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How Nitric Oxide Protects the Brain

by Jeff Butterworth

Brain health is often overlooked until it’s too late. And research shows dementia can start in our early 30s.

This is where NITRIC OXIDE enters the discussion. As we age Nitric Oxide reduces.

Nitric oxide (NO) plays a surprisingly important role in brain health, particularly in relation to blood flow, inflammation, and neuronal signalling, all of which are factors in dementia risk and progression.

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Brain health is often overlooked until it’s too late. And research shows dementia can start in our early 30s.

This is where NITRIC OXIDE enters the discussion. As we age, Nitric Oxide reduces.

Nitric oxide (NO) plays a surprisingly important role in brain health, particularly in relation to blood flow, inflammation, and neuronal signalling, all of which are factors in dementia risk and progression.

It’s not just a “cardiovascular molecule.” In the brain, nitric oxide acts more like a neuro-vascular regulator and signalling messenger.

Here’s how it connects to dementia:

1. Cerebral Blood Flow

Nitric oxide is one of the main substances that tells blood vessels to relax and dilate.

In the brain this means:
• Better oxygen delivery
• Better glucose delivery
• Improved waste removal (including beta-amyloid clearance)

When nitric oxide levels decline:
• Blood vessels stiffen
• Micro-circulation reduces
• Chronic low-grade hypoxia

This pattern is strongly associated with vascular dementia and is also seen in Alzheimer’s disease.

Aging naturally reduces endothelial nitric oxide production by ~30–50%, which is one reason dementia risk rises with age.

2. Blood–Brain Barrier Integrity

Nitric oxide helps regulate the tight junctions in the blood–brain barrier.

Low NO → barrier becomes more permeable →
• Increased neuro-inflammation
• Higher exposure to toxins and inflammatory molecules

Chronic inflammation is one of the strongest contributors to neurodegeneration.

3. Amyloid and Tau Clearance

There is evidence that adequate nitric oxide levels help:
• Maintain cerebral perfusion
• Support glymphatic drainage
• Improve enzymatic clearance of beta-amyloid

Reduced NO has been associated with greater plaque accumulation in animal and human studies.

4. Mitochondrial Function

Nitric oxide at physiological levels supports mitochondrial efficiency and biogenesis.

But this is dose-dependent:
• Too low: poor energy production, neuronal fatigue
• Too high (especially inducible NO from inflammation): oxidative stress and mitochondrial damage

The dementia relationship is therefore a U-shaped curve, not simply “more is better.”

5. Neurotransmission and Synaptic Plasticity

Nitric oxide acts as a retrograde neurotransmitter involved in:
• Learning
• Memory consolidation
• Long-term potentiation

Reduced NO signalling has been linked to impaired synaptic plasticity which is a key feature in early cognitive decline.

Nitric Oxide in the Dementia Context

Beneficial

Endothelial Nitric Oxide (eNOS)
• Supports blood flow
• Anti-inflammatory
• Anti-atherosclerotic
• Neuroprotective

What Low Nitric Oxide Is Commonly Associated With
• Insulin resistance
• Hypertension
• High LDL / ApoB
• Smoking
• Sedentary lifestyle
• Poor oral microbiome (mouthwash overuse)
• Aging endothelial dysfunction

These are the same risk factors seen in both cardiovascular disease and dementia, which is why the two conditions often track together.

Practical Implication

Interventions that support healthy nitric oxide production tend to overlap with dementia-prevention strategies:
• Regular aerobic and resistance exercise
• Nitrate-rich vegetables (beetroot, spinach, arugula) Ultimate cardio
• Good oral microbiome health
• Adequate sunlight and vitamin D
• Medicinal Mushrooms in Boost
• Blood pressure and glucose control

Interestingly, many dementia risk reduction programs now mirror cardiovascular optimisation protocols because the vascular-neuro link is so strong.

In Short

Nitric oxide is a bridge molecule between cardiovascular health and brain health.
Low endothelial nitric oxide contributes to:
• Reduced cerebral perfusion
• Increased inflammation
• Impaired mitochondrial function
• Poor amyloid clearance
• Reduced synaptic plasticity

While excessive inflammatory nitric oxide contributes to oxidative damage.

The emerging consensus is that maintaining balanced nitric oxide signalling is one of the central mechanisms in preserving cognitive function with age. Hence why I am educating people around the Ultimate Cardio for increasing nitric oxide levels and BOOST 3 for the medicinal mushrooms to support cardiovascular and cognitive health as we age.

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