Try This: Optimal Metabolic Health Labs

Hi ,Every year we walk into the doctor’s office for our annual checkup. Typically our doctors run a comprehensive metabolic panel and maybe a few other tests and send us on our way. But few of us stop to look at the actual lab work, especially when we’re told, “Everything is normal.” Yet more than a third of Americans have prediabetes, 68 percent of Americans struggle with sleep, and 47 million of us have metabolic syndrome. Not to mention, most people feel like crap most of the time. So while our numbers are “normal,” we may not be as healthy as we think. But can we stop things like high blood pressure, high cholesterol, and type 2 diabetes well before we’re diagnosed? The answer is yes. Today’s newsletter is a continuation of a previous newsletter where I provided research-backed optimal reference ranges for a bunch of different lab tests. This week, my goal is to build on that newsletter by providing more context around blood glucose and cholesterol biomarkers so you can understand how they work together, what impacts their levels, which ones we need to pay extra attention to, and which ones may not be as scary as we’ve been led to believe. That way you can feel empowered knowing what’s going on with your metabolic health and not have to solely rely on your doctor to put the pieces of the puzzle together for you.And by the way—that’s not a diss on doctors! Conventional medicine doctors are trained to look at metabolic biomarkers separately rather than look at them for what they are: dynamic and interconnected. Additionally, there’s no intervention that takes place until the patient’s numbers are out of the standard reference range—but by that point there’s already some metabolic dysfunction going on, and the treatment usually involves medication. We need to shift away from this “wait and see” approach and start focusing on preventive medicine, which requires looking at the full picture: what’s impacting these markers and why they change. If we know this information, we can make adjustments to our diet and lifestyle earlier to keep our levels in the optimal range and prevent chronic diseases.Before we dive into the blood glucose and cholesterol markers I want to talk about today, let’s first address the limitations of routine lab tests: Limitations of Routine Lab Tests Routine blood work is typically only done a couple of times a year, making it difficult to track when certain metabolic markers change and what exactly we’re doing that’s causing them to change (for better or worse) from one lab report to the next.  This is why I’m such a huge fan of continuous glucose monitors (CGM) because I can see how my blood glucose changes in real time and use that feedback to make changes to my diet right away. Blood glucose is only one piece of the puzzle, though. The key is to understand it in the context of how it influences your other metabolic biomarkers, which is the focus of today’s newsletter.   Reference ranges are determined based on the average health of the population, but 88 percent of Americans are metabolically unhealthy. That means what’s “normal” is far from optimal, so if you’re on the borderline it’s likely that there’s already some metabolic dysfunction going on. I wrote about standard reference ranges and the problems that come with them in a previous newsletter. Some tests that can help detect early signs of metabolic dysfunction are not included in routine lab work. Fasting insulin, for example, is a pretty affordable test that’s often overlooked, even though it's the best test for detecting early signs of insulin resistance. You can ask for a fasting insulin test, but doctors don’t routinely order it because they aren’t trained on its ability to be a leading indicator of chronic disease.I recently sat down with my good friend and cofounder of Levels (the CGM company), Dr. Casey Means, to talk about the importance of metabolic lab tests in addition to blood glucose and how the two are dynamically related. In the interview, we covered strategies to get the most out of your lab tests and discussed the limitations around routine blood work I mentioned above.Levels is offering an exciting new service to their community to tackle some of routine lab work’s limitations. But before I tell you about it, I want to disclose that I am an investor in Levels. I genuinely believe in Levels’ mission to help put an end to the metabolic health crisis by making CGMs available to the public and providing free information on their blog to help educate people about the importance of maintaining optimal metabolic health. Levels’ Metabolic Health PanelLevels’ Metabolic Health Panel is a new service that allows you to get a comprehensive metabolic lab test—including fasting insulin—from the comfort of your own home. All you have to do is sign up and schedule your appointment, and a licensed phlebotomist will come to YOU to collect a sample. It’s super easy, it’s convenient, and the turnaround time is quicker than regular lab tests. Levels uploads your results right to their app for easy access and even provides a summary of what the lab tests mean and how your results compare to their optimal reference ranges selected by experts. There’s no limit to how many lab tests you can get with Levels, which is an added bonus because you can track how your blood glucose and cholesterol change over time to see how adjustments to your diet and lifestyle are working for you. You have to be a member of Levels to use their service and each test costs $179, although that’s a pretty fair price compared to paying out of pocket if you wanted to get these tests outside of routine lab work.How to Get the Most out of Your Routine Lab TestsEven if you can’t commit to a service like Levels, there’s still plenty of information you can gather from standard blood glucose and cholesterol panels. All it takes is some simple math and knowing how to read between the lines—but don’t worry! I’m going to walk you through how to do this, step by step.In this next section, I will give you a summary of the importance of several metabolic lab tests, their optimal reference ranges, and the limitations that come with them. This information came from a Levels blog titled The Ultimate Guide to Understanding Your Cholesterol Panel and Metabolic Blood Tests. In the article, my friend and business partner Dr. Mark Hyman is joined by Dr. Casey Means and Levels’ team of metabolic health advisors (Dr. Ben Bikman, Dr. Sarah Gottfried, Dr. Rob Lustig, and Dr. Molly Maloof, to name a few) whose views are based on the latest research. Ready? Let’s get to it!Fasting GlucoseWhat is it? A measure of your blood glucose levels, unaffected by a recent meal.Why is it important? Fasting blood glucose tells us how well our insulin and glucose pathways function in the absence of food. High fasting blood glucose is linked to coronary heart disease, metabolic dysfunction, diabetes, and a greater risk of all-cause mortality. Although it is always included on metabolic lab tests, no preventive diet or lifestyle guidance is typically provided to keep patients’ levels from creeping up towards the prediabetes and diabetes ranges where they qualify for insulin therapy. If fasting blood glucose comes back high, that’s a sign that insulin resistance has been going on for a while, which is one limitation of this test—it can’t detect insulin resistance early on like a fasting insulin test would.Standard Reference Ranges:  Normal: <100 mg/dL  Prediabetes: 100-125 mg/dL Diabetes: 126 mg/dLOptimal Reference Range: 72-85 mg/dL Fasting InsulinWhat is it? A measure of your insulin, unaffected by a recent meal. Insulin is a hormone produced by our pancreas that’s responsible for delivering the glucose in our blood stream to our cells. Why it's important: Fasting insulin is a marker of how your body regulates your blood glucose levels and is the most upstream test for detecting insulin resistance because it can catch it before it's full blown.A high fasting insulin means your pancreas works extra hard to produce insulin to keep your blood sugar balanced. If a person has a fasting blood glucose of 80 ng/dL and fasting insulin of less than 2 mIU/dL, their insulin sensitivity is high. But if somebody has a fasting blood glucose of 80 ng/dL and fasting insulin of 20 mIU/dL, that means their pancreas is working much harder to keep their blood glucose levels stable. That’s why fasting insulin is the gold standard, because it can help predict insulin resistance in people with normal fasting blood glucose or who appear to be healthy.How does having high fasting insulin lead to insulin resistance? Too much insulin in your bloodstream over time eventually causes your cells to lose their sensitivity and become resistant to it. Fasting insulin is a pretty affordable test at around $15, but you have to ask your doctor for it, since they don’t routinely test it.Standard Reference Range: <25 mIU/LOptimal Reference Ranges: 2–5 mIU/mL >10 mIU/mL is concerning >15 mIU/mL is significantly elevatedHemoglobin A1C (HbA1c)What is it? Your hemoglobin A1C (HbA1c) is the percentage of hemoglobin in your blood with glucose molecules attached to it. HbA1c is a common test ordered by doctors because it's a marker of your blood glucose levels over time.Why it's important: HbA1c is a measure of the average glucose in your blood over three months. This test is more accurate than fasting blood glucose because it indicates how much glucose is in your blood on average.Some experts think HbA1c has some limitations because it doesn’t account for the blood glucose variability that happens on a daily basis from stress, diet, exercise, hormonal changes, etc. Others claim it’s beneficial for detecting prediabetes and diabetes because high HbA1c is a sign that there’s more glucose circulating in your bloodstream, which itself is a sign of insulin resistance.Another limitation of the HbA1c test is that it only has a sensitivity of 60 percent, which means patients with glucose intolerance could go undetected 40 percent of the time. Moreover, it doesn’t consider the biological variability between ethnic groups.Standard Reference Ranges:  Normal: <5.7%  Prediabetes: 5.7-6.4%  Diabetes: >6.5%Optimal Reference Range: <5.5%, but <5% is idealLDL CholesterolWhat is it? Known as “bad cholesterol,” low-density lipoprotein (LDL) transports cholesterol and delivers it to our tissue. Why it's important: High LDL cholesterol is associated with an increased risk for coronary artery disease, heart attack, and stroke. LDL cholesterol can get lodged in the arteries and create an inflammatory immune response that can cause plaque buildup, artery stiffening, and reduced blood flow. This mechanism suggests high LDL is a risk for heart disease, but current evidence shows that it's not your LDL number but the size of your LDL particles that’s associated with heart disease, heart attack, and stroke. Dr. Mark Hyman and Dr. Rob Lustig recommend getting a cholesterol test called the nuclear magnetic resonance spectroscopy, or NMR, lipid test so you can see your size and number of cholesterol particles (see “Bonus Tests” for further explanation of NMR) to fully understand your cardiometabolic risk. In the words of Dr. Molly Maloof, “LDL IS A GARBAGE TEST.” High LDL is associated with 30 percent greater odds of heart disease, whereas high triglycerides are associated with 80 percent higher odds. Your best bet for understanding your risk of heart disease—or any chronic disease—is your triglyceride-to-HDL ratio, followed by your total-cholesterol-to-HDL ratio. Standard Reference Ranges: <70 mg/dL for those with heart or vascular disease <100 mg/dL for those at high risk Optimal Reference Range: <100 mg/dL. <70 mg/dL is considered optimal by some experts, but an NMR test can give you a comprehensive look at how problematic your LDL is. HDL CholesterolWhat is it? Known as “good cholesterol,” high-density lipoprotein (HDL) cholesterol carries cholesterol away from the arteries and tissues and to the liver to be redistributed, metabolized, or excreted. Why it's important: Having a high HDL cholesterol is desirable, but experts say the standard reference ranges are arguably still too low to be cardioprotective. If somebody has an HDL cholesterol on the low end of the standard reference range—say 45 mg/dL—and triglycerides that are on the high end but not quite out of range—say 148 mg/dL—they may be told that they’re in good shape, even though they are still at high cardiometabolic risk. HDL cholesterol tends to go down if you are insulin resistant and have high triglycerides. That’s why calculating your triglycerides-to-HDL ratio (see below) provides a more complete picture of cardiometabolic health. In addition to the reference range being too low, another limitation of the HDL test is that it doesn’t tell us about the functionality of the HDL cholesterol. You can have high HDL cholesterol, but if it's not functioning properly, it's not going to be as protective. According to Dr. Sarah Gottfried, “In order for HDL to be cardioprotective, it must be functional…. Increased intake of virgin olive oil, nuts, legumes, whole grains, and fish improves HDL functionality.”Standard Reference Range: >45 mg/dLOptimal Reference Range: >60 mg/dL is good, but >90 mg/dL is optimalTotal CholesterolWhat is it? The sum of all the cholesterol in your blood (HDL and LDL). Why it's important: This test doesn’t tell us much on its own, because just looking at total cholesterol doesn’t tell us how much of each type of cholesterol you have and how they are behaving in your body. You can have a total cholesterol that’s “normal” and still be at risk for chronic disease. How? Because what really matters is how much