Scientific Opinion on the substantiation of health claims related to
L-carnitine and faster recovery from muscle fatigue after exercise (ID 738,
1492, 1493), skeletal muscle tissue repair (ID 738, 1492, 1493), increase in
endurance capacity (ID 4305, 4684), maintenance of normal blood
LDL-cholesterol concentrations (ID 1494, 4684), contribution to normal
spermatogenesis (ID 1822), “energy metabolism” (ID 1821), and increasing
L-carnitine concentrations and/or decreasing free fatty acids in blood
during pregnancy (ID 1495) 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:
L-Carnitine
endurance capacity
energy metabolism
fatigue
fatty acids
health claims
pregnancy
skeletal muscle
spermatogenesis
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claim is carnitine (as L-carnitine).
Carnitine is a quaternary ammonium salt synthesised primarily in the liver and kidneys from amino acids, lysine and methionine. In living cells carnitine is required for the transport of fatty acids from the cytosol into the mitochondria for beta-oxidation. L-carnitine is the form commonly used in food supplements. The content of L-carnitine in foods can be measured by established methods. This opinion refers to the effects of L-carnitine when consumed as food supplements in addition to a protein adequate diet.
The Panel considers that the food constituent, L-carnitine, which is the subject of the health claims, is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Szybsze ustępowanie zmęczenia mięśni po wysiłku (ID 738, 1492, 1493)
The claimed effects are “fat metabolism” and “muscle metabolism/recovery after exercise”. The Panel assumes that the target population is adults performing strenuous exercise.
In the context of the proposed wordings, the Panel assumes that the claimed effects refer to recovery from muscle fatigue after exercise.
Fatigue can be defined as the loss of peak force or power output. Therefore, muscle fatigue recovery can be defined as the regain of maximal muscle strength or muscle power after performance of strenuous exercise which has induced muscle fatigue.
The Panel considers that faster recovery from muscle fatigue after exercise is a beneficial physiological effect.
2.2. Wpływ na regenerację mięśni szkieletowych (ID 738, 1492, 1493)
The claimed effects are “fat metabolism” and “muscle metabolism/recovery after exercise”. The Panel assumes that the target population is adults performing resistance exercise.
In the context of the proposed wordings, the Panel assumes that the claimed effects refer to the rebuilding of structural protein within the skeletal muscle tissue after exercise which has caused muscle damage.
The Panel considers that skeletal muscle tissue repair is a beneficial physiological effect.
2.3. Wzrost wytrzymałości (ID 4305, 4684)
The claimed effects are “ergogenic role in sports and exercise”, and “fat metabolism by mediating the transport of long-chain fatty acids across the inner mitochondrial membrane”. The Panel assumes that the target population is adults performing endurance exercise.
In the context of the proposed wordings, the Panel assumes that the claimed effects refer to an increase in endurance capacity by promoting fat oxidation. Endurance capacity refers to the exercise time to self-reported fatigue when exercising at a constant workload or speed.
The Panel considers that an increase in endurance capacity is a beneficial physiological effect.
2.4. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 1494, 4684)
The claimed effects are “heart health” and “fat metabolism by mediating the transport of long-chain fatty acids across the inner mitochondrial membrane”. 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 LDL-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 (>4.1 mmol/L), may compromise the normal structure and function of the arteries.
The Panel considers that maintenance of normal blood LDL-cholesterol concentrations is a beneficial physiological effect.
2.5. Udział w prawidłowym tworzeniu plemników (spermatogenezie) (ID 1822)
The claimed effect is “sexual organs, hormone activity”. The Panel assumes that the target population is the general male population.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to contribution to normal spermatogenesis.
The Panel considers that contribution to normal spermatogenesis is a beneficial physiological effect.
2.6. Metabolizm energetyczny (ID 1821)
The claimed effect is “energy metabolism”. The Panel assumes that the target population is the general population.
The claimed effect is not sufficiently defined, and no further details were given in the proposed wordings. No clarifications have been provided by Member States.
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.
2.7. Wzrost stężenia L-karnityny i/lub zmniejszenie stężenia wolnych kwasów tłuszczowych u kobiet w ciąży (ID 1495)
The claimed effect is “pregnancy”. The Panel assumes that the target population is pregnant women.
