The Right Way to Implement and Assess Lab Testing

Most people trying to figure out how to optimize metabolism are looking at the wrong numbers. Standard lab panels catch inflammatory markers and cholesterol, but those are outcomes, not causes. While helpful, a deep dive into advanced metabolic testing, covering everything from urinary organic acids to plasma amino acids to carnitine profiles, reveals just how far downstream conventional testing really is. If your energy, fat burning, or overall health feels off and your standard labs look "normal," the problem is probably that nobody has measured your actual metabolism.

Why Standard Lab Testing Misses the Root Cause

Most lab testing is not truly root cause oriented.

Inflammatory markers are good to know, and you can improve your health by knowing them. But they still just tell you the result, rather than the cause.

Why is your cholesterol high? Why are you inflamed?

The goal with this testing was to measure the ultimate root cause: METABOLISM.

Below is a simplified view of metabolism. You'll quickly realize everything affects everything. Any interruption in any of these interconversions can drive an excess or deficiency of another compound, which does the same for another, and so on.

This also means any interruption in any of these reactions can drive essentially any symptom or disease, depending on the person, and what compounds get influenced. Things you wouldn't classically think could happen, can.

Energy is what ties all of this together. All of these reactions are dependent on energy. If you can't generate energy, you have nothing. Thus, energy is the ultimate root cause, its focus the ultimate holistic frontier.

What else causes interruptions in this chain?

• Environmental factors
• Nutrient deficiencies

Advanced testing can go a long way to identify exactly where in the system things are out of whack.

I'll walk you through my own personal data and exactly how it applies to health, as an example.

The Comprehensive Metabolic Panel: Blood Glucose and Liver Health

A comprehensive metabolic panel (CMP) measures 14 different markers.

Most important: blood glucose.

Too high means poor glucose metabolism or insulin resistance. Too low means an issue with blood sugar stability. Mine was 86 mg/dL, which is a great sign for these areas of metabolism.

The CMP also has various markers of liver health. These are all enzymes or components that exist within the liver or are produced by the liver, so their levels can signify liver health. Not really what I was interested in, but it's good to know my liver is in optimal shape.

Kidney Markers: EGFR, Creatinine, and BUN

Next are the kidney markers.

• EGFR (estimated glomerular filtration rate) - how much your kidneys are capable of handling
• Creatinine - a byproduct of creatine, which should be filtered out by the kidneys
• BUN (blood urea nitrogen) - measures the amount of urea in the blood, which should also be filtered by the kidneys

My BUN was high. But I do not think this is because my kidneys are doomed, considering how good my other kidney markers were.

Urea is a byproduct of protein metabolism. Any time you break down protein for energy, you need to get rid of the nitrogen from it. The nitrogen comes off as ammonia. It is then excreted in the urine as urea.

I believe my BUN being high is either due to:

1. A high protein meal the night prior, necessitating more urea production
2. Elevated protein breakdown, necessitating more urea production
3. Some other kind of impairment in my urea cycle functioning, causing excess urea to be produced

Ammonia and Bicarbonate: Nitrogen Handling and Metabolic Acidity

Problems with nitrogen handling (urea cycle) are pretty common as far as metabolic issues go. This is why I measured ammonia.

Ammonia is a toxic byproduct of protein metabolism. High ammonia can cause a ton of issues, and is caused mainly due to issues with the urea cycle. My ammonia was perfect.

Bicarbonate (carbon dioxide) is very important for understanding metabolism. It buffers excess acidity, and this acidity can cause a whole number of issues. It's why baking soda is amazing. Impairments in metabolism deplete bicarbonate.

Lactic Acid: A Key Signal of Metabolic Impairment

The main metabolite that can cause acidity is lactic acid. It's a sign things are going wrong.

• Anxiety / panic attacks
• Fatigue, especially in muscle
• Shortness of breath

These are all signs of high lactic acid. It is produced in large amounts when metabolism is impaired (Warburg Effect). This is famous for happening in cancer.

Excess lactic acid also drives stress via the sympathetic nervous system and HPA axis.

Lactic acid builds up in countless issues with metabolism, the primary one being poor metabolism of pyruvate into acetyl CoA, which is dependent on vitamin B1. Though any issue with metabolism can do it. My lactic acid was great, so we have no reason to believe this right now.

Iron Panel and Complete Blood Count

I also got a full iron panel. Too much or too little iron can destroy your metabolism and overall health.

