2.1. Prawidłowa gospodarka hormonalna (ID 243)

The claimed effect is “an essential co-factor in fatty acid metabolism that impacts upon hormonal health”. The Panel assumes that the target population is the general population.
“An essential co-factor in fatty acid metabolism that impacts upon hormonal health” is not sufficiently defined and no further details were provided in the proposed wording.
The Panel considers that 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.

2.2. Zmniejszenie zmęczenia (ID 244)

The claimed effect is “vitamin/mineral supplementation to reduce fatigue and tiredness in situations of inadequate micronutrient status”. The Panel assumes that the target population is the general population.
The Panel considers that reduction of tiredness and fatigue is a beneficial physiological effect.

2.3. Udział w prawidłowym przebiegu funkcji psychicznych (psychologicznych) (ID 245, 246)

The claimed effects are “the role of vitamins and minerals in mental performance (where mental performance stands for those aspects of brain and nerve functions which determine aspects like concentration, learning, memory and reasoning)” and “brain function”. The Panel assumes that the target population is the general population.
The Panel considers that contribution to normal psychological functions, which encompass cognitive and affective domains, is a beneficial physiological effect.

2.4. Utrzymanie prawidłowego stężenia glukozy we krwi (ID 342)

The claimed effect is “carbohydrate metabolism and insulin sensitivity”. The Panel assumes that the target population is the general population.
In the context of the proposed wording, the Panel assumes that the claimed effect refers to the maintenance or achievement of normal blood glucose concentrations.
The Panel considers that long-term maintenance of normal blood glucose concentrations is a beneficial physiological effect.

2.5. Utrzymanie prawidłowego ciśnienia tętniczego (ID 344, 366, 379)

The claimed effects are “cardiovascular system”, “blood pressure” and “circulation”. 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 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 the normal arterial and cardiac function.
The Panel considers that maintenance of normal blood pressure is a beneficial physiological effect.

2.6. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 351)

The claimed effect is “antioxidant properties”. The Panel assumes that the target population is the general population.
Reactive oxygen species 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 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 DNA, proteins and lipids from oxidative damage may be a beneficial physiological effect.

2.7. Utrzymanie prawidłowego funkcjonowania układu odpornościowego (ID 352)

The claimed effect is “immune system”. The Panel assumes that the target population is the general population.
In the context of the proposed wording, the Panel assumes that the claimed effect refers to the normal function of the immune system.
The Panel considers that maintenance of the normal function of the immune system is a beneficial physiological effect.

2.8. Utrzymanie prawidłowego ciśnienia tętniczego podczas ciąży (ID 367)

The claimed effect is “pregnancy”. The Panel assumes that the target population is women of child- bearing age.
In the context of the proposed wording, the clarifications provided by Member States and the references submitted, the Panel assumes that the claimed effect refers to the maintenance of normal blood pressure during pregnancy.
The Panel considers that maintenance of normal blood pressure during pregnancy is a beneficial physiological effect.

2.9. Odporność na stres (ID 375, 381)

The claimed effects are “système nerveux” and “magnésium et stress: magnesium is a mineral involved in stress and its reactions. On one hand, stress tends to reduce the magnesium status and, on the other hand, an exogenous or endogenous deficit in magnesium increases the stress response. It matters to maintain a suitable magnesium status in order to better react against stress”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and from the references provided, the Panel assumes that the claimed effects refer to resistance to mental stress. Resistance to mental stress can be measured by established methods.
The Panel considers that resistance to mental stress might be a beneficial physiological effect.

2.10. Redukcja zawartości kwasu w żołądku (ID 376)

The claimed effect is “acid-base balance/gastric acidity”. 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 a reduction of gastric acid levels.
The Panel considers that the evidence provided does not establish that reducing gastric acid levels is a beneficial physiological effect for the general population.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of magnesium and a beneficial physiological effect for the general population related to the reduction of gastric acid levels.

2.11. Utrzymanie prawidłowego metabolizmu tłuszczów (ID 378)

The claimed effect is “fat metabolism: acid base balance”. The Panel assumes that the target population is the general population.
In the context of the proposed wording and the clarifications provided by Member States, the Panel assumes that the claimed effect refers to the maintenance of normal fat metabolism.
The Panel considers that maintenance of normal fat metabolism is a beneficial physiological effect.

3.1. Zmniejszenie zmęczenia (ID 244)

A decline in magnesium status is associated with various symptoms such as nausea, muscular weakness, fatigue or staggering (FAO/WHO, 2001; Rude and Shils, 2006; Volpe, 2006).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of magnesium and a reduction of tiredness and fatigue.

