Why Normal Labs Miss Early Metabolic Damage and What to Test Instead

What’s Inside This Episode?

• Why “normal” CBC, CMP, and lipid panels rarely explain fatigue, brain fog, or weight gain

• The 3 types of dysfunction standard labs always overlook

• Critical immune and mitochondrial markers to catch early burnout and chronic inflammation

• Functional ranges and “gray zone” patterns that reveal trouble before red flags

• How genetics can guide smarter test selection (even without expensive panels)

• Overlooked tools for catching methylation, detox stress, and early insulin resistance

• Why GGT, uric acid, and homocysteine might be your most powerful early-warning tools

• How to interpret functional trends over time and avoid falling into the “normal trap”

Resources and Links:

• Download the transcript here
• Download our FREE Comprehensive Blood Chemistry Guide
• Join the Next-Level Health Practitioner Facebook group here for free resources and community support
• Visit INEMethod.com for advanced health practitioner training and tools to elevate your clinical skills and grow your practice by getting life-changing results.
• Check out other podcast episodes here

 

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Transcript

 

Dr Ritamarie 

What if the labs you're relying on are only telling you 10% of the story and the other 90% is silently driving inflammation, mitochondrial breakdown, cognitive decline, and insulin resistance? 

 

In today's episode, we're diving into the markers most practitioners aren't ordering, the ones that reveal metabolic dysfunction years before a diagnosis. 

 

Before we dive in, grab my comprehensive blood chemistry guide, your cheat sheet for interpreting blood markers in a functional way. It highlights the key markers, the patterns most practitioners miss, and how to spot dysfunction long before lab values turn on the red flags. You can download it using the link in the show notes.

 

Today we're talking about why standard lab tests are failing people and what we should be doing instead. Most people walk into your practice with quote unquote normal labs. There's CBC, CMP, Lipid Panel, maybe even a TSH. 

 

None of it explains their fatigue, their brain fog, their neuropathies, their gut issues, and their weight loss resistance. And that's because standard labs were never meant for early detection. They're not meant for functional physiology or pattern recognition. They're designed to flag disease once it's already progressing. But if you understand advanced markers, and you know how to interpret the gray zones, you can spot metabolic breakdown years before symptoms become life-altering. 

 

Today, I'm going to walk you through the advanced markers I wish every practitioner ordered. I'm going to show you how to interpret the gray zone patterns that signal early dysfunction, how genetics can guide smarter test selection, and the foundational panels that catch what normal labs miss. 

 

Dr Ritamarie (02:14)

Standard panels miss three things. Number one is function. They only flag obvious dysfunction. They ignore subtle upward trends or downward shifts in markers over time. They miss the interrelationships between the various markers, between the connected pathways. 

 

For example, a normal GGT doesn't mean detoxification is fine. A normal TSH doesn't mean thyroid function is fine. A normal hemoglobin A1c doesn't mean glucose regulation is fine. The real question is, what is the physiology doing behind the numbers? 

 

So these are some advanced markers every practitioner should consider. One, cell-mediated immunity. This is critical for understanding susceptibility to chronic viral activation, immune aging, and inflammatory load. 

 

So what are some key markers? Well, there's the subsets of lymphocytes. There's a CD4-CD8 ratio. There's the NK cell activity. There's HS-CRP and ESR, erythrocyte sedimentation rate. 

 

And not all of these need to be run on everybody, but we need to consider them when we have the right presentation. The presentation of somebody with chronic symptoms with no other causes and chronic immune issues. So they reveal how resilient a person's immune system actually is, not just whether they're currently infected. 

 

The second one is mitochondrial markers. Fatigue, brain fog, insulin resistance, and inflammation often come down to mitochondrial dysfunction. Blood markers to look for are HS-CRP.  Mitochondria are inflammatory sensors and sadly, there's a lot of doctors who still don't do HS-CRP. They leave it off as an extra not needed marker. 

 

GGT, the mitochondria are super sensitive to toxicity and that's where GGT is measuring. And CoQ10, which is the mitochondrial function, right? It's a super important nutrient. And with so many people on statins these days disrupting their CoQ10, that's a problem, right?

 

Dr Ritamarie (04:30)

Some other markers that are not necessarily in the blood test, but are good tests to be doing, organic acid tests. There's lactate and pyruvate, carnitine profiles. These are all things that you can do as part of more functional tests like the organic acids, the NutrEval, the metabolomix. The OAT alone, the organic acids, gives you direct visibility into mitochondrial function, what's happening in there? Detoxification stress, neurotransmitter metabolism, microbial overgrowth, and nutrient deficiencies. 