• Total iron binding capacity (TIBC)
• Complete blood count

TIBC and transferrin saturation were slightly low, so I might be heading towards iron excess, but not worried. Something I will keep an eye on going forward.

The complete blood count (CBC) measures different types of blood cells, different immune cells, as well as red blood cells and their parameters. Helpful in further understanding iron status, as well as:

• Nutrient deficiencies
• Infections / allergies
• Chronic inflammation

Mine were all optimal.

The Carnitine Profile: A Metabolic Marker That Never Gets Tested

A key metabolic marker that NEVER gets tested is the carnitine profile.

Carnitine is a component of fatty acid metabolism. You need it in order to burn fat properly. Elevated free carnitine and carnitine esters are signs carnitine is not being used properly, and thus you have a problem with burning fat.

My carnitine levels were very low, so my fat metabolism is elite.

This study further details carnitine's role in fatty acid oxidation and what happens when that process breaks down.

Plasma Amino Acids: Deep Metabolic Insight From 36 Markers

Plasma amino acids also provide deep metabolic insight. Amino acids do way more than just build muscle.

• Intermediates in energy metabolism
• Intermediates in urea metabolism
• Products of the methylation process

In context with other labs, they can provide a ton of excellent information.

Our plasma amino acids package measures 36 of them. 35 were optimal. ONE was off: Ornithine was high.

Ornithine is also part of the urea cycle. My urea was also high. This indicates either:

1. High activity of arginase, the enzyme that converts arginine to ornithine and urea
2. Low activity of ornithine transcarbamylase, an enzyme that metabolizes ornithine
3. Low activity of ornithine decarboxylase, another enzyme that metabolizes ornithine (into polyamines)

High activity of arginase, high urea, and high ornithine could be simply from a high protein dinner the night prior, necessitating excess nitrogen disposal. I was also required to hold in my morning urine for the lab test, where I would normally get rid of a lot of urea, so things got backed up.

Either way, I am now VERY interested in ornithine and urea metabolism. I have also found that personally I feel better in general when I have moderate protein instead of high protein, so this seems to add up.

Ornithine decarboxylase is a vitamin B6 dependent enzyme, so now I am curious to supplement that and see if it uniquely affects me.

Urinary Organic Acids: The Deepest View Into Cellular Metabolism

Finally, the urinary organic acids. Our package measures 94 metabolites, and I researched every last one of them. This is the absolute deepest you can go into your metabolism that we were able to gather.

Lactic and Pyruvic Acid Ratio

First, another measure of lactic acid, but in unison with pyruvic acid.

Pyruvic acid (pyruvate) is a key product of the breakdown of glucose (carbs). Pyruvic acid can either be broken down further for more energy, or it can get converted into lactic acid (lactate). That is dependent on the NADH/NAD+ ratio, a metric for metabolic health.

• Lower NADH/NAD+ = more conversion into energy
• Higher NADH/NAD+ = more conversion into lactic acid

My lactic and pyruvic acids were both low, with the ratio between them also being very low. This means my redox balance, NADH/NAD+, or my metabolism in the cytoplasm of my cells, is excellent.

Ketones and Mitochondrial Function

Next, the ketones. If you are not on a keto diet, ketones can become elevated if you have impairments in the ability to break down glucose, which prevents ketones from being formed in the mitochondria, and also prevents excess fat from escaping the fat tissue and going to the liver where they can get turned into ketones.

I am not on a keto diet (though I was fasting overnight), so I am happy to see there are no ketones in my urine.

The ketone ratio is also an excellent indicator of metabolism. Similar to lactic acid and pyruvic acid, beta hydroxybutyrate (3-OH butyric acid) and acetoacetic acid are in balance governed by the NADH/NAD+ ratio. The main difference is that the ketone ratio is indicative of NADH/NAD+ balance IN THE MITOCHONDRIA.

My ratio was nonexistent (0/0), but it was not high, so that is GOOD. That means my mitochondria are churning out energy properly. I have written more about how to support mitochondrial function here.

