Scientific Opinion on the substantiation of health claims related to
pomegranate/pomegranate juice and maintenance of normal blood
cholesterol concentrations (ID 1162, 1320, 2107, 2167), maintenance of
normal erectile function (ID 1163), protection of lipids from oxidative
damage (ID 1201, 1319, 2123), “antioxidant and anti-aging properties”
(ID 1901), increase in appetite after unintentional weight loss leading to an
increase in energy intake (ID 2122) and maintenance of normal blood
glucose concentrations (ID 4471) pursuant to Article 13(1) of Regulation
(EC) No 1924/2006[sup]1[/sup]
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3
European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe:
Pomegranate/pomegranate juice
anti-aging
antioxidant
appetite
blood cholesterol
blood glucose
energy intake
erectile function
health claims
lipids
polyphenols
punicalagin and ellagic acid
skin
weight loss
1. Charakterystyka żywności / składnika
The food that is the subject of the health claims is pomegranate/pomegranate juice and polyphenols in pomegranate/pomegranate juice.
The information provided (e.g. food, conditions of use) for the majority of the health claims on pomegranate and pomegranate juice refers to the type and/or amount of polyphenols in pomegranate/pomegranate juice that should be consumed daily in order to achieve the claimed effect. The Panel assumes that such phenolic compounds are also mentioned (and occasionally quantified) to allow standardisation of pomegranate juice, for which information on composition and on the manufacturing process has not been provided. In the remaining health claims, reference is made to dried fruit or herb powders for which the information on composition and on the manufacturing process has not been provided.
Polyphenols comprise a very wide group (several thousands of compounds) of plant secondary metabolites including flavonoids, isoflavonoids, phenolic acids, proanthocyanidins and other tannins, and lignans with different biological activities. Polyphenol content in foods is usually expressed as gallic acid equivalents (GAE), but also other phenolic compounds such as catechin/epicatechin or caffeic acid which are used for standardisation. This standardisation refers to traditional spectrophotometrical measurement of total polyphenols using the Folin-Ciocalteau method (Singleton and Rossi, 1965), which is based on reducing capacity. The method is not specific for polyphenols because other reducing compounds such as ascorbic acid, sugars and proteins will also be included in the quantification, thus leading to an overestimation of the actual polyphenol content. The total polyphenol content assessed with this method is not suitable for characterisation of polyphenols in foods.
Regarding the nature of specific polyphenols in pomegranate (Prunus granatum), punicalagin and ellagic acid have been specified in the conditions of use. Punicalagins are tannins that are known to be hydrolysed in vivo into smaller polyphenols such as ellagic acid. Punicalagin and ellagic acid can be measured in foods by established methods. Pomegranate polyphenols are bioavailable (Mertens- Talcott et al., 2006; Seeram et al., 2006).
The Panel considers that, whereas pomegranate/pomegranate juice and polyphenols in pomegranate/pomegranate juice are not sufficiently characterised, the food constituents, punicalagin and ellagic acid in pomegranate/pomegranate juice, which the Panel assumes to be the subject of the health claims, are sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Utrzymanie prawidłowego stężenia cholesterolu we krwi (ID 1162, 1320, 2107, 2167)
The claimed effects are “heart health”, “cardiovascular health” and “maintaining cholesterol”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effects relate to the maintenance of normal blood cholesterol concentrations.
Low-density lipoproteins (LDL) carry cholesterol from the liver to peripheral tissues, including the arteries. Elevated LDL-cholesterol, by convention >160 mg/dL (>4.14 mmol/L), may compromise the normal structure and function of the arteries. High-density lipoproteins (HDL) act as cholesterol scavengers and are involved in the reverse transport of cholesterol in the body (from peripheral tissues back to the liver).
The Panel considers that maintenance of normal blood cholesterol concentrations is a beneficial physiological effect.
2.2. Utrzymanie prawidłowej erekcji (ID 1163)
The claimed effect is “sexual health in men”. The Panel assumes that the target population is the general male population.
In the context of the proposed wordings and the clarifications provided by Member States, the Panel assumes that the claimed effect refers to the maintenance of normal erectile function.
The Panel considers that maintenance of normal erectile function is a beneficial physiological effect.
2.3. Ochrona lipidów przed uszkodzeniem oksydacyjnym (ID 1201, 1319, 2123)
The claimed effects are “antioxidative function”, “antioxidant properties”, and “antioxidants and immunity”. The Panel assumes that the target population is the general population.
The Panel considers that “immunity” is not sufficiently defined for a scientific evaluation and the proposed wordings or scientific references submitted for this claim (ID 2123) do not provide further information. The Panel also considers that no evidence has been provided to establish that having antioxidant properties is a beneficial physiological effect.
