ID 664 - Arginina

PL: Arginina
EN: Arginin
Pdf: L-arginine

Oświadczenie (2)

1. Charakterystyka żywności / składnika

The food constituent that is the subject of the health claims is L-arginine.
Arginine is an alpha-amino acid present in foods from animal and vegetable origin. The L-form is the most commonly found form in nature and in food supplements. L-arginine is also known as (S)-2- amino-5-guanidinopentanoic acid and (S)-2-amino-5-[(aminoiminomethyl)amino] pentanoic acid. The terms L-arginine and arginine are frequently used interchangeably. The content of L-arginine in foods can be measured by established methods.
Arginine is a conditionally indispensable amino acid provided by mixed dietary protein intakes from different sources. Arginine can also be consumed in the form of food supplements as L-arginine.
The Panel considers that the food constituent, L-arginine, which is the subject of the health claims, is sufficiently characterised.

2.3. Prawidłowe tworzenie erytrocytów (czerwonych krwinek) (ID 456, 664, 1443, 1712)

The claimed effects are “vascular system (blood pressure, circulation, vessels)”, “vascular health; blood circulation”, and “for muscle integrity and haematopoiesis (red blood cells building)”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and the clarifications provided by Member States, the Panel assumes that the claimed effects refer to normal formation of red blood cells.
Panel considers that normal red blood cell formation is a beneficial physiological effect.

2.4. Utrzymanie prawidłowego ciśnienia tętniczego (ID 664, 1443)

The claimed effects are “vascular system (blood pressure, circulation, vessels)” and “vascular health; blood circulation”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and the clarifications provided by Member States, the Panel assumes that the claimed effects refer to the maintenance of normal blood pressure.
Blood pressure is the pressure (force per unit area) exerted by circulating blood on the walls of blood vessels. Elevated blood pressure, by convention above 140 mmHg (systolic) and/or 90 mmHg (diastolic), may compromise normal arterial and cardiac function.
The Panel considers that maintenance of normal blood pressure is a beneficial physiological effect.

2.5. Poprawa rozszerzenia naczyń krwionośnych zależnego od śródbłonka (ID 664, 1443, 4680)

The claimed effects are “vascular system (blood pressure, circulation, vessels)”, “vascular health; blood circulation”, and “normal blood circulation as a nitric oxide precursor”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and the clarifications provided by Member States, the Panel assumes that the claimed effects refer to the improvement of endothelium-dependent vasodilation.
The Panel considers that an improvement of endothelium-dependent vasodilation may be a beneficial physiological effect.

3.2. Prawidłowe tworzenie erytrocytów (czerwonych krwinek) (ID 456, 664, 1443, 1712)

The references provided for the scientific substantiation of the claim included narrative reviews and opinion papers with no reference to the role of arginine on red blood cell formation, references on food constituents other than arginine, intervention studies using intravenous arginine administration, which is not relevant to human nutrition, and studies on the effects of arginine consumption on health outcomes other than red blood cell formation. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-arginine and normal red blood cell formation.

