Citrus aurantium and weight loss -
However, more rigorous human research is needed An ongoing study is also exploring the use of limonene as a treatment for COVID However, the results are not yet known. Bear in mind that limonene cannot prevent or cure COVID Another protoalkaloid found in bitter orange is p-octopamine.
However, little to no p-octopamine exists in bitter orange extracts. The leaves of the bitter orange plant are rich in vitamin C , which acts as an antioxidant. Antioxidants are substances that may protect your body from disease by preventing cell damage. They work by deactivating free radicals, which are unstable compounds that damage your cells, increasing inflammation and your disease risk 15 , Protoalkaloids are plant compounds found in bitter orange that have anti-inflammatory and antiviral properties.
They have been shown to be safe for consumption. Many weight loss supplements use bitter orange extracts in combination with other ingredients.
However, scientific studies have not thoroughly examined the composition of these supplements to determine which ingredient, if any, supports weight loss.
Notably, p-synephrine has been shown to increase fat breakdown, raise energy expenditure, and mildly suppress appetite , all of which may contribute to reduced weight.
Yet, these effects occur at high doses that are discouraged due to the lack of safety information 4 , 8 , Bitter orange and its extracts are used in Traditional Chinese Medicine TCM to treat indigestion, diarrhea, dysentery, and constipation.
In other regions, the fruit is used to treat anxiety and epilepsy 3. Another study noted that the bitter orange compound p-synephrine may improve athletic performance though by increasing total reps and volume load, or your ability to train harder A stimulant is a substance that increases your heart rate and blood pressure 1.
Several sports organizations, such as the National Collegiate Athletic Association NCAA , list synephrine as a stimulant. Furthermore, one study determined that bitter orange juice contains furanocoumarin, a compound that may cause the same medication interactions as grapefruit juice Therefore, people taking decongestants or those who have high blood pressure, an irregular heartbeat, or glaucoma should avoid the juice and fruit of bitter oranges.
Despite numerous studies showing that bitter orange extracts are not stimulants, widespread controversy exists, and the NCAA has listed it as a banned substance.
Bitter orange may also interact with certain medications. Generally, bitter orange extracts in dietary supplements are safe to consume in doses of 50—98 mg per day 1 , One study showed that 40 mg of synephrine combined with mg of caffeine is a safe dose of these combined ingredients 3. In another study, eating a whole bitter orange containing Still, people who are pregnant or breastfeeding should avoid bitter orange due to a lack of safety information 1.
Bitter orange is likely safe in doses ranging from The juice of the bitter orange can be used as a marinade to flavor fish and meat. Bitter orange has several other household uses outside of the kitchen.
These include 2 :. Bitter orange is a citrus fruit with several household and industrial uses, ranging from food additives to perfumery. You may want to avoid this fruit and its extracts if you have high blood pressure, an irregular heartbeat, or glaucoma. Likewise, bitter orange supplements are banned for NCAA athletes.
Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Some argue that orange peels contain important nutrients and should be eaten rather than thrown away.
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Some studies suggest vaping may help manage your weight, but others show mixed…. No significant differences in heart rate or blood pressure were observed in response to the product relative to baseline and control values.
No significant effects of the product were noted as compared to the placebo group with respect to blood pressure, heart rate, electrocardiographic data, fasting blood glucose, renal function, hepatic function or complete blood count with differentials over the 14 days of the study.
The treated group experienced a significant reduction in fatigue levels, while sleep quality was negatively impacted. At the end of the study, the treated group experienced a reduction in diastolic blood pressure as compared to the placebo group The authors concluded that the product was safe over the course of the study [ 20 ].
No weight loss was observed over the two weeks of the study. Half of the subjects were randomly assigned to either the treatment or control group.
After 8 weeks the experimental group had lost a significantly greater amount of weight than the control group 3. The daily intake of p -synephrine 10 mg was small, and its relative contribution to the overall weight loss cannot be determined.
The study was a 14 day, placebo-controlled double-blinded crossover protocol where subjects received two capsules of the product or placebo for the first seven days and four capsules per day for the next seven days.
Analyses were conducted at baseline, and days seven and No significant differences were observed at any time point between treated and placebo control with respect to systolic and diastolic blood pressures, heart rate, or heart valve function and left ventricular ejection fraction as determined by serial echocardiograms or Doppler echocardiograms.
The maximum amount of p -synephrine 10 mg per day was small compared to the maximum amounts of ephedrine 40 mg per day and caffeine mg per day. A statistically larger proportion of subjects taking the product reported minor adverse effects as dry mouth, increased activity, and sleep disorders, but there were no serious adverse events and no significant difference with regard to cardiovascular measurements heart rate, blood pressures, serial echocardiograms and Doppler echocardiograms between the treated and placebo groups.
Gurley et al. The daily consumption of p -synephrine was The authors concluded that a supplement containing C. aurantium extract did not appear to significantly modulate cytochrome P enzyme activities in human subjects, and therefore posed minimal risk for cytochrome Pmediated, herb-drug interactions.
The bitter orange extract had no significant effect on CYP1A2, CYP2D6, CYP2E1 or CYP3A4, the major drug-metabolizing cytochrome enzymes. No adverse effects were observed.
The authors did not assess the possible effects on body weight or blood chemistry. The study was not published Table 2 , but a copy of the final report is available on line.
Of the 65 adults enrolled, 54 completed the study with 6 dropouts from the placebo group and 5 subjects from the product treatment group. The product contained extracts of bitter orange, guarana and green tea as well as 7-oxo-dehydroandrostenedione DHEA , conjugated linoleic acid and chromium picolinate.
The daily consumption of bitter orange extract was mg but the p -synephrine content was not noted. At the completion of the 8 week study, the treated group lost an average of 2.
No significant differences occurred between the treatment and placebo groups with respect to systolic and diastolic blood pressures, heart rate or temperature. Furthermore, there were no significant differences in serum chemistry profiles and complete blood counts between the two groups.
There was also no difference in the reported incidence of adverse events between the two groups and no serious adverse events were reported [ 25 ]. It is not possible to determine the role of p- synephrine and the bitter orange extract in the observed effects. This was a randomized, double-blind placebo-controlled study involving healthy, overweight adults.
A total of 35 subjects completed the 8 week study. Each adult received three capsules of the weight-loss product twice daily or a placebo in conjunction with a calorie-restricted diet and an exercise program.
The product also contained 3-acetyloxo-dehydroepiandrosterone 17 mg , Coleus forskohlli extract 50 mg extract, 10 mg forskolin , yerba mate extract mg , guarana extract mg extract, 51 mg caffeine , piperine 1.
The most significant finding of the study was a 7. No significant differences were noted between the treated and the placebo-controlled groups with respect to body weight, body fat, or lean tissue [ 26 ].
No changes in heart rate or blood pressure were observed and no serious adverse events were reported. The relative role of each of the ingredients cannot be determined. Min et al. This randomized, placebo-controlled, double blind and crossover study involved 18 healthy subjects.
The rate-corrected QT QTc interval and blood pressure were measured before dosing and at 1, 3, 5 and 8 hrs after dosing. The bitter orange extract did not significantly alter the QTc interval or the systolic or diastolic blood pressures at any time point.
Haller et al. The protocol consisted of a randomized, double blind, placebo-controlled crossover design involving 10 subjects with a one-week washout between treatments. The results showed that the dietary supplement but not the p- synephrine-containing bitter orange extract increased both systolic and diastolic blood pressures at two hours post-treatment, while heart rate increased at six hours by The authors concluded that the pressure effects were not likely caused by the C.
aurantium alone since no blood pressure effect was observed with an 8-fold higher dose of p -synephrine. The authors also concluded that the increase in blood pressure may be attributable to caffeine and other stimulants in the dietary supplement.
The increase in heart rate reported for p -synephrine at 6 hours is not consistent with the pharmacokinetics of p- synephrine or a number of other studies, and is discussed in detail below. The amounts of the ingredients in the products were verified by analytical analysis. Bui et al.
Heart rate and blood pressure were measured every hour for six hours. These investigators reported small but clinically insignificant increases in heart rate, and systolic and diastolic blood pressures for up to five hours.
The difference in the results between this study and the study of Min et al. However, these effects on heart rate and blood pressure were small and have not been observed in other studies. Sale et al. As noted above, this product contained bitter orange, guarana and green tea extracts.
Subjects received either the placebo or the product and were followed for seven hours or exercised on a treadmill for 60 min. The product had no effect on ATP utilization under resting or exercise conditions relative to control. Fatty acid oxidation to ATP decreased while plasma levels of fatty acids increased in response to the product.
The product had no effect on resting heart rate or blood pressure. Gougeon et al. No other ingredients were present in the product. The thermic effect of food on a 1. Five capsules of the C. aurantium extract provided 26 mg p -synephrine, and 4 mg or less each of other phenethylamines Advantra Z ®.
The thermic effect of food was determined on an initial 30 subjects. A subset of 11 men and 11 women were additionally studied after ingestion of the bitter orange extract in conjunction with the protein meal, while a another subset of 12 women and 8 men were studied a third time following ingestion of the C.
aurantium -containing capsules alone. The thermic effect of the bitter orange extract was greater in men than women in the absence of a meal.
A significant increase in the respiratory quotient occurred in both sexes in response to the bitter orange extract alone. No significant changes occurred in systolic and diastolic blood pressures or pulse rates when compared with base line values following exposure to the bitter orange extract.
Hoffman et al. aurantium extract, Garcinia cambogia and chromium JavaFit TM over a three hour period of time in a randomized, double blind study which involved 10 healthy, physically active subjects Table 1. The enriched coffee product contained mg caffeine, Significant increases were observed in responders with respect to resting metabolic rate and respiratory exchange ratio.
No significant differences were observed in average heart rate or diastolic blood pressure while a 3 mm Hg increase was observed in the systolic blood pressure. The modest effect on blood pressure is not surprising based on the amount of caffeine in the product.
Talbott et al. aurantium extract product Advantra Z ® while the other half of the subjects received the placebo Table 2. Heart rate and blood pressures were determined at the start of the study and after six weeks. No significant differences were observed between the treated and placebo control groups at the conclusion of the study with respect to these cardiovascular parameters.
No effects on body weight were reported. This study represents the highest dose of p -synephrine for the longest period of time that has been reported. The study was presented at a scientific meeting but never published.
The product Ripped Fuel Extreme Cut TM contained 21 mg p -synephrine and mg caffeine, as well as other ingredients including herbal extracts of green tea, ginger root, cocoa seed, willow bark, and wasabi.
The product or placebo was taken one hour prior to 30 min of moderately intense exercise. No significant treatment-related differences in systolic blood pressure, heart rate or body temperature were observed.
Product-related increases in diastolic blood pressure 8. Exercise was perceived as being less strenuous after consumption of the product. Due to the poly-alkaloidal and protoalkaloidal nature of this product, the factor or factors responsible for the effects on blood glucose and diastolic blood pressure cannot be determined.
Seifert et al. The product contained 13 mg p -synephrine as Advantra Z ® , mg caffeine as guarana , and The study involved 14 females and 9 males in a placebo-controlled, crossover design. Subjects ingested one capsule with each of three meals on day one of treatment, and one more capsule on the morning of the second day.
Data were collected 60 min after the last administration of the product. No differences were observed in heart rate or blood pressure following treatment. This was an acute study which did not provide information on long-term effects, but did demonstrate an increase in energy expenditure.
Stohs et al. The study was a randomized, placebo-controlled, double blind design with the vehicle for the p -synephrine being one ounce of tomato juice. The amount of p -synephrine in the product was verified by independent analysis. Measurements were taken at baseline prior to consuming the product and at 75 min.
At this time point, a 6. No significant effects were observed with respect to blood pressure or heart rate, nor were there any significant differences in responses to a 10 item self-report questionnaire which addressed such issues as nervousness, tension, anxiety, hunger, energy, headache, general discomfort, and sleepiness.
Longer term safety and efficacy studies involving p -synephrine alone are warranted. The amount of p- synephrine in the capsules was determined by high pressure liquid chromatographic analysis. Electrocardiograms, blood pressures, heart rates, blood chemistries and blood cell counts with differentials were determined at baseline, 30 min, 60 min, 90 min, 2 hours, 4 hours, 6 hours and 8 hours, as well as after 5, 10 and 15 days.