In the context of the proposed wordings and conditions of use, the Panel assumes that the claimed effects relate to the protection of lipids from oxidative damage caused by free radicals.
Reactive oxygen species (ROS) including several kinds of radicals are generated in biochemical processes (e.g. respiratory chain) and as a consequence of exposure to exogenous factors (e.g. radiation, pollutants). These reactive intermediates damage biologically relevant molecules such as DNA, proteins and lipids if they are not intercepted by the antioxidant network which includes free radical scavengers such as antioxidant nutrients.
The Panel considers that protection of lipids from oxidative damage may be a beneficial physiological effect.
2.4. Właściwości antyoksydacyjne i ograniczające starzenie (ID 1901)
The claimed effect is “antioxidant and anti-aging properties”. The Panel assumes that the target population is the general population.
The Panel considers that no evidence has been provided to establish that having “antioxidant properties” is a beneficial physiological effect. In addition, no definition has been provided of having “anti-aging properties” in relation to the antioxidant properties of foods.
The Panel considers that this claimed effect is general and non-specific and does not refer to any specific health claim as required by Regulation (EC) No 1924/2006.
2.5. Wzrost apetytu po niezamierzonej utracie masy ciała prowadzący do zwiększenia ilości przyjmowanej energii (ID 2122)
The claimed effect is “digestion”. The Panel assumes that the target population is underweight individuals willing to increase their energy intake.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to the increase in appetite after unintentional weight loss.
The Panel considers that an increase in appetite after unintentional weight loss leading to an increase in energy intake, if sustained, might be a beneficial physiological effect.
2.6. Utrzymanie prawidłowego stężenia glukozy we krwi (ID 4471)
The claimed effect is “glucose metabolism”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to the maintenance of normal blood glucose concentrations.
The Panel considers that long-term maintenance of normal blood glucose concentrations is a beneficial physiological effect.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka
3.1. Utrzymanie prawidłowego stężenia cholesterolu we krwi (ID 1162, 1320, 2107, 2167)
Most of the references provided in the list addressed topics other than polyphenols in pomegranate/pomegranate juice and the claimed effect. These include narrative reviews on polyphenols, food composition, and human studies investigating the effects of polyphenols on anti- angiogenic potential, angiotensin converting enzyme activity, blood pressure, lipid oxidation, oxidative stress, platelet aggregation, or in relation to cancer prevention. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
In a pilot, single arm, uncontrolled intervention study, the effects of consuming a concentrated pomegranate juice (40 g per day) for eight weeks on the blood lipid profile were investigated in 22
diabetic patients (Esmaillzadeh et al., 2004, 2006). The Panel considers that no conclusions can be drawn from this small and uncontrolled study for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and the maintenance of normal blood cholesterol concentrations.
3.2. Utrzymanie prawidłowej erekcji (ID 1163)
Four references were provided in relation to this claim, which included a human intervention study on the effects of pomegranate juice on prostate-specific antigen (PSA) progression. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
A randomised, double-blind, placebo-controlled, crossover intervention study (described as a pilot study) which investigated the ability of pomegranate juice to improve erections in 53 male subjects with mild to moderate erectile dysfunction (ED) was provided (Forest et al., 2007). Subjects consumed daily eight ounces of pomegranate juice (total dose of 1.5 mmol polyphenols per day) and eight ounces placebo juice for 28 days each with a two-week washout period in between. Efficacy was assessed using the International Index of Erectile Function (IIEF) and the Global Assessment Questionnaires (GAQ). The Panel notes that pomegranate juice has not been characterised with respect to polyphenols (i.e. punicalagin and/or ellagic acid) and that there was no significant effect of pomegranate juice on erectile function measured using either the Global Assessment Questionnaires (GAQ) score or the International Index of Erectile Function (IIEF).
The two remaining references (one full article and one letter to the editor) refer to a study on the effects of different fruit juices, including pomegranate juice, in a rabbit model of arteriogenic erectile dysfunction. The Panel considers that the evidence from this animal study is not sufficient to predict an occurrence of an effect of polyphenols (i.e. punicalagin and/or ellagic acid) in pomegranate/pomegranate juice on the maintenance of normal erectile function in humans.
The Panel concludes that a cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and maintenance of normal erectile function.
3.3. Ochrona lipidów przed uszkodzeniem oksydacyjnym (ID 1201, 1319, 2123)
Most of the references provided in the list addressed topics other than polyphenols in pomegranate/pomegranate juice and the claimed effect. These references included narrative reviews on polyphenols, food composition tables, in vitro testing of antioxidant properties and human studies investigating the effects of polyphenols on anti-angiogenic potential or in relation to cancer prevention. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
A single arm, uncontrolled intervention study in 13 healthy male volunteers which assessed the effects of pomegranate juice consumption (50 mL per day containing 1.5 mmol total polyphenols) for two weeks on changes in the ex vivo activity of serum paraoxonase (an HDL-associated esterase), in plasma lipid peroxides (AAPH induced spectrophotometric method), and in the oxidation lag time of low-density lipoproteins (LDL) ex vivo was provided (Aviram et al., 2000). A second single arm (Rosenblat et al., 2006), uncontrolled intervention study in 10 healthy subjects and 10 non-insulin dependent diabetes mellitus (NIDDM) patients under pharmacological treatment was provided with the consolidated list. All subjects consumed 50 mL per day of pomegranate juice containing 1979 mg/L of tannins (1561 mg/L of punicalagin and 417 mg/L of hydrolysable tannins), 384 mg/L of
anthocyanins (delphinidin 3,5-diglucoside, cyanidin 3,5-diglucoside, delphinidin-3-glucoside, cyanidin 3-glucoside and pelargonidine 3-glucoside) and 121 mg/L of ellagic acid derivatives for three months. Serum concentrations of lipid peroxides, thiobarbituric acid reactive substances (TBARS), serum SH groups, serum paraoxonase 1 (PON1) activity, cellular peroxides and glutathione content in monocytes-derived macrophages (HMDM), and oxidised LDL uptake by HMDM were measured at the beginning and end of the intervention. The Panel considers that no conclusions can be drawn from these small and uncontrolled studies for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and the protection of lipids from oxidative damage.
3.4. Wzrost apetytu po niezamierzonej utracie masy ciała prowadzący do zwiększenia ilości przyjmowanej energii (ID 2122)
None of the references provided in relation to this claim provided scientific data on the effects of polyphenols (i.e. punicalagin and/or ellagic acid) in pomegranate/pomegranate juice on appetite in humans. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and a sustained increase in appetite after unintentional weight loss leading to an increase in energy intake.
3.5. Utrzymanie prawidłowego stężenia glukozy we krwi (ID 4471)
None of the references provided in relation to this claim provided scientific data on the effects of polyphenols (i.e. punicalagin and/or ellagic acid) in pomegranate/pomegranate juice on blood glucose concentrations in humans. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and maintenance of normal blood glucose concentrations.
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituents, punicalagin and ellagic acid in pomegranate/pomegranate juice, which are the subject of the health claims are sufficiently characterised.
Maintenance of normal blood cholesterol concentrations (ID 1162, 1320, 2107, 2167)
The claimed effects are “heart health”, “cardiovascular health” and “maintaining cholesterol”. The target population is assumed to be the general population. Maintenance of normal blood cholesterol concentrations is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and the maintenance of normal blood cholesterol concentrations.
Maintenance of normal erectile function (ID 1163)
The claimed effect is “sexual health in men”. The target population is assumed to be the general male population. Maintenance of normal erectile function is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and maintenance of normal erectile function.
Protection of lipids from oxidative damage (ID 1201, 1319, 2123)
The claimed effects are “antioxidative function”, “antioxidant properties”, and “antioxidants and immunity”. The target population is assumed to be the general population. Protection of lipids from oxidative damage may be a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and the protection of lipids from oxidative damage.
“Antioxidant and anti-aging properties” (ID 1901)
The claimed effect is “antioxidant and anti-aging properties”. The target population is assumed to be the general population. No evidence has been provided to establish that having antioxidant properties is a beneficial physiological effect. In addition, no definition has been provided of having “anti-aging properties” in relation to the antioxidant properties of foods.
The claimed effect is general and non-specific and does not refer to any specific health claim as required by Regulation (EC) No 1924/2006
Increase in appetite after unintentional weight loss leading to an increase in energy intake (ID 2122)
The claimed effect is “digestion”. The target population is assumed to be underweight individuals willing to increase their energy intake. An increase in appetite after unintentional weight loss leading to an increase in energy intake, if sustained, might be a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and a sustained increase in appetite after unintentional weight loss leading to an increase in energy intake.
Maintenance of normal blood glucose concentrations (ID 4471)
The claimed effect is “glucose metabolism”. The target population is assumed to be the general population. Long-term maintenance of normal blood glucose concentrations is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of punicalagin/ellagic acid in pomegranate/pomegranate juice and maintenance of normal blood glucose concentrations.