In the context of the proposed wordings, the Panel assumes that the claimed effect relates to increasing L-carnitine concentrations, and to decreasing free fatty acids, in blood during pregnancy.
The Panel considers that the evidence provided does not establish that increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy in the context of a protein adequate diet is a beneficial physiological effect per se.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-carnitine and a beneficial physiological effect related to increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka -
3.1. Szybsze ustępowanie zmęczenia mięśni po wysiłku (ID 738, 1492, 1493)
The references provided in relation to this claim included a number of narrative reviews, commentary papers, textbook chapters and animal studies. These references were either on food constituents (e.g. L-propionylcarnitine, and a combination of caffeine, carnitine and choline) unrelated to the food constituent which is the subject of the claim, or addressed outcomes (e.g. fatty acid oxidation, and muscle pain) unrelated to the claimed effect. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
One reference reporting on a pilot human intervention study on the effects of L-carnitine supplementation on muscle recovery after exercise in six trained and six untrained subjects was provided as a symposium report. The report contained insufficient information regarding randomisation and statistical analyses for a full scientific evaluation (Maggini et al., 2000). The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.
The Panel concludes that a cause and effect relationship has not been established between consumption of L-carnitine and faster recovery from muscle fatigue after exercise.
3.2. Wpływ na regenerację mięśni szkieletowych (ID 738, 1492, 1493)
The references provided in relation to this claim included a number of narrative reviews, commentary papers, textbook chapters and animal studies. These references were either on food constituents (e.g. L-propionylcarnitine, and a combination of caffeine, carnitine and choline) unrelated to the food constituent which is the subject of the claim, or addressed outcomes (e.g. fatty acid oxidation, and muscle pain) unrelated to the claimed effect. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
No references were provided which assessed the effects of L-carnitine consumption on muscle tissue repair after exercise.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-carnitine and skeletal muscle tissue repair.
3.3. Wzrost wytrzymałości (ID 4305, 4684)
The references provided in relation to the claim included narrative reviews and human studies which addressed outcomes (e.g. fatty acid oxidation, protein turnover, body weight and cardiac disorders) unrelated to the claimed effect.
One uncontrolled, open label human intervention study investigated the effect of L-carnitine supplementation (2 g/day for six weeks) on endurance capacity assessed using progressive treadmill tests until exhaustion in seven elite male marathon runners (Swart et al., 1997). The Panel notes the uncontrolled nature of the study, and considers that no conclusions can be drawn from this study 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-carnitine and increase in endurance capacity.
3.4. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 1494, 4684)
Some of the references provided were narrative reviews, and human, animal and in vitro studies, which reported on health outcomes (e.g. therapeutic efficacy in acute myocardial infarction, congestive heart failure and post-infarction; markers of recovery after exercise; electrocardiogram changes during exercise; delayed muscle pain after eccentric effort; long-chain fatty acid oxidation; protein turnover; glutathione redox state and mitochondrial enzymes in muscle and heart tissue) unrelated to the claimed effect. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
Seven human intervention studies which investigated the effect of L-carnitine consumption on blood lipids were provided.
El-Metwally et al. (2003) and Vesela et al. (2001) assessed the effect of L-carnitine consumption on blood lipids in 24 children with chronic renal failure undergoing long-term haemodialysis, and in 12 dialysed adult patients, respectively. The Panel considers that the evidence provided does not establish that patients with chronic renal failure undergoing haemodialysis are representative of the general population with regard to blood lipids and lipid metabolism, and that the results obtained in these studies with respect to changes in LDL-cholesterol concentrations cannot be extrapolated to the general population. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
In a one arm study (Stefanutti et al., 1998), the effect of L-carnitine consumption (3x1 g daily) on blood lipids was assessed in 24 subjects (aged 39-64 years) on a diet aiming to reduce blood cholesterol concentrations. The Panel notes the lack of a control group and considers that no conclusions can be drawn from this uncontrolled study for the scientific substantiation of the claim.