Blood samples were drawn after 2 hours after the first dose as well as at 5, 10 and 15 days to measure p -synephrine levels to ensure compliance. p -Synephrine had no significant effect on heart rate, blood pressure, blood chemistries, or blood cell counts, and caused no cardiovascular abnormalities.
Bloomer et al. Methyl-synephrine is purported to occur in nature, does not occur in bitter orange extract, and is of synthetic origin in this product and other products that have been marketed. For the sake of completeness, the results of these studies will be summarized, but these results will not be incorporated into the general discussion of bitter orange extract and p -synephrine provided below.
Both studies examined the effects of the product on metabolic rate, and plasma free fatty acids, glycerol, norepinephrine and epinephrine levels.
The initial study [ 38 ] measured changes over a 90 min time frame in 10 healthy male subjects. The second study [ 39 ] measured the same parameters over a six hour time frame in 10 healthy male and 10 healthy female subjects. Increases in each of the parameters were observed, with a It is also important to note that significant increases in heart rate as well as systolic and diastolic blood pressure occurred in both studies in response to the consumption of the product.
The authors note that the product may be useful in healthy, normotensive, closely monitored individuals. However, it is not a product that should be recommended to the general public. In a study similar to those reported by Bloomer et al. Over a three hour time period following ingestion of the product significant increases in resting oxygen uptake and caloric expenditure were occurred.
However, increases in heart rate, systolic blood pressure, tension and confusion were also observed, confirming the highly undesirable properties of this synthetic product. Stohs [ 41 ] has reviewed and assessed the 22 FDA adverse event reports AERs from April through October associated with bitter orange C.
aurantium -containing products, as well as 10 clinical case reports published during this time interval regarding the possible involvement of bitter orange-containing weight management products with cardiovascular incidents and other adverse events.
In all reported AERs and case cases, the products involved were poly-herbal, poly-alkaloidal and poly-protoalkaloidal. Adverse events that have been purported in conjunction with the published clinical case reports included: acute lateral-wall myocardial infarction, exercise-induced syncope associated with QT prolongation, ischemic stroke, ischemic colitis, vasospasm and stroke, variant angina, coronary vasospasm and thrombosis, exercise induced rhabdomyolysis, ST segment myocardial infarction, and ventricular fibrillation [ 41 ].
In one case report it was suggested that a bitter orange-containing dietary supplement may have masked bradycardia and hypotension while exacerbating weight loss in an individual with anorexia nervosa, although no evidence was provided that an adverse event had actually occurred. Although the products consumed were all multi-ingredient, in each case reference was specifically made to C.
aurantium, bitter orange or p -synephrine as the most likely causative agent. A more probable culprit for at least some of these effects may have been the high caffeine intake associated with the products in question. Another factor to be considered is the occurrence of up to mg p -synephrine per quarter liter of various Citrus juices [ 42 , 43 ] which are widely consumed without the report of adverse events.
Millions of individuals ingest p -synephrine and bitter orange-containing food products as orange juices and marmalades as well as dietary supplements on a daily basis. Therefore, although these case reports should raise the level of awareness with regard to the use of complex weight management products, it is not possible to extrapolate the cause of these adverse effects to the p -synephrine which may have been present in the products.
No evidence showing a direct link between bitter orange extract and the adverse events is provided [ 41 ]. A total of 23 published and unpublished studies involving a total of approximately total human subjects were reviewed.
The authors located information regarding the unpublished studies through presentations at scientific meetings and availability of research reports on the internet, as well as information from the investigators involved in the studies.
Seven of the studies were not published in peer reviewed journals [ 17 - 20 , 25 , 33 , 37 ] Table 2. However, six of these studies were presented at national meetings [ 18 - 20 , 25 , 33 , 37 ], and one of these six studies is in the process of being submitted for consideration for publication [ 37 ].
As noted in the references, information including presentations and final reports are available on the internet regarding these unpublished studies. The results associated with these unpublished studies Table 2 in general are consistent with the results of the published studies Table 1.