3.2. Udział w prawidłowym przebiegu funkcji psychicznych (psychologicznych) (ID 245, 246)

A decline in magnesium status is associated with various symptoms such as depression, psychosis, irritability or confusion (Rude and Shils, 2006; FAO/WHO, 2001; O'Brien, 1999).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of magnesium and contribution to normal psychological functions.

3.3. Utrzymanie prawidłowego stężenia glukozy we krwi (ID 342)

The references provided for the substantiation of the claimed effect include textbooks, one reference unrelated to the food constituent, a general narrative review on magnesium metabolism, status and deficiency, and publications on health outcomes unrelated to the claimed effect: tension headaches and muscle tension, stress and neuropsychiatric disorders, cardiovascular disorders, sports, myocardial infarction. Also, a reference reporting on intracellular changes in magnesium before and after insulin stimulation in diabetic and obese children was provided. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
One meta-analysis of double-blind randomised controlled trials (RCTs) (Song et al., 2006) and four intervention studies in humans (Purvis et al., 1994; Rodriguez-Moran and Guerrero-Romero, 2003; Paolisso et al., 1989b; Guerrero-Romero et al., 2004) on the effects of oral magnesium supplementation on different outcomes were provided. Seven out of the nine trials considered in the meta-analysis (Gullestad et al., 1994; Purvis et al., 1994; Eibl et al., 1995; Erikson and Kohvakka, 1995; de Lourdes et al., 1998; de Valk et al., 1998; Rodriguez-Moran and Guerrero-Romero, 2003), including two of the intervention studies (Purvis et al., 1994; Rodriguez-Moran and Guerrero- Romero, 2003) provided, were performed in diabetic subjects under antidiabetic medications. The Panel considers that the evidence provided does not establish that interactions between magnesium and antidiabetic medication can be excluded. The two remaining trials in the meta-analysis (Paolissoet al., 1989a; 1994) and the two remaining intervention studies (Paolisso et al., 1989b; Guerrero-Romero et al., 2004), which were all performed in insulin resistant subjects or type-2 diabetic subjects under dietary treatment only, did not report on outcomes related to long-term blood glucose control but rather on insulin sensitivity using the euglycaemic-hyperinsulinaemic clamp technique (Paolisso et al., 1989a, 1994) or the surrogate HOMA index (Guerrero-Romero et al., 2004), or on the secretory capacity of the pancreas after stimulation with arginine or glucose (Paolisso et al., 1989b). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Seven observational studies dealt with dietary intake, serum concentrations or urinary excretion of magnesium in very-low-birth-weight pre-term children in pre-school years (Bo et al. 2007), type 1- diabetic patients (Brown et al., 1999), obese children (Huerta et al., 2005), adults (Ma et al., 2006; Rumawas et al., 2006; Song et al., 2004) and nursing home residents (Worwag et al., 1999). Parameters such as fasting glucose or insulin, HOMA-IR, HbA1c, quantitative insulin sensitivity check index, intravenous glucose tolerance test, post-challenge plasma glucose and insulin, or risk or prevalence of diabetes were considered. The Panel notes that no conclusions can be drawn from these studies for the scientific substantiation of the claimed effect because residual confounding by other dietary and lifestyle factors inherent to the observational study design cannot be excluded.
The Panel considers that no conclusions can be drawn from the meta-analysis for the scientific substantiation of the claim owing to the inclusion of studies that cannot be used for the substantiation
of the claim, from the individual trials provided owing to inappropriate study groups or endpoints and from the observational studies provided owing to inadequate control of possible confounding factors.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of magnesium and maintenance of normal blood glucose concentrations.

