The 2024 Levels Guide to understanding your cholesterol panel and blood tests

The "normal" ranges for cholesterol and other blood tests are far from optimal. We asked eight leading metabolic health experts what you should really aim for.

WRITTEN BY

The Levels Team

UPDATED: 09 Oct 2024

PUBLISHED: 22 Oct 2021

🕗 29 MIN READ

Most of us get a standard panel of blood tests—cholesterol, glucose—every year or two at a physical. We assume that if any particular result is too high or low, the doctor will let us know. In other words, no news is good news. Maybe we Google a number if it looks higher than the standard ranges, but even when we do, it’s difficult to know what one sort-of-high number means.
This is not the path to optimal health.

We believe you should be empowered to make sense of those results yourself. You should know what the values tell you about what’s going on in your body. And you should have a sense of not just the “standard” ranges for each test, but the optimal levels for each test and how they interact with each other.

For example, despite all the scaremongering, LDL cholesterol on its own doesn’t actually tell us that much unless it’s at very rare high levels. What matters more is what types of LDL particles we have, specifically the ratio of small dense LDL particles (the problem-causing ones) to big fluffy ones. But since the test for that is hard to get, you can get a sense of it from your triglyceride-to-HDL ratio.

When we talk about optimal ranges for these values, there’s still a lot of nuance and disagreement, but one thing is clear: They’re much stricter than the “standard” ranges you see on the pamphlet with your results. Even so-called normal levels may be an indication of a problem that’s already taken root and needs to be addressed.

It’s also important to understand that none of these markers exists in isolation. For Americans to become metabolically healthier, we need to begin looking at metabolic labs in a more nuanced way and understanding the labs in context with each other.

We put together this guide by talking to eight Levels advisors who are experts in metabolic health. We’ve compiled their feedback below along with a general consensus. The point isn’t to give you more challenging numbers to aim for, but to help you understand that blood test markers are complex, they represent inter-related systems in your body, and they’re worth investing time to understand.

Print out your last lab results, grab a pen and this article, and dig in.

⚠️ This information does not constitute medical advice. This is compiled expert opinion for educational purposes. Your doctor knows you best. Talk to your doctor for specific questions about your personal lab results.

The Tests

1. High sensitivity C-reactive protein (hsCRP)

2. Hemoglobin A1c (HbA1c)

3. Fasting Glucose

4. Fasting Insulin

5. Low-Density Lipoprotein Cholesterol (LDL-C)

6. Triglycerides

7. High-Density Lipoprotein Cholesterol (HDL-C)

8. Total Cholesterol

9. Total Cholesterol-to-HDL Ratio

10. Triglyceride-to-HDL Ratio

11. Post-Meal Glucose

12. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

Quick Summary of Expert Guidance

The Advisors:

• Ben Bikman, PhD: Associate Professor at Brigham Young University, leading insulin researcher and author of Why We Get Sick.
• Dom D’Agostino, PhD: Associate Professor at University of South Florida, leading researcher in neuro implications of keto, runs Keto Nutrition.
• Dr. Sara Gottfried: Director of Precision Medicine at the Marcus Institute of Integrative Health-Jefferson Health, pioneering physician-scientist, author of four books; research focus on metabolic phenotypes and prediabetes development.
• Dr. Mark Hyman: Head of Strategy and Innovation at the Cleveland Clinic Center for Functional Medicine, author of 14 best-selling books, focuses on the role of food as medicine.
• Dr. Rob Lustig: Professor emeritus of Pediatrics at UCSF, research and clinical focus on childhood obesity and diabetes, author of four books about the dangers of sugar and processed food.
• Dr. Molly Maloof: Functional medicine physician and biotech consultant, Stanford lecturer on “Healthspan: Living Better Longer;” focuses on personalized medicine and longevity.
• Dr. Casey Means: Chief Medical Officer and co-founder of Levels; Associate Editor of the International Journal of Disease Reversal and Prevention; Stanford-trained physician.
• Dr. David Perlmutter: Associate Professor at the University of Miami School of Medicine, leading expert in neurodegeneration and metabolic health, author of five best-selling books, including Grain Brain.

High sensitivity C-reactive protein (hsCRP)

A protein made by the liver that rises in blood concentration when you have inflammation.

Why is it important?

Dr. Hyman: The easiest way to measure hidden inflammation in the body is C-reactive protein. C-reactive protein is significantly elevated in most people with diabesity (aka, insulin resistance). As the diabesity gets better, the inflammation goes down.

Dr. D’Agostino: High CRP levels are found in those with obesity, heart disease, diabetes, Alzheimer’s disease, leaky gut, infection, cancer, sleep disorders (like obstructive sleep apnea, or OSA) and other states of chronic inflammation. Notably, all features of metabolic syndrome are associated with increased levels of CRP. There is high value in keeping track of your hsCRP levels from both a preventative and treatment standpoint.

Dr. Maloof: When CRP is too high, it means too much inflammation. This may be caused by autoimmunity, pathogen mediated immunity, senescent cell secretory proteins (part of “inflamm-aging”), and other inflammatory conditions.

Dr. Means: Inflammation is a key driver of metabolic dysfunction, and metabolic dysfunction leads to further inflammation. hsCRP can give you a signal of how much general inflammation is going on in the body. Higher BMIs, abdominal obesity, and increasing levels of insulin resistance are all associated with higher levels of CRP.

