Try This: Optimal Metabolic Health Labs Q&A Follow-Up

A couple of weeks ago, I wrote a newsletter on the best lab tests to ask your doctor for and how to interpret them to understand what’s going on with your metabolic health. This was inspired by my most recent conversation with Dr. Casey Means.

I want to use this week’s newsletter as an opportunity to answer some of the top questions we received in response to our Try This: Optimal Metabolic Health Labs newsletter. 

Sometimes, the more we learn about a topic the more questions we have, and that’s a beautiful thing! It means we want to know more so we can feel confident that we have all the information necessary before making a change or having a conversation with our doctor.

You guys know I’m all about covering the gray area, so I’m excited to use this time to answer some of your questions and hopefully clear up any confusion.

⚠️ Disclaimer: As always, these newsletters are for educational purposes only. These cheat sheets are designed to help you ask better questions of your medical practitioner. Information is power, and by working together with your doctor, you can design a plan that’s best for your long-term health.

All right—without further ado, let’s get started with our first question!

Question #1: If LDL results are garbage and total cholesterol does not tell you much, then why give optimal ranges at all? That sends mixed messages. – Jill

Answer: You’re right! What I should have said instead was, “If your LDL cholesterol comes back high, that’s a sign that you need to look at other markers (i.e., triglycerides, HDL cholesterol, and triglycerides-to-HDL ratio). This provides more context around whether or not high LDL is a concern for your health and overall risk for disease.”

It was misleading for me to say LDL is “garbage” because you can still get some information from looking at your LDL number. Having high LDL cholesterol could be a potential red flag for metabolic dysfunction. However, we need to be aware that LDL by itself doesn’t tell us the full story. LDL is only a garbage test if your LDL number comes back high and your doctor wants to put you on a statin without considering your full profile of metabolic markers.

New research shows an association between high LDL cholesterol and lower rates of all-cause mortality in adults over age 60 and that low LDL cholesterol could actually be a risk factor for neurodegenerative diseases due to cholesterol’s role in brain and cellular health.

This is obviously inconsistent with everything we’ve been taught about cholesterol, but it raises the important point that high LDL cholesterol warrants further investigation—and especially before prescribing a drug that could have potential long-term side effects. An NMR test can give you the size and number of LDL cholesterol particles so you can know the full picture of whether or not it’s problematic.

So, do I think that LDL cholesterol is an important biomarker? Yes. It can be a good start for scratching the surface of how much cholesterol your body is making. Do the experts that I look up to (Dr. Mark Hyman, Dr. Casey Means, and Dr. Robert Lustig) think it’s the gold standard for detecting signs of heart disease? Absolutely not.

Question #2: My mother has recently been told she has polygenic hypercholesterolemia, and it would be interesting to know how genetic factors influence treatment/recommendations/actions. – Catherine

Answer: As someone who has a genetic predisposition to hypercholesterolemia, here are a few key points I’ve learned along the way on my own personal health journey:

  1. I mentioned it above, but I’ll say it again because it is super important: Looking at one cholesterol marker doesn’t give us the full picture. We need to look at all of them, and the ratios of certain markers, to have a comprehensive understanding of whether or not high cholesterol levels are actually problematic.
  2. Personally, I’ve seen that cutting down on processed foods, refined starches, and sugar has helped get my lipids—and my family’s lipids—in the optimal ranges. As an added bonus, nearly every single one of my metabolic markers has improved as well (i.e., fasting blood glucose, fasting insulin, HbA1c, and triglycerides-to-HDL ratio).
  3. If possible, I would recommend your mother ask her doctor for a full NMR test for peace of mind to know what type of cholesterol (small, dense LDL or light, fluffy VLDL) is making up her total cholesterol number to know whether or not her numbers are problematic.Even if her results come back that they are the artery-damaging, small, dense LDL cholesterol, significant improvements can be made to her metabolic health in a matter of a few months with the right diet and lifestyle changes. Sometimes medicine can be helpful, but improving her diet and lifestyle definitely can’t hurt and will probably have an added benefit that medicine alone can’t provide.I asked my brother-in-law and board-certified cardiologist, Dr. Neel Patel, to review this week’s newsletter and he had some insightful commentary on the effects of glucose and certain hormones have on each other and familial hypercholesterolemia:“It’s also worth noting that the molecules in the bloodstream (glucose, cortisol, adrenaline, cholesterol, etc) all influence each other. So even if you have true homozygous familial hypercholesterolemia, adjusting the other concentrations of molecules in your blood can help minimize the potential damage the excess cholesterol has on your arterial walls.”
  4. Epigenetics tells us that our genes are not our fate. Just because we’re genetically predisposed to high cholesterol levels doesn’t mean that heart disease is inevitable. Genetics may put you at a higher risk, but you can make the right choices for your health to keep those genes turned off. This requires eating a whole-foods diet, managing stress, being physically active, filling in nutritional gaps, and having a community for support.

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Question #3: Is there a standard for what “fasting” (glucose, insulin, etc) means—12 hours, 18 hours, 36 hours? Is there a defined period, like anything greater than 12 hours, for example? Or can one skew the results by fasting beyond a certain number of hours? – Doug

Answer: Generally, when doctors ask their patients to fast before getting blood work, they typically mean not eating for between eight and 12 hours prior to giving blood. Fasting for a longer period generally helps stabilize blood glucose, so one would likely see an improvement in their fasting blood glucose the longer they go without eating.