One parallel, randomised intervention study (Digiesi et al., 1994) in 37 subjects (mean age 60 years) with essential hypertension examined the effect of L-carnitine and antihypertensive medication on total cholesterol concentrations among other variables. Subjects received antihypertensive medication plus 2 g L-carnitine per day (group A1), antihypertensive medication only (group A2) or L-carnitine only (2 g/day, group B). Subjects in groups A1 and A2 (n=28) followed the intervention for 22 weeks,
and subjects in group B (n=9) for 10 weeks. The Panel notes the lack of a direct statistical comparison between the study groups, and thus the uncontrolled nature of the study, and considers that no conclusions can be drawn from this uncontrolled study for the scientific substantiation of the claim.
In a randomised, double-blind, placebo-controlled study with a parallel design (Pistone et al., 2003) 84 subjects (aged 70-92 years) with onset of fatigue after slight physical exercise were recruited to receive either L-carnitine (2x2 g/day, n=42) or placebo (n=42) for 30 days following a 2-week run-in phase in which subjects had followed a National Cholesterol Education Program (NCEP) Step 2 diet. All analyses were performed in the intent-to-treat population. In the L-carnitine group, total and LDL-cholesterol concentrations significantly decreased compared to placebo (-1.2 vs. +0.1 mmol/L, and -1.1 vs. -0.2 mmol/L, respectively, p<0.01). Total fat mass and total muscle mass also changed significantly in the L-carnitine compared to the placebo group (-3.1 vs. -0.5 kg and +2.1 vs. +0.2 kg, respectively, p<0.01). The Panel notes that this study showed an effect of L-carnitine on total and LDL-cholesterol concentrations when L-carnitine was consumed for 30 days. However, the Panel also notes that the constituents of the placebo were not reported, and that the study duration does not allow conclusions to be drawn on the sustainability of the effect.
In a double-blind, placebo-controlled intervention (Sirtori et al., 2000), 36 hyperlipidaemic subjects (mean age 55.9±9.3 years) with plasma Lp(a) ranging between 40 and 80 mg/dL and on isocaloric diets with a ratio of polyunsaturated/saturated fatty acids of 1.0 for the management of hyperlipidaemia were randomised to receive either L-carnitine (2 g/day, n=18) or placebo (n=18) for 12 weeks. Twelve subjects were taking low-dose acetylsalicylic acid and were on antihypertensive therapy, and eight subjects had either suffered from a myocardial infarction, had a transient ischaemic attack, or had stable angina or intermittent claudication and were taking medication (not specified) for these conditions. No statistically significant changes in total, LDL- or HDL-cholesterol concentrations were observed between groups. No body weight changes were observed during the study. The Panel notes that no information was provided on drop-outs during the study, or on the medication taken by some subjects. The Panel also notes that this study does not show an effect of L-carnitine on total, LDL- or HDL-cholesterol concentrations.
In a double-blind, placebo-controlled intervention study with a parallel design (Derosa et al., 2003), 94 hypercholesterolaemic subjects (mean age 51±6.5 years) with newly diagnosed type 2 diabetes mellitus managed with diet only were randomised after a 4-week placebo wash-out period to receive either L-carnitine (2x1 g/day, n=46) or placebo (n=48) for six months. Sixteen subjects were taking low-dose acetylsalicylic acid and were on antihypertensive therapy. Subjects were instructed to follow a standardised diet providing 1,400 to 1,600 kcal/day (55 % carbohydrates, 25 % proteins, 20 % fat, of which <7 % saturated fat), 105 mg cholesterol and 36 g fibre, and to perform aerobic exercise for at least 30 minutes on three to four days per week. Sample size calculations were not reported. It is unclear whether per protocol or intention-to-treat analyses were performed. No statistically significant changes in total or LDL-cholesterol concentrations were observed between groups. Body weight and BMI did not change significantly during the study in either group. The Panel notes that this study does not show an effect of L-carnitine on total or LDL-cholesterol concentrations.
The Panel notes that although one short-term human intervention study (30 days) reported a significant effect of L-carnitine consumption on the reduction of total and LDL-cholesterol concentrations, two human intervention studies of longer duration (12 weeks and six months, respectively) did not show an effect. The Panel considers that the human intervention studies provided did not show a sustained effect of L-carnitine consumption on blood cholesterol concentrations.
Two animal studies in rats (Mondola et al., 1988) and rabbits (Diaz et al., 2000) reported on the effects of L-carnitine on plasma lipoproteins and the apolipoprotein pattern. The Panel considers that results from studies in rats and rabbits cannot be extrapolated to humans because of major differences in lipid metabolism between species.
The Panel notes that no evidence for a plausible mechanism by which L-carnitine could exert the claimed effect in humans has been provided.
In weighing the evidence, the Panel took into account that the human intervention studies provided did not show a sustained effect of L-carnitine consumption on blood cholesterol concentrations, that results from studies in rats and rabbits cannot be extrapolated to humans because of major differences in lipid metabolism between species, and that no evidence for a mechanism by which L-carnitine could exert the claimed effect in humans has been provided.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-carnitine and maintenance of normal blood LDL-cholesterol concentrations.
3.5. Udział w prawidłowym tworzeniu plemników (spermatogenezie) (ID 1822)
Most of the references provided were not related to the food constituent which is the subject of the claim. One narrative review on sperm quality did not provide any original data for the substantiation of the claim. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claim.
One animal study examined the effect of L-carnitine on testicular ischaemic reperfusion injury in rats (Dokmeci et al., 2007). The Panel considers that evidence provided in animal studies is not sufficient to predict the occurrence of an effect of L-carnitine consumption on spermatogenesis in humans.
The Panel concludes that a cause and effect relationship has not been established between the consumption of L-carnitine and contribution to normal spermatogenesis.
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, L-carnitine, which is the subject of the health claims, is sufficiently characterised.
Faster recovery from muscle fatigue after exercise (ID 738, 1492, 1493)
The claimed effects are “fat metabolism” and “muscle metabolism/recovery after exercise”. The target population is assumed to be adults performing strenuous exercise. In the context of the proposed wordings, it is assumed that the claimed effects refer to recovery from muscle fatigue after exercise. Faster recovery from muscle fatigue after exercise is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of L-carnitine and faster recovery from muscle fatigue after exercise.
Skeletal muscle tissue repair (ID 738, 1492, 1493)
The claimed effects are “fat metabolism” and “muscle metabolism/recovery after exercise”. The target population is assumed to be adults performing resistance exercise. In the context of the proposed wordings, it is assumed that the claimed effects refer to the rebuilding of structural protein within the skeletal muscle tissue after exercise which has caused muscle damage. Skeletal muscle tissue repair is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of L-carnitine and skeletal muscle tissue repair.
Increase in endurance capacity (ID 4305, 4684)
The claimed effects are “ergogenic role in sports and exercise”, and “fat metabolism by mediating the transport of long-chain fatty acids across the inner mitochondrial membrane”. The target population is assumed to be adults performing endurance exercise. In the context of the proposed wordings, it is assumed that the claimed effects refer to an increase in endurance capacity by promoting fat oxidation. An increase in endurance capacity is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of L-carnitine and skeletal muscle tissue repair.
Maintenance of normal blood LDL-cholesterol concentrations (ID 1494, 4684)
The claimed effects are “heart health” and “fat metabolism by mediating the transport of long-chain fatty acids across the inner mitochondrial membrane”. The target population is assumed to be the general population. In the context of the proposed wordings, it is assumed that the claimed effects refer to the maintenance of normal blood LDL-cholesterol concentrations. Maintenance of normal blood LDL-cholesterol concentrations is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of L-carnitine and maintenance of normal blood LDL-cholesterol concentrations.
Contribution to normal spermatogenesis (ID 1822)
The claimed effect is “sexual organs, hormone activity”. The target population is assumed to be the general male population. In the context of the proposed wordings, it is assumed that the claimed effect refers to contribution to normal spermatogenesis. Contribution to normal spermatogenesis is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of L-carnitine and contribution to normal spermatogenesis.
“Energy metabolism” (ID 1821)
The claimed effect is “energy metabolism”. The target population is assumed to be the general population.
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.
Increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during
pregnancy (ID 1495)
The claimed effect is “pregnancy”. The target population is assumed to be pregnant women. The evidence provided does not establish that increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy in the context of a protein adequate diet is a beneficial physiological effect per se.
A cause and effect relationship has not been established between the consumption of L-carnitine and a beneficial physiological effect related to increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy.