Are you metabolically healthy?

What does that mean anyways?

In the functional medicine and holistic health world… Metabolic health is defined by the optimal functioning of the body’s metabolism, which is the set of chemical processes that convert food into energy and sustain life.

Being metabolically healthy goes beyond the absence of disease; it refers to a state in which all metabolic systems—such as blood sugar regulation, fat metabolism, hormone balance, and inflammatory responses—are operating efficiently and harmoniously.

Integrative Health

What Is Metabolic Health, And How Is It Measured?

What is the Definition?

“It’s important to note that there is no universally agreed-upon definition of metabolic health,” says Maddie Pasquariello, M.S., RDN. And some clinicians and scientists even view metabolic health as the absence of metabolic concerns (which isn’t frustratingly unspecific, nor does it define what optimal metabolic health is).

In general, there are five main factors measured via a blood test or through a clinical evaluation that go into evaluating a person’s metabolic health.

If those values are higher or lower than a given cutoff, it’s an indicator of poor metabolic function. And if a person has three or more of these signs, they would be considered to have suboptimal metabolic health 1.

Excess abdominal fat: A waist circumference of 40 inches or more for men and 35 inches or more for women

High triglyceride levels: 150 mg/dL or higher

High fasting blood glucose (sugar): 100 mg/dL or higher

High blood pressure: Greater than (or equal to) 130/85 mmHg or higher

Low high-density lipoprotein cholesterol levels: 40 mg/dL or less (men) and 50 mg/dL or less (women)

How can you tell if you have poor metabolic health?

It’s easy to make assumptions about your metabolic health from stepping on a scale. But there’s a reason weight—and BMI for that matter—are left off of the list above.

https://www.mindbodygreen.com/articles/what-is-metabolic-health-and-how-to-tell-if-your-metabolically-healthy

A person is considered metabolically healthy when:

Blood Sugar Balance: Normal fasting blood glucose levels, insulin sensitivity, and stable blood sugar throughout the day. This means the body efficiently manages glucose and insulin without excessive spikes or crashes.
Healthy Body Composition: Ideal levels of body fat and muscle mass, especially visceral fat (fat stored around organs), which is a key marker of metabolic health.
Lipid Profile: Healthy levels of cholesterol and triglycerides, with high HDL and low LDL (small particle size) and triglycerides.
Blood Pressure Regulation: Blood pressure within a healthy range, indicating good cardiovascular function and balanced fluid retention.
Hormone Balance: Proper regulation of hormones such as insulin, cortisol, thyroid hormones, and sex hormones (estrogen, progesterone, testosterone), which influence metabolism, energy, and overall health.
Low Inflammation: Minimal chronic, systemic inflammation, which can be measured through markers like C-reactive protein (CRP) and cytokines.
Energy Levels: Consistent energy throughout the day, free from fatigue, brain fog, or mood swings.
Optimal Gut Health: A balanced gut microbiome with proper digestion, nutrient absorption, and minimal gut inflammation.
Detoxification Pathways: Efficient detoxification processes, ensuring the body can eliminate waste and toxins effectively.

In functional health, the focus is on identifying and addressing the underlying causes of metabolic dysfunction, such as chronic stress, poor nutrition, lack of exercise, or environmental toxins. Holistic approaches to maintaining metabolic health may include lifestyle changes, personalized nutrition, stress management, functional lab testing, and targeted supplementation.

Is the definition of METABOLIC Health updated for 2024?

To update the metabolic health markers for a more comprehensive view of insulin resistance and cardiovascular risk, we need to go beyond the traditional focus on glucose levels and basic cholesterol readings. Here’s how we can enhance these markers:

1. Insulin Sensitivity and Insulin Resistance

Traditionally, metabolic health assessments often rely on fasting blood glucose or HbA1c levels, which can miss early signs of insulin resistance. To address this, we should include:

