Carnitina è un derivato aminoacidico dell'organismo umano, un enzima ed è stata scoperta all'inizio di questo secolo, ma è stata quasi dimenticata dai biochimici fino a quando l'interesse per il metabolismo degli acidi grassi l'ha rimessa in evidenza circa 50 anni or sono.

Industrialmente si presenta in forma di polvere bianca

A cosa serve e dove si usa

Cosmetica 

Funzioni INCI

Agente antistatico. L'accumulo di elettricità statica ha un'influenza diretta sui prodotti e causa adsorbimento elettrostatico. L'ingrediente antistatico riduce l'accumulo di elettricità statica e la resistività superficiale sulla superficie della pelle e dei capelli. 

Agente condizionante per capelli. In uno shampoo per capelli possono coesistere una quantità rilevante di ingredienti con scopi specifici e mirati: detergenti, condizionanti, addensanti, opacizzanti, sequestranti, fragranze, conservanti, additivi particolari. Tuttavia gli ingredienti indispensabili sono i detergenti ed i condizionanti in quanto necessari e sufficienti per la pulizia e la gestibilità dei capelli. Gli altri hanno funzioni accessorie commerciali e non indispensabili come: aspetto estetico, profumo, colorazione ecc. Gli agenti condizionanti per i capelli hanno il compito di aumentarne la lucentezza, la maneggevolezza ed il volume, ridurne l'elettricità statica soprattutto dopo trattamenti quali colorazione, stiratura, ondulazione, asciugatura e spazzolatura. Sono, in pratica, dispersori che possono contenere tensioattivi cationici, addensanti, emollienti, polimeri. La tipologia degli agenti condizionatori per capelli comprende: condizionatori intensivi, condizionatori istantanei, condizionatori addensanti, condizionatori per l'asciugatura. 

Agente di pulizia. Ingrediente che pulisce pelle senza sfruttare le proprietà tensioattive che producono un abbassamento della tensione superficiale dello strato corneo. 

Tensioattivo - Agente di pulizia. I prodotti cosmetici utilizzati per detergere la pelle utilizzano l'azione tensioattiva che produce un abbassamento della tensione superficiale dello strato corneo facilitando la rimozione di sporco e impurità. 

Tensioattivo - Foam booster. Ha la funzione di introdurre bolle di gas nell'acqua per un fattore meramente estetico, che non incide sul procedimento di pulizia, ma soddisfa unicamente l'aspetto commerciale del detergente aiutando però a spalmare il detergente sui capelli. Questo aiuta nel successo commerciale di una formulazione di shampoo. Poiché il sebo ha un'azione inibente sulla bolla, nell'eventuale secondo shampoo viene prodotta più schiuma.

Agente di aumento della viscosità, acquoso. Poiché la viscosità è importante per aumentare la stabilità chimica e fisica del prodotto, l'Agente di aumento della viscosità acquoso costituisce un importante fattore di dosaggio in gel, sospensioni, emulsioni, soluzioni. Aumentare la viscosità rende le formulazioni meno sedimentose e più omogeneamente addensate. 

Agente condizionante della pelle.  Rappresenta il perno del trattamento topico della pelle in quanto ha la funzione di ripristinare, aumentare o migliorare la tolleranza cutanea a fattori esterni, compresa la tolleranza dei melanociti. La funzione più importante dell'agente condizionante è prevenire la disidratazione della pelle, ma il tema è piuttosto complesso e coinvolge emollienti ed umettanti che possono essere aggiunti nella formulazione.

Medicina

La Carnitina viene sintetizzata in molti organismi eucariotici e la sua biosintesi è avviata dalla metilazione della lisina. Essa svolge un ruolo fondamentale nel metabolismo degli acidi grassi nei mitocondri (1).

Carnitina tuttavia non è considerata una sostanza nutritiva essenziale ed è presente in molti alimenti, principalmente quelli provenienti da fonti animali.  Lisina e metionina sono ingredienti necessari per la biosintesi della carnitina. 

Tutti i tessuti del corpo possono produrre deossi-carnitina ma, negli esseri umani, l'enzima che consente l'idrossilazione della deossi-carnitina alla carnitina si trova solo nel fegato, nel cervello e nei reni (2).

Sulla Carnitina sono stati selezionati gli studi più rilevanti con una sintesi dei contenuti:

Carnitina studi

• Formula molecolare: C₇H₁₅NO₃
• Peso molecolare: 161.201 g/mol
• CAS: 406-76-8  461-06-3
• EC Number: 206-976-6

Sinonimi: 

• DL-Carnitine
• 3-hydroxy-4-(trimethylammonio)butanoate
• Carnitine [INN]
• Carnitine chloride
• (+-)-Carnitine
• 3-Hydroxy-4-trimethylammoniobutyrat
• 3-hydroxy-4-(trimethylazaniumyl)butanoate
• (3-Carboxy-2-hydroxypropyl)trimethylammonium hydroxide inner salt
• (1)-(3-Carboxy-2-hydroxypropyl)trimethylammonium hydroxide

Ingredienti che contengono carnitina:

Butyryl-L-carnitine      

Empirical Formula (Hill Notation): C11H21NO4

Molecular Weight: 231.29

CAS Number: 25576-40-3

Isobutyryl-L-carnitine

Empirical Formula (Hill Notation): C11H21NO4

Molecular Weight: 231.29

CAS Number: 25518-49-4

Propionyl-L-carnitine

Empirical Formula (Hill Notation): C10H19NO4

Molecular Weight: 217.26

CAS Number: 20064-19-1

Decanoyl-L-carnitine

Empirical Formula (Hill Notation): C17H33NO4

Molecular Weight: 315.45

CAS Number: 3992-45-8

L-Carnitine hydrochloride

Linear Formula: (CH3)3N+CH2CH(OH)CH2CO2H · Cl-

Molecular Weight: 197.66

CAS Number: 6645-46-1

L-Carnitine inner salt

Linear Formula: (CH3)3N+CH2CH(OH)CH2COO-

Molecular Weight: 161.20

CAS Number: 541-15-1

(±)-Carnitine hydrochloride

Linear Formula: (CH3)3N(Cl)CH2CH(OH)CH2COOH

Molecular Weight: 197.66

CAS Number: 461-05-2

Bibliografia____________________________________________________________________

(1) Bremer J.  Carnitine—metabolism and functions. