Month: November 2024

Rethinking Cardiovascular Health: Beyond LDL as a Marker for Disease

Fellow physicians,

For decades, we’ve relied on LDL as the primary marker for assessing cardiovascular disease (CVD) risk. However, recent research and patient outcomes are prompting us to reconsider this approach. Cardiovascular health is multifaceted, and addressing root causes rather than singular markers like LDL can guide us to better patient outcomes, particularly in our current environment of rising metabolic and liver disease.

1. GLP-1 Medications: A Bridge, Not a Solution

While medications like Rybelsus (a GLP-1 receptor agonist) offer short-term weight-loss benefits, they come with limitations. Long-term use is costly and can bring side effects such as nausea, diarrhea, and gallbladder issues. Our patients may be drawn to the “quick fix,” but as we know, sustainable health often demands a lifestyle overhaul.

GLP-1s should be viewed as a temporary tool—a way to kick-start weight loss and motivate patients while emphasizing that lifestyle adjustments provide a sustainable path. Ideally, these medications serve as a bridge to instill healthier habits rather than a permanent solution.

2. The Real Culprit: Insulin Resistance and NAFLD

While elevated LDL is traditionally seen as a red flag for CVD, the underlying issue for many patients is actually insulin resistance. Insulin resistance is at the heart of metabolic syndrome, which drives non-alcoholic fatty liver disease (NAFLD)—a condition increasingly common, even among adolescents.

By focusing on insulin resistance rather than LDL alone, we tackle the metabolic issues that lead to NAFLD. Evidence shows that low-carb diets like keto can reverse fatty liver by lowering triglycerides and reducing liver fat, often leading to improved liver enzyme levels and overall liver health.

3. Better Metrics for Cardiovascular Health: TG/HDL Ratio and LDL Particle Size

Assessing cardiovascular risk requires a broader perspective. Rather than fixating on LDL, consider the triglyceride-to-HDL (TG/HDL) ratio—a stronger indicator of metabolic health. A lower TG/HDL ratio typically correlates with better heart health. Studies have shown that keto and low-carb diets improve this ratio by raising HDL and lowering triglycerides.

Additionally, while LDL levels may not change dramatically on a low-carb diet, LDL particles often shift to a larger, safer size, further reducing cardiovascular risk. These changes are more predictive of positive outcomes than LDL levels alone.

Moving Forward: An Integrated Approach to Patient Health

Incorporating GLP-1s can help patients get started, but it’s lifestyle modifications that will sustain them. Addressing insulin resistance with targeted lifestyle changes like low-carb eating can help reverse NAFLD, improve metabolic health, and reduce the risk of CVD.

Our role is to guide patients not only toward initial success but also to long-term, sustainable health. By shifting the focus from LDL to insulin resistance, we can empower them to achieve better outcomes and transform their health for the future.

Explaining How Glucose and Ketones Become ATP: Why Ketosis and Fat Adaptation Boost Health

Fuel Sources

When it comes to energy, the body has two primary fuel sources: glucose and ketones. While glucose is often the default source, especially on a typical high-carb diet, ketones become the primary fuel under low-carb or fasting conditions. Ketosis, the metabolic state where the body produces ketones from fat, isn’t just about an alternative fuel source; it also offers several health benefits, including weight loss, improved metabolic health, reduced cardiovascular disease risk, and fat adaptation. Let’s dive into how glucose and ketones each produce ATP and why ketosis is a preferred metabolic state for overall health.

ATP: The Body’s Essential Energy Currency

ATP (adenosine triphosphate) fuels virtually every function in our bodies, from muscle contractions to cognitive activities. The body produces ATP by metabolizing nutrients through complex biochemical pathways, using glucose and ketones as primary fuels. Interestingly, ketones produce more ATP per molecule than glucose, making them an efficient energy source, especially beneficial during ketosis.

Pathway 1: Converting Glucose to ATP

Under normal dietary conditions, glucose is the body’s main energy source. Here’s how glucose becomes ATP through a process called cellular respiration:

Step 1: Glycolysis

  1. Breakdown of Glucose: In the cytoplasm, glucose is split into two molecules of pyruvate.
  2. Initial ATP Yield: Glycolysis yields 2 ATP per glucose molecule and produces NADH (an electron carrier for later stages).

Step 2: Pyruvate to Acetyl-CoA

  1. Conversion in the Mitochondria: Pyruvate enters the mitochondria and is converted to acetyl-CoA, releasing CO₂ and generating more NADH.

Step 3: Citric Acid Cycle (Krebs Cycle)

  1. Energy Harvesting: Acetyl-CoA enters the citric acid cycle, where it is broken down to produce NADH and FADH₂, which fuel ATP production in the next step.

Step 4: Electron Transport Chain (ETC)

  1. Main ATP Production: NADH and FADH₂ donate electrons to the ETC, which powers ATP synthase to produce ATP as protons flow back across the mitochondrial membrane.

ATP Yield: Glucose metabolism produces approximately 30-32 ATP per molecule, though it also creates byproducts that can contribute to oxidative stress.