Dr. Gottfried: hsCRP is a clinical biomarker of general and cardiac-related inflammation.

Dr. Lustig: The problem with hsCRP is that it is an “acute-phase reactant”. In other words, if you have a virus or other acute disease, it can raise hsCRP irrespective of your metabolic status. This makes hsCRP sensitive, but not specific, for inflammation.

Dr. Bikman: Whether from hypertrophic adipocytes, arterial foam cells, or simple white blood cells doing their job, hsCRP is a solid indicator of subclinical systemic inflammation. Accordingly, it can be a canary in the coal mine of things to come–insulin resistance, atherogenesis, and more.

Standard ranges:

• Lower risk of heart disease: hs-CRP level less than 2.0 mg/L
• Higher risk of heart disease: hs-CRP level equal to or greater than 2.0 mg/L

Source: Mayo Clinic

What levels are optimal?

Dr. D’Agostino: High sensitivity CRP (hs-CRP) detects CRP in the range of 0.5–10 mg/L and is more useful in detecting more subtle changes in inflammation, immune response and even cardiovascular risk when in excess of 3 mg/L, whereas below 1 mg/L would be low risk.
Ideal: <1.0 mg/L
Average: 1.0–3.0 mg/L
High: 3.0–6.0 mg/L
Pathologically High: >6.0 mg/L

Dr. Maloof: Shoot for <0.5 mg/L.

Dr. Gottfried: I aim for <0.5 mg/L in most of my healthy patients who are not elite athletes.

Dr. Hyman: Less than 1.0 mg/L is ideal.

Dr. Lustig: The lower the better; try for less than 1.0 mg/L.

Summary:

<1.0 mg/L is important, and some even push this to <0.5 mg/L.

What is hsCRP, and why does it matter?

This blood test helps reveal inflammation, a key driver of metabolic dysfunction and other conditions. Here's how to understand your results.

Hemoglobin A1c (HbA1c)

A way to measure blood glucose averages over the preceding three months; based on glycation, the process by which glucose molecules attach to hemoglobin in red blood cells (which tend to live around three months, although this varies person to person). The value is expressed as a percentage of hemoglobin molecules that are glycated.

Why is it important?

Dr. Lustig: Hemoglobin A1c is the blood test that assesses glucose control over the preceding three months. The problem with HbA1c is that by the time it rises, the horse is out of the barn; it’s one of the last things to change with metabolic dysfunction.

Dr. Hyman: Hemoglobin A1c, or glycosylated hemoglobin, can tell you if your overall blood sugar has been high over the previous six weeks. This test is used in monitoring diabetics but has now been proposed as a better way of diagnosing diabetes than just a random fasting blood sugar test. Even in the face of normal fasting blood sugar your hemoglobin A1c can be high, because it measures your average suga**r**, including the effects of all the food you eat throughout the day. I use it to screen for overall blood sugar balance.

Dr. Gottfried: Hemoglobin A1c is useful because it is a 3 month summary of glucose excursions represented as a mean.

Dr. D’Agostino: HbA1C is a measure of the formation of the sugar-hemoglobin linkage (“glycation”) that is indicative of the presence of excessive sugar in the bloodstream over a period of three months. The fraction of glycated hemoglobin increases in a predictable way and is associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy.

Dr. Maloof: The hemoglobin A1C (HbA1c) blood test measures the percentage of a patient’s hemoglobin that is coated in glucose, which reflects their average blood glucose levels from the past three months. It is the recommended diagnostic test for diabetes and prediabetes. It is more convenient than other blood glucose tests as it does not require fasting or a glucose challenge testing. Second, it is less affected by acute perturbations like stress, nutrition, exercise, and smoking. And third, it does a better job of catching chronic hyperglycemia than fasting glucose.

What are the limitations of this test?

Dr. Maloof: As a diagnostic, HbA1c has a sensitivity of only 60%, which means 40% of patients with impaired fasting glucose and/or impaired glucose tolerance will go under-diagnosed, delaying their opportunity for treatment. One study found that in comparison to fasting glucose and the two-hour oral glucose tolerance test, HbA1c has a false negative rate of 64.9% for prediabetes and 75.1% for diabetes, and a false positive rate of 20.1% for prediabetes and 0.6% for diabetes.

HbA1c also does not address glycemic variability nor does it explain more than 30% of the variation in fasting plasma glucose. And while some people equate HbA1c to estimated average glucose, an estimated average glucose of 154 mg/dL could fall between the HbA1c range of 6% and 8%, encompassing both prediabetes and diabetes. This issue alone makes the use of HbA1c questionable for guiding clinical decisions.

There are also problems with biological variability between various ethnic groups, as well as a variety of conditions that influence red blood cell turnover. For example, people of African, Mediterranean, or Southeast Asian descent may have a variant of hemoglobin other than hemoglobin A (e.g. hemoglobin S, C, or E) that leads to false results. Hemoglobinopathies, anemia, blood loss, malaria, high triglycerides, chronic liver disease, and certain drugs can all cause falsely low HbA1c test results. On the other hand, iron deficiency, B12 deficiency, alcoholism, uremia, hyperbilirubinima, and some drugs can cause falsely high HbA1c.