 

Nothing in a standard CMP will show you any of that. 

 

Advanced stool testing is also important. I'm not talking about the simple culture that most conventional docs or even GI docs do. I'm talking about not just occult blood, even though that's an important marker.

 

What I'm talking about is sequence-based analysis that’s done on tests like Gut Zoomer, GI Effects, and GI-MAP. And key markers there are on microbial balance and dysbiosis index and beta-glucuronidase and secretory IGA, calprotectin, butyrate, and short-chain fatty acids. There's also opportunistic pathogens and fungal organisms and viral signatures. And the digestive enzyme output gives you an idea of how well the pancreas is working.

 

These advanced digestive markers are super important when some symptoms don't match with a normal GI panel, right? They don't have Giardia. And there's also detoxification and methylation markers that are often overlooked, and these are incredibly powerful. 

 

So when we look at genes, which a lot of us are doing these days, I look at them extensively. Say someone carries the most common genetic variant, this SNP called MTHFR, methyl tetrahydrofolate reductase.

 

Also MTRR, MTR, COMT, GST, that's glutathione, GSTM1 and GSTP1, NQ01, which is related to the CoQ10, and SOD. These are all important detox-related pathways. And when we see somebody on their genetics having these pathways out of balance, it's really important for us to do the right testing to see if these SNPs are expressing.

 

They of course don't diagnose disease, but they tell you which pathway to watch more closely. It's clues, right? And the labs that matter most here are things like homocysteine, right? 

 

Homocysteine is related to the methylation pathways and shortage of B12 and B9 and B6 and magnesium and B2, right? The other one is methylmalonic acid, which is a signature for B12 deficiency. Serum folate and RBC folate. Both of them give us indications of how the folate pathway is working, which is a key principle in those methylation pathways. B12 serum, I'm not a big fan of, but some places, I think mostly over in Europe, they do holo-transcobalamin. That's the full, active form of B12.

 

 Uric acid, it's been left off of so many panels I've looked at. Uric acid is super important for determining oxidative stress and detox overload. 

 

GGT elevations can be a phase two depletion and cause of detox stress. And again, it used to be a standard thing measured. And I see a lot of tests that are not measuring GGT at all. 

 

ALT and AST, so the ratio of AST to ALT is actually a sign of mitochondrial signaling. And yes, most tests look at ALT, and they look at AST, but they don't necessarily look at the ratio.

 

There's another one that's done on the DUTCH test and also on the metabolomics test is 8-0HdG. 8-0HdG is an oxidative marker, a marker of DNA damage. And genetics point to the fact that we may have some issues here. 

 

Genetics gives us a map. It gives us a map about what areas to look at as potential weaknesses in this person. But the labs tell us how that map is currently expressing. 

 

So when someone has slow methylation, poor glutathione recycling, or impaired detoxification potential, these markers catch the issues years before they have a diagnosis, right? Years before. 

 

Inflammation and metabolic dysfunction markers are also super important. And again, sadly overlooked, even though we know that inflammation is the underlying cause of just about all of our chronic diseases.

 

So insulin resistance, chronic inflammation, and early metabolic decline show well before the hemoglobin A1C shifts and the fasting glucose shifts. So in addition to fasting glucose, I recommend we get fasting insulin. That's the earliest marker to shift in metabolic dysfunction. Look at C-peptide. What's the pancreatic reserve look like? 

 

Look at the hemoglobin A1C, which is an average over the last three months. but fructosamine can be more accurate or more short-term, like with interventions, because it's usually over the last three to four weeks. HS-CRP, an inflammatory marker that's so overlooked, and in some cases, we look at advanced markers like pro-insulin and leptin and adiponectin. 

 

Dr Ritamarie (09:43)

And then there's ways to test for early fatty liver with Fib4 plus GGT. These are early warning symptoms, and we owe it to our clients to find things early, not to wait until they're diseased and need a drastic intervention. 

 

So how do you interpret these gray zones? This is where most practitioners struggle. A number may be normal, but the pattern isn't. For example, a ferritin of 20 is technically normal by lab standards, but it's biologically insufficient. An ALT of 28 by lab standards looks just fine, but it's functionally high, indicating that there's some liver stress, that there's some oxidation happening in the liver. A homocysteine of 10? The lab says it's okay, but it's functionally too high. We really want to look at the status of some of these nutrients that play in there, and it's inflammation. It's causing inflammation and damage to the arteries, the endothelial lining, and the brain.

