Dr. Justin Marchegiani and Evan Brand in today’s podcast talk about functional medicine lab testing where they differentiate the conventional lab testing from the functional testing. This conversation picks up diagnoses done by endocrinologists and about functional imbalance.Â
Find out what functional medicine doctors and specialists see when they look at conventional lab tests. Learn what adrenal dysfunction is compared to Addison’s or Cushing’s disease. Discover why the functional medicine testing for thyroid is different from your simple conventional TSH test and why you shouldn’t self-treat with hormones and the need to work with a functional medicine specialist when doing so.
In this episode, topics include:
00:42Â Â Conventional lab testing vs functional medicine testing
3:24Â Â Endocrinology from a functional perspective
6:22Â Â Serum-based cortisol test, ACTH stimulation test
7:25Â Â Adrenal dysfunction
11:30Â Â Functional testing for thyroid
13:21Â Â DHEA and hormones
Dr. Justin Marchegiani: Evan Brand, itâs Dr. Justin here. Whatâs going, man?
Evan Brand:Â Howdy! Â Itâs going great, drinking some vitamin C to fuel my adrenals for this podcast.
Dr. Justin Marchegiani: Â Â I almost thought youâd be drinking matcha teaâmatcha.
Evan Brand:   IâIâm actually running out. Iâm getting close to running out. Iâve been sending out some invites to different companies to send me some samples so I can find one to carry, but I donât have those in the mail yet.
Dr. Justin Marchegiani:   Very cool. Well, today we are in overdrive. We just did an awesome podcast on Tom Bradyâs diet and lifestyle secrets. So if you havenât listened to that, check that out. Weâre going two in a row today. We gotâweâre cooking with fire. So today weâre gonna be talking about some functional medicine lab testing, kinda differentiating the conventional lab testing from the functional testing. I get these questions a lot from my patient. You do as well. So weâre gonna kind of get to the bottom of it here today.
Evan Brand:   Yeah, so I had a guy last week and he was so confused and conflicted on how he could go to his endocrinologist and get a perfect bill of health. He gets his cortisol measure done via blood and he is perfect, maybe even high. He may have even appeared high on that blood test so he thinks high cortisol is the problem or maybe that he doesnât have that much of a problem at all. But then when we run the functional test for salivary adrenal hormones for cortisol, heâs low all day in his output. I believe his cortisol sum was 7 units, which is just a fraction of where it should be and he was like, âOh, my God.  This doesnât make sense. My blood said I was fine.â And thatâs itâthatâs a very common thing that you and I both experience is people get these blood tests and they get the perfect bill of health, come back next year for your blood work and youâll be just fine. And thatâs a very poor way to keep track of your health.
Dr. Justin Marchegiani:   Absolutely. So this person more than likely went to their endocrinologist, and first things first, right? Endocrinologist are not these gods about hormones, right? They arenât. Endocrinologist are really good and awesome at treating endoâendocrine diseases, right? Weâre talking severe disease, especially tumors, especially hyperthyroid conditions. Theyâre good at picking it up and detecting it. Now we can argue about, you know, pituitary issues, too, right? We can argue about maybe their treatments arenât the most effective; a lot of times, itâs gonna evolve especially with the thyroid, cutting of the gland out or destroying it with radioactive iodine, et cetera. And again, a lot of the other conditions, itâs typically letâs say they find aâa tumor on the genitals or in the testicles, they remove the testicle. Great, youâre on hormones now for life. The question is, what if we have a functional imbalance? Thatâs the issue, right?  What if we have a functional imbalance?  Or what ifâwhat if we haveâweâre not diabetic but weâre kinda in betweenâweâre pre-diabetes, right? A lot of endocrinoâ or all the endocrinologists diagnose diabetes, too, right? But theyâre just giving them Glucophage, metformin, maybe if they progress long enough, theyâre giving them insulin, right? Whether itâs long-acting or shortâshort-acting insulin to cover up all the sugar in their blood stream. So these docs, theyâre just kinda managing diseases.  Theyâre doing a good job when it comes to certain things like pulling out a thyroid during maybe Gravesâ disease to kind of avoid a thyroid storm. Theyâre trying to, you know, prevent that these rare things, but we wanna pop in here and use functional medicine because functional medicine, one, itâs very conservative. Itâs more cost-effective and a lot of times when it comes to your thyroid, weâre gonna be able to keep your thyroid gland, especially if weâre able to make diet and supplement changes. When it comes to diabetes, we can almost reverse diabetes by just changing our diet, by giving nutrients to help make our body more sensitive to blood sugar. So when you look at endocrinology from a functional perspective, weâre doing different things. Itâs a different perspective, right? So we just gotta know what weâre looking at when you go see a functional medicine doctor thatâs utilizing a functional endocrinology. Weâre looking at functional imbalances that may lead up to disease or pathology, right? Pathology is the realm of the endocrinologist MD. The functional doctor, theyâre gonna be at thatâin that functional range. And thatâs where most people lie and most people that areâgo to the doctor, come back home after being told theyâre fine, itâs all in their head, or âHey, you know, hereâs this anti-depressant,â or âHey, you got this hormone issue, hereâs a birth control pill.â Those are the people that are gonna do really well, would be seeing a functional medicine doctor or nutritionist.
Evan Brand:   Yeah, perfect, perfect way toâto start that thing because many people willâtheyâll send over their blood work to us and weâll look at it and weâll see things, I mean, you know, weâll look at blood chemistry and thatâs helpful because you canât get some good measures, you know, HSCRP or inflammation and vitamin D status is helpful to checking your blood and things like that. But generally speaking, most of these measures are just kind of giving you a false sense ofâofâof I guess, not a false sense of hope but maybe a false sense of health. I mean, a lot of these markers, your body is gonna go through incredible things to make sure that say, your sodium and your potassium and your magnesium levelsâmost of those times, those numbers are not gonna change unless thereâs a severe, severe issue and you really donât have the same sensitivity as basically what you were kind of alluding to, is what weâre looking forâvery sensitive, very small fractions of hormones and things like that compared to the bigger picture that that doesnât really provide as much info.
Dr. Justin Marchegiani:   Yeah, and all functional issues or functional symptoms, meaning Iâm tired but I could still get up and go to work, thatâs different than Addisonâs disease where your adrenals are totally exhausted. Thatâs where the endocrinologist focuses on and again, itâs like black and white. If youâre not on that, you know, one side of the spectrum or the other, youâre told youâre normal even if youâre creeping towards one side or the other. So we wanna really elucidate are you heading in the direction of pathology; you may never even get there, but we know that the symptoms are there and that we could start basically putting the car in reverse and going backwards which is analogous to healing. So with this personâs test that you talked to me about pre-show, I think they got a serum-based cortisol test. Is that correct?
Evan Brand: Â Â Exactly.
Dr. Justin Marchegiani:   So youâre typical endocrinologist is using serum-based cortisol to look at adrenal function from an Addisonâs or Cushingâs perspective, right? Cushingâs think pushâcortisol is pushed up highâcush, push. And Addisonâs disease is adrenal failure where cortisol is really, really low. So theyâre looking for super, super high cortisol, typically drive by a lot of times a pituitary tumor sometimes, right?  Or a adrenal tumor. And number two, theyâre looking for adrenal failure and then a lot of times, theyâll give you a ACTH stimulation test where they give you some compound that stimulates the adrenals to make a whole bunch of cortisol and if the cortisol from the adrenals doesnât double or increase significantly, then the adrenal glandsâsomethingâs wrong with it, right? And thatâs where Addisonâs comes in to play. Thatâs the ultimate adrenal failure. Now if youâre working with us or youâre working with functional medicine doctors, you probably head this word adrenal fatigue before. Now weâre not talking about Addisonâs or Cushingâs here. So I just wanna make sure weâre on the same page. Weâre talking about a functional imbalance that exist in between these two spectrums which conventional medicine, your conventional endocrinologist ignores, is the adrenal dysfunction. And Iâm using the word adrenal dysfunction more than fatigue because well, fatigue kinda gives you thatâit feels like failure, right? Iâm fatigued, Iâm failâitâitâs, you know, working to fatigue, working to failure if weâre in the gym, right? And itâs not quite the same thing. So dysfunction is great because dysfunction does a couple of things. It looks at the cortisol rhythm for instance. So if weâre just doing that sample cortisol serum test, thatâs not really giving us the information we want about the adrenals because we donât have the rhythm aspect to it. Just going to get your blood drawn by itself is a stressor which could increase cortisol. So maybe that cortisol is a lot better than what it would be because that needle created a stress response, i.e. increased the cortisol and then number three, is weâre not looking at that cortisol throughout the day. We donât have a morning, noon, afternoon, nighttime level just because of the fact that just getting pricked 4 x a day will be really difficult andâand tough and that would alter the test just byâby itself. So we are missing those couple of pieces and also when weâre looking at saliva-based testing, weâre looking at free fraction, meaning a serum-based test is looking at 100% of the hormone coming out of the gland, where saliva is looking at 2% of whatâs biologically free, meaning whatâs not bound up by protein, whether itâs albumin or globulin. So 2% of the hormone is free. Saliva looks at that. Blood for the most part unless it says serum-free, itâs gonna be looking at 100% of the hormone. And thatâs helpful when youâre looking at glandular dysfunction from a disease or cancer-based perspective, not helpful when youâre looking at functional because itâs the free fraction that can bind the receptor site and hormones work like a lock and key. The lockâor the key has to go into the lock for it to work. Same like the free fraction of the hormone that has to go into the hormone receptor site dock and then create that metabolic, anabolic, or anti-inflammatory effect, whether weâre talking about testosterone, progesterone, estrogen, or cortisol.
Evan Brand:   Yeah, and so this guy, he couldnât put a finger on why he was feeling so exhausted noon and afternoon. So he goes in the morning and gets to this cortisol measured on with his blood and, you know, heâs told that heâs fine. But once we actually run this functional adrenal profile on him and see how tanked that he truly is, his noon level was equivalent to my midnight level and Iâve tested myself, and you know, you and I both are always running tests on ourselves just to make sure weâreâweâre staying in the right place. He hadâI think it was .7 units of output for noon whichâ
Dr. Justin Marchegiani: Â Â Itâs terrible.
Evan Brand:   Thatâs even worse thanâthatâs even less than you would normally output at midnight and I told this guy. I said, âMan, Iâm honestly not surprised based on this reading here that you are able to continue working and you donât have to just go home and take a nap with this rate.â
Dr. Justin Marchegiani:   Exactly and most people that have energy issues and theyâre going to see theirâtheir doctor or their endocrinologist, theyâre primarily looking at 2 things. Maybe adrenals, maybe theyâll run that serum-based cortisol and if that cortisolâs low, theyâllâtheyâll made you an ACHâACTH stim test. Or number two, they may just run a simple TSH. Thatâs a thyroid stimulating hormone test. And theyâll look at how high their pituitary is, talking to their thyroid, right? The higher it is, right? That means, the lower the thyroidâs outputting or their output is. So itâs kind of an opposite thing. High TSH means low thyroid. Now thatâs important because once thatâs ruled out, letâs say your TSHâletâs say your TSH is 4. In functional medicine world, thatâs pretty darned high. Anything above 3, we start getting concerned. Letâs say their cortisolâs fine. Well, youâre totally ruled out now for any fatigue issues. Youâre gonna be told just go along your merry way, youâre just getting older, or you know, hereâs some stimulant medication or theyâre gonna say, itâs all in your head, if you just keep coming back. So in our functional world here, weâre looking at thyroid a full spectrum test that involves free fraction, not just TSH, and weâre also gonna be looking at cortisol from a free fraction as well but weâre gonna be looking at the rhythm component and also weâre gonna be looking at DHEA, because DHEAâDHEA-sulfate which is made from the adrenal glands, thatâs another indication of adrenal dysfunction. So if DHEA is starting to drop which in a lot people does. Now DHEA is this precursor hormone to a lot of our anabolic hormones. So itâll precursor to theâit will be a precursor to estrogen in a lot of females and more testosterone in males. And the older we get, the more we rely on DHEA from our adrenals to kind of give us that anabolic push. Now if thatâs typically never looked at in a conventional setting because what are you gonna do with that information. So we look at that as well and that gives us a great information, great informative kind of background on whatâs happening with the adrenals above and beyond cortisol serum, and also in conjunction with that free fraction, weâre looking at the rhythm of the cortisol, and then weâre also looking at the thyroid, not just TSH, but the whole entire domino line-up, meaning TSH, the T4 free and total, T3 free and total, T3 uptake, reverse T3, and antibody. So we have the trifecta going and if we keep this fatigue pattern going, weâre also wanna look at the mitochondria, which weâll probably talk about that in a separate podcast. I think we already have but the mitochondria is a really important piece of the puzzle because B vitamins and certain metabolic kreb cycle nutrients are important for fatigue as well and a lot of my patients may have decent mitochondria, or decent adrenals and decent thyroid, but itâs their mitochondria that really is weak. And when we start supporting that with nutrition and we fix the gut issues, itâs amazing how fatigue gets better and better.
Evan Brand:   Yeah, so to add to this whole loopâweâll use the same guy to the example, you know, his DHEA level was actually pretty good. He was at like at a 7.5 which isâ
Dr. Justin Marchegiani: Â Â Itâs good.
Evan Brand: Â Â Yeah.
Dr. Justin Marchegiani: Â Â Itâs really good.
Evan Brand:   Andâand well, thatâs what I thought at first. And he goes, âOh, and I forgot to put on myâmy supplement on my new client paperwork that Iâve been taking 50 mg of DHEA because I read an article a couple of years ago about how good it was for you. So Iâve been basically self-treating with DHEA.â I was likeâ
Dr. Justin Marchegiani:   Oh, forget it. So heâs automatically adrenally fatigued. If heâs at 50 mg and heâs coming up normal or in theâyou know, in a good range, that means without it, heâsâdoesnât have a leg to stand on.
Evan Brand:   Uh-hmm. Because thatâs whatâthatâs what I was kind ofâand IâI wanna break this down a little bit further with you. Thatâs what I was mind blown about because, you know, I see such a low cortisol sum, I mean, like I said his noon level, he wasâhe was tanked out on thisâon this graph, and IâI could notâI couldnât really picture what was keeping him afloat. And then we see, okay, so DHEA looks okay and then he tells me that, and I mean, if you were to just go cold turkey on that, heâd probably be in bed rest. What do you think?
Dr. Justin Marchegiani:   Absolutely. And also I think his DHEA was probably artificially lowering his cortisol. DHEA biochemically, given without cortisol support can actually lower cortisol. So the fact that he was doing 50 mg which is pretty darn high for a guy by the way, I mean, I like giving much smaller doses, but especially the lower your cortisol is, you actually have to be careful with DHEA because DHEA and cortisol have this seesaw relationship. So if cortisol is lower and DHEA is low, you actually wanna give a lower amount of DHEA just because of the fact youâll push cortisol even lower which is what I hypothesize happened in this patientâs case.
Evan Brand:   Yeah, so itâitâs just amazing and it makes me really wonder and I donât know what your estimate is, how many people are out there doing this self-treating model, theyâre not working with somebody that is actually using functional lab testing and itâs kinda scary because thereâs so many people out there and weâve discussed this before about theory. People talking about theory. Oh, and then in isolation, this thing, DHEA, itâit protects you, itâs good for you, blah blah blah. And everybody goes willy-nilly taking it and thatâs not the way to do it and now heâsâheâs on for a long journey. And by the way, heâs 28 years old.
Dr. Justin Marchegiani: Â Â Wow.
Evan Brand:   With this type. I mean, this is worse than Iâve seen some guy that is 65 years old. I mean, heâs got a worse rhythm, worse output than somebody 40 years older. Itâs mind blowing.
Dr. Justin Marchegiani:  And DHEA and any hormone in general needs to be given ideally at the lowest physiological level possible. When you go too high, the problem with hormones is, too high of a hormone level can actually create the same symptoms of low hormones, which is kinda whereâitâs like wrap your head around that but we have something known as receptor site downregulation where the receptor sites, where hormones dock, actually become numb to the hormone itself.  So even if a lot of hormones there, it can actually feel like thereâs very little there because the receptor sites become numb to the hormone, because hormones are present in the body at very, very small levels. I mean, these things are measured in like pictograms and nanograms which is like to the billionth and millionth level. So, I mean, very, very sensitive thing, so we wanna treat hormones with the utmost respect.  Itâs not like taking vitamin C. Oh, I take 1 gram or 3 grams or 5 grams. Who cares, right? Hormones, itâs different. We gotta be very, very careful and use them at the very smallest level as possible ideally and try to use them sublingual as a better way to go just to maximize absorption. If we just give things orally, we tend to have to give 3 to 4 times a higher dose of that hormone because a lot of it gets deactivated by the liver. So when youâre trying to give hormones via a pill that you swallow, you gotta go 3 to 4 times higher because the liver is kind of deactivating things as you put the hormone in your body.
Evan Brand:   Makes sense.  I mean, could you even call this, sort of like how insulin resistance is when youâre constantly creating these blood sugar spikes and crashes? I mean, would you almost call that hormone resistance or almost like if you were adding in too much GABA for example and you cause aâa downregulation of those production there? Whatâis that similar toâto whatâs going on with DHEA?
Dr. Justin Marchegiani:   Yeah, itâs very, very similar. And many patients have this.  They are hormones supplementally because they just treat hormones like itâs a nutrient and itâs okay if I give a little bit more of something, but we gotta be careful with hormones and you know, not to mentionânot to mention you can give a hormone âtil the cow comes home but if the diet piece isnât address, the lifestyle piece isnât addressed, or thereâs an underlying gut or malabsorption thing, then youâre just gonna be, you know, reâyou know, addressing icing on the cake, right? You gotta be just re-icing the cake of a cake thatâs all moldy underneath, right? We actuallyâ
Evan Brand: Â Â Yeah.
Dr. Justin Marchegiani:   Wanna fix the underlying issue which should be, you know, the actual foundation of that cake or in our body, our gut and infections and immune and nutrient absorption, not just giving some hormones. And a lot of the anti-aging doctors I find are the most guilty of this.
Evan Brand: Â Â Of what?
Dr. Justin Marchegiani: Â Â Of just using hormones like supplements and just getting a palliative effect, meaning great, you feel better, awesome, and now youâre done.
Evan Brand: Â Â Yeah.
Dr. Justin Marchegiani: Â Â And weâre notâweâre not gonna go any deeper.
Evan Brand:   Right. Yeah and I mean, thatâthatâs something that you and I will do is to help with symptoms. Say if they are fatigued, weâll help get their energy better, but eventually weâve gotta work backwards far enough or deep enough rather to get to whatâs causing it, you know. I mean, itâs tough to tell somebody, âHey, we have to eliminate yourâyour gut infection.â Maybe we canât go straight there but weâll help you feel better first, so that you actually have theâthe motivation to get going to that and I totally agree with you that most people they get cut short and they have all these puzzle pieces, IâI like to use the puzzle now as you were there, itâs like their shuffling all these puzzle pieces on top of the table, but theyâre still missing some from the drawer, that 4 drawers down; they never pull that piece out and thatâs why theyâreâtheyâre puzzle is never complete and theyâre always gonna have some type of lingering symptom or issue.
Dr. Justin Marchegiani:   Absolutely, so looking at this personâs test here. Just remember blood test typically if itâs a hormone, itâs always gonna be serum-based and thatâs gonna look at 100% of the hormone; itâs ignoring the 2%. So if you want, get the free portion of it, and we can do it via saliva. Some tests we can do it via blood as well. We can order an estradiol free. I donât think you can do a progesterone free via blood so you have to do that via saliva. We can order a thyroid free, right? T4, thyroxin free. We can order T3 free. So we can do that via saliva. We can do testosterone total and free which is nice. So we have, you know, a lot of latitude with some of the blood testing, and also when we look at blood test, weâre looking at it differently. I mean, the high and low ranges basically are 2.5% of the population, high and low, which we know 95% isnât normal. So weâre looking at these lab tests functionally speaking which is really important because we want people to be in that middle 30% or so and if you start creeping outside of that, it can mean something where conventional doctor they just look at it and make sure nothingâs flagged which would potentially indicate pathology or something more severe, it depends. When weâre looking at cholesterol, itâs not the case. Thatâs another podcast. Weâll haveâ
Evan Brand: Â Â Oh yeah.
Dr. Justin Marchegiani:   To do that later. Cholesterol is actually one of these markers thatâs more overly sensitive and because weâre not looking at other things like inflammation and particle size andâand those things. But for the most part, blood tests are gonna miss a lot of things if youâre not looking at it with a functional medicine eye to it.
Evan Brand: Â Â Totally, thatâs a great point.
Dr. Justin Marchegiani: Â Â Anything you wanna add, Evan?
Evan Brand:   No, I mean, this wasâthis was good. I donât know if I have much more to say about this topic. I think weâve crushed it.
Dr. Justin Marchegiani:   Alright, well, great podcast. Take home is just understand kinda what your blood test youâre looking at. If youâre getting hormones done, look at free and look at total fraction or serum, you know, fraction as well. And then make sure you have a complete picture, right? Know what the MD is looking at which is disease and pathology and then know what the functional medicine doctor is looking at. Theyâre looking at functional imbalance. If you get that, then you have the right take home message.
Evan Brand:   Yeah, and IâI guess I would add one last thing here, you know, my goal andâand your goal is not toâto instill fear and say that if you have say some blood work that looks like itâs perfect, not to be paranoid and think that Iâm not perfect now because of this podcast, but that you do want to reach out to one of us or reach out to someone that knows how to look at this stuff from the functional perspective, that way youâre getting a little bit more help, because my grandfather, for example, I mean, heâs gone year after year after year, and he gets a perfect bill of health on his blood work but once I go over there and put the magnifying glass to it, itâs like, âWow, look at this! According to here and here and here, youâre super dehydrated. Thereâs inflammation here and itâs like, âNo, youâre not perfect bill. We need to dial some things in together.ââ And thatâs a totally realistic goal and itâs a fun process to do and thereâs so much more potential that you can have. So donât ever sell yourself short and just say that itâs good enough. Be happy. Be happy with where you are but thereâs always one little higher bar of where you can likely feel and be with your energy, your sleep, the way you look, your sex drive, I mean everything.   Thereâsâthereâs so much more potential out there for you.
Dr. Justin Marchegiani:   Well, most patients that I see, they already have symptoms. Theyâve gotten this testing done. They go to their MD because well, theyâre in their network, why not?
Evan Brand: Â Â Yeah.
Dr. Justin Marchegiani:   And then theyâre looking for answers and then their MD says, âYouâre fine.â And then theyâre like, âBut I know Iâm not. Like I felt this slow degradation over the last couple of years, somethingâs not right.â And then they push it. They come back again. They go to someone in their network. The other doctor sees the notes and theyâre like, âYeah, youâre fine. I think this is all in your head.â And then once that hits or once theyâre thrown an anti-depressant or some kind of medication thatâs just palliative and just covering up symptom and they know about it.  Then theyâre BS and then theyâre like, âMan, IâmâI gotta go see someone else.â And then once we do the functional testing, itâs a relief once they find a bug or they see some nutrients off, or we find theirâtheir dietâs off or we find something is wrong and then we fix it and they start feeling better. Itâs like, âWow!â So thatâs total freedom when we get to the root and then they see improvement versus hey, when you tell someone theyâre making something up and they have no reason to make it up because people that are spending money on food andâand really being conscious of things, theyâre not making things up. Thatâs not how it works, right?  Thereâs always something deeper there and people intuitively know it and they donât need a lab test a lot of times to even say somethingâs wrong.
Evan Brand:   Exactly. I totally agree and I think thatâs what helps you and I sleep good at night is because once you help somebody to find that answer or to find that piece of the puzzle that was never looked at deep enough, itâs like, âOh, my God, Iâm finally heard. Iâm finally getting an explanation that makes sense of why this is happening. I knew something wasâwas wrong but I couldnât identify what it was.â And then just we use a different set of tools and now thereâs an answer, and oh gosh, does that feel good!
Dr. Justin Marchegiani:   Love it. Love it, Evan. Great! Any other closing comments?
Evan Brand: Â Â Thatâs it.
Dr. Justin Marchegiani: Â Â Evan, great podcast today, man.
Evan Brand: Â Â Likewise.
Dr. Justin Marchegiani: Â Â Take care.
Evan Brand:   I agree. Alright see ya.  Bye!
Dr. Justin Marchegiani: Â Â Bye!