Dr. Gottfried: This test has many limitations as it’s not a reflection of what’s happening day to day, like variability. It can also be falsely low in some of my patients with hypoglycemia at night, something I see in a lot of perimenopausal and menopausal women.

Dr. Lustig: By everyone’s estimation, under 5.5% is normal, while over 6.5% is frank type 2 diabetes. It’s what goes on in between that’s up for grabs and it’s in this grey zone where most adults live. The higher it is, the greater the glycemic excursions, and the more risk for metabolic disease.

Dr. Bikman: As the A1c test came into prominent use, it replaced the oral glucose tolerance test (regrettably). One consideration with A1c is that while many view it as an indicator of glucose levels, others could view it as an indicator of red blood cell (RBC) longevity. Simply put, if a person has robust and long-lived RBCs, it’s more likely that some will be glycosylated even if the person has normal glucose levels. In other words, a false positive. In contrast, a person with more fragile RBCs, but high glucose, would have an artificially low A1c, not because the glucose is low, but because the RBCs aren’t alive long enough to be glycosylated; a false negative.

Standard ranges:

• Under 5.7 percent is considered normal.
• Between 5.7 and 6.4 percent is diagnostic for prediabetes.
• 6.5 percent or above is diagnostic for diabetes.

Source: American Diabetes Association

What levels are optimal?

Dr. D’Agostino:
Optimal : <5.0% (common in with low carbohydrate diet, or calorie restriction)
Normal: <5.7%
Prediabetes: 5.7–6.4%
Diabetes: >6.4%

Dr. Maloof: Optimal: 4.5%–5.3%

Dr. Gottfried: The American Diabetes Association would say <5.6%, but I like <5.2%. In some people with prediabetes, I’m aiming for <5%.

Dr. Hyman: Ideally it should be less than 5.5%.

Dr. Lustig: I like to see 5.5% or less. Glucose intolerance is pretty likely at HbA1c > 6%.

Dr. Perlmutter: The average A1c should ideally be in the range of 5.2%.

Summary:

Shoot for <5.5%, but some experts say that <5.0% is even better.

What is HbA1c, and why does it matter?

Unlike other blood sugar tests, HbA1c reflects your average glucose levels over time. Here's why it's a useful marker for minding blood sugar.

Fasting Glucose

A measure of your blood sugar levels unaffected by a recent meal.

Why is it important?

Dr. Maloof: A fasting blood glucose level can help identify problems with carbohydrate metabolism. If it is too high, it may be due to diabetes, either from pancreas disease (Type 1 diabetes) or insulin resistance disease (Type 2 diabetes).

Dr. Gottfried: Fasting glucose tells us how the body performs vis-a-vis insulin and glucose pathways in the absence of food.

Dr. D’Agostino: Fasting blood glucose is the easiest blood biomarker to track and is highly correlated with metabolic syndrome, cardiovascular risk, dementia and many other chronic diseases.

Dr. Lustig: Every practitioner gets a fasting glucose on all their adult patients, looking for type 2 diabetes. Yet this is the single worst parameter to measure, because it’s the last thing to change. Once the fasting glucose rises over 100 mg/dl (signifying glucose intolerance; 126 mg/dL or above means frank diabetes), metabolic syndrome is in full force, and there are no options for prevention anymore; now you’re in full-fledged treatment mode. But in fact, a fasting blood glucose of 90 mg/dL is already questionable.

Dr. Hyman: There are six stages of diabesity or insulin resistance. The first stage of insulin resistance is high spiking levels of insulin 30 minutes, one hour, and two hours after the introduction of a sugar load. Your blood sugar may stay completely normal in these time frames. The second stage is elevated levels of fasting insulin with a perfectly normal blood sugar level while fasting and after a glucose challenge test. The third stage is the elevation of blood sugar and insulin after a sugar load at 30 minutes, one hour, or two hours. The fourth stage is an elevation of your fasting blood sugar level higher than 90 or 100 mg/dl and elevation of fasting insulin. As you can see, by the time fasting blood sugar is higher than 90 or 100 mg/dl, this is far down the progression of insulin resistance.

Dr. Bikman: Blood glucose matters—chronically high levels will damage blood vessels and nerves through several distinct mechanisms. However, to be most valuable, glucose needs to be viewed dynamically—how does it rise and fall in response to certain stimuli (e.g., diet, exercise, sleep).

Standard ranges:

• Fasting blood sugar levels under 100 milligrams/deciliter (mg/dL) are considered normal.
• Levels between 100 and 125 mg/dL indicate prediabetes.
• Levels equal to or greater than 126 mg/dL are diagnostic for diabetes.

Source: American Diabetes Association

What levels are optimal?

**Dr. D’Agostino:**Optimal: < 90 mg/dL
Normal: <100 mg/dL
Pre-Diabetic: 100–125 mg/dL
Diabetic: >126 mg/dL

Dr. Maloof: According to ADA criteria, a normal fasting glucose level is between 70–99 mg/dL. A fasting glucose between 100–125 mg/dL is a sign of prediabetes, while levels greater than 126 mg/dL suggests diabetes.
My clinical approach:
Optimal: 72–89 mg/dL
May have increased risk of prediabetes: 90–100 mg/dL
Prediabetes: 100–125 mg
Diabetes: >125 mg/dL

Dr. Gottfried: I target 70–85 mg/dL, or even 65–85 mg/dL in my patients in ketosis.

Dr. Hyman: Fasting blood sugar should be less than 85 mg/dL.

Dr. Means: Aim for a fasting glucose of 72–85 mg/dL. Multiple research studies show that as fasting glucose increases, there is an increased risk of health problems like diabetes and heart disease—even if it stays within the normal range. Keeping fasting glucose in the low-normal range between 72–85 mg/dL is optimal.

Dr. Lustig: Once fasting glucose rises over 100 mg/dL, metabolic syndrome is in full force. A fasting glucose of 90 mg/dL is already questionable.

Dr. Bikman: Fasting glucose under 100 mg/dL is a comfortable range. However, rather than only relying on fasting levels, explore the response to a carbohydrate challenge. If glucose levels fail to fall to 100mg/dL two hours after consuming around 75g of glucose, that’s a problem.

Summary:

Once fasting glucose has gotten to 100 mg/dL, insulin resistance is in full force. Try to keep fasting glucose <90 mg/dL, but as low as 65 mg/dL may be normal in patients in ketosis. Aim for the 70s–low 80s.

Fasting Insulin

A measure of insulin levels unaffected by a recent meal; insulin is the hormone that helps shuttle glucose into cells (among many other things).

Why is it important?

Dr. Lustig: The body will do everything it can to maintain a fasting serum glucose below 100 mg/dL, including increasing insulin (that’s insulin resistance!). So, irrespective of fasting glucose, you want to have a simultaneous fasting insulin level, which tells you how hard the pancreas is working. Many academic societies (including the American Diabetes Association) don’t advocate getting a fasting insulin level. They have several arguments against it such as cost (about $15), reproducibility, and the fact that fasting insulin doesn’t correlate with BMI—which is exactly the point. It’s not about obesity; it’s about metabolic health. If you don’t measure fasting insulin, you’re missing all the people who are normal-weight metabolically ill people (TOFIs: “thin on the outside, fat on the inside”).

Dr. Hyman: The second stage of diabesity is elevated levels of fasting insulin with a perfectly normal blood sugar level while fasting and after a glucose challenge test. The first stage is a spike in insulin after a meal or a glucose challenge test.

Dr. Bikman: Too much insulin causes insulin resistance. To be precise about it, for every one micro unit increase in fasting blood insulin, a person can experience an approximately 20% increase in insulin resistance. This might seem like a strange cause-and-effect, but it represents a fundamental feature of how the body works—when a process is excessively activated, the body will often dampen its response to the excess stimulus in order to reduce the activation. At its simplest, insulin resistance is a reduced response to the hormone insulin. When a cell stops responding to insulin, it becomes insulin resistant. Ultimately, as more cells throughout the body become insulin resistant, the body is considered insulin resistant. In this state, certain cells need more than normal amounts of insulin to get the same response as before. That’s the key feature of insulin resistance: blood levels of insulin are higher than they used to be, and the insulin often doesn’t work as well.

We can have a scenario where a person is steadily becoming more and more insulin resistant, but the insulin is still working well enough to keep blood glucose in a normal range. This can develop over years, even decades. But because we more typically look at glucose as the problem, we don’t recognize there’s an issue until the person is so insulin resistant that their insulin, no matter how much they produce, is no longer enough to keep their blood glucose in check. It’s at this point, possibly years after the problem started, that we finally noticed the disease.

This is why so many people with insulin resistance are undiagnosed—we look at it wrong.

Standard ranges:

Normal range is considered < 25 mIU/L.

Source: MedScape

What levels are optimal?

Dr. Hyman: Fasting insulin should be between 2–5 IU/dL; anything greater than 10 IU/dL is concerning, and over 15 IU/dL is significantly elevated.

Dr. Lustig: A fasting insulin should be less than 10 microunits/mL. Anything greater than 15 microunits/mL means significant insulin resistance, and risk for metabolic disease. From the glucose and insulin levels together, you can calculate an index called the homeostatic model assessment of insulin resistance (HOMA-IR = glucose x insulin / 405), which assesses your risk for diabetes. A HOMA-IR of <2.0 is excellent, 4.0 is average, and anything higher means trouble.

Dr. D’Agostino: Optimal fasting insulin should be in the 2–6 μIU/mL range.

Dr. Perlmutter: Fasting insulin level should target 8 or lower.

**Dr. Bikman:
**10 uIU/mL or lower = insulin sensitive
11-20 uIU/mL = warning range
20s or beyond = red line, strong insulin resistance

Summary:

Fasting insulin is an extremely important test because fasting insulin rises long before fasting glucose does, so may be an early warning sign for metabolic disease. Optimal levels of fasting insulin are probably somewhere between ~2-6 uIU/mL.

What are normal levels of insulin and why don't we test it more?

Insulin is the key hormone for maintaining stable glucose, yet it's rarely tested. Here's why and what you should look for when tested.

Low-Density Lipoprotein Cholesterol (LDL-C)

Low-density lipoprotein accompanying cholesterol; often implicated in plaque buildup leading to atherosclerosis, sometimes called “bad” cholesterol.

Why is it important?

Dr. D’Agostino: For a fixed level of HDL, the cardiovascular risk increases 3-fold as LDL varies from low to high. Oxidized LDL is involved in atherosclerosis, and in the context of glucose dysregulation the elevation of LDL could be a strong cardiovascular risk factor. Risk factors associated with high LDL is a factor in the context of other elevated biomarkers (Triglycerides, HbA1c, hsCRP, etc.)