Five published studies [ 6 , 24 , 27 , 31 , 36 ] and two unpublished studies [ 33 , 37 ] reported no cardiovascular effects when using p -synephrine bitter orange only containing products. The published studies involved a total of subjects with a total of 31 subjects in the two unpublished studies.
However, in one of these studies [ 24 ] consisting of 12 subjects it is not clear that effects on heart rate and blood pressure were specifically examined, with the authors simply reporting that no adverse effects were observed.
Five published studies [ 15 , 21 , 22 , 26 , 30 , 35 ] using p -synephrine in combination with other ingredients reported no cardiovascular effects. A total of 88 subjects were involved in these studies.
Small cardiovascular effects were reported by Bui et al. Small cardiovascular effects were reported for three studies that involved subjects consuming p -synephrine plus caffeine [ 28 , 32 , 34 ]. reported an increase in heart rate [ 28 ] and diastolic blood pressure [ 34 ] 10 subjects.
Upon careful review, the study of Haller et al. p -Synephrine Advantra Z ® alone had no effect on systolic or diastolic blood pressure.
The authors reported an increase in heart rate six hours after treatment. The half-life of p -synephrine is two to three hours [ 28 , 34 , 45 ]. As a consequence, an increase in heart rate after two to three half-lives when the p- synephrine blood levels will have dropped to one-fourth to one-eighth the peak blood levels would not be expected.
Furthermore, a major complicating factor is that all subjects consumed a meal three hours after ingesting the p -synephrine The cardiovascular and thermic effects of food are well known [ 31 ], and an increase in heart rate in the control group was also observed. Thus, it is not plausible to attribute the increase in heart rate to p -synephrine, or an increase in heart rate and blood pressure to a product that contained very little p -synephrine 5.
This study did show that the commercial product Xenadrine EFX® which contained only 5. This product was reported to also contain 5. aurantium extracts are either devoid of octopamine or contain only trace amounts [ 3 ], thus the product being used [ 28 ] appears to have been adulterated.
Hansen et al. These doses represent over 13 times the usual daily dose for p -synephrine and the equivalent of the caffeine in about three cups of coffee given together as a single bolus dose to these animals.
When caffeine was added, increases in heart rate and blood pressure were observed [ 46 ]. These studies indicate that in rats at very high doses of p -synephrine the combination with caffeine may result in cardiovascular effects.
However, due to the highly inequivalent dosing between this study in rats and typical dosing in humans, the results of this study in rats cannot be directly extrapolated to humans. A dose of 3. Various studies indicate that the lipolytic activity of p -synephrine is due to binding to β-3 adrenergic receptors in adipose tissues [ 10 ].
These same β-3 adrenergic receptors are also associated with cardiovascular tissues, and their activation results in a down-regulation of cardiovascular stimulation [ 48 , 49 ]. Thus, p -synephrine stimulation of β-3 adrenoreceptors in the cardiovascular system does not result in an increase in blood pressure or heart rate but may exhibit a modulating rather than a stimulatory effect.
This cardiovascular receptor response may explain why an increase in heart rate or blood pressure is not seen in most cases when p -synephrine is used alone or in combination with caffeine in dietary supplements, in spite of the fact that caffeine alone may produce modest increases in these parameters under some conditions [ 50 , 51 ].
Approximately half of the clinical studies involved the use of commercial products. In only one case [ 28 ] was the actual amount of p -synephrine and other protoalkaloids determined, while in the remaining studies involving commercial products the reported amounts of p -synephrine and caffeine were simply based on label claim.
The amount of p -synephrine was independently determined in two studies in which bitter orange extract was used as a single ingredient product [ 36 , 37 ]. Various studies have shown that there are not always good correlations between the label claim of marketed products or the product data sheet and the amount of p -synephrine shown to be present by independent analysis [ 52 - 56 ].
Therefore, the actual amount of p -synephrine consumed in the majority of the studies was not verified. Finally, nine studies involving the administration of bitter orange extract alone or in combination with other constituents have demonstrated an increase in metabolic rate without an increase in heart rate or blood pressure [ 18 - 20 , 26 , 30 - 32 , 35 , 36 ].