Pathway 2: Converting Ketones to ATP – A More Efficient Pathway

When carbohydrate intake is low, the body shifts to using fat for fuel, producing ketones in the liver. Ketones offer several advantages over glucose, not least of which is their higher energy yield.

Step 1: Ketogenesis in the Liver

  1. Fat Conversion to Ketones: In the liver, fatty acids are converted into ketones (mainly beta-hydroxybutyrate and acetoacetate) through ketogenesis.
  2. Transport to Tissues: These ketones are released into the bloodstream and delivered to cells for energy.

Step 2: Ketone Conversion to Acetyl-CoA

  1. Entry into the Mitochondria: Once inside the cell, ketones are converted back to acetyl-CoA, entering the mitochondria to power the next steps in ATP production.

Step 3: Citric Acid Cycle and Electron Transport Chain

  1. High ATP Yield: Ketones enter the citric acid cycle, generating NADH and FADH₂, which support the electron transport chain.

Why Ketones Produce More ATP: Ketones, specifically beta-hydroxybutyrate and acetoacetate, produce ATP efficiently but with unique metabolic advantages. When fully oxidized, beta-hydroxybutyrate yields approximately 21.5 ATP per molecule, and acetoacetate provides about 19 ATP, giving a combined total of about 40.5 ATP per pair of ketone molecules. In comparison, one molecule of glucose goes through glycolysis, the citric acid cycle, and the electron transport chain to produce around 30-32 ATP in total. Though glucose produces a comparable amount of ATP, ketones offer metabolic stability, lower oxidative stress, and more efficient energy production in low-carb states, making them an effective and sustainable fuel source, especially during fasting or ketogenic conditions.

Why Ketosis and Fat Adaptation Are Beneficial

The body’s ability to switch from glucose to ketones isn’t just a backup mechanism; it provides significant health benefits. This metabolic flexibility is key for weight loss, metabolic health, and cardiovascular protection. Here’s why ketosis, and the fat adaptation that comes with it, is so advantageous:

  1. Weight Loss: Ketosis and fat adaptation (when the body becomes efficient at using fat for fuel) are incredibly effective for weight loss. Since the body can tap into stored fat for energy, people in ketosis burn more fat while maintaining stable energy levels. Ketosis also suppresses hunger hormones, making it easier to stick to a calorie deficit.
  2. Metabolic Syndrome Management: Ketosis helps combat metabolic syndrome by reducing insulin resistance. In ketosis, blood sugar levels are more stable, and the body becomes less reliant on insulin to manage glucose levels. This stability can reverse metabolic syndrome symptoms, which often include high blood pressure, high triglycerides, and abdominal obesity, reducing the risk of type 2 diabetes.
  3. Reduced Cardiovascular Disease Risk: Ketosis supports cardiovascular health by reducing triglyceride levels and increasing HDL (good) cholesterol. Additionally, ketones produce fewer reactive oxygen species (ROS), meaning less oxidative stress and inflammation, both of which contribute to heart disease. The anti-inflammatory effects of ketosis make it beneficial for long-term cardiovascular protection.
  4. Fat Adaptation for Enhanced Energy: Fat adaptation is the process where the body becomes efficient at using fat and ketones as its primary energy source. Once fat-adapted, the body can seamlessly access stored fat for sustained energy, which is especially useful for endurance activities and fasting. People who are fat-adapted experience stable energy without the spikes and crashes associated with glucose, making fat adaptation a valuable state for consistent physical and cognitive performance.
  5. Brain Health and Focus: Ketones readily cross the blood-brain barrier, providing a steady fuel for brain cells. Many people report improved mental clarity, focus, and cognitive endurance in ketosis due to the brain’s ability to efficiently use ketones as fuel, especially when blood sugar levels are low.

Embracing Metabolic Flexibility

By optimizing metabolic pathways to use both glucose and ketones efficiently, the body achieves metabolic flexibility, the ability to switch seamlessly between fuel sources. This flexibility promotes balanced energy levels, reduces cravings, and supports long-term health.

In Summary

  • Glucose Pathway: The body breaks down glucose through glycolysis and the citric acid cycle, yielding around 30-32 ATP. However, glucose metabolism can lead to oxidative stress and relies on stable blood sugar levels for consistent energy.
  • Ketone Pathway: Ketones are produced in the liver from fatty acids and yield more ATP per molecule than glucose. This efficiency, along with reduced byproducts, makes ketones a cleaner and more sustainable fuel, especially during ketosis and fat adaptation.

Ketosis not only provides a high-yield, steady energy source but also supports fat loss, metabolic syndrome improvement, and cardiovascular health. By fostering metabolic flexibility, ketosis allows the body to switch efficiently between glucose and ketones, supporting optimal energy levels and overall health.


This article emphasizes how ketones provide a cleaner, higher-yielding fuel source that supports fat loss, improved metabolic health, and cardiovascular protection. For those looking to optimize their health, embracing ketosis and fat adaptation offers a powerful way to achieve lasting vitality and metabolic balance.

Scroll to top