P-synephrine, a substance found in the skin of bitter oranges (Citrus aurantium ssp. aurantium), is also found in other species of Citrus. P-synephrine, as well as other ingredients obtained from Citrus spp. fruits, is used in many food supplements which allegedly reduce body fat or can modify body composition.
Weight problems, whether objectively or subjectively perceived, create fertile ground for the use of these types of products by certain individuals who tend to use them either alone or in combination with a diet and/or physical exercise.
Nutrivigilance: 18 adverse effect reports received
In 2009, as one of its missions, ANSES set up its nutrivigilance scheme. Since its creation, it has received 18 well-documented reports or adverse effects potentially linked to the consumption of so-called "weight-loss" food supplements containing Citrus spp. fruits, which are a source of p-synephrine.
Of these 18 reports, 13 cases showed a very likely, likely or possible causal link to conditions including cardiovascular effects, liver damage, hyperphosphoremia and neurological damage.
Isolated cases of severe adverse effects, mainly cardiovascular in nature, have also been reported in the literature. It should however be noted that for these severe cases, it is rarely possible to unequivocally attribute the reported adverse effects to Citrus spp. In fact, the existence of other etiologies, co-morbidities, and complex associations makes it difficult to establish a correlation.
In addition, intake of p-synephrine through food supplements should be distinguished from common food-based intake – through the consumption of citrus fruit juices in particular. Ingestion of p-synephrine through common foods does not appear to expose the general public to any risks when it is taken along with a balanced diet and the daily dose does not exceed 20 mg. The food supplements containing Citrus spp. extracts which have been the subject of declarations of cardiovascular effects within the context of the nutrivigilance scheme provide between 1 and 72 mg of p-synephrine per day, according to the doses recommended by the manufacturer, and all contain caffeine.
Agency conclusions and recommendations
Following its assessment, ANSES:
- considers that a dose of 20 mg/day, corresponding to the dose ingested by consumers of large amounts of citrus fruit, may be a reference value representing the p-synephrine intake level not to be exceeded in food supplements (although it is not strictly speaking a safety limit as such);
- notes that many of the food supplements currently on the market provide a daily intake of this substance which surpasses the above reference value; these food supplements therefore should not be made available to the consumer;
- recommends not combining p-synephrine with caffeine, preparations containing caffeine, or any substance possessing cardiovascular effects similar to those of caffeine, due to the cumulative, and possibly synergistic effects of these two substances. For these reasons, synephrine and caffeine should not be combined into a single food supplement;
- strongly discourages the consumption of p-synephrine by individuals with heightened risks of adverse effects (people under treatment for high blood pressure, heart disease or depression in particular), pregnant or breastfeeding women, children and adolescents. This information should be made clearly available to consumers;
- strongly discourages taking food supplements containing p-synephrine during physical exercise due to its possible effects on blood pressure. These effects could heighten cardiovascular risk in overweight or obese subjects, and reduce the beneficial effects of prolonged physical activity on blood pressure at rest.
In addition, due to the contexts in which food supplements containing p-synephrine are commonly used, ANSES feels it is necessary to reiterate the main recommendations it issued in 2010 following its risk assessment of dietary weight-loss practices (ANSES 2010). Weight-loss diets pose a risk to health, and may have harmful effects on the bones, kidneys and heart, as well as on behaviour and psychological well-being, and may pose a risk of regaining the weight lost. Without monitoring by a healthcare professional, and in situations other than those where weight loss is medically justified, weight-loss diets are not recommended.