Fasting Insulin Levels: A low fasting insulin level (under 6 µIU/mL) is a strong indicator of insulin sensitivity. High fasting insulin (above 10 µIU/mL) often indicates early-stage insulin resistance even if glucose levels are still normal.
HOMA-IR (Homeostatic Model Assessment of Insulin Resistance): This calculation uses fasting glucose and fasting insulin to assess insulin resistance. A HOMA-IR score of greater than 1.9 suggests insulin resistance.
Glucose Tolerance Test with Insulin Measurement: Instead of just measuring glucose response, testing insulin levels during a glucose tolerance test can reveal whether the body is overproducing insulin to manage blood sugar. High insulin spikes indicate insulin resistance even if glucose levels appear normal.
Glycated Albumin or Fructosamine: These markers provide short-term insight into blood sugar control (over 2-3 weeks), complementing HbA1c for understanding overall glycemic health.

2. Advanced Lipid Profile for Cardiovascular Risk

Traditional cholesterol panels focus on total cholesterol, LDL-C, HDL-C, and triglycerides, which don’t always give an accurate picture of cardiovascular risk. Here’s how we should update these markers:

LDL Particle Size and Number (LDL-P): Instead of just measuring LDL cholesterol (LDL-C), we should focus on the number of LDL particles (LDL-P) and their size. Small, dense LDL particles are more likely to penetrate arterial walls and cause atherosclerosis, making them a higher-risk factor than large, buoyant LDL particles.
- Small, Dense LDL: These are considered more atherogenic (riskier for heart disease), as they are more likely to oxidize and cause arterial plaque buildup. Testing for LDL subfractions can differentiate between small, dense LDL and large LDL.
Apolipoprotein B (ApoB): ApoB is a protein found on the surface of atherogenic lipoproteins, including LDL, VLDL, and IDL. Elevated ApoB levels indicate a high number of potentially harmful particles, making it a more accurate predictor of cardiovascular risk than LDL-C alone.
- ApoB-to-ApoA1 Ratio: This ratio compares the levels of atherogenic (ApoB) to anti-atherogenic (ApoA1) particles. A higher ApoB-to-ApoA1 ratio suggests an increased risk of cardiovascular events.
Lipoprotein(a) [Lp(a)]: Lp(a) is a genetic risk factor for cardiovascular disease. Elevated Lp(a) levels are associated with a higher risk of atherosclerosis and thrombosis, even in individuals with normal cholesterol levels. Testing for Lp(a) is critical in assessing genetic predisposition to cardiovascular disease.

3. Inflammatory and Oxidative Stress Markers

Chronic inflammation and oxidative stress contribute to metabolic dysfunction and cardiovascular disease. Key markers to assess include:

C-Reactive Protein (CRP): High-sensitivity CRP (hs-CRP) measures low levels of inflammation that are often predictive of cardiovascular risk. Elevated hs-CRP suggests ongoing inflammation, which is linked to insulin resistance, metabolic syndrome, and heart disease.
Oxidized LDL (oxLDL): oxLDL is a specific form of LDL that has been damaged by oxidative stress. It is highly atherogenic and directly linked to the development of plaque in the arteries. Measuring oxLDL can provide insight into cardiovascular risk.
Fibrinogen: Elevated levels of fibrinogen, a clotting factor, are associated with an increased risk of cardiovascular disease, as it indicates a pro-thrombotic (clot-forming) state and inflammation.

4. Liver Health Markers

Liver function is crucial for metabolic health, particularly in regulating lipid and glucose metabolism. Fatty liver disease, often linked to insulin resistance, is a major risk factor for metabolic and cardiovascular disease. Key markers to assess include:

ALT (Alanine Aminotransferase) and AST (Aspartate Aminotransferase): Elevated levels of these liver enzymes can indicate liver inflammation or damage, such as non-alcoholic fatty liver disease (NAFLD), which is closely tied to insulin resistance.
GGT (Gamma-Glutamyl Transferase): GGT is another liver enzyme often elevated in metabolic dysfunction and can serve as an early warning sign for liver and cardiovascular issues.

5. Triglyceride-to-HDL Ratio

This ratio is a simple and powerful predictor of metabolic and cardiovascular risk. A higher ratio suggests insulin resistance and increased risk for heart disease.

