Phytochemical compounds in sport nutrition: Synephrine and hydroxycitric acid (HCA) as examples for evaluation of possible health risks

Bakhiya, Nadiya; Ziegenhagen, Rainer; Hirsch‐Ernst, Karen Ildico; Dusemund, Birgit; Richter, K; Schultrich, Katharina; Pevny, Sophie; Schäfer, Bernd; Lampen, Alfonso

doi:10.1002/mnfr.201601020

Cited by 24 publications

(21 citation statements)

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“…Questions have been raised regarding the safety of p-synephrine because it has some structural similarity to ephedrine, and p-synephrine is widely referred to as a stimulant and is assumed to exhibit cardiovascular activity because of its structural similarity to ephedrine (see, for example, Penzak et al, 2001;Bent et al, 2004;Fugh-Berman and Myers, 2004;Haaz et al, 2010, Anon, 2010Inchiosa, 2010;Rasmussen et al, 2012;Natural Medicines Comprehensive Database, 2016;OPPS, 2017;Bakhiya et al, 2017). However, the chemical differences between p-synephrine and ephedrine greatly alter the stereochemistry, pharmacokinetic, adrenergic receptor binding, and physiological/pharmacological properties .…”

Section: Introductionmentioning

confidence: 99%

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

Stohs

2017

Phytotherapy Research

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Citrus aurantium L. (bitter orange) extracts that contain p‐synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p‐synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p‐synephrine. Numerous studies have been conducted with respect to p‐synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p‐synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p‐synephrine exerts its effects through multiple actions, which are discussed. Because p‐synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p‐synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

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Section: Introductionmentioning

confidence: 99%

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

Stohs

2017

Phytotherapy Research

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“…Confusion exists regarding the efficacy and safety of p ‐synephrine for a number of reasons (Stohs, ; Stohs et al, ; Stohs & Preuss, ). As the result of structural similarities between p ‐synephrine (Figure ), m ‐synephrine (phenylephrine; Figure ), and ephedrine (Figure ), it is frequently assumed that p ‐synephrine exhibits cardiovascular and stimulant effects similar if not identical to these and other structurally related biogenic amines (Anon, ; Bakhiya et al, ; Bent, Padula, & Neuhaus, ; Fugh‐Berman & Myers, ; Haaz, Williams, Fontaine, Allison, ; Inchiosa, ; Natural Medicines Comprehensive Database, ; OPPS, ; Penzak et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…As the result of structural similarities between p-synephrine (Figure 1), m-synephrine (phenylephrine; Figure 2), and ephedrine (Figure 3), it is frequently assumed that p-synephrine exhibits cardiovascular and stimulant effects similar if not identical to these and other structurally related biogenic amines (Anon, 2010;Bakhiya et al, 2017;Bent, Padula, & Neuhaus, 2004;Fugh-Berman & Myers, 2004;Haaz, Williams, Fontaine, Allison, 2010;Inchiosa, 2011;Natural Medicines Comprehensive Database, 2016;OPPS, 2017;Penzak et al, 2001). p-Synephrine is a phenylethylamine derivative with a hydroxy group in the para position on the benzene ring of the molecule.…”

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confidence: 99%

“…p-Synephrine (bitter orange extract) is widely consumed in conjunction with caffeine(Jung et al, 2017;Ratamess et al, 2015;Stohs et al, 2012). Because concerns have been raised regarding the use of caffeine in combination with p-synephrine(Bakhiya et al, 2017;Marles, 2011), blood levels of caffeine were also determined. The consumption of caffeine was shown to vary widely among participants in this study.…”

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confidence: 99%

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Safety evaluation of p‐synephrine following 15 days of oral administration to healthy subjects: A clinical study

Shara

Stohs

Smadi

2017

Phytotherapy Research

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Extracts of bitter orange (BOE, Citrus aurantium L.) and its primary protoalkaloid p-synephrine are extensively consumed as dietary supplements. p-Synephrine is also present in foods and juices prepared from various Citrus species. The safety of p-synephrine has been questioned as a result of structural similarities with ephedrine. This study assessed the cardiovascular (stimulant) and hemodynamic effects of BOE (49 mg p-synephrine) daily given to 16 healthy subjects for 15 days in a placebo-controlled, cross-over, double-blinded study. A physical evaluation by a cardiologist, as well as heart rates, blood pressures, and electrocardiograms were determined, and blood samples were drawn at baseline, and Days 5, 10, and 15. Serum levels for caffeine and p-synephrine were measured at 1 and 2 weeks. Subjects completed a 10-item health and metabolic questionnaire at baseline and on Day 15. No significant changes occurred in heart rate, electrocardiograms, systolic blood or diastolic pressures, blood cell counts, or blood chemistries in either the control or p-synephrine treated groups at any time point. No adverse effects were reported in response to the bitter orange (p-synephrine). Caffeine consumed by the participants varied markedly. Under these experimental conditions, BOE and p-synephrine were without stimulant (cardiovascular) and adverse effects.

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“…The assessment of the botanical G. sylvestre was also challenging also to the insufficient number of studies containing relevant data for the safety assessment, the poor methodological approaches or poor study design, the lack of systematic data on dose and effect relationship and poor reporting or presentation of the outcomes in the scientific publications. Along these lines, it appears possible that unwanted or adverse effects resulting from the use of certain botanical preparations may be underreported (Bakhiya et al., ).…”

Section: Discussionmentioning

confidence: 99%

Risk assessment of substances used in food supplements: the example of the botanical Gymnema sylvestre

Marakis¹,

Ziegenhagen²,

Lampen³

et al. 2018

EFS2

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Botanicals and preparations derived from these are among the substances frequently added to foods and food supplements, yet the safety of many botanicals has not been systematically assessed. In the context of the EU‐FORA fellowship programme, the fellow performed an assessment on the safety of the botanical Gymnema sylvestre, in accordance with EFSA's guidance on the assessment of safety of botanicals. Although preparations of G. sylvestre are marketed as food supplements, they may appeal to people who are suffering from metabolic syndrome and/or diabetes mellitus. A scientific literature search was carried out using PubMed/MEDLINE and EMBASE electronic databases. Experience was gained by the fellow in systematic data extraction from scientific publications, structuring of the data and evaluating toxicological key parameters, outcomes of clinical significance, pharmacokinetic and pharmacodynamic interactions, uncertainties and methodological shortcomings of studies. Limited evidence from toxicological in vivo studies and human clinical studies suggested lack of relevant adverse effects of this botanical. However, human studies provided some indications that certain Gymnema extracts may enhance the glucose‐lowering effects of certain antidiabetic drugs. Considering the uncertainties for the composition of different Gymnema preparations, potential herb–drug interactions and the indications of glucose lowering or hypoglycaemic effects, the use of Gymnema‐based food supplements in combination with authorised antidiabetic drugs may be associated with risks. The procedures learned for the safety evaluation of Gymnema may be similarly applied by the fellow for the risk assessment of other substances with nutritional or physiological effect added to foods and food supplements. Furthermore, apart from learning by conducting exercises in risk assessment, the fellow was able to develop other skills (e.g. communication skills), diversify his competencies and expand his network of scientific connections for future collaborations in the field of nutritional risk assessment.

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Phytochemical compounds in sport nutrition: Synephrine and hydroxycitric acid (HCA) as examples for evaluation of possible health risks

Cited by 24 publications

References 80 publications

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

Safety evaluation of p‐synephrine following 15 days of oral administration to healthy subjects: A clinical study

Risk assessment of substances used in food supplements: the example of the botanical Gymnema sylvestre

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