3.3. Utrzymanie prawidłowego ciśnienia tętniczego (ID 664, 1443)

The references provided for the scientific substantiation of the claim included narrative reviews and opinion papers with no original data on the effects of arginine intake on blood pressure, references on food constituents other than arginine, intervention studies using intravenous arginine administration, which is not relevant to human nutrition, and studies on the effects of arginine administration on health outcomes other than blood pressure (e.g. endothelial function, clinical course of myocardial infarction, insulin sensitivity, wound healing, immune parameters and erectile function). The Panel
considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
Miller (2006) investigated the effects of L-arginine (1,050 mg, as sustained-release preparation) twice daily (total 2.1 g daily) for one week on blood pressure in 29 healthy subjects in an open-label, single-arm intervention. The Panel notes the short duration and uncontrolled nature of the study, and considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.
Clarkson et al. (1996) performed a randomised, double-blind, cross-over study in 27 hypercholesterolaemic subjects aged 19-40 years. Subjects taking HMG CoA reductase inhibitors in a stable dose for >6 months who met the entry criteria for blood cholesterol concentrations (>162 mg/dL) were recruited. Subjects on vasoactive medications were excluded. Subjects received 3x7 g L-arginine daily or placebo during four-week periods, separated by a four-week wash-out period. Plasma arginine concentrations rose from 115 to 231 μmol/L during L-arginine intake. No significant changes in supine blood pressure during the L-arginine or placebo treatment phases were observed. Blood pressure values (systolic/diastolic) before and after treatment did not show any difference. The Panel notes that this study does not show an effect of L-arginine consumption on blood pressure.
Lerman et al. (1998) performed a randomised, double-blind, placebo-controlled parallel intervention to assess the effect of 3 g/day of L-arginine on blood pressure in 26 patients (age ≈49 years) with non-obstructive coronary artery disease. Patients were on cardiovascular treatment during the study, but all medication (except for study treatment) was discontinued one week prior to the measurements. During six months of treatment, no statistically significant difference was observed in mean arterial blood pressure. Data on systolic and diastolic blood pressure were not reported. The Panel notes that this study does not show an effect of L-arginine consumption on blood pressure.
Siani et al. (2000) performed a randomised, single-blind, cross-over intervention study in six healthy men, aged ≈39 years, who received three isocaloric diets during one week each with no wash-out period between the diets. Diet 1 (control) was relatively low in L-arginine (3.4–4 g/day). Diet 2 was an L-arginine-enriched diet (10 g/day) based on natural foods, mainly lentils and nuts. Diet 3 was identical to the control diet, but was supplemented with 10 g/day of an oral L-arginine preparation given three times a day. During Diet 2, potassium and fibre intakes were considerably higher (+0.9 g and +25 g, respectively) than during Diets 1 and 3, because of dietary changes. Blood pressure was significantly lower after the L-arginine diets compared to Diet 1 (control), i.e. -6.2 mmHg (95% CI, -0.5 to -11.8) systolic and -5.0 mmHg (95% CI, -2.8 to -7.2) diastolic for Diet 2, and -6.2 mmHg (95% CI, -1.8 to -10.5) systolic and -6.8 mmHg (95% CI, -3.0 to -10.6) diastolic for Diet 3. The Panel notes the small number of subjects included in the study, the lack of assessment of carry-over effects between interventions, and the short duration of the intervention, which does not allow conclusions to be drawn on the sustainability of the effect. The Panel considers that only limited conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
Evans et al. (2004) studied the effect on blood pressure of different doses of arginine (3, 9, 21 and 30 g/day) given for consecutive periods of one-week each to 12 healthy subjects. No significant changes in systolic or diastolic blood pressure were observed during the study. The Panel notes that this study does not show an effect of L-arginine consumption on blood pressure.
Three randomised, placebo-controlled, human intervention studies assessed the acute effects of L-arginine intake on blood pressure (i.e. arginine consumption lasting up to three days, Huynh and Tayek, 2002; Lekakis et al., 2002; Nagaya et al., 2001). Whereas L-arginine consumption acutely decreased brachial systolic and diastolic blood pressure (Huynh and Tayek, 2002) and mean pulmonary arterial blood pressure (Nagaya et al., 2001) in two studies, no effect on brachial systolic or diastolic blood pressure was observed in the third study (Lekakis et al., 2002). The Panel considers that results obtained in these studies are inconsistent with respect to the acute effects of arginine
consumption on blood pressure, and that no conclusions can be drawn from these studies for a sustained effect of L-arginine on blood pressure.
In weighing the evidence, the Panel took into account that although a small scale short-term (one-week) only partially controlled intervention study observed an effect of arginine consumption on blood pressure (Siani et al., 2000), two small longer-term studies did not observe a significant effect (Clarkson et al., 1996; Lerman et al., 1998), and that the results from the studies assessing the acute effects of arginine consumption on blood pressure are inconsistent.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-arginine and maintenance of normal blood pressure.