Optimal Ratio: A triglyceride-to-HDL ratio of less than 2 is considered ideal, while a ratio higher than 3 indicates insulin resistance and elevated cardiovascular risk.

6. Other Key Markers for Comprehensive Metabolic Health

Adiponectin: This hormone helps regulate glucose levels and fatty acid breakdown. Higher adiponectin levels are associated with improved insulin sensitivity and metabolic health.
Leptin: Leptin is a hormone involved in regulating energy balance and fat storage. High leptin levels, particularly with leptin resistance, are linked to obesity, insulin resistance, and metabolic dysfunction.
NMR (Nuclear Magnetic Resonance) Lipoprotein Analysis: This advanced lipid test measures the size and number of lipoprotein particles, providing a more detailed risk assessment for heart disease compared to a standard lipid panel.

Updated Metabolic Health Markers Should Include:

Fasting Insulin and HOMA-IR: To assess insulin resistance directly.
ApoB and LDL Particle Size: To gauge cardiovascular risk more accurately.
Triglyceride-to-HDL Ratio: As a simple indicator of insulin sensitivity.
Lp(a): To assess genetic risk for cardiovascular disease.
Oxidized LDL and hs-CRP: To measure inflammation and oxidative stress.
Liver Health Markers: ALT, AST, and GGT to assess metabolic-related liver function.
Adiponectin and Leptin: To understand energy regulation and fat metabolism.

By expanding the focus from basic glucose and cholesterol markers to include insulin levels, particle size of LDL, ApoB, inflammatory markers, and oxidative stress, we can better assess the risk for insulin resistance, cardiovascular disease, and overall metabolic health. This more nuanced approach allows for earlier detection of metabolic dysfunction and more personalized interventions to prevent long-term health complications.

Metabolic health and mitochondrial health are deeply interconnected because the mitochondria—the energy powerhouses of cells—are responsible for converting nutrients into usable energy (ATP) through cellular respiration.

When mitochondria function optimally, they drive efficient metabolism, which is essential for overall health.

Here’s how metabolic health relates to mitochondrial function:

1. Energy Production (ATP Generation)

Mitochondria’s Role:
- Mitochondria convert carbohydrates, fats, and proteins into adenosine triphosphate (ATP), the body’s primary energy currency.
- This process happens through the Krebs cycle (citric acid cycle) and oxidative phosphorylation.
Metabolic Health Connection:
- Optimal mitochondrial function ensures that nutrients are efficiently converted into energy.
- If mitochondria are damaged or functioning poorly (mitochondrial dysfunction), energy production is compromised, leading to fatigue, poor metabolic efficiency, and reduced exercise capacity.

2. Insulin Sensitivity and Glucose Metabolism

Mitochondria’s Role:
- Mitochondria play a central role in glucose metabolism by oxidizing glucose to generate ATP.
- When mitochondria function well, cells efficiently use glucose, and insulin sensitivity is maintained.
Metabolic Health Connection:
- Poor mitochondrial function is linked to insulin resistance, where cells become less responsive to insulin.
- This leads to elevated blood sugar and impaired glucose metabolism, a hallmark of metabolic dysfunction seen in conditions like type 2 diabetes.

RABBIT HOLE…The link between poor mitochondrial function and insulin resistance stems from the mitochondria’s central role in energy production and cellular metabolism.

When mitochondria don’t function properly, this can disrupt metabolic processes that are critical for maintaining insulin sensitivity.

Here’s how the mechanism works:

1. Impaired Fatty Acid Oxidation

Mitochondria’s Role: Mitochondria are responsible for fatty acid oxidation, a process where fats are broken down to produce ATP. This process occurs in response to the body’s energy needs, especially during fasting or exercise.

Mechanism in Insulin Resistance: When mitochondrial function is impaired, cells can’t oxidize fatty acids efficiently. This leads to an accumulation of incomplete fatty acid breakdown products (such as diacylglycerol and ceramides) inside cells, particularly in muscle and liver tissues. These lipid intermediates interfere with insulin signaling pathways by activating stress-related kinases such as PKC (Protein Kinase C), which inhibit the insulin receptor’s ability to activate IRS-1 (Insulin Receptor Substrate-1), a key protein in the insulin signaling cascade.