HDL cholesterol makes up your total cholesterol—that’s why calculating your total-cholesterol-to-HDL ratio (see below) is a much better predictor of cardiometabolic health than total cholesterol by itself. Standard Reference Ranges: 20 years old or younger: 75-169 mg/dL 21 years old and older: 100-199 mg/dLOptimal Reference Range: <180 mg/dLTotal-Cholesterol-to-HDL-Cholesterol Ratio (TC:HDL)Why it's important: Together these numbers provide more information about your risk for heart disease than any one of them on its own. The complete metabolic panel your doctor orders does not calculate your ratio of total cholesterol to HDL cholesterol, but you can easily calculate it yourself by dividing your total cholesterol by your HDL cholesterol. TC:HDL = Total Cholesterol ➗ HDL The higher your ratio is, the greater your risk for diseases like obesity, type 2 diabetes, non-alcoholic fatty liver, heart disease, and metabolic syndrome. Standard Reference Ranges: Most health-care providers prefer a ratio of 5:1 or less 3.5:1 is considered very goodOptimal Reference Ranges: <3.5:1 is good <2:1 is idealTriglyceridesWhat is it? Triglycerides are produced when excess calories are not being used. These excess calories are converted into triglycerides by your liver and stored as fat.Why is it important? Triglycerides are a major indicator of the overall quality of someone’s diet. If a person has high triglycerides, that’s a sign they’re eating a diet that’s rich in refined carbs and sugar. When we consume concentrated sources of sugar all at once from refined flours, sugar, and fructose (from things like fruit juice and products with high fructose corn syrup), our liver turns on its fat-production switch and starts making triglycerides. Why does our liver turn excess sugar into fat?Sugar used to only be available on occasion—usually in the form of fruit—and if it was around our ancestors would eat as much of it as they could. Now, sugar is at our fingertips all the time, and the majority of people are getting way too much of it in their diet. Uric acid is produced as a byproduct of breaking down sugar, and high levels of uric acid tell our liver to become insulin resistant and to start producing fat. This was a survival mechanism that gave our ancestors energy reserves when food was scarce. As my friend Dr. David Perlmutter, who was recently on my podcast, says, we are experiencing an evolutionary mismatch because our ultra-processed diet keeps our metabolic switch on all the time. People who have high triglycerides usually have higher high-sensitivity C-reactive protein, which is an inflammatory marker (see below). This makes sense because most chronic diseases that present with high triglycerides (obesity, type 2 diabetes, and metabolic syndrome, for example) are also associated with chronic inflammation. The interesting thing about triglycerides is that they only take a month or so to change. So any changes you make to your diet can be reflected in your numbers pretty quickly.Standard Reference Range: <150 mg/dLOptimal Reference Range: <100 mg/dL, although some experts say <80 mg/dL or <50 mg/dLTriglycerides-to-HDL Ratio (TG:HDL)Why is it important? If your doctor can’t order a fasting insulin test for you, your triglycerides-to-HDL ratio is going to be the next best thing. Your TG:HDL ratio can tell you what’s going on with your insulin sensitivity. If your ratio is low, it means you are insulin sensitive. If the ratio is high, there’s most likely insulin resistance present. Your TG:HDL ratio also gives insight into what’s going on with your LDL cholesterol if you can’t get an NMR test. If your ratio of triglycerides to HDL cholesterol is high, there’s a good chance that your LDL cholesterol is small and dense—the kind that’s damaging to arteries.Just like TC:HDL, this ratio oftentimes isn’t calculated for you, but you can calculate it yourself by dividing your triglycerides by your HDL. TG:HDL = Triglycerides ➗ HDL Lower is always better. Experts agree that the most powerful test to predict your risk of heart disease is the ratio of your triglycerides to HDL. One study found that people with the highest triglycerides to HDL ratio had a 600 percent increased risk for heart disease. Optimal Reference Range: <1Note: >2.5:1 in Caucasians and >1.5:1 in African Americans indicates metabolic syndrome. High-Sensitivity C-Reactive Protein (hsCRP)What is it? A marker of chronic inflammation.Why is it important? High-sensitivity CRP (hsCRP) tells us about the inflammation going on in the body. CRP is typically elevated in the presence of insulin resistance, high triglycerides, metabolic dysfunction, and chronic disease. A limitation of hsCRP is that it can also be elevated if you’re fighting off an infection, if you’ve been exposed to environmental toxins, or if you have an autoimmune disease. These confounding factors can make it difficult to sort out what’s causing CRP to be elevated.  