BH4 (tetrahydrobiopterin)

BH4, in full tetrahydrobiopterin, is a cofactor made by the body from the group of pterins. The body produces it itself, starting from GTP, a building block of energy metabolism; the first enzyme of this pathway is called GTP cyclohydrolase I. BH4 does not need to be taken in with food. BH4 is measured in urine, in the evidence profiles on stress, burnout, exhaustion, depression and long/post-COVID and in the analysis of tryptophan metabolism – in each case together with the neurotransmitters, neopterin and the parameters for nitrosative stress. The value shows how much BH4 the body forms and excretes.

What BH4 does in the body

BH4 is indispensable for enzymes that convert amino acids using oxygen. Phenylalanine hydroxylase uses BH4 to convert phenylalanine into tyrosine. Tyrosine hydroxylase forms L-DOPA from it, the precursor of dopamine, noradrenaline and adrenaline. Tryptophan hydroxylase uses BH4 to make the precursor of serotonin and melatonin. All three nitric oxide synthases need BH4 to form nitric oxide (NO), which widens blood vessels, transmits signals between nerve cells and takes part in immune defence. In these reactions BH4 is used up and has to be continuously regenerated via enzymes that draw on NADH and folate metabolism. BH4 is also very sensitive to oxidation.

Low BH4 – what happens in the body?

When little BH4 is available, less serotonin, melatonin, dopamine, noradrenaline and adrenaline are formed; this can affect mood, drive, sleep, concentration and stress processing. Phenylalanine is broken down more slowly. The effect on the NO synthases has particularly far-reaching consequences: when BH4 is lacking, they form the radical superoxide instead of nitric oxide. Together with existing NO this can give rise to peroxynitrite, which in turn oxidises BH4 – a self-reinforcing cycle of oxidative and nitrosative stress that also strains the inner wall of the vessels. Reasons for low levels are persistent oxidative stress, chronic inflammation, a lack of folate or of cofactors for regeneration and – very rarely – congenital enzyme defects.

High BH4 – what happens in the body?

Messengers of the immune system such as interferon-γ and other inflammatory signals increase the activity of GTP cyclohydrolase I, the first enzyme of BH4 formation. In many cells more BH4 is then produced, whereas human scavenger cells mainly produce neopterin, because they largely lack a downstream enzyme. Raised BH4 levels in urine can therefore reflect an activated immune defence and are considered together with neopterin. Intake of BH4 as a medicine also raises the value. Plentiful BH4 generally supports the formation of neurotransmitters and nitric oxide. Whether a high value is due to increased formation or increased excretion only becomes clear in connection with the other values.

The interpretation is given in your report.