Dr. Maloof: LDL is the cholesterol that clogs blood vessels. It is called “bad” cholesterol because it can transport lipids into artery walls and harden the arteries. Major prevention trials have demonstrated a linear relation between LDL levels and the coronary event rate.

Dr. Hyman: We measure and treat LDL because it is what we have the best drugs to treat it, not because it is the most important marker of your risk of heart disease. In fact your LDL cholesterol is a very bad predictor of your risk of heart disease when compared with the total cholesterol-to-HDL ratio. And this is not as good a predictor as the triglyceride-to-HDL ratio.

What are the limitations of this test?

Dr. Hyman: Unfortunately, the old way of testing cholesterol can lead to deceptive conclusions. You may have a totally normal total and LDL cholesterol but be at very high risk of a heart attack because it is the wrong type of cholesterol. In fact, more than 50 percent of people who show up in the emergency room with heart attacks have normal cholesterol. But they have small cholesterol particles, which are caused by insulin resistance. The newer cholesterol test I recommend is called nuclear magnetic resonance spectroscopy, or NMR lipid testing. Studies have found that people who have a cholesterol level of 300 mg/dl but have very large cholesterol particles have very little risk of cardiovascular disease. On the other hand, people with a “normal” cholesterol level—such as 150 mg/dl—but very small and numerous LDL and HDL cholesterol particles have an extremely high risk of heart disease. But what causes these small dangerous cholesterol particles? It is the sugar and refined carbohydrates in our diet. Insulin resistance causes these small cholesterol particles to form, and taking statins won’t fix the problem. The NMR test for cholesterol is one of the most essential tests in evaluating the degree of insulin resistance and cardiovascular risk. Smaller particles are dangerous. They act like BB pellets, damaging arteries and putting your health at greater risk. Light, fluffy beach-ball-like cholesterol particles, on the other hand, are harmless and bounce off arteries regardless of the overall LDL cholesterol number.

Dr. Lustig: The takeaway of the Framingham Heart Study was that if you had very high LDL-C, you were more likely to suffer a heart attack. But when the data were analyzed, unless LDL-C was very high (over 200), it wasn’t a risk factor. Those with an LDL-C less than 70 develop relatively little heart disease. But for the rest of the population, LDL-C is not a great predictor of who will suffer a heart attack. More people are suffering heart attacks with lower LDL-Cs than before, because the standard test of cholesterol assumes all the LDL particles are the same. There are two different LDLs, but the lipid profile test measures them together. The majority (80 percent) of circulating LDL species are called large buoyant, or type A LDL, which are increased by dietary fat consumption. This is the species reduced by eating low-fat or taking statins. However, large buoyant LDL are cardiovascularly neutral – meaning it’s not the particle driving the accumulation of plaque in the arteries leading to heart disease. There’s a second, less common (only 20 percent) LDL species called small dense or type B LDL, and it is predictive of risk for heart attack. The problem is that statins will lower your LDL-C because they are lowering the type A LDL, which is 80 percent of the total; but they’re not doing anything to the type B LDL, which is the problematic particle.

If you have a high LDL-C level, your provider is likely to tell you to eat a low-fat diet. Similar to statins, while your LDL will go down, it’s only affecting the large buoyant LDL and not the small dense LDL, which is the actual problem. Small dense LDL rises because they are responsive to dietary refined carbohydrates (ie fiberless food) and especially sugar consumption.

Your fasting lipid profile test also measures another particle, which is much more egregious than LDL: triglycerides. The main reason for high triglycerides has nothing to do with LDL-C; rather, it’s the refined carbohydrates and sugars in your diet. The #1 risk factor for heart disease isn’t LDL-C; it’s the insulin resistance of metabolic syndrome, of which triglycerides is a much better marker than LDL-C. The serum triglyceride, which unloaded of its fat at the adipose tissue, becomes the small dense LDL. Therefore, the triglyceride-to-HDL ratio – the real ratio of bad to good cholesterol – is the best biomarker of small dense LDL, the best biomarker of cardiovascular disease, and the best surrogate marker for insulin resistance and metabolic syndrome.

Dr. Maloof: LDL IS A GARBAGE TEST. You want particle numbers (i.e., amount of small density and large density LDL particles.)

Dr. Gottfried: I measure ApoB and NMR Lipoprotein fractionation which I consider more important and a deeper view of lipoprotein metabolism (NMR Lipoprotein fractionation measures particle sizes, like small density LDL and high density LDL). LDL is very old school, though it’s still used in mainstream guidelines.

Dr. Bikman: LDL is a very misunderstood molecule. The degree to which it contributes to heart disease is very unclear. More clear, however, is its role in immunity. LDL has the capacity to bind and “neutralize” infectious, pro-inflammatory pathogens, escorting them to the liver to be further eliminated from the body. This could be why people with the lowest LDL levels have a significantly higher risk (5X) of frequent fevers and serious infections (i.e., sepsis).

Standard ranges:

• Less than 70 mg/dL for those with heart or blood vessel disease and for other patients at very high risk of heart disease (those with metabolic syndrome)
• Less than 100 mg/dL for high risk patients (for example: some patients who have diabetes or multiple heart disease risk factors)
• Less than 130 mg/dL otherwise

Source: Cleveland Clinic

What levels are optimal?