Standard Reference Range: <2.0 mg/L Optimal Reference Range: <1.0 mg/L, although some experts say <0.5 mg/LBonus TestsNMR: The NMR test tells you what percent of your LDL cholesterol is actually dangerous by measuring your LDL particle sizes.Why it's important: Small, dense LDL cholesterol is the most dangerous LDL particle size because they act like BB pellets, damaging your arteries upon contact. If your small, dense LDL is high, that’s also a sign of insulin resistance. On the contrary, very low-density LDL cholesterol (VLDL) particles are like beach balls; they are light and fluffy, gently bouncing off your arterial walls and less likely to cause damage. So, someone can have low LDL cholesterol and still be at high risk for heart disease if their LDL is mostly the small, dense cholesterol type, and someone can have high LDL cholesterol and be at low risk for heart disease if their cholesterol is mostly VLDL. Traditional medicine emphasizes LDL cholesterol because we have powerful drugs that are effective at lowering it. However, if our LDL is high, our triglycerides are low, and our HDL is high, the likelihood of a cardiovascular event is still very low. In fact, that person would likely be in good cardiometabolic health even if their LDL is high. But this part of the story has been conveniently left out, making it easy for statins to be prescribed. Moreover, if our small, dense LDL particles are high due to insulin resistance, statin drugs aren’t going to resolve that problem. On top of that, when patients have high LDL, doctors usually give the general advice to go on a low-fat diet. While this might drive total LDL down, your small, dense LDL will remain the same—or increase even further—from eating a low-fat, carb-rich diet. Apolipoprotein B: ApoB is a peptide found on the surface of lipoproteins, namely LDL, which carries more than 90 percent of the apoB particles in our body. This means apoB closely represents the number of LDL particles in your plasma. Why it's important: ApoB is a measure of the number of potentially dangerous small, dense LDL cholesterol particles in the blood and can predict the risk for atherosclerotic cardiovascular disease.Further Reading: Peter Attia on apoB​​Levels currently doesn't have these bonus tests on their panel, but they are working on adding them in the future. In the meantime, if you haven't gotten your labs done recently I would highly recommend getting your Metabolic Health Panel done with them or asking your current doctor to make sure the tests in this newsletter are included the next time you get your blood work done.Final ThoughtsRoutine lab work can help us understand the bigger picture of what’s going on with our metabolic health, but it does have its limitations. If we have a general understanding of our blood glucose and cholesterol markers, what influences them, and the optimal reference ranges to strive for, we can become the CEO of our own health and see where adjustments might need to be made if our levels start to lean in the direction of metabolic dysfunction. That doesn’t mean you have to know the ins and outs of all these lab markers, but knowing the context around how your blood glucose and cholesterol are related and how they influence each other can help you feel empowered knowing that your health lies in your hands.It's all about personalization and figuring out what diet works best for you; metabolic lab tests are an important part of the equation. To easily refer back to these optimal reference ranges, use my cheat sheet below. You can always go back and read or reference this newsletter or any of my previous Try This newsletters on my blog. ⚠️ As always, these newsletters are for educational purposes only. None of the information included in today's article, or any past Try This newsletter, is medical advice. These cheat sheets are designed to help you ask better questions of your medical practitioner. Information is power, and working together with your doctor you can design a plan that’s best for your long-term health. If you have questions about your unique medical situation please consult your healthcare practitioner.--Here’s to your health,Dhru Purohit

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