Result: When IRS-1 is inhibited, glucose transport into the cell via GLUT4 transporters is impaired, causing insulin resistance. This leads to elevated blood glucose levels, as cells become less responsive to insulin and can’t efficiently take up glucose.

2. Reactive Oxygen Species (ROS) and Oxidative Stress

Mitochondria’s Role: During normal energy production (ATP synthesis), mitochondria produce small amounts of reactive oxygen species (ROS) as byproducts. In healthy cells, ROS levels are balanced by antioxidants that neutralize them.

Mechanism in Insulin Resistance: When mitochondria are dysfunctional, they produce excessive amounts of ROS. High levels of ROS cause oxidative stress, damaging cell membranes, proteins, and lipids. This oxidative damage can impair insulin signaling by modifying key proteins involved in the insulin signaling pathway, such as the insulin receptor and IRS-1.

Result: The oxidative stress disrupts the insulin receptor’s function and prevents normal glucose uptake into cells, contributing to insulin resistance.

3. Mitochondrial Dysfunction in Muscle Cells

Mitochondria’s Role: Skeletal muscle is one of the primary tissues where glucose uptake is regulated by insulin. Mitochondria in muscle cells are responsible for both glucose and fatty acid metabolism.

Mechanism in Insulin Resistance: When mitochondrial function in muscle cells is impaired, it decreases the cell’s ability to efficiently switch between using glucose and fatty acids for energy. This leads to metabolic inflexibility, where muscle cells rely too heavily on glucose or fat, causing an imbalance.

Result: The inability to switch between energy substrates makes cells less responsive to insulin, as the metabolic machinery needed to respond to insulin (e.g., GLUT4 transporters) is compromised. Over time, this can lead to a reduced glucose uptake and insulin resistance.

4. Mitochondrial Biogenesis and Insulin Sensitivity

Mitochondria’s Role: Mitochondrial biogenesis (the creation of new mitochondria) is crucial for maintaining cellular energy demands and metabolic health. Pathways such as AMPK (AMP-activated protein kinase) and PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) regulate this process.

Mechanism in Insulin Resistance: Impaired mitochondrial biogenesis reduces the number of functional mitochondria, limiting the cell’s capacity for energy production and metabolic activity. This leads to a reduced ability to handle glucose and fatty acids, contributing to metabolic overload. Reduced mitochondrial biogenesis is linked to lower insulin sensitivity, as the cell’s energy needs cannot be met efficiently.

Result: Insufficient mitochondrial biogenesis reduces the ability of cells to respond to insulin and take up glucose, contributing to insulin resistance.

5. Mitochondrial Dysfunction and Inflammation

Mitochondria’s Role: Mitochondria play a role in controlling inflammation by regulating immune responses and maintaining cellular homeostasis.

Mechanism in Insulin Resistance: Dysfunctional mitochondria trigger the release of pro-inflammatory signals, such as TNF-alpha and IL-6, and activate the NLRP3 inflammasome, a key regulator of inflammation. Chronic low-grade inflammation, often referred to as metaflammation, impairs insulin signaling by disrupting normal cellular pathways. Inflammatory molecules can block insulin receptor signaling and promote insulin resistance by activating serine kinases that phosphorylate IRS-1 in a way that inactivates it.

Result: The persistent inflammatory state damages insulin signaling pathways, leading to insulin resistance and impaired glucose metabolism.

6. Decreased ATP Production and Energy Deficiency

Mitochondria’s Role: Mitochondria generate ATP, which fuels virtually all cellular processes, including those involved in insulin signaling.

Mechanism in Insulin Resistance: When mitochondrial ATP production declines, cells experience an energy deficit. This energy deficiency impairs the activation of insulin receptors and reduces the ability of cells to take in glucose. The ATP-dependent processes that transport GLUT4 vesicles to the cell membrane (to allow glucose entry into the cell) are also compromised.

Result: With less ATP available, the cell’s ability to respond to insulin and take up glucose diminishes, leading to insulin resistance.

Summary of the Mechanism:

Poor mitochondrial function leads to insulin resistance through multiple mechanisms:

Impaired fatty acid oxidation increases lipid intermediates (like diacylglycerol and ceramides), which block insulin signaling.

Excessive ROS production causes oxidative stress, damaging insulin receptors and disrupting glucose uptake.

In muscle cells, mitochondrial dysfunction leads to metabolic inflexibility, impairing glucose utilization.

Reduced mitochondrial biogenesis limits the cell’s energy capacity, weakening insulin sensitivity.

Mitochondrial dysfunction triggers inflammation, further disrupting insulin signaling.

Decreased ATP production leaves cells unable to effectively respond to insulin, impairing glucose uptake.

This multi-faceted disruption of normal cellular processes links mitochondrial dysfunction to insulin resistance and metabolic health issues like type 2 diabetes and metabolic syndrome.

3. Fat Metabolism (Oxidation)

Mitochondria’s Role: Mitochondria are key to beta-oxidation, the process of breaking down fatty acids into ATP. Healthy mitochondria enhance the body’s ability to burn fat for energy.
Metabolic Health Connection: When mitochondria are functioning properly, the body can shift between using carbohydrates and fats for fuel efficiently. In metabolic dysfunction, fat oxidation is impaired, leading to fat accumulation (especially visceral fat) and a higher risk of metabolic syndrome.

4. Oxidative Stress and Inflammation

Mitochondria’s Role: During energy production, mitochondria also produce reactive oxygen species (ROS), a type of free radical. In healthy mitochondria, the body balances ROS production with antioxidants. However, when mitochondria are damaged, ROS levels increase, leading to oxidative stress.
Metabolic Health Connection: Chronic oxidative stress damages cells, tissues, and mitochondria themselves, contributing to systemic inflammation and metabolic diseases such as obesity, type 2 diabetes, and cardiovascular conditions.

5. Mitochondrial Biogenesis and Longevity

Mitochondria’s Role: The process of making new mitochondria, known as mitochondrial biogenesis, is crucial for maintaining metabolic health. This process is regulated by factors like AMPK and PGC-1α, which are activated during physical activity, caloric restriction, and cold exposure.
Metabolic Health Connection: Promoting mitochondrial biogenesis enhances the body’s energy production capacity and supports overall metabolic function. This also contributes to longevity and better aging by maintaining cellular energy efficiency and reducing metabolic stress.

6. Metabolic Flexibility

Mitochondria’s Role: Metabolic flexibility is the body’s ability to switch between burning carbohydrates and fats for fuel based on availability and demand. Mitochondria are at the center of this process.
Metabolic Health Connection: Poor mitochondrial function impairs metabolic flexibility, making it harder for the body to efficiently utilize different energy sources. This can lead to reliance on carbohydrates, fat storage, and metabolic imbalances like insulin resistance.

7. Hormonal Regulation

Mitochondria’s Role: Mitochondria play a role in hormone production, particularly steroid hormones like estrogen, testosterone, and cortisol, which are synthesized in mitochondria-rich tissues such as the adrenal glands and gonads.
Metabolic Health Connection: Hormonal imbalances, such as elevated cortisol or insulin, can impair mitochondrial function, leading to metabolic disorders. Conversely, improving mitochondrial health supports balanced hormone levels, improving metabolic outcomes.

8. Detoxification and Waste Removal

Mitochondria’s Role: Mitochondria are involved in detoxification processes and the removal of waste products through pathways like the urea cycle and apoptosis (programmed cell death).
Metabolic Health Connection: Efficient mitochondrial detoxification supports liver function and prevents the accumulation of toxins, which can otherwise contribute to metabolic dysfunction and systemic inflammation.

Conclusion:

Mitochondrial health is foundational to metabolic health because mitochondria control energy production, nutrient metabolism, fat burning, and oxidative stress management. Poor mitochondrial function leads to metabolic imbalances, insulin resistance, chronic fatigue, inflammation, and ultimately, metabolic diseases. Supporting mitochondrial function through lifestyle factors such as proper nutrition, exercise, stress management, and targeted supplementation is essential for achieving and maintaining optimal metabolic health.