The BH4 cycle: The hidden driver of mood, energy, and focus

When we talk about mindset, we often think of sleep, exercise, or stress management. But deep inside your cells, there’s a little-known biological process that quietly shapes how you feel every day: the BH4 cycle.

BH4 (short for tetrahydrobiopterin) is a molecule your body can’t do without. It’s a cofactor: a helper that ensures enzymes can perform the reactions that keep you balanced. And when it comes to your brain chemistry, BH4 is the spark that lights the fuse.

Why BH4 matters

The BH4 cycle underpins some of your body’s most important processes:

• Neurotransmitter metabolism: BH4 helps turn amino acids like tryptophan and tyrosine into mood-shaping chemicals: serotonin, dopamine, norepinephrine, and melatonin.
• Thyroid health: BH4 supports the production of thyroid hormones that regulate energy and metabolism.
• Nitric oxide production: needed for healthy blood flow, circulation, and cardiovascular health.
• Detoxification & inflammation control: BH4 contributes to the urea cycle, helping convert ammonia into a less harmful form.

When your BH4 cycle is running smoothly, your body keeps neurotransmitters in balance, your mood stays steadier, and your energy is more reliable. But if the cycle slows or stalls, the effects can ripple through your whole system, from disrupted sleep to irritability, low mood, or fatigue.

The DNA connection

How efficiently your BH4 cycle works isn’t just about lifestyle. Your genes also play a role. Variants in a few key genes can change how quickly you make, recycle, or use BH4 and how sensitive you are to imbalances.

• MTHFR: Converts folate into its active form (5-MTHF), which is essential for regenerating BH4. Certain variants can make this process less efficient, meaning you may need higher folate intake.
• COMT: Breaks down dopamine, noradrenaline, and adrenaline. Slower COMT activity can leave you with higher levels, linked to stress reactivity or mood swings.
• VDR: Encodes the vitamin D receptor, which helps convert tyrosine into dopamine. Variants here can increase demand for vitamin D and dopamine precursors.
• MAOA: Helps clear away serotonin, melatonin, and noradrenaline. Variants can affect how quickly (or slowly) these neurotransmitters are broken down.
• MAOB: Plays a similar role to MAOA, clearing dopamine and histamine. Like MAOA, this gene sits on the X chromosome, meaning males carry only one copy so the effect of a variant may be more pronounced.

And here’s the surprising part: at Stride, we’ve analysed thousands of DNA profiles through our StrideDNA tests. Our data shows that 98% of StrideDNA customers have some level of BH4 cycle impairment and around 40% are totally impaired, meaning only a tiny fraction run this pathway at full efficiency.

So if your BH4 cycle isn’t perfect, you’re not alone.

Explore each pathway in depth: Folate, Methionine, Transsulfuration, Urea

Supporting your BH4 cycle

Your DNA sets the blueprint, but lifestyle, nutrition, and environment have the power to change the outcome. Here’s how you can support BH4 health in daily life:

• Folate & B-vitamins: Leafy greens, beans, and whole foods rich in folate, plus B2, B6, and B12, are essential cofactors.
• Vitamin D: Sunlight or supplementation supports VDR-linked pathways and dopamine production.
• Stress management: High stress and oxidative load can deplete BH4, so practices like mindfulness, breathwork, or simply walking outside matter.
• Avoid toxins: Heavy metals and chronic inflammation interfere with BH4 recycling. Reducing exposure and keeping inflammation low supports balance.
• Know your genes: Understanding your variants helps personalise your approach - whether you need more folate, extra vitamin D, or strategies for balancing neurotransmitter activity.

Why clarity matters

The BH4 cycle doesn’t often make headlines. Yet it’s central to how your brain chemistry, hormones, and energy systems talk to each other.

At Stride, we believe that when you understand your biology, you can act with clarity. Knowing your BH4 cycle efficiency can help explain why you might be more sensitive to stress, prone to sleep disruption, or need extra nutritional support.

And when you see the full picture - DNA, bloods, and biome - you stop guessing and start optimising.

EXPLORE STRIDEONE