When Fuel Is Abundant, but Energy Is Scarce

Lactate, LDH, and Futile Lipid Cycling in the ERM Framework

For decades, lactate has been misunderstood. Often labeled as a waste product or a marker of “anaerobic metabolism,” it has been blamed for fatigue, poor performance, and disease. A major symposium review in The Journal of Physiology helps finally put this misconception to rest—and in doing so, it provides strong mechanistic support for a central idea in the Exposure-Related Malnutrition (ERM) framework: glycolytic bias driven by mitochondrial congestion.

The symposium’s core thesis

The review argues that:

• Lactate is the normal end-product of glycolysis, even when oxygen is present.

• Mitochondria do not directly “burn” lactate in their matrix; lactate must first be converted to pyruvate outside the matrix.

• Rising lactate usually reflects a mismatch between glycolytic flux and mitochondrial processing capacity, not oxygen deficiency.

In short:

Lactate rises when mitochondria are saturated, not when they are absent.

This is a crucial distinction—and it fits seamlessly with ERM.

ERM lens: mitochondrial congestion, not mitochondrial failure

In ERM, mitochondrial congestion describes a state where mitochondria are structurally present and oxygenated, but their ability to process incoming substrates and reducing equivalents is exceeded. This can occur under chronic stress, inflammation, nutrient overload, aging, or disease.

When this happens:

• Glycolysis continues to run fast (often driven by stress signals).

• Mitochondrial oxidative throughput cannot keep up.

• Cytosolic redox pressure rises.

• LDH shifts metabolism toward lactate to regenerate NAD⁺ and keep glycolysis alive.

Here, LDH is not the villain. It is an emergency redox valve.

Why lactate alone doesn’t tell the full story

Lactate explains carbohydrate overflow, but ERM also needs to explain something that often confuses clinicians and patients:

“If there is plenty of fat available, why does the body still rely so heavily on glycolysis?”

This is where futile lipid cycling completes the picture.

Futile lipid cycling: when fat burns ATP instead of making it

Under mitochondrial congestion:

• Fatty acids enter cells and are activated (an ATP-consuming step).

• β-oxidation is limited by redox backpressure and impaired OXPHOS.

• Instead of being fully oxidized, fatty acids are repeatedly:

  • esterified,

  • partially oxidized,

  • and recycled.

This process is called futile lipid cycling:

• It consumes ATP

• Produces little usable energy

• Generates heat and metabolic noise

• Further drains bioenergetic reserves

So even though fat is abundant, it is energetically inefficient to use under congestion.

Lactate + futile lipid cycling = a glycolytic trap

Together, these two processes explain why glycolysis dominates in ERM:

Pathway	What happens under mitochondrial congestion
Glycolysis → lactate	Fast ATP + NAD⁺ regeneration
Fatty-acid oxidation	Redox-limited, slow, inefficient
Fatty-acid cycling	ATP-consuming, low return

The result is not a “preference” for glycolysis—but a forced reliance on the least bad option.

This creates a self-reinforcing loop:

1. Mitochondrial congestion limits oxidative resolution

2. Lactate accumulates to protect redox balance

3. Fatty acids cycle futilely, consuming ATP

4. Bioenergetic reserve declines

5. Glycolytic dependence deepens

This is bioenergetic debt in action.

Why this matters clinically

This integrated view explains many real-world observations:

• Fatigue despite normal oxygen levels

• Elevated lactate without shock or hypoxia

• Insulin resistance alongside fat accumulation

• Poor response to single-substrate strategies (“just burn fat” or “just cut carbs”)

Most importantly, it reframes the narrative:

You’re not lacking fuel. You’re struggling to process it.

The big takeaway

The symposium review helps clarify how lactate behaves under mitochondrial constraint.

When combined with the concept of futile lipid cycling, it strengthens the ERM argument that:

Glycolytic bias is an adaptive response to mitochondrial congestion—one that preserves short-term survival at the cost of long-term energetic resilience.

Understanding this shift is the first step toward restoring metabolic flexibility and resolving bioenergetic debt.

Glancy, B., Kane, D. A., Kavazis, A. N., Goodwin, M. L., Willis, W. T., & Gladden, L. B. (2021). Mitochondrial lactate metabolism: History and implications for exercise and disease. The Journal of Physiology, 599(3), 863–888. https://doi.org/10.1113/JP278930