Dr. Lustig: If LDL cholesterol is below 100 mg/dL, the small dense fraction can’t be high enough to be harmful. If it’s over 300 mg/dL, you might have the rare genetic disease familial hypercholesterolemia (FH) and you can’t clear LDL, and you need a statin. If it’s between 100–300 mg/dL, then you need to look at the triglyceride level. If the triglyceride level is above 150 mg/dL, that’s metabolic syndrome until proven otherwise.

**Dr. D’Agostino:
**Normal: 100–150 mg/dL (lower risk for cardiovascular disease)
Optimal: <150 mg/dL
Potentially Higher Risk: >150 mg/dL (although, less of a concern for those following a high fat/low carb diet)

Dr. Maloof: Optimal: <100
European guidelines optimal: <115 mg/dL
Sub-optimal: 101–130 mg/dL
High: 130–190 mg/dL
Critically high: 191mg/dL

Dr. Gottfried: <70 mg/dL

Dr. Hyman: LDL cholesterol < 70 mg/dL is optimal, however, it depends on the size and the number of the LDL particles which cannot be determined by measuring the LDL-C alone.

Summary:

Absolute values of LDL can be misleading, as the types of LDL that make up the total number matter more, including the amount of small dense LDL particles and high-density LDL particles. Triglycerides and triglyceride-to-HDL ratio can give us additional insight into our cardiovascular health and risk. Overall, shoot for LDL <100 mg/dl, but less than 70 mg/dL is considered optimal by some. And, look at the LDL value in the context of triglyceride-to-HDL ratio, as this ratio is a helpful biomarker for risk of cardiovascular disease and the presence of insulin resistance

Why ApoB may be a better cholesterol marker

ApoB reveals more about heart health than traditional cholesterol tests—but most people haven't heard of it. Here's why that's changing.

Triglycerides

A type of lipid stored in fat cells when calories go unused; mainly carried through the blood by very-low-density lipoproteins (VLDL), which become LDL once they give up their triglycerides.

Why is it important?

Dr. D’Agostino: High serum triglycerides indicate metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) and also increase the risk of acute pancreatitis. It is an indication that excess calories are being consumed, typically in the form of sugar and fructose, which has the greatest negative impact when consumed in excess.

Dr. Lustig: Your fasting lipid profile test also measures another particle, which is much more egregious than LDL: triglycerides. The main reason for high triglycerides has nothing to do with LDL-C; rather, it’s the refined carbohydrates and sugars in your diet. The #1 risk factor for heart disease isn’t LDL-C; it’s the insulin resistance of metabolic syndrome, of which triglycerides is a much better marker than LDL-C.

Dr. Gottfried: Triglycerides reflect a type of fat in the blood, and may indicate caloric excess.

Dr. Hyman: Very often patients with diabesity have normal LDL and total cholesterol, but very high triglycerides and very low HDL. For example, it is not uncommon to see patients with triglycerides of 300 mg/dl and HDL of 30 mg/dl. This is much more of a concern to me than someone with total cholesterol of 300 mg/dl and LDL of 140 mg/dl but triglycerides of 60 and HDL of 80. So assessing triglycerides and HDL is critical.

Dr. Maloof: Elevated levels can indicate poor control of blood sugar and are linked to coronary heart disease and untreated diabetes mellitus. Inadequate patient fasting, thiazide diuretics, beta-blockers, and oral estrogen therapy can all lead to high triglyceride levels.

Triglycerides are a type of fat formed by combining glycerol with three molecules of fatty acid. They enable the bidirectional transference of adipose fat and blood glucose from the liver. Triglycerides are responsible for storing extra calories and providing your body with energy when it is needed.

Dr. Means: Triglycerides are a good marker of dietary quality. In my practice, I have seen triglycerides drop more than 80 mg/dL in less than one month in patients who eliminate refined and processed foods (refined grains and sugars), and eat whole unprocessed foods rich in fiber.

Standard ranges:

Goal is less than 150 mg/dl.

Source: Cleveland Clinic

What levels are optimal?

**Dr. D’Agostino:**Optimal: <100 mg/dL
Normal: 100–150 mg/dL
High Risk: >150 mg/dL

**Dr. Maloof:**Optimal: <80 mg/dL
Lowest: <90 mg/dL
Better: <100 mg/dL
Considered normal: <150 mg/dL
Borderline-high: 150–199 mg/dL
High TG: ≥200 mg/dL

Dr. Gottfried: Stay <150 mg/dL, and I aim lower in my patients in whom we’re optimizing metabolic health; i.e., <100 mg/dL or even <50 mg/dL.

Dr. Hyman: Triglycerides <100 mg/dL, ideally under 70 mg/dL.

Dr. Perlmutter: Triglycerides <50 mg/dL would be ideal.

Dr. Lustig: Triglycerides >150 mg/dL is indicative of dyslipidemia and risk for heart disease.

Summary:

Triglycerides are a very important marker of metabolic syndrome and insulin resistance. You definitely want them to be <150 mg/dL, but optimal is likely less than <100 mg/dL, or even lower (some say <80 mg/dL or <50 mg/dL).

