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Higenamine is a stimulant found in traditional Chinese herbal medicines that have been used for centuries to treat conditions such as heart disease and asthma. Supplements containing higenamine have recently been marketed for use in pre-workout regimens and weight loss. Read on to learn more about the health benefits and risks of higenamine.

What Is Higenamine?

Higenamine, also known as norcoclaurine, is a naturally occurring compound found in many Asian plants, including the seeds of Nelumbo nucifera (lotus), the fruit of Nandina domestica (heavenly or sacred bamboo), and the root of Aconitum carmichaelii (Wolf’s bane) [R].

Both “natural” or “herbal” and synthetic higenamine are available in supplements. The source of higenamine is often noted in labeling of the supplement. Purified or synthetic higenamine is more commonly the form given by IV in clinical trials [R].

When used as a medicine or a supplement, higenamine increases fat burning, heart rate, and muscle strength [R, R, R].

Currently, in the United States, higenamine has no government regulation for human use and is considered a dietary supplement.

Higenamine has been used by athletes to enhance their performance, which led to it being banned by the World Anti-Doping Agency in 2017 [R].

Higenamine Mechanisms

Higenamine stimulates muscles by activating beta-adrenergic receptors, which are responsible for smooth muscle relaxation (β2) and heart contractions (β1). This means that muscles can exert more force. Higenamine functions like other activators of the β2 adrenergic receptor, such as ephedrine and caffeine [R].

Adrenergic receptors are involved in:

  • Smooth muscle relaxation (β2 receptors) [R]
  • Heart contractions (β1 receptors) [R]
  • Controlling muscle tone (constriction/dilation) in the respiratory system (β2 receptors) [R]
  • Controlling blood flow by relaxing or tightening arteries (α2 receptors) [R]

Given orally, higenamine is rapidly absorbed and reaches peak levels in the blood after 10 minutes. However, higenamine is poorly absorbed, with only 3 to 22% entering the bloodstream [R].

Higenamine lasts in blood circulation for about 8 minutes, and nearly all higenamine is eliminated from the body within 30 minutes [R].

Higenamine Health Effects

1) Higenamine Has Stimulant Properties

Higenamine functions as a stimulant, temporarily increasing energy and alertness by raising heart rate and blood pressure, similar to caffeine [R, R].

Higenamine is a weak inhibitor of the α2-adrenergic receptor, reversing the effect of sedatives and anesthetics that act on the α2-adrenergic receptor, such as dexmedetomidine and clonidine [R, R, R].

2) Higenamine Is an Antioxidant

Higenamine reduces oxidative stress by scavenging free radicals (superoxides), particularly in the heart and liver. Higenamine also boosts the body’s other defense systems by increasing production of heme-oxygenase and other antioxidant proteins [R].

3) Higenamine Reduces Inflammation

The higenamine contained within aconite root has been used in Asia for centuries to treat inflammation. Higenamine reduces the production of nitric oxide (NO), which decreases inflammation that can occur from over-activation of the immune system [R].

4) Higenamine May Boost Weight Loss

Higenamine increased calorie expenditure, as measured by respiratory exchange ratio (RER) in 16 healthy human subjects that were given a higenamine-containing supplement. Blood tests also found higher levels of free fatty acids, suggesting a possible increase in the breakdown of fat (lipolysis) in the body [R].

However, the supplement used in this study also contained caffeine and Yohimbe bark extract, so it’s not possible to know how much of these effects were specifically because of higenamine by itself.

5) Higenamine May Help Manage Diabetes

Interestingly, higenamine lowers blood glucose levels without involving insulin, suggesting that it may help manage blood sugar levels in diabetes patients, who often lose their sensitivity to insulin [R].

6) Higenamine May Help Treat Asthma

Higenamine can make breathing easier by relaxing the muscles that control the airways. Traditionally, herbal remedies made from plants containing higenamine have long been used to treat breathing difficulties [R].

7) Higenamine Might Increase Muscle and Improve Sports Performance

Higenamine is often marketed for use to improve workout efficiency. This may be in part due to higenamine increasing the number of calories burned from fat, which increases the total amount of energy available to the body. Higenamine may increase endurance by increasing heart rate and improving oxygen use. Higenamine can also increase the speed and force of muscle contractions [R, R].

8) Higenamine May Prevent Blood Clots

Higenamine reduced the ability of blood to form clots in rats and mice, which may prevent heart attacks and strokes. It is thought that higenamine prevents platelets from sticking to each other as a result of higenamine’s inhibition of the α2-adrenergic receptor [R].

9) Higenamine May Help Treat Erectile Dysfunction

Higenamine works differently than many first-line drugs for erectile dysfunction (PDE5 inhibitors) and works to supplement treatment. In cell studies, higenamine stimulates β-adrenoceptors, which causes the penis (the corpus cavernosa) to relax, allowing blood to flow into it more easily, leading to an erection [R].

10) Higenamine May Treat Symptoms of Septic Shock

Higenamine may be useful in the treatment of low blood pressure that occurs with septic shock. In both rats and mice, injections of higenamine decreased levels of nitric oxide that are produced in response to septic shock [R, R].

