Reductive Stress Creates Oxidative Stress

In bioenergetics, the foundational cause of metabolic disease is something called Reductive Stress. This occurs in the mitochondrial respiratory chain, usually in the complexes themselves, when electrons are not efficiently flowing forward to complex 4 and attaching to oxygen. This process increases oxidative stress and induces everything downstream of insulin resistance.

This article is a bit technical, but if you can grasp it, you’ll have the key to unlocking chronic disease.

TLDR:

1. Reductive stress aka Reverse Electron Transfer is characterized by a reversal of electron flow along the electron transport chain in mitochondria

2. This lowers energy production, increases ROS (oxidative stress), and lowers CO2 production

3. Polyunsaturated fat (PUFA), LPS (pathogenic gut bacteria), lack of CO2, micronutrient deficiencies, and cortisol are the underlying causes of reductive stress

4. Grounding, Methylene Blue, and NAD+ immediately relieve reductive stress providing a patch until you’ve remediated the underlying causes

To understand reductive stress we need to explore a concept called Redox. Redox stands for reduction-oxidation reactions and refers to the transfer of electrons. If something is reduced, it gains electrons and if it is oxidized it loses electrons. Most of us have heard of oxidative stress and that its detrimental to healthy aging. Oxidative stress refers to a pathological loss of electrons. Examples of damaging oxidants are the free radicals like reactive oxygen species (ROS), reactive nitrogen species (RNS) and hydroxyl free radicals. Reductive stress creates ROS.

In the mitochondrial electron transport chain, electrons get dropped off at complex 1 by a carrier called NADH. From complex 1 the electrons flow through the chain eventually reducing oxygen at complex 4 to produce water. The electrical current created by this flow produces a gradient that draws hydrogen ions through ATP synthase at the very end to produce ATP.

If there are blockages at any of these complexes, electrons cannot flow and once a threshold is reached they begin to flow backwards. This is Reductive Stress (or Reverse Electron Transfer) and it spawns a few serious problems.

First and foremost, if you don’t have efficient forward flow of electrons you will have decreased energy production in the form of less ATP. Also, since the electrons from NADH cannot be dropped off and there’s a buildup NADH.

What should happen in healthy electron flow is that after the electron is dropped off at complex 1, NADH oxidizes back to NAD+ and is recycled in the Krebs Cycle where it is used to pick up another electron (reduced to NADH again) and during this process creating CO2.

But in a state of reductive stress we instead get a buildup of NADH relative to NAD and a deficiency of CO2. It may seem counterintuitive but the lack of CO2 further complicates things by creating hypoxia in the the cell.

The Bohr effect states that hemoglobin's oxygen binding affinity is inversely related to CO2 concentration in the blood. In other words, if there’s not enough CO2 in the blood (from the mitochondrial Krebs cycle), hemoglobin will not release oxygen into the cell. This oxygen won’t transfer to the electron transport chain to accept that final electron at complex 4. This creates hypoxia which induces nitric oxide production. This nitric oxide is a major inhibitor of complex 4 and cause of reductive stress!

So let’s review the outcome of reductive stress:

I’ve discussed the dangers of PUFA and LPS in other articles so I’d like to explore a different causative factor in reductive stress - excessive fat burning. This process, called beta oxidation, produces more of NADH and FADH (than sugar burning) and, if chronically elevated, creates a buildup of electrons at Coenzyme Q10 (reductive stress). Compared to sugar burning, fat burning produces less CO2. Simply changing your macros to 50% carbs, 25% fat, 25% protein while eating enough calories can shift you out of reductive stress.

Part of this disfunction involves fasting (including 16-8), low carb/keto, carnivore, and caloric restriction. All of these diets trigger stress hormone release to induce lipolysis for a backup power supply. Chronic lipolysis from these practices releases free fatty acids into the blood for beta-oxidation in the mitochondria which in turn causes the buildup at CoQ10. The easy way to see this is to get a non-esterified fatty acids (NEFA), cortisol and glucagon blood test.

The big takeaway: Chronically elevated free-fatty acids (FFAs) cause insulin resistance. And, chronically elevated stress hormones like cortisol and glucagon caused by low carbohydrate intake elevate FFAs.

Short-term Tools for Eliminating Reductive Stress

  • Methylene blue acts as an secondary electron carrier in the ETC when complexes are blocked

  • Grounding aka earthing helps restore redox balance by discharging excess electrons

  • NAD+ therapy can restore the NAD/NADH ratio

  • Near-infrared light and sunlight can disassociate nitric oxide from complex 4

 

Action Items: Restoring Efficient Electron Flow

  1. Eat at least 50% carb, 200g +/day and reduce fat to about 25% of total calories

  2. Get enough micronutrients used in the ETC especially B complex, magnesium, and copper from foods like beef liver and oysters or supplementing

  3. Eliminate seeds oils (PUFA), eat less than 4g/2000 cals of PUFA/day and replace with saturated fat

  4. Remediate your gut to prevent excessive LPS

  5. Practice nose-breathing throughout the day and exercise to nose-breathing tolerance to maintain CO2 in the blood

  6. Get enough sleep as sleep deprivation has shown to increase NEFA/fat-burning

To your health, Jonathan

This is for informational purposes only and should not replace professional medical advice. Consult with your physician or other health care professional if you have any concerns or questions about your health.

Quantum Yoga