Blood pressure and heart rate effectsBlood pressure and heart rate effects following a single dose of bitter orange.
BACKGROUND: The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR).
OBJECTIVE: To determine the effects on BP and HR after a single dose of bitter orange in healthy adults.
METHODS: In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration.
RESULTS: SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p < 0.0001); the peak difference was 7.3 +/- 4.6 mm Hg. Although the baseline DBP was higher than after administration of both placebo and bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p < or = 0.02); the peak difference was 2.6 +/- 3.8 mm Hg. HR was significantly increased after bitter orange versus placebo for hours 2-5 (p < 0.01); the peak difference was 4.2 +/- 4.5 beats/min.
CONCLUSIONS: SBP, DBP, and HR were higher for up to 5 hours after a single dose of bitter orange versus placebo in young, healthy adults.
Full Text - http://jb.asm.org/content/122/3/866.full.pdfMicrobial metabolism of phenolic amines: degradation of dl-synephrine by an unidentified arthrobacter.
Microorganismscapableofdegradi ngdl-synephrinewere isolatedfromsoilof Citrusgardensbyenrichmentcultu re,withdl-synephrineas thesolesource of carbonandnitrogen.Anorganismwh ichappears tobean arthrobacter,but whichcannotbeidentifiedwithany ofthepresentlyrecognizedspecie swas predominantintheseisolates.Itw as foundtometabolizesynephrinebya pathway involvingp-hydroxyphenylacetaldehyde, p-hydroxyphenylacetic acid, and3,4-dihydroxyphenylaceticacidas intermediates.Someoftheenzymes of thispathwaywere demonstratedincell-freeextracts.Anaromaticoxygena se, whichcouldalsobereadilyobtaine dina cell-freesystem,was foundtodegrade 3,4-dihydroxyphenylacetic acid by meta cleavage.
Synephrine [l-p-hydroxy-a-(methylaminomethyl)benzyl alcohol] and octopamine [l-phydroxy-a-(aminomethyl)benzyl alcoholJ, which are well known sympathomimetic amines in animal metabolism and are structurally related to epinephrine and norepinehrine, are present in Citrus plants (17, 18). The proposed pathway for the biosynthesis of synephrine in Citrus (21) and the probable metabolic relationship of synephrine and few other phenolic compounds in animals (4, 13) are summarized in Fig. 1 and 2. Synephrine occurs at levels as high as 2 g/kg (fresh weight) in the leaves of Citrus reticulata (Tangerine and Cleopatra mandarin varieties) (22). Although the role of phenolic amines in animal metabolism and their mode of operation are far from completely understood, even less is known of their function in the plant world and no information is available on the mode of disposal of synephrine and related phenolic amines in nature. In Aerobacter aerogenes ATCC 9621, tyramine, however, is used as a source of carbon and nitrogen (11) and is probably degraded to p-hydroxyphenylacetaldehyde by a monoamine oxidase reaction followed by its subsequent conversion to p-hydroxyphenylacetic acid and then to 3,4-dihydroxyphenylacetic acid (2). The present communication describes the isolation from soil and partial characterization of an unidentified arthrobacter which metabolizes dl-synephrine.
it has been said that p-Synephrine could be converted to epinephrine by the hydroxylase enzymes in the liver but it doesnt appear as so
Full Text - http://www.hindawi.com/journals/oximed/2011/482973/A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects
Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.
Oral dose of 46.9mg p-Synephrine will reach a blood concentration of 2 ng/mL and has a half life of 2-3 hours. Also p-Synephrine doesnt seem to agonize the alpha-1 receptor as much as m-Synephrine does
A analysis on fat burner products containing synephrine has found both m-Synephrine and p-Synephrine in them.Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?
Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers.
More on p-synephrine vs. m-synephrine - http://www.tampabayanalytical.com/Roman_ICSB2007.pdf