The Other 90 Organic Acids

There are literally 90 more organic acids, so briefly, the classes:

• Byproducts / intermediates of branched chain amino acid metabolism: the most abundant and common. Elevated levels suggest you have a problem in metabolizing these amino acids.
• Byproducts / intermediates of tyrosine or phenylalanine metabolism: same thing.
• Byproducts / intermediates of fatty acid metabolism: also common. High levels mean you have an issue metabolizing fat.
• Intermediates of energy metabolism: especially important. This is where all of your metabolism converges. If you have high levels of any of these, then you have a "backup" in your energy production.
• Bacterial / fungal metabolites: you might have an infection or overgrowth if you see these.
• Byproducts of sulfur metabolism: you could have an issue with sulfur metabolism.

So What's the Takeaway?

You obviously do not have to do what I did right off the bat. If you are not as big into all of this as I am, then that doesn't make sense.

But trying these different markers and digging in deep might be cumbersome, and you might find that 99% of your numbers are good. That 1% might be the key to your health, and it might all be worth it.

Especially if you've already tried a bunch of things and are a bit stuck, running a good panel of tests can be that next step for you.

Frequently Asked Questions

What is the best way to optimize metabolism at the root cause level?

Measure it directly. Standard inflammatory markers tell you the result, not the cause. Advanced testing, including urinary organic acids, plasma amino acids, carnitine profiles, and a full iron panel, can identify exactly where in the metabolic chain things are out of whack. Energy production is the ultimate root cause.

What does the NADH/NAD+ ratio tell you about metabolism?

It's a metric for metabolic health. A lower ratio means more conversion of pyruvate into energy. A higher ratio means more conversion into lactic acid. You can assess this in the cytoplasm via the lactic acid to pyruvic acid ratio, and in the mitochondria via the ketone ratio (beta hydroxybutyrate to acetoacetic acid).

What is the Warburg Effect and why does it matter for metabolism?

The Warburg Effect describes how lactic acid is produced in large amounts when metabolism is impaired. It is famous for happening in cancer. Symptoms of high lactic acid include anxiety, panic attacks, fatigue in muscle, and shortness of breath. It also drives stress via the sympathetic nervous system and HPA axis.

What causes high BUN on a blood test?

BUN (blood urea nitrogen) measures urea in the blood, which is a byproduct of protein metabolism. A high BUN can be caused by a high protein meal the night prior, elevated protein breakdown, or some impairment in urea cycle functioning causing excess urea production. It does not automatically mean kidney failure, especially if other kidney markers like EGFR and creatinine are normal.

What does a high ornithine level mean in a plasma amino acid panel?

Ornithine is part of the urea cycle. High ornithine can indicate high arginase activity (the enzyme that converts arginine to ornithine and urea), low ornithine transcarbamylase activity, or low ornithine decarboxylase activity. Ornithine decarboxylase is a vitamin B6 dependent enzyme. High ornithine alongside high urea can also simply reflect a high protein intake the prior evening.

What is the carnitine profile and why does it matter for fat metabolism?

Carnitine is a component of fatty acid metabolism. You need it to burn fat properly. Elevated free carnitine and carnitine esters are signs carnitine is not being used properly, meaning you have a problem burning fat. Low carnitine levels indicate the opposite: that carnitine is being actively utilized and fat metabolism is functioning well.

What do urinary organic acids measure?

Urinary organic acids measure byproducts and intermediates of metabolism in the urine. A comprehensive panel of 94 metabolites can reveal problems in branched chain amino acid metabolism, tyrosine and phenylalanine metabolism, fatty acid metabolism, energy metabolism, bacterial or fungal overgrowth, and sulfur metabolism. It is the deepest available window into how your metabolism is actually functioning at the cellular level.

Why do elevated ketones matter if you are not on a keto diet?

If you are not on a keto diet and ketones appear elevated, it can signal impairments in the ability to break down glucose. This prevents ketones from being formed properly in the mitochondria and also prevents excess fat from escaping fat tissue and being converted into ketones in the liver.

What is the role of bicarbonate in metabolic health?

Bicarbonate (carbon dioxide) buffers excess acidity. Impairments in metabolism deplete bicarbonate. The main metabolite that drives acidity is lactic acid, which builds up when metabolism is impaired.

What is ammonia's role in metabolism and when does it become a problem?

Ammonia is a toxic byproduct of protein metabolism. When you break down protein for energy, the nitrogen comes off as ammonia. It is normally excreted in the urine as urea. Problems with the urea cycle cause ammonia to accumulate, and high ammonia can cause a wide range of issues. Measuring ammonia directly alongside BUN gives a clearer picture of nitrogen handling.