need to be adjusted by race since C-peptide values and ratios of fasting C-peptide to fasting insulin have been found to be significantly lower in African Americans compared to Mexican Americans and white Americans (R).

What Will You Do With This Information?

If you're serious about your health, dig out your past CBCs and CMPs to look for any of the hidden clues discussed in his article, or if you would like somebody to do that for you, feel free to connect with us at Bio-Individual Wellness. 

You can learn more about our approach by downloading the Bio-Individual Blueprint Roadmap and watching the walkthrough video. If you have already done that, you can schedule a free 15-minute or 45-minute consultation.