3.4. Utrzymanie prawidłowego ciśnienia tętniczego (ID 344, 366, 379)

The references provided for the substantiation of the claimed effect included textbooks, a website from a government body, a reference from an authoritative body on prevention, detection, evaluation and treatment of high blood pressure that did not mention magnesium, publications on magnesium- containing medicinal waters, narrative reviews and references that were either very general or did not address relevant endpoints, and one intervention study on the effects of dietary modifications on blood pressure. Endpoints addressed were ischaemic heart disease; clinical and analytical aspects related to magnesium; magnesium metabolism, deficiency and supplementation; sport; myocardial infarction; tension headaches and muscle tension; stress and neuropsychiatric disorders; and various cardiovascular aspects including atherogenesis. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
One meta-analysis of randomised controlled trials (RCTs) (Jee et al., 2002), a systematic review of epidemiological and intervention studies (Burgess et al., 1999), and three intervention studies on the effects of magnesium on blood pressure in humans were provided (Borello et al., 1996; Itoh et al., 1997; Kyriazis et al., 2004).
The Panel notes that the meta-analysis and the systematic review included trials that cannot be used for the substantiation of the claim (e.g. uncontrolled trials and trials with pharmacologically treated hypertensive subjects in which the evidence provided does not establish that interactions between magnesium intake and pharmacological treatment can be excluded), and that in one of the intervention studies magnesium was administered intravenously, which is not a route considered relevant for human nutrition (Kyriazis et al., 2004). The Panel considers that no conclusions can be drawn from these references (Jee et al., 2002; Burgess et al., 1999; Kyriazis et al., 2004) for the scientific substantiation of the claim.
Among the 20 RCTs which investigated the effects of magnesium supplementation on blood pressure considered in the meta-analysis by Jee et al. (2002), which were also included in the systematic review by Burgess et al. (1999), 15 (including Itoh et al., 1997) were performed in subjects with no pharmacological treatment for hypertension. The number of subjects ranged from 13 to 461, magnesium doses from 10.0 to 40 mmol/day, and intervention periods between 3 and 24 weeks. Seven trials were crossed over, eight had a parallel design, and all but one were double blind. One trial observed a significant decrease (Purvis et al., 1994) and one trial a significant increase (Nowson and Morgan, 1989) in systolic blood pressure in the magnesium group compared to controls, whereas two trials observed a significant decrease (Widman et al., 1993; Witteman et al., 1994) and two trials a significant increase (Nowson and Morgan, 1989; Patki et al., 1990) in diastolic blood pressure. The Panel notes that no significant differences between the magnesium and control groups were observed on either systolic or diastolic blood pressure in ten trials (Capuccio et al., 1985; Zemel et al., 1990; Lind et al., 1991; The TOHP (trials of hypertension prevention) Collaborative Research Group, 1992; Ferrara et al., 1992; Plum-Wirell et al., 1994; Sanjuliani et al., 1996; Itoh et al., 1997; Sacks et al., 1998; Doyle et al., 1989), including the two trials with the largest sample sizes (The TOHP (trials of hypertension prevention) Collaborative Research Group, 1992; Sacks et al., 1998, with n=461 and n=153, respectively). The Panel also notes that the third largest study (Witteman et al., 1994, n=91) observed a significant reduction in diastolic blood pressure only. The Panel considers that the evidence provided by these studies for a blood-pressure lowering effect of magnesium is weak and inconsistent.
The remaining trial, which was not included in the meta-analysis, was a double-blind RCT (Borello et al., 1996) which reported on the effects of magnesium supplementation (200 mg/day of magnesium oxide) in 83 mildly hypertensive patients without previous anti-hypertensive treatment (n=42 in the magnesium group, n=41 in the placebo (unspecified) group). All patients had periodic measurements of blood pressure and heart rate taken. In addition, a 24-hour ambulatory blood pressure monitoring was performed at the beginning and end of the study. A statistically significant reduction in systolic blood pressure was observed at the 12-week follow-up in the magnesium group compared to the placebo (148.5+/-7.1 mmHg versus 155.2+/-8.2 mmHg; p<0.01), whereas no significant difference was observed in diastolic blood pressure. The more robust 24-hour ambulatory monitoring of blood pressure showed no significant differences in systolic or diastolic blood pressure values between groups. The Panel considers that the findings of this study are not consistent regarding an effect of magnesium on blood pressure.
As regards epidemiological data, low dietary magnesium intakes have been reported to be inversely associated with blood pressure (Rude and Shils, 2006). The mechanism by which magnesium might affect blood pressure is not clear (Rude and Shils, 2006). In the systematic review by Burgess et al., 1999, five epidemiological studies were considered. Two were performed in women: one showed an association between a diet high in magnesium and a reduced risk of hypertension (based on self- reported blood pressure), the other, performed in the same population four years later after a modification in the food frequency questionnaire used to assess magnesium intakes, showed no association. Two studies performed in men did not show a clear association. The other study in both sexes showed a correlation between magnesium intake and measured blood pressure in women but not in men. The Panel considers that the epidemiological evidence for a relationship between magnesium intake and blood pressure or prevention of hypertension is weak and inconsistent.
In their joint Guidelines for the Management of Arterial Hypertension, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), in line with other authoritative bodies, stated that the evidence for a blood pressure lowering effect of supplemental magnesium is inconsistent (Mancia et al., 2007). In their scientific statement on dietary approaches to prevent and treat hypertension (Appel et al., 2006), the American Heart Association considered data as insufficient to recommend supplemental magnesium as a means to lowering blood pressure.
In weighing the evidence, the Panel took into account that no conclusions could be drawn from the meta-analysis and the systematic review for the scientific substantiation of the claimed effect owing to the inclusion of studies that cannot be used for the substantiation of the claim, that in 16 RCTs in subjects with no pharmacological treatment for hypertension evidence for a blood-pressure lowering effect of magnesium was weak and inconsistent, and that in five epidemiological studies evidence for a relationship between magnesium intake and changes in blood pressure or prevention of hypertension was weak and inconsistent.
The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the dietary intake of magnesium and maintenance of normal blood pressure.

