Evodiamine supplement side effects, benefits, does use lead to weight loss? available as pure powder capsules and extract
Feb 27 2014 by Ray Sahelian, M.D.

Evodiamine is an alkaloid extract from a plant called Evodiae Fructus. There have been many studies with this compound, but almost all have been done either in a laboratory on isolated cells or in rodents. No published human trials could be found. Evodiamine has been promoted as a weight loss agent but it is not clear at this time whether it is effective. If you would like to eat less, consider the following.

Based on the available studies, we can say that evodiamine
Raises body temperature
Has lead to weight loss in animal studies
Inhibits the growth and metastases of certain cancer cells in vitro
Influences the metabolism of certain drugs
Influences the secretion of catecholamines from the adrenal glands.

Breast cancer
PLoS One. 2013. Anti-Proliferative Effects of Evodiamine on Human Breast Cancer Cells.

Potential influence on sexuality and erectile dysfunction
J Chem Biol. 2012. Effect of novel synthetic evodiamine analogue on sexual behavior in male rats. Department of Pharmacology, AISSMS College of Pharmacy, Kennedy Road, Near R.T.O, Pune, 411 001 India.AbstractCurrently phosphodiestrase5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction. Drugs such as sildenafil and tadalafil are available as PDE5 inhibitors which are potent and reversible but lack selectivity with side effects such as headache, facial flushing, dyspepsia, and visual disturbances. We herein report for the first time novel condensed thienopyrimidines as evodiamine analogue and their effect on sexual behavior in male rats hitherto unreported. Novel synthetic evodiamine significantly showed improvement in male rat copulatory behavior.

Pharmacological profile of evodiamine in isolated rabbit corpus cavernosum.
Eur J Pharmacol. 2002.
This study was designed to examine the pharmacological properties of evodiamine in isolated rabbit corpus cavernosum. In phenylephrine-precontracted cavernosal strips, evodiamine  induced a concentration-dependent relaxation. In summary, evodiamine possesses a potent corporal relaxing effect which is attributable to endothelium-independent properties probably linked to charybdotoxin-sensitive K(+) channel activation in the cavernosal vasculature and by nonselective interfering phosphodiesterase to prevent cyclic nucleotide degradation. Furthermore, the physiological effects of evodiamine on the aged animals may implicate a potential for the treatment of erectile dysfunction.

Evodiamine dosage
Proper dosage of evodiamine supplement use is not clearly understood.

Evodiamine side effects
I have personally not tried an evodiamine supplement so I don't know if evodiamine has side effects. I have not seen such reports in the medical literature. It does increase body temperature in rodent studies.

Review and summary
Not much can be said for certain about an evodiamine product since I cannot find any human trials. As to its promotion as a weight loss agent, this may be premature. See weight loss for options on how to help maintain proper weight. Supplements to consider as diet aids include green tea extract, garcinia cambogia, choline, carnitine, 5-HTP which works to increase serotonin levels, and perhaps hoodia.

Evodiamine raises body temperature
Pharmacological properties of galenical preparation. XIV. Body temperature retaining effect of the Chinese traditional medicine, "goshuyu-to" and component crude drugs.
Chem Pharm Bull (Tokyo). 1991.
We orally administered Goshuyu-to or Evodia fruit extract and Ginger extract to untreated rats, and found a slight but not significant rise in their body temperature. In rats treated with chlorpromazine, the administration of Goshuyu-to prevented decrease in the body temperature. After administration of each extract of component crude drugs (Evodia fruit, Ginger, Ginseng: Jujube: such an effect was recognized only by Evodia fruit, and other component crude drugs exhibited no body temperature retaining effect in this experiment system. We further studied the effect of Evodia fruit alkaloid hydroxyevodiamine, evodiamine, rutaecarpine and evocarpine used individually and confirmed that the body temperature retaining effect occurred mainly with evodiamine.

Evodiamine and weight loss
Weight loss studies with evodiamine in rodents look promising, but human studies are lacking.

Evodiamine improves diet-induced obesity in a uncoupling protein-1-independent manner: involvement of antiadipogenic mechanism and extracellularly regulated kinase/mitogen-activated protein kinase signaling.
Endocrinology. 2008. Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Japan.
Evodiamine is an alkaloidal compound with antiobesity effects that have been thought to be due to uncoupling protein-1 (UCP1) thermogenesis similar to the effects of capsaicin. Our findings suggest that evodiamine has a potential to prevent the development of diet-induced obesity in part by inhibiting adipocyte differentiation through ERK activation and its negative cross talk with the insulin signaling pathway.

Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist.
Planta Med. 2001.
Evodiamine, a major alkaloidal principle of Evodia fruits (Evodia rutaecarpa), showed vanilloid receptor agonistic activities comparable to capsaicin. The Chinese literature refers to Evodia fruits as a "hot nature" herb. In spite of the similarities in the actions of evodiamine and capsaicin in vitro, evodiamine has no perceptible taste, including a peppery hot taste. Therefore, the effectiveness of evodiamine and the extract of Evodia fruits in preventing obesity on male C3H mice, or male SD rats were examined. When evodiamine was supplemented at 0.03% of the diet and fed to mice for 12 days, the perirenal fat weight became significantly lower than in the control group. The epididymal fat mass was also decreased in the evodiamine diet group. When evodiamine was supplemented at 0.02% in the form of ethanol extract of Evodia fruits to the high-fat diet and fed to rats for 21 days, the body weight, the perirenal fat weight, epididymal fat weight, the levels of serum free fatty acid, total lipids in the liver, triglyceride in the liver, and cholesterol level in the liver were significantly reduced as compared with the control diet group. In conclusion, we have demonstrated that a novel non-pungent vanilloid receptor agonist, evodiamine, mimics the characteristic anti-obese effects induced by capsaicin. Evodiamine would induce heat loss and heat production at the same time and dissipate food energy, preventing the accumulation of perivisceral fat and the body weight increase.

Evodiamine and cancer
Inhibitory effects of evodiamine on the growth of human prostate cancer cell line LNCaP.
Int J Cancer. 2004.
Evodiamine, isolated from a Chinese herbal drug named Wu-Chu-Yu, possesses many biological functions. Recently, it has been reported that Wu-Chu-Yu exerts an antiproliferative effect on several cancers. Prostate carcinoma initially occurs as an androgen-dependent tumor and is the second leading cause of cancer death in American males. In the present study, the effect of evodiamine on the growth of androgen-dependent prostate cancer cell line LNCaP in vitro was examined. These results suggested that evodiamine inhibits the growth of prostate cancer cell line, LNCaP, through an accumulation of cell cycle at G2/M phase and an induction of apoptosis.
  
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Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells.
Cancer Sci. 2003.
We found that evodiamine, a major alkaloidal component of Evodiae Fructus (Goshuyu in Japan), inhibited proliferation of several tumor cell lines, but had less effect on human peripheral blood mononuclear cells (PBMC). We used human cervical cancer cells, HeLa, as a model to elucidate the molecular mechanisms of evodiamine-induced tumor cell death. The results showed that evodiamine induced oligonucleosomal fragmentation of DNA in HeLa cells and increased the activity of caspase-3, but not that of caspase-1, in vitro. Taken together, our data indicated that evodiamine alters the balance of Bcl-2 and Bax gene expression and induces apoptosis through the caspase pathway in HeLa cells.

Anti-invasive and metastatic activities of evodiamine.
Biol Pharm Bull. 2002.
We have recently reported that evodiamine can suppress in vitro invasion and lung metastasis by colon 26-L5 carcinoma cells. To extend our study, we examine here the anti-invasive and metastatic effects of evodiamine on Lewis lung carcinoma (LLC) and B16-F10 melanoma in addition to colon 26-L5 carcinoma. Critical structures of evodiamine for the activities were also evaluated by comparison with compounds possessing structures similar to that of evodiamine. Evodiamine concentration-dependently inhibited the invasion of B16-F10, LLC and colon 26-L5 cells. These results suggest that evodiamine may be useful as a leading compound for agents in tumor metastasis therapy.