High-Density Lipoprotein Cholesterol (HDL-C)

High-density lipoproteins are a type of complex made of proteins and fat that carry cholesterol in the blood. When cholesterol is in an HDL particle, it is sometimes called “good” cholesterol because HDL carries some cholesterol back to the liver, where it is broken down and passed out of the body through waste.

Why is it important?

Dr. Hyman: Triglycerides go up and HDL (or “good cholesterol”) goes down with diabesity (insulin resistance).

Dr. D’Agostino: Epidemiological studies have shown that higher concentrations of HDL (>60 mg/dL) are associated with reduced cardiovascular risk. For a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low.

Dr. Maloof: HDL particles remove lipids from cells and blood vessels. A high level is considered protective against heart disease. A low HDL level accelerates the development of atherosclerosis (hardening of the arteries) due to impaired reverse cholesterol transport and is associated with an increased risk for coronary heart disease.

Dr. Gottfried: HDL is known for its ability to scavenge for and ferry LDL cholesterol away from the arteries and back to the liver for redistribution, metabolism, and elimination. It’s also known for its anti-inflammatory, antithrombotic, anti-immune, and antioxidative activity. The prevailing dogma for the past 30 years was that high total HDL was cardioprotective, because it reflected better clearance of LDL. However, the emerging narrative is that HDL is far more heterogeneous than previously understood. In order for HDL to be cardioprotective, it must be functional. The main takeaway is that because of the heterogeneity of HDL, measurement of HDL cholesterol alone does not provide a complete picture of the protective qualities of HDL.

Increased intake of virgin olive oil, nuts, legumes, whole grains, and fish improves HDL functionality. Blue and red colored plants contain anthocyanins which make positive changes to biomarkers related to HDL function in several patient populations. Pomegranate seeds have been shown to allow HDL to better transport LDL out of the cells. Green tea extract, or EGCG, can also change the protein or fat content of HDL so that the composition is not damaged by things like oxidative stress or inflammation, thereby reducing the risk of HDL dysfunction.

Standard ranges:

Greater than 45 mg/dl (the higher the better).

Source: Cleveland Clinic

What levels are optimal?

**Dr. D’Agostino:**Optimal: >60 mg/dL
Normal: 50–60 mg/dL
Low: <50 mg/dL
High Risk: <40 mg/dL

Dr. Maloof: Aim for 50–90 mg/dL.

Dr. Hyman: HDL cholesterol >60 mg/dl is optimal.

Dr. Lustig: If it’s over 60 mg/dl, it almost doesn’t matter what the other fractions of cholesterol are, as this is a sign of good cardiovascular health. If the HDL is under 40 mg/dl (men) or under 50 mg/dl (women), then your predisposition for heart disease is much higher.

Summary:

HDL goes down in the setting of insulin resistance, and low HDL is associated with heart disease risk. It should be above 60 mg/dL, but the higher the better (i.e., up towards 90 mg/dL).

Total Cholesterol

A measure of all the cholesterol in your blood, including HDL and LDL.

Why is it important?

Dr. Hyman: Very often patients with diabesity have normal LDL and total cholesterol, but very high triglycerides and very low HDL. For example, it is not uncommon to see patients with triglycerides of 300 mg/dl and HDL of 30 mg/dl. This is much more of a concern to me than someone with total cholesterol of 300 mg/dl and LDL of 140 mg/dl but triglycerides of 60 and HDL of 80. So assessing triglycerides and HDL is critical.

Standard ranges:

• 75–169 mg/dL for those age 20 and younger.
• 100–199 mg/dL for those over age 21.

Source: Cleveland Clinic

What levels are optimal?

Dr. Hyman: Total cholesterol < 180 mg/dl.

Summary:

Total cholesterol should be less than 180 mg/dL. But there’s more to it, as this number needs to be taken in context with triglyceride and HDL levels.

Total Cholesterol-to-HDL Ratio

Why is it important?

Dr. Hyman: Your LDL cholesterol is a very bad predictor of your risk of heart disease when compared with the total cholesterol-to-HDL ratio. And this is not as good a predictor as the triglyceride-to-HDL ratio (which, incidentally, is the best way to check for insulin resistance other than the insulin response test).

Dr. D’Agostino: For a given level of total cholesterol, the risk of heart disease increases 10-fold as the HDL varies from high to low. Men have double the risk for heart disease if their ratio reaches 9.6:1, and they have roughly half the average risk for heart disease with a cholesterol ratio of 3.4:1.

Dr. Maloof: Together, these numbers provide more information about your coronary heart disease risk than knowing only one of the numbers. The higher the ratio, the higher the risk.

Standard ranges:

• Most healthcare providers want the ratio to be below 5:1.
• A ratio below 3.5:1 is considered very good.

Source: University of Rochester Medical Center

What levels are optimal?

**Dr. D’Agostino:**Optimal: <2:1
Normal: 2:1–5:1
High Risk: >5:1

Dr. Maloof: Most healthcare providers want the ratio to be below 5:1. A ratio below 3.5:1 is considered very good.

Dr. Hyman: Total cholesterol/HDL ratio <3:1

Summary:

Keep the total cholesterol-to-HDL ratio less than 3.5:1, but optimally as low as <2:1.

Triglyceride-to-HDL Ratio

Why is it important?

Dr. Hyman: This test is the best way to check for insulin resistance other than the insulin response test. According to a paper published in Circulation**, the most powerful test to predict your risk of a heart attack is the ratio of your triglycerides-to-HDL. If the ratio is high, then your risk for a heart attack increases 16-fold—or 1,600 percent!** This is because triglycerides go up and HDL or good cholesterol goes down with diabesity (insulin resistance).

Dr. D’Agostino: Triglycerides to HDL-cholesterol ratio has been shown to show the strongest association with cardiovascular disease than any other lipid marker or ratio.

Dr. Maloof: Triglyceride-to-HDL-C ratio is an important indicator of heart disease risk from standard testing.

Dr. Lustig: The triglyceride to HDL ratio is the best biomarker of small dense LDL, the best biomarker of cardiovascular disease, and the best surrogate marker of insulin resistance and metabolic syndrome.

What levels are optimal?

**Dr. D’Agostino:**Optimal: <1:1
Normal: 1:1–2:1
High Risk : >2:1

Dr. Maloof: Healthy Range: 1:1 (0.5:1–1.4:1) Less than 1:1 means you are insulin-sensitive which is optimal. Above 1.9:1 indicates early insulin resistance. Above 2.9:1 indicates significant insulin resistance.

Dr. Hyman: Optimal triglyceride-to-HDL ratio is <4:1. Abnormal is >4:1.

Dr. Lustig: For reasons that are completely unclear, race matters with triglyceride levels. If the triglyceride-to-HDL ratio is over 2.5:1 in Caucasians or over 1.5:1 in African Americans, that’s a correlate of metabolic syndrome.

Summary:

This is a marker you should focus on. Many experts agree that the triglyceride-to-HDL ratio is one of the best surrogate markers of insulin resistance and metabolic syndrome. If the triglyceride-to-HDL ratio is over 2.5:1 in Caucasians or over 1.5:1 in African Americans, that’s a correlate of metabolic syndrome. Lower is better.

Post-Meal Glucose 

A measure of your blood sugar concentration two hours after eating.

Why is it important?

Dr. D’Agostino: Post-prandial (post-meal) glycemia is an important contributing factor in the development of atherosclerosis through endothelial dysfunction. Repeated postprandial “hyperglycemic spikes” (high glucose spikes) are important contributors to cardiovascular disease. It is universally accepted that this is an important risk factor, although more research is needed to further elucidate the impact this has on overall health.

Dr. Maloof: Post-prandial peaks are the highest peak your glucose rises to after a meal. If it goes above 160 mg/dL sugar will spill into your urine through your kidneys. If it’s above 135 mg/dL it will damage your blood vessels.

Dr. Gottfried: There are many roads to metabolic dysfunction. Not all people with prediabetes have high fasting glucose, so we want to look at the full dynamic range, including after meals.

Standard ranges:

Less than 140 mg/dL two hours after eating.

Source: University of Rochester Medical Center

What levels are optimal?

Dr. Hyman: Thirty-minute, one-hour, and two-hour glucose should not rise above 110 mg/dl; some say 120 mg/dl.

Dr. Maloof: Most healthy is keeping glucose <110 mg/dL after meals.
According to the American Association of Clinical Endocrinology, ideal is <120 mg/dL after meals.
You will have damage to large blood vessels at a glucose level >135 mg/dL.
You will have damage to small blood vessels at a glucose level >160 mg/dL.
You will have glucose spill into the urine from the kidneys at a glucose 160-180 mg/dL.

**Dr. D’Agostino:**Optimal level: <120 mg/dL
Normal: <160 mg/dL
High-risk: >180 mg/dL

Dr. Gottfried: Mainstream cut off is <140 mg/dL at two hours after a meal. I like 115 mg/dL, but I also like to assess glucotype—i.e., how spikey you are.

Summary:

Aim for glucose levels to stay under ~110–115 mg/dL at any time point after meals.

Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

An indirect measure designed to indicate how your body’s insulin is working in dealing with glucose; identifies insulin resistance, the state where your cells are less sensitive to insulin, and the beginning of many health problems.

Equation:

Score = (Fasting insulin) x (Fasting glucose) / 405

Online calculator

Why is it important?

Dr. Maloof: If you know your fasting blood glucose and your fasting insulin, the HOMA-IR equation can tell you how insulin sensitive or insulin resistant you are.

If your fasting blood sugar is 5.7 mmol/L (103 mg/dL) and your insulin is high, too (over 12 μU/mL), you are insulin resistant and on your way to type 2 diabetes. If your blood sugar is 5.7 mmol/L but your fasting insulin is under 9 μU/mL, you are insulin sensitive and likely in glucose refusal mode from a low-carb diet.

Dr. D’Agostino: Valuable equation-based measurement to determine insulin sensitivity and β-cell function from paired fasting plasma glucose and insulin, specific insulin, or C-peptide concentrations. Insulin resistance precedes Type 2 diabetes and would help to manage or even prevent it from happening.

Standard ranges:

Ranges vary by gender, age and health status, but generally a healthy range is .5-1.4.

Source: The Blood Code

What levels are optimal?

**Dr. Maloof:**Optimal insulin sensitivity: < 1
Early insulin resistance: > 1.9
Significant insulin resistance: > 2.9

**Dr. D’Agostino:**Optimal: <0.5
Normal: 0.5–1.4
High-risk: >1.4
Very-high-risk: >2.9

Dr. Gottfried: <1 indicates an insulin-sensitive state.

Summary:

Aim for <1.