L-histidine is a non-essential amino acid in human nutrition. Histidine is converted to histamine via the action of histidine carboxylase, which is expressed in many tissues including the central nervous system. Histamine is released from cells as part of the allergy reaction where it acts locally to affect adjacent cells. Blocking the receptors for histamine is an effective anti-allergy strategy. Histamine is also an important neurotransmitter in the central nervous system. In the brain a number of functions for histamine have been discovered including a role in appetite regulation, anxiety, stress and control of the sleep-wake cycle. In the brain histamine binds to H3 receptor, whereas in the periphery of the body histamine bind to H1 and H2 receptors. Disruption of histamine metabolism in the brain may be involved in the development of a number of disorder including narcolepsy, eating disorders, dementias, Tourette’s syndrome and depression. However, the role of histamine as a neurotransmitter is not fully understood.
The role of histamine in the development of anxiety has been investigated using animals models. For example, in one study1, researchers investigated the effects of a dietary histidine deficiency on the development of anxiety linked behaviour in mice. Histamine is unable to cross the blood brain barrier easily, and so histamine is produced locally through the decarboxylation of histidine. By feeding the mice either a low or high histidine diet the researchers were able to alter the production of histamine in the brains of the animals. When the mice were assessed for their ability to cope with anxiety inducing situations, the researchers found that the low histidine diet mice suffered from increased anxiety. However, other behavioural characteristics such as social interaction, locomotive activity and memory were not affected. Dietary histidine may therefore be able affect brain histamine levels, and this may have an effect on anxiety levels in mice. However, it is unclear if low histamine levels are a cause of anxiety disorder in humans.
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