3.5. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 351)

Two references were cited for the scientific substantiation of the claimed effect.
In a RCT on patients (n=92) with acute myocardial ischaemia undergoing coronary artery bypass graft (Kurian et al., 2007), subjects received either magnesium supplementation (42 male, 10 female), or a placebo (30 male, 10 female). Serum concentrations of copper, zinc, iron, calcium, magnesium, sodium and potassium were measured as well as plasma TBARS and antioxidant enzyme (catalase, glutathione peroxidase, superoxide dismutase, caeruloplasmin) activities, and cardiac marker enzymes. The Panel considers that TBARS are not reliable markers of lipid peroxidation and notes
that induction of antioxidant enzymes provides an indication of response to oxidative stress, but it is non specific and does not reflect oxidative damage to cells or molecules.
The second study was an in vitro study which reported on the hydroxyl radical generating ability and scavenging activity of magnesium, manganese and zinc compounds. The Panel considers that evidence provided in in vitro studies is not sufficient to predict the occurrence of an effect of the dietary intake of magnesium on the protection of DNA, proteins and lipids from oxidative damage in humans.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of magnesium and protection of DNA, proteins and lipids from oxidative damage.

3.6. Utrzymanie prawidłowego funkcjonowania układu odpornościowego (ID 352)

Three references, including a website from a government body, were cited for the scientific substantiation of the claimed effect. Another reference was a narrative review reporting on several outcomes: effects of dietary magnesium on inflammation, apoptosis and innate immune cell populations in animal models, apoptosis in vitro, and the importance of magnesium homeostasis in relation to asthma or in athletes and elderly people. The Panel considers that no conclusions can be drawn from these two references for the scientific substantiation of the claimed effect.
The remaining reference was an animal study reporting on effects of supplementation with manganese and magnesium on the immune function of rats. The Panel considers that while effects shown in animal studies may be used as supportive evidence, human studies are required for the substantiation of a claim and the evidence provided in animal studies alone is not sufficient to predict the occurrence of an effect of the dietary intake of magnesium on the normal function of the immune system in humans.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of magnesium and maintenance of the normal function of the immune system.

3.7. Utrzymanie prawidłowego ciśnienia tętniczego podczas ciąży (ID 367)

Five references were cited for the scientific substantiation of the claimed effect, including tables of dietary reference intakes set by the IoM (1997); a narrative review on the status of various micronutrients during pregnancy and outcomes for infants in developing countries; a narrative review on chronic gestational magnesium deficiency mainly focusing on pre-term birth and sudden infant death syndrome; a narrative review on magnesium and obstetrics (pre-eclampsia and eclampsia), cardiology and other clinical areas. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The remaining reference (Villar et al., 2003) reported on systematic reviews and individual RCTs published before July 2002 on nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and pre-term delivery. The authors indicated that a Cochrane review (Makrides and Crowther, 2001), which included two trials for this outcome, showed no apparent effect of dietary magnesium supplementation on the prevention of pre-eclampsia (mean supplement dose of 365 mg and 500 mg/day).
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of magnesium and maintenance of normal blood pressure during pregnancy.