3.4. Poprawa rozszerzenia naczyń krwionośnych zależnego od śródbłonka (ID 664, 1443, 4680)

The references provided for the scientific substantiation of the claim included narrative reviews and opinion papers with no original data on the effects of arginine intake on vasodilation, references on food constituents other than arginine, intervention studies using intravenous arginine administration, which is not relevant to human nutrition, and studies on the effects of arginine administration on health outcomes other than endothelium-dependent vasodilation (e.g. blood pressure, clinical course of myocardial infarction, insulin sensitivity, wound healing, immune parameters and erectile function). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
In one study in hypertensive patients, only the acute effect of arginine intake on endothelium-dependent vasodilation was assessed, and no information on sustained effects was provided (Lekakis et al., 2002). The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
Miller (2006) investigated the effects of L-arginine (1,050 mg, as sustained-release preparation) twice daily (total 2.1 g daily) for one week on endothelial function in 29 healthy subjects in an open-label, single-arm intervention. The Panel considers that no conclusions can be drawn from this uncontrolled study for the scientific substantiation of the claim.
Lerman et al. (1998) performed a six-month randomised, double-blind, placebo-controlled parallel intervention to assess the effect of 3 g/day of L-arginine on coronary blood flow and epicardial coronary artery diameter in response to selective infusion of acetylcholine in 26 patients (age ≈49 years) with non-obstructive coronary artery disease. Patients were on cardiovascular treatment during the study, but all medication (except for study treatment) was discontinued at least 72 hours prior to the measurements. None of the subjects received cholesterol-lowering medications. All the patients were referred for the evaluation of stable exertional chest pain suspected to be of cardiac origin. Before the coronary angiogram, 10 patients (77 %) from each group underwent a non-invasive functional test, which was positive and consistent with myocardial ischemia in six patients from group 1 and five patients from group 2. Measures of peripheral endothelial function, for example flow-mediated dilation of the brachial artery, were not obtained in this study. The Panel considers that the evidence provided does not establish that patients with non-obstructive coronary artery disease including myocardial ischemia are representative of the general population with respect to the endothelial function of the coronary arteries. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
Blum et al. (2000) provided 9 g/day of L-arginine or placebo to ten healthy post-menopausal women (aged 55±5 years) in a randomised cross-over study. Intervention periods lasted one month and were separated by a one-month wash-out period. The study was powered to detect a difference of 1.7 % in flow-mediated (endothelium-dependent) dilation after hyperaemia between the study periods. Plasma L-arginine concentrations significantly increased during the intervention, whereas no significant changes were observed in serum nitric oxide or soluble cell adhesion molecules (E-selectin, ICAM-1
and VCAM-1). No significant differences between treatment periods were observed on endothelium-dependent vasodilation. The Panel notes that this study does not show an effect of L-arginine consumption on the improvement of endothelium-dependent vasodilation.
Clarkson et al. (1996) performed a randomised, double-blind, cross-over study in 27 hypercholesterolaemic subjects aged 19-40 years. Those taking HMG CoA reductase inhibitors in a stable dose for >6 months who met the entry criteria for blood cholesterol concentrations (>162 mg/dL) were recruited. Subjects on vasoactive medication were excluded. Subjects received 3x7 g L-arginine daily or placebo during four-week periods, separated by a four-week wash-out period. The non-invasive assessment of endothelium-dependent dilation was performed before and at the end of each treatment period. Post-treatment studies were performed between 1 and 2 h after the last dose of L-arginine or placebo. Plasma arginine concentrations rose from 115 to 231 μmol/L during L-arginine intake. There was a significant improvement in flow-mediated dilation in subjects while taking L-arginine (1.7±1.3 % to 5.6±3.0 %) compared with placebo (2.3±1.9 % to 2.3±2.4 %). The change with L-arginine was 3.9±3.0 % vs. 0.1±2.2 % with placebo (p<0.001). No significant differences were observed in endothelium-independent vasodilation (i.e. in response to nitroglycerine). Flow-mediated dilation improved, by more than 2 %, in 67 % of the subjects who consumed L-arginine. The Panel notes that the observed changes in endothelium-dependent vasodilation could have been due to an acute effect of arginine occurring 1-2 hours after intake in the second flow-mediated dilation test. The Panel also notes that the evidence provided does not establish that acute changes in endothelium-dependent vasodilation constitute a beneficial physiological effect per se.
In weighing the evidence, the Panel took into account that one study did not show an effect of L-arginine consumption on endothelium-dependent vasodilation, and that in a second study the observed changes in endothelium-dependent vasodilation could have been due to an acute effect of arginine rather than to a sustained effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-arginine and improvement of endothelium-dependent vasodilation.

Warunki i możliwe ograniczenia stosowania oświadczenia

225 mg daily;(15 % of the lower (1500 mg) therapeutic dose