Epinephrine and norepinephrine are two neurotransmitters that also serve as hormones, and they belong to a class of compounds known as catecholamines. As hormones, they influence different parts of your body and stimulate your central nervous system. Having too much or too little of either of them can have noticeable effects on your health.
Chemically, epinephrine and norepinephrine are very similar. However, epinephrine works on both alpha and beta receptors, while norepinephrine only works on alpha receptors. Alpha receptors are only found in the arteries. Beta receptors are in the heart, lungs, and arteries of skeletal muscles. It’s this distinction that causes epinephrine and norepinephrine to have slightly different functions.
The Norepinephrine / Epinephrine ratio is an indicator of epinephrine (adrenaline) conversion (epinephrine is synthesized from norepinephrine). Anxiety, burnout, and poor blood sugar control are associated with a relative epinephrine depletion, and thus an elevated Norepi:Epi ratio.
Upper range N/E ratio is consistent with poor conversion of norepinephrine to epinephrine. This conversion is driven by the phenylethanolamine N-methyltransferase (PNMT) enzyme that requires SAMe, magnesium and cortisol (adequate HPA axis function) as cofactors. Suggest interpretation in context of cortisol levels/HPA axis function, with subsequent optimization of HPA axis function when clinically warranted.
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Additional note:
Adrenal function (DHEA, Cortisol and the catecholamines - norepinephrine and epinephrine) is depressed in andropause. Cortisol and catecholamine depletion is commonly a consequence of adrenal fatigue. This is particularly true when Metabolic Syndrome or insulin resistance is present. Testosterone levels are inversely related to insulin levels. Consider repletion when assessment indicates deficiency. In addition, the patient may benefit from a low glycemic diet and increased exercise. In cases where either or both are high, the adrenals have not reached Selye’s Exhaustion Phase, their reserves are not yet depleted and support is useful in the face of continuing stressors. Literature review finds a documented positive relationship between testosterone and dopamine. When both are adequate, healthy vigor, libido and drive are present. Patients who present with low dopamine in conjunction with symptoms of andropause may be candidates for a comprehensive sex hormone profile. Apathy is defined as lack of interest, ambition, and/or drive and is frequently associated with low catecholamines, especially dopamine and norepinephrine. Dopamine is associated with the concept of salience why we do what we do. Salience is connected with reward-seeking behaviors. Dopamine also strongly influences libido, drive, and focus, while norepinephrine also plays a role in focus, memory, and even sleep. Low or low normal levels of either neurotransmitter may play a role in apathetic states. Apathy can be concurrent with symptoms of depression, and balancing serotonin along with catecholamine levels in these particular cases may be beneficial. Patient’s low dopamine levels along with symptoms of apathy indicate a need for catecholamine support. Low levels of catecholamines that are consistently low with retesting have been observed in patients with toxicities - such as heavy metals and other environmental toxins. The practitioner might also consider assessing sex hormone levels particularly in light of testosterone and DHEA’s role in dopaminergic agonist function.
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Anxiety, burnout, and poor blood sugar control are associated with a relative epinephrine depletion, and thus an elevated Norepinephrine / Epinephrine ratio.
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Elevated Ratio: Norepi/Epi may be consistent with poor conversion of norepinephrine to epinephrine. This conversion is driven by the phenylethanolamine N-methyltransferase (PNMT) enzyme that requires SAMe, magnesium and cortisol (adequate HPA axis function) as cofactors.
- Consider the actual levels of both neurotransmitters, and interpret in the ratio in context of cortisol levels/HPA axis function.
- Optimization of HPA axis function may be clinically warranted.
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The Norepi:Epi ratio is an indicator of adrenaline conversion (Epinephrine is synthesized from norepinephrine).
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