The Best Norepinephrine Supplements

Mark Stein
OptimizeBetter
Published in
6 min readMay 20, 2020

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Top 9 Evidence-Based Supplements List for Depression and ADHD

As a primary neurotransmitter, norepinephrine, also called noradrenaline, it is involved in the body’s stress response. Norepinephrine is a catecholamine, or a stress hormone, we produce from dopamine. Along with epinephrine, these two make up our sympathetic nervous system.

We commonly recognize this primary sympathetic stress response as a “fight-or-flight” response. As part of the sympathetic nervous system norepinephrine is released for adrenergic actions, or “wake and respond”, whereas in the parasympathetic nervous system, we release acetylcholine to support cholinergic actions, or “rest and digest” actions.

Produced in the locus coeruleus in the brain and the adrenal glands, norepinephrine regulates attention, memory, vigilance, alertness, and arousal. Excess norepinephrine can lead to anxiety and restlessness.

The enzyme, norepinephrine beta-hydroxylase (DBH), facilitates the conversion of norepinephrine into epinephrine. Our bodies then create epinephrine from norepinephrine.

While similar to epinephrine, norepinephrine acts on blood vessels, with epinephrine acts on the heart. While dopamine, norepinephrine, and epinephrine are catecholamines, DBH regulates the balance between norepinephrine and norepinephrine.

Imbalances can lead to common conditions such as high blood pressure, ADD, ADHD, depression, and dementias such as Alzheimer’s and Parkinson’s disease. Stimulating the heart and blood pressure, while producing epinephrine, norepinephrine boosts blood clotting and breathing capacity.

Current research continues its focus on the two enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) and how they regulate dopamine, norepinephrine, and epinephrine in mood and cognitive disorders.

What are the Top 9 Evidence-Based Norepinephrine Supplements?

#1 Mucuna Pruriens

The amino acid levodopa, (L-DOPA) is the strongest compound in mucuna pruriens, affecting dopamine by its ability to cross the blood-brain barrier and thus enter the brain. This is noteworthy, as dopamine cannot do this.

As we use levodopa in the treatment of Parkinson’s disease, there is some support showing that mucuna pruriens with a standardized 15–40% l-dopa is a superior delivery form, possibly because of other alkaloids in the bean. Interestingly enough, the bean has trace amounts of tryptamine, a naturally occurring psychedelic compound.

#2 Coffee

Who doesn’t love coffee? Recent research is uncovering the protective role of this magical bean in our body and brain.

While research is still undergoing debates about what the most efficient daily dose is, it remains one of the very best options for activating the adrenergic response. Studies continue to confirm the nootropic value of caffeine-containing coffee on cognition, focus, and mood.

#3 Cocoa

While many cannot drink coffee, because of the “jitter-effect”, those still in need of caffeine, find drinking cocoa a much smoother beverage choice in terms of effects on the body and brain. Along with very low caffeine content and containing phenylalanine and theobromine, cocoa gives users a long-lasting smooth energy and mood boost.

#4 Matcha Green Tea

Matcha green tea might provide an even smoother effect on the body and mind, while still delivering energy, mood, and cognitive benefits. Green tea contains potent antioxidants delivering meaningful health benefits along with L-theanine, which causes an even greater effect on focus while delivering some added calming and relaxing effects.

In fact, L-theanine, because of its well-known effects on calm and focus, remains one of the most popular nootropic supplements on the market. Overall, matcha green tea contains many more times the antioxidants as regular green tea and as well can be a more pure product, with a taste that grows on its users overtime.

#5 Krill or Vegan Algae Oil

Proven for dopamine and serotonin synthesis, emerging studies show that omega-3’s in the phospholipid form of either krill or algal oil may be superior to omega-3’s in the form of fish oil or cod liver oil, because of structural differences. Likewise, we believe that phospholipids are more bioavailable and efficient for absorption, as every cell membrane in the human body is made of phospholipids.

Finally, in this form, they are much more shelf-stable than fish oil, allowing the use of lower dosages. While we need more human studies, initial studies are very promising.

#6 Tyrosine

One of the twenty amino acids in the body, tyrosine is as well a precursor and cofactor involved in the production of dopamine. This means without tyrosine, dopamine production will not happen.

As a non-essential amino acid, we can synthesize it both from diet and as well within the body, from phenylalanine derived from sufficient protein intake. Animal studies have shown that tyrosine supplements increase dopamine levels and cognition.

Tyrosine remains a very popular dopamine supplement within the nootropic community for those with insufficient and/or low protein diets and/or those with difficulty digesting protein.

#7 Alpha-GPC

Much like CDP-choline, alpha-GPC appears to increase dopamine levels along with other major neurotransmitters such as acetylcholine and serotonin, when combined with B-vitamins and uridine monophosphate and as well Omega-3’s. Supporting evidence confirms the use of alpha-GPC for its cognition-enhancing properties in this manner.

Many nootropics users will combine alpha-GPC with one of the racetams.

#8 Creatine

Powerful evidence exists for the use of creatine supplements to increase phosphocreatine stores in the brain to support ATP levels. Creatine appears to increase mitochondrial function and dopamine levels.

Some nootropics users are now combining creatine with d-ribose, another mitochondria booster, and cardioprotective supplement. We have theorized creatine improves cognition, not only through increased energy but likewise via neuroprotection.

More and more evidence continues to emerge supporting creatine for use as much more than just a popular workout supplement. Finally, creatine appears to be an area of deficiency and potential supplement target for vegans.

#9 Curcumin

Curcumin is the primary active polyphenol compound in turmeric that gives it its bright yellow color. Several curcumin studies support its dopamine effects through potent antioxidant and anti-inflammatory mechanisms.

While researchers question the low bioavailability of curcumin, one study highlights the BCM-95 curcumin form as effective for dopamine-related depression. Other areas of curcumin research involve its effect on BDNF, working memory, NMDA, glutamate, attention, mood, and cortisol.

Top 9 Notables

CDP-choline, DLPA, D-ribose, ginkgo biloba, huperzine A, oil of oregano, nicotine, SAMEe, TMG.

Essential Cofactors

Copper, Vitamin C (Ascorbic Acid or Ascorbate).

Agonists

Sympathomimetics, Clonidine, Isoprenaline.

Antagonists

Tricyclic Antidepressants, Beta Blockers, Antipsychotics.

Biosynthesis

Phenylalanine => Tyrosine => L-Dopa => Norepinephrine = Norepinephrine (Norepinephrine β-Hydroxylase)

Norepinephrine Receptors

α1, α2, β1, β3.

Precursors

Norepinephrine.

Others

American ginseng, Asian ginseng, BPC-157, bacopa monnieri, black tea, bromantane, butyric acid, COQ10, Cacao, cannabidiol (CBD), carvacrol, chocolate, clary sage, caffeine, cacao, coca leaf, cod liver oil, coffee, D-ribose, EPA, DHA, DPA, danshen, eleuthero (Siberian ginseng), fenugreek, fish oil, green tea, Gotu kola, hemp, holy basil, iron, kratom (low dose), Korean ginseng (Panax Ginseng), L-DOPA, L-theanine, LPA, maca, matcha Tea, Muira Pauma, N-acetyl-cysteine (NALT), omega-3, oregano, PQQ, phenethylamine, phenylalanine, prebiotics, pregnenolone, probiotics, protein, resistant starch, resveratrol, Rhodiola Rosea, rosemary, SAM-e, shilajit, St. John’s Wort, soluble fiber, ubiquinol, white oolong tea.

Your Friend in Health

Mark Stein

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