Abstract

Fructose is not only something we eat — the body can also make its own fructose through the polyol pathway [ENDO-L2013]. In response to stressors such as high glucose, salt, dehydration, alcohol, or low oxygen, glucose is converted into sorbitol and then fructose.

This pathway once served vital survival functions — helping conserve water, slow metabolism, and store fat under stress [NAT-J2020]. But in the modern world, where these triggers are constant, the same mechanism now drives chronic energy failure.

This paper explains how endogenous fructose production works, what triggers it, and why it creates a self-fulfilling cycle of weight gain and fragility.

1. Introduction

The ability to produce fructose internally reframes decades of debate. Carbohydrates, salt, alcohol, stress — once treated as separate culprits — are actually different triggers of the same pathway [CORE-RSTB2023].

The polyol pathway converts glucose into fructose during stress. This once protected survival in times of drought, famine, or hypoxia [ENDO-P2017]. Today, however, these triggers are constant, and the pathway contributes to fragile, energy-starved cells.

2. The Polyol Pathway: From Glucose to Fructose

1. Glucose → Sorbitol
   Enzyme: aldose reductase
   Activated by high glucose or osmotic stress; consumes NADPH.
2. Sorbitol → Fructose
   Enzyme: sorbitol dehydrogenase (SDH)
   Produces fructose as the final step.

This pathway is active in the liver, kidney, brain, vasculature, and eyes [ENDO-H2017].

3. Primary Triggers and Their Survival Functions

3.1 High Glucose (Spikes & Chronic Elevation)

Trigger: Excess glucose activates aldose reductase during post-meal spikes or chronic hyperglycemia [ENDO-L2013].
Survival function: Diverting glucose into fructose reduced glucose toxicity and promoted fat storage; glycogen-bound water aided hydration.
Modern cost: Frequent hyperglycemia keeps this pathway running even in sugar-restricted diets.

3.2 Salt, Dehydration & Osmolality

Trigger: High salt or dehydration raises plasma osmolality.
Survival function: Fructose metabolism conserved water by reducing energy expenditure and generating metabolic water [ENDO-AH2021].
Modern cost: Chronic salt intake and low hydration sustain this water-saving mode, leading to obesity and hypertension.

3.3 Alcohol

Trigger: Ethanol metabolism shifts NADH/NAD⁺ balance, pushing glucose toward sorbitol and fructose.
Survival function: Fermented fruit alcohol once signaled seasonal scarcity, storing energy as fat [NAT-D2004].
Modern cost: Alcohol now compounds dehydration and mimics sugar’s metabolic harm, promoting fatty liver and cravings.

3.4 Hypoxia & Ischemia

Trigger: Low oxygen activates aldose reductase; hypoxia reduces oxidative phosphorylation.
Survival function: Endogenous fructose allowed energy production under low O₂ — an adaptation seen in naked mole-rats [ENDO-P2017].
Modern cost: In obesity and sleep apnea, nightly hypoxia chronically activates this same conservation switch.

3.5 Stress Hormones

Trigger: Cortisol and adrenaline raise glucose and alter redox balance, driving sorbitol → fructose conversion.
Survival function: Under acute stress, storing fat aided recovery.
Modern cost: Chronic psychological stress keeps this pathway active daily, worsening cravings and metabolic fragility.

4. Taste and Survival Signals

The most attractive tastes — sweet, salty, and umami — correspond to triggers of the fructose pathway:

• Sweet: carbohydrate availability → glucose spikes → fructose synthesis.
• Salty: sodium → osmotic stress → endogenous fructose [ENDO-AH2021].
• Umami: purine-rich foods → uric acid → amplifies fructose metabolism [MECH-L2012].

These preferences evolved to conserve energy and water during scarcity, yet modern abundance keeps the pathway chronically activated.

5. The Self-Fulfilling Cycle

Endogenous fructose explains why weight gain reinforces itself [CORE-RSTB2023]:

• Obesity → chronic dehydration and hypoxia (sleep apnea, poor circulation).
• These trigger the polyol pathway → more fructose → ATP depletion and fat storage.
• Fructose further stimulates carbohydrate cravings, deepening the cycle.

The body misreads obesity as a stress state — dehydration, oxygen shortage, excess glucose — and keeps the conservation switch locked on.

6. Beyond Diabetes: A Broader Role

Once tied only to diabetic complications, the polyol pathway is now seen as broadly active across organs [ENDO-L2013]:

• Kidney: salt-triggered fructose promotes hypertension and renal injury.
• Brain: endogenous fructose linked to memory loss and Alzheimer’s [ENDO-J2020].
• Liver: internal fructose production contributes to fatty liver.
• Eye: sorbitol accumulation drives cataracts.

It represents a general survival program that has become maladaptive in modern abundance.

7. Why This Matters

• Not just about sugar: the body can make fructose internally.
• Unified mechanism: carbs, salt, alcohol, stress, hypoxia all converge on the same pathway.
• Adaptive origins: a once-protective switch now chronically engaged [NAT-J2020].
• Intervention target: Address both triggers and the metabolic core via fructokinase (KHK) inhibition and uric-acid control [INT-SH2020].

8. Conclusion

Endogenous fructose production is a survival pathway. When blood becomes too salty, concentrated, oxygen-poor, or glucose-rich, the body converts glucose into fructose — conserving water, slowing metabolism, and storing fat. Alcohol, stress, and purine-rich foods amplify the same cascade through uric acid.

What was once protective is now perpetually engaged. Constant salt intake, dehydration, obesity, sleep apnea, alcohol, and stress keep this switch on — a self-fulfilling cycle where obesity and energy failure feed each other.

Breaking the cycle requires targeting the entire pathway — from environmental triggers to fructose metabolism to uric-acid amplification — restoring the body’s ability to exit conservation mode and regain metabolic resilience.

These relationships form a coherent, testable framework to be addressed in forthcoming experimental protocols.

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(Selected sources linked inline; full citations in the Master Bibliography.)