But that’s only if you practice intermittent fasting or time-restricted eating on a regular basis. For example, fasting for 16 hours (time-restricted eating) would likely improve your fasting blood glucose in the short term, and if you did it regularly you would see improvements in your fasting blood glucose in the long term as well.

The exception would be in someone who has blood sugar dysregulation, prediabetes, or diabetes; who has gone for an extended period of time without food—say, overnight; and who has their fasting blood glucose checked in the morning. It’s not uncommon for an overnight fast to yield a high fasting blood glucose in diabetics. Why?

Well, it could be due to two reasons. I will address one of the reasons here and the second one (the dawn phenomenon) in the answer to our next question. High morning fasting blood glucose could be due to the Somogyi effect (also referred to as rebound hyperglycemia). The Somogyi effect happens at night when your blood sugar drops too low and your body releases stress hormones like cortisol and adrenaline to bring it back up.

These stress hormones tell your liver to release glycogen to bring your blood sugar levels up, but it overcompensates and releases larger amounts than usual. We’re already more prone to being insulin resistant in the morning because our cortisol levels naturally rise, which makes us more glucose intolerant. But a person with diabetes is already glucose intolerant, and this surge in cortisol can exacerbate the effects of insulin resistance and lead to high blood sugar.

A note from Dr. Patel: Some people experiencing rebound hyperglycemia report waking up feeling like they had just had a bad dream. If you are prediabetic or diabetic and have experienced this, it could be the Somogyi effect.

Question #4: Dhru—another excellent newsletter, but I wanted to mention two things. Some people (myself included) always have a fasting glucose of around 105mg/dL, no matter what we eat. I believe this is because of the “dawn effect,” which causes blood sugar to rise just before dawn in some people. – Robert

Answer: This is true! The dawn phenomenon is when your body starts to release glucose in the early hours of the morning (from about 3 a.m. to 8 a.m.) to get your body prepared for getting up the next day. Growth hormone, cortisol, and adrenaline levels rise, which also increases insulin resistance, resulting in high morning blood sugar.

Typically, morning blood glucose levels go back down to baseline after being up for the first hour of your day. If your blood sugar is not going below 105mg/dL after the first few hours of the day, I wouldn’t chalk that up to just the “dawn effect”. That would be cause for me to dig deeper with my doctor and see if stress levels, too much caffeine, or sleep apnea are playing a role in your morning fasting blood glucose being higher than what most doctors would consider optimal.

Question #5: Of all these measurements, would there be a top three-to-five tests that would provide the best overall metabolic health? – David

Answer: Here are the top three lab tests that my dear friend Dr. Casey Means recommended in our conversation together on my podcast:

  • Triglycerides-to-HDL-cholesterol ratio
  • Fasting insulin
  • Hemoglobin A1C (HbA1c)

Click here for a detailed overview of what these tests mean and how to interpret them.

Question #6 (more of a comment than a question): Apparently, optimal health is only going to be achieved by the wealthy who can afford all the necessary technology, tests, and resources. Subscriptions and prices on supplements are not affordable for many, many Americans. I guess good health is like buying a house: only the well-off can afford it. And yes, I know you can make healthy food choices and so on, but that is also expensive—look at the demographics of the unhealthiest in the US. – Lisa

Commentary: I completely agree that technology, supplements, and resources typically aren’t accessible to the people and communities who need them the most. But I don’t think reaching a baseline of good health requires any of those things. You don’t need fancy technology, testing, or memberships to get your health on the right track. Yes, they can play a part, but I believe that the journey to better health starts with education and having a community for support.

A big reason behind why I was inspired to start the Try This newsletter is to provide free health information to the public using evidence-based, simple, practical tips that anyone can try.

My intention for my previous Optimal Reference Ranges newsletter and this Optimal Metabolic Health Labs newsletter was to raise awareness that

  1. it’s not normal to feel like crap;
  2. optimal reference ranges can help catch metabolic dysfunction and prevent disease sooner than traditional reference ranges; and
  3. understanding what your metabolic lab results mean can help you feel confident and comfortable talking with your doctor to get what you need to make sure that your health is headed in the right direction.

I hope our newsletters can help you feel empowered on your health journey to do just that.

For anyone who wants to learn more about the systemic issues around food and the socioeconomic disparities driving the metabolic health crisis, my business partner, Dr. Mark Hyman, has written a book called Food Fix that breaks down these problems and presents a detailed, multifaceted solution.

Concluding Thoughts:

I hope this week’s newsletter was helpful for expanding on the discussion of important points and questions our audience members brought to our attention. There’s always more conversation to be had, more nuance to cover, and more details to address.

I wish I could get to all of the gray areas in these newsletters, but I’m sure you understand it’s tough to get to everything! That’s why I love hearing what you guys have to say and what stood out or resonated the most with you!

If you ever have any questions about any Try This newsletter, I encourage you to always feel free to reply back using the feedback feature below.

We can’t always answer everybody’s questions, but we read everything—and hey, who knows, maybe you’ll see one of your questions answered in another follow-up newsletter like this one.


Here’s to your health,
Dhru Purohit

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