 

When a GGT is 18, it looks normal on paper, but it suggests oxidative overload, especially in light of other things than other history findings, but also in light of what's going on with their genetics. 

 

So functional medicine requires us to ask, “Is this optimal?” Not, “Is this normal?” I don't know about you, but I don't want to be normal in today's day and age, because so many people are ill. So many people have metabolic dysfunction.

 

Estimates say 93% have metabolic dysfunction. I'm not waiting until I get there.

 

So here's the deal. The trends tell us the stories. Rising liver enzymes can be an early insulin resistance. I did another podcast episode on that a while back. Dropping albumin can indicate chronic inflammation or poor digestion. White blood cells at the low end, that's chronic immune suppression. And let's look at other causes of that. Uric acid creeping up, that's oxidative stress and mitochondrial dysfunction.

 

When you connect those gray zones, you see the real picture. By the way, if you want a simple cheat sheet for interpreting these gray zones, grab my comprehensive blood chemistry guide. It's a perfect companion to what we're covering today. The link is in the show notes.

 

Dr Ritamarie (12:04)

So let's do a brief look at how to use genetics to select the labs. You don't need genetics testing to have great clinical outcomes, but when you do have it, it sharpens your focus and a lot of people have them. 

 

Let's take detoxification and methylation genes as an example. 

 

So for example, now we have somebody who has MTHFR, MTRR, COMT, there's some variants here, GST, maybe it's null, maybe it's their variants, SOD.

 

When you see these things, you immediately know they might struggle with methylation deficiency, especially if they're living a lifestyle that's putting stress on the system. If their diets are not optimal, their sleep is not optimal. So they may be poorly able to neutralize oxidative stress. And if they're under a lot of oxidative stress, this is where we really need to be careful and look. They may be more vulnerable to chemical exposures, right?

 

We have chemicals all over in the air, the products we use, in our paints, et cetera. Their glutathione recycling may be impaired, which is important for toxins to be eliminated, and they may accumulate toxins faster than they eliminate them. And these situations stress the mitochondria and the thyroid receptors. 

 

This can lead to fatigue, depression, sluggish bowels, and all these other symptoms of thyroid dysfunction, even when the thyroid tests are normal. And I'll beg to differ with that. because usually they don't fully test, but I've seen that situation where all the tests, TSH, T4, free T4, free T3, antibodies are all normal, but they have other signs of thyroid. What's going on there? 

 

It's probably a receptor problem. What causes the most common receptor problems? Well, elevations of things like homocysteine and other inflammatory markers and low nutrients. 

 

So we really need to look at this in the full picture. So when we do the right labs, they become early detection tools, things like homocysteine and MMA and GGT. They're really important ones. 

 

Uric acid, looking at the ratio of AST and ALT. Oxidative stress markers. Organic acids, not necessary for everybody, but it's important for these people who are chronically having problems, and have seen a lot of practitioners, and have done a lot of good stuff, but they're not getting well. So we look at the organic acids for detox intermediates. Genetics is good for telling us where to look. Labs tell us what's happening right now.

 

So lifestyle and nutrition correct the path. So you could have someone with lots of genetic variants. I have them, yet they're living a clean lifestyle. They don't have a lot of toxic exposures. They're managing their stress, they're sleeping, and we're not seeing expressions. And another person with the same genetics may have a completely different outcome because of the way they're living their life. 

 

So why advanced markers are a practitioner's superpower? Well, most people show up with normal labs and worsening symptoms. And when you add the advanced markers, you catch dysfunction years before. You personalize the interventions, you avoid guesswork, you prevent mysterious declines, and you become the practitioner who sees patterns that other people miss. 

 

This is how we reinvent healthcare together. And we are the future of healthcare.

Those of us like myself and our practitioners in our training programs who are committed to going beyond the symptoms, to putting the care and the health back into healthcare and getting away from a disease management, symptoms management system.

 

This means that we must address the root causes of imbalance. Doing the right labs can help us to detect these things early. 

 

In this episode, we covered some of those advanced markers that reveal early dysfunction. We covered the gray zones that most practitioners overlook, and we looked at how genetics can guide smarter test selection. 

 

So if you're ready to take your practice to the next level, visit inemethod.com and learn more. And if you want to go deeper into functional lab mastery, remember to grab my comprehensive blood chemistry guide. The link is in the show notes. It'll show you which markers reveal early trouble, even when the “normal” panel looks normal.

 

Together, let's continue the movement to reinvent healthcare. And until next time, shine on.