Evodiamine Research
Effects of evodiamine on gastrointestinal motility in male rats.
Eur J Pharmacol. 20026.
The effects of evodiamine on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in male rats. Evodiamine, isolated from the dry unripened fruit of Evodia rutaecarpa Bentham (a Chinese medicine named Wu-chu-yu), has been recommended for abdominal pain, acid regurgitation, nausea, diarrhea, and dysmenorrhea. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)51CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay (RIA). After administration of evodiamine (0.67-6.00 mg/kg), both gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the evodiamine-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that evodiamine inhibits both gastric emptying and gastrointestinal transit in male rats via a mechanism involving CCK release and CCK(1) receptor activation.

The bronchoconstrictive action of evodiamine, an indoloquinazoline alkaloid isolated from the fruits of Evodia rutaecarpa, on guinea-pig isolated bronchus: possible involvement on vanilloid receptors.
Planta Med. 2000.
Evodiamine, a constituent of Evodiae Fructus (Evodia rutaecarpa Benth., Rutaceae), produced a bronchial contraction that is resistant to atropine and abolished by pretreatment with a mixture of the NK1 and NK2 receptor antagonists. Contractile responses to evodiamine were examined in guinea-pig isolated bronchus and compared with those to capsaicin. Both compounds evoked bronchial contraction in a concentration-dependent manner. These results suggest that the evodiamine-induced contractile response of the bronchus could be attributed to the resultant tachykinin release from sensory neurons by binding of evodiamine to vanilloid receptors. Rutaecarpine, which belongs to the same indoloquinazoline-type alkaloid as evodiamine, showed neither bronchoconstrictive, desensitizing effects nor vanilloid antagonistic effects.

The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action.
Eur J Pharmacol. 1992.
The roles of the endothelium, Ca2+ and K+ fluxes in the evodiamine-induced attenuation of vascular contractile responses to vasoactive agents were examined. These results suggest that block of the Ca2+ influx through receptor-mediated Ca2+ channels may be the major mechanism underlying the vasodilator effect of evodiamine. (3) A K+ channel blocker, tetraethylammonium, almost completely abolished the vasodilatation induced by minoxidil (a known K+ channel opener) but not evodiamine. The possible involvement of K+ channel activation of the vasodilator effect produced by evodiamine was therefore excluded.

Antianoxic action and active constituents of evodiae fructus.
Chem Pharm Bull (Tokyo). 1989.
Methanol extract from a Chinese medicine, evodia (fruits of Evodia rutaecarpa Benth. or E. officinalis Dode), had a significant effect in the KCN-induced anoxia model in mice and therefore the active constituents were further examined. The results indicated that the antianoxic action of evodia was found in the fraction containing evodiamine. Further analysis of the active constituent indicated that evodiamine and rutaecarpine, indole-alkaloids found in large amounts in the Chinese medicine evodia, were mainly responsible for the antianoxic action.

Uterotonic effect of Evodia rutaecarpa alkaloids.
J Nat Prod. 1980.
Rutaecarpine and dehydroevodiamine were isolated from the unripe fruit of Evodia rutaecarpa. In vitro uterotonic assay on rat uterus showed both alkaloids to be active. Dehydroevodiamine was further shown to be active in the in vivo uterotonic assay using rats as the animal model. Reference evodiamine hydrochloride was also evaluated and found to be devoid of uterontonic activity at the doses administered.

Raw material cost
In 2011, evodiamine was being sold at about 500 dollars per kilo.

Evodiamine supplement and extract questions
Q. Have you researched the effect of evodiamine or have you found an effect on muscle inflammation during of as a result of prolonged muscle contraction? In other words have you not considered researching the effect as an anti-inflammatory agent that might reduce recovery time for long distance runners, weightlifters and or bodybuilders?
   A. I have personally not evaluated evodiamine in my practice on done any research with this substance.

Q. I recently received an email on Evothin Evodiamine 98%. Vanilloid receptor agonists such as evodiamine, capsaicin and ginger represent a new option in post-ephedra weight loss. Mimicking the thermogenic effects of capsaicin, evodiamine offers a non-pungent alternative in vanilloid receptor agonists. Recent studies suggest evodiamine increases energy expenditure by triggering heat production. Compared to the typical 10-20% ingredients, Evothin 98% Evodiamine is unmatched in quality and cost effectiveness. What are your thoughts on this ingredient?
   A. I do not have a strong opinion since I have not been able to locate a human study to confirm these claims.