3.8. Odporność na stres (ID 375, 381)

The references cited for the scientific substantiation of the claimed effect include textbooks or general publications, one consensus opinion from a national authoritative body (without any mention about mental stress) and one opinion of a European authoritative body. Many other provided references reported on outcomes not directly related to the claimed effect: physical exercise, extreme physical stress, alcohol and drug use by students before exams, delayed-type hypersensitivity and chronic fatigue syndrome, recommended dietary amounts, magnesium metabolism and deficiency, dietary intakes, sleep electroencephalogram and nocturnal hormonal secretion in the elderly, psychiatric disorders, depression, pregnancy-related outcomes, premenstrual symptoms, biorhythms, anxiety- depressive states in epilepsy, cardiovascular outcomes and atherosclerosis. The Panel considers that these endpoints are not relevant for the claimed effect and that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
One reference, reporting on changes in the concentration of non-esterified fatty acids and magnesium in emotional stress, was in Russian, and the English translation was not available to the Panel. In addition, the provided narrative reviews on stress reactions and those specifically on noise-induced stress, did not provide any primary data for the scientific substantiation of the claimed effect.
One reference (Hanus et al., 2004) reported on the effects of a combination of two plant extracts and magnesium on mild-to-moderate anxiety disorders. The Panel considers that no conclusions can be drawn from a study using a fixed combination for the scientific substantiation of the claimed effect on magnesium alone. Another reference (James et al., 1989) reported on the inhibition by intravenous magnesium sulphate of catecholamine release associated with tracheal intubation. The Panel considers that the evidence provided does not establish that results obtained in studies on patients with tracheal intubation can be extrapolated to oral consumption and to the general population.
One reference (Cernak et al., 2000) reported on plasma magnesium and oxidative status in young volunteers exposed to chronic stress (political intolerance, awareness of potential military attacks, permanent stand-by duty and reduced holidays for more than 10 years) or sub-chronic stress consisting of everyday mortal danger in military actions lasting more than three months. Porta et al. (1994) reported on the differential regulation of free and bound plasma magnesium in healthy volunteers exposed to various forms of stress, and patients screened for thyroid disorder. Another reference (Grases et al., 2006) reported on alterations of calcium and magnesium excretion in urine in relation to stress and anxiety in university science students, in basal conditions and during exams, using stress and anxiety questionnaires. The reference of Mocci et al. (2001) reported on urinary catecholamine excretion and serum concentration and urinary excretion of magnesium and other related electrolytes in relation to a short-term exposure to loud noise, in healthy volunteers. Joachims et al. (1987) reported on the correlation between noise-induced hearing loss and serum magnesium concentration in air force pilots. Takase et al. (2004) reported on the effects of chronic stress on endothelial function and intracellular magnesium concentrations in humans. The Panel notes that in the absence of intervention studies with magnesium, changes in blood, intracellular and urinary magnesium in response to stress cannot be used for the scientific substantiation of the claimed effect.
Seven references were animal studies which reported on the effects of various magnesium salts and combinations thereof on the development of stress ulcers and cardiac necroses, antidepressant and anxiolytic-like activity, prevention of stress-induced damage and noise-induced hypertension. The Panel considers that evidence provided in animal studies is not sufficient to predict the occurrence of an effect of the dietary intake of magnesium on resistance to mental stress in humans.
The Panel notes that no human data were provided from which conclusions could be drawn for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between dietary intake of magnesium and resistance to mental stress.

3.9. Utrzymanie prawidłowego metabolizmu tłuszczów (ID 378)

Five references were cited for the scientific substantiation of the claimed effect, including one nutrition textbook and one review on the effects of magnesium deficiency on atherosclerosis. This reference was in Japanese and the English translation was not available to the Panel. Another narrative review on the role of magnesium and potassium in the pathogenesis of arteriosclerosis was also cited, but did not provide any primary data for the scientific substantiation of the claimed effect.
The other references reported on the effects of magnesium deficiency on various parameters, notably liver or plasma triglycerides, serum lipoproteins or the fatty acid pattern of total plasma lipids in animal models. The Panel considers that while effects shown in animal studies may be used as supportive evidence, human studies are required for the scientific substantiation of a claim, and that the evidence provided in animal studies alone is not sufficient to predict the occurrence of an effect of the dietary intake of magnesium on maintenance of normal fat metabolism.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of magnesium and maintenance of normal fat metabolism.

4.1. Zmniejszenie zmęczenia (ID 244)

The Panel considers that the following wording reflects the scientific evidence: “Magnesium can contribute to a reduction of tiredness and fatigue”.

4.2. Udział w prawidłowym przebiegu funkcji psychicznych (psychologicznych) (ID 245, 246)

The Panel considers that the following wording reflects the scientific evidence: “Magnesium contributes to normal psychological functions”.