11) Higenamine as a Cough Medicine

Higenamine relaxes the trachea and relieves the symptoms of a sore throat by acting upon the beta-2-adrenoreceptor. In Japan, the fruit of the sacred bamboo (Nandina domestica) is one of the ingredients in a popular over-the-counter throat lozenge.

The amount of higenamine in each lozenge was determined to be 2.2 μg/drop, much lower than amounts found in supplements intended for pre-workout use or weight loss [R].

12) Higenamine May Treat Arthritis

Higenamine may prevent and treat arthritis by preventing the breakdown of collagen in the joints. Higenamine reduces inflammation in the joints that may also help prevent further damage and treat pain [R].

13) Higenamine May Help Treat Spinal Cord Injury

In mice, high doses of higenamine (10 mg/kg of body weight) is a promising treatment for spinal cord injuries. Higenamine enhances the body’s repair process by decreasing the inflammation that often prevents recovery from spinal injuries [R].

14) Higenamine May Treat Damage Due to Heart Disease

Historically, higenamine has been used in traditional Asian medicine to strengthen the heart. Modern scientific studies have backed this up, showing that higenamine protects the heart in 3 major ways [R]:

  • Its antioxidant effects protect heart cells from damage and death.
  • Its ability to prevent blood clots reduces the risk of strokes and other conditions involving blocked blood flow.
  • Intravenous injections of higenamine restore the heart to a normal rhythm in patients and animals with irregular heartbeats (arrhythmia) [R, R, R].

Higenamine Side Effects

Higenamine is typically safe for healthy individuals. Higenamine functions like other activators of the β2 adrenergic receptor, such as ephedrine and caffeine. However, this can sometimes result in adverse effects (such as a dangerous increase in heart rate and blood pressure) in people who are at risk.

Clinical studies in people have reported mild and temporary side effects such as dizziness, heart palpitation, chest congestion, and dry mouth [R, R, R].

Supplements containing higenamine have been linked to liver damage, although there may be other ingredients such as aegeline, caffeine, and yohimbine in these supplements that may be more responsible for this effect than higenamine itself [R].

A case study was reported where one individual experienced severe muscle pain and break down a day after consuming 1.5x the recommended dose of a higenamine-containing workout supplement. The symptoms persisted for nearly 4 months after consumption of the supplement [R].

Side effects may be rare, but must be taken into consideration when the user has other medical conditions.

Higenamine Drug Interactions

Higenamine may decrease the effectiveness of blood pressure medication and drugs used to prevent blood clots [R, R].

Higenamine may also decrease the excretion rate of the cancer chemotherapy drug Epirubicin, which could result in a higher level of the drug accumulating in the blood [R, R].

Natural Sources of Higenamine

Higenamine is found in varying quantities in the following plant sources [R]:

  • Wolf’s bane or aconite root (Aconitum carmichaelii)
  • Seeds of the sacred lotus (Nelumbo nucifera)
  • Fruit of heavenly or sacred bamboo (Nandina domestica)
  • Wild ginger (Asarum heterotropoides)
  • Lamarck’s bedstraw (Galium divaricatum)
  • Sugar apple (Annona squamosa)
  • Willow-leafed magnolia (Magnolia salicifolia)
  • Argemone mexicana
  • Coptis japonica
  • Radix Aconiti Lateralis Preparata

However, caution should be used when selecting a source of higenamine. Chemically synthesized higenamine usually has higher purity, but it is not a “natural” source. Conversely, naturally-derived plant sources of higenamine, including aconite (Wolf’s bane) and fruit of the sacred bamboo, may contain substances that are toxic to animals and humans [R, R].

Higenamine Dosage

Currently, there is no evidence to support an optimal dose of higenamine for improving athletic performance or aiding in weight loss. Higenamine-containing supplements usually contain 20 to 40 mg, although some supplements contain as much as 75 mg per recommended serving or dose [R].

In throat lozenges, the amount of higenamine is 2.2 μg, which is about 10,000 times lower than quantities present in pre-workout supplements. However, this lower dose may be effective for treating coughs and other conditions, since the lozenges release higenamine directly to the affected areas without having to go through the whole digestive system first [R].

User Reviews

Stimulant effects of increased heart rate and better mental focus were the most frequently reported effects from people taking higenamine-containing supplements. One user reported that the increase in heart rate was similar to an anxiety attack.

There are conflicting reports regarding whether higenamine stimulates the growth of skeletal muscles, but this may also contribute to its popularity as a workout supplement.

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  • Alan

    This is gold for me. I think I will get the lozenges first. Currently I do not have a cough but a lozenge 2 or 3 times a day should discourage a cough at the same time I can see if there are any side effects for me. I may be moving home shortly, so I will get genetically tested once I am comfortable in my new home. Being from Oz pardon my ignorance, but I have heard in US medical dramas, call for the use of Norco. In Oz Norco used to be a popular brand of butter. I imagine the lozenges are available from iherb?
    Thanks again

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