These results suggest that bitter orange extract and p -synephrine may be beneficial in weight management. The results involving both published and unpublished clinical studies indicate that p -synephrine alone or in combination with caffeine does not appear to produce significant adverse cardiovascular effects or pose a risk to human health at doses commonly ingested orally.
No adverse effects have been directly attributable to bitter orange extract or p- synephrine. The results indicate that bitter orange extract and p -synephrine increase metabolism and energy expenditure.
The data accumulated to date do not support hypothesized concerns regarding potential adverse effects of p -synephrine particularly with respect to the cardiovascular system due to a paucity of binding to α-, β-1 and β-2 adrenergic receptors while exhibiting modest binding to β-3 adrenergic receptors.
All authors have served as consultants for Nutratech, Inc. Nutratech Inc. provided some of the unpublished research reports. Chen JK, Chen TT. Zhi Shi Fructus Aurantii Immaturus. Chinese Medical Herbology and Pharmacology. City of Industry, CA USA: Art of Medicine Press.
Stohs SJ, Shara M. A review of the safety and efficacy of Citrus aurantium in weight management. In: ed. Bagchi D, Preuss HG.
Obesity: Epidemiology, Pathophysiology, and Prevention. Boca Raton, FL, USA: CRC Press. Pellati F, Benvenuti S. Chromatographic and electrophoretic methods for the analysis of phenethylamine alkaloids in Citrus aurantium.
J Chromatog A. Sander LC, Putzbach K, Nelson BC. et al. Certification of standard reference materials containing bitter orange. Analyt Bioanalyt Chem. Evans RL, Pho AN, Roman MC, Betz JM. Penzak SR, Jann MW, Cold JA. Seville sour orange juice: synephrine content and cardiovascular effects in normotensive adults.
J Clin Pharmacol. Bent S, Padula A, Neuhaus J. Safety and efficacy of Citrus aurantium for weight loss. Amer J Cardiol. Nasir JM, Durning SJ. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clinic Proceed. Stephensen TA, Sarlay JrR. Ventricular fibrillation associated with use of a synephrine containing dietary supplement.
Military Med. Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p -synephrine as related to its pharmacological effects. Oxid Med Cell Long. Stohs SJ, Preuss HG. Stereochemical and pharmacological differences between naturally occurring p -synephrine and synthetic p -synephrine.
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International Journal of Wurantium Sciences. Global reach, higher impact. Int Cktrus Med Sci ; 9 7 Sidney J. Stohs 1Harry G. Preuss 2Mohd Shara 3. Dean Emeritus, Creighton University Medical Center, Omaha, NEUSA; 2.Video
Woman Almost Dies after Taking Daily Supplements? Obesity is a serious GI and energy levels problem Citrus aurantium and weight loss the world. More than aurantikm of U. adults weighf obese. The inability of many individuals to keep their weight in check by diet and exercise has created a need for additional therapeutic means to combat obesity. Despite great effort, the pharmaceutical industry has not come up with the solution; because most weight-loss drugs to date have serious adverse effects to health and well-being.Citrus aurantium and weight loss -
Food and Drug Administration because it raises blood pressure and has been linked to heart attacks and strokes. Like ephedra, synephrine may speed up your heart rate and raise your blood pressure. Strokes and heart attacks have been reported in some people after taking bitter orange alone or in with other stimulants such as caffeine.
In addition, bitter orange may interact with some prescription medications. Remember, just because an herbal supplement might be natural doesn't mean it's safe.
Talk with your doctor before taking herbal supplements. All rights reserved. Terms of Use. Weather: Closings and Delays Weather: Closings and Delays.
Large amounts of orange peel have caused intestinal colic, convulsions, and death in children. One text on Chinese medicine cautions against the use of bitter orange in pregnancy. Decoctions of bitter orange substantially increased blood levels of cyclosporine in pigs, causing toxicity.
Bitter orange might, therefore, interact with drugs that are metabolized by CYP3A. To be on the safe side, bitter orange should not be combined with prescription medications, unless someone is under the care of an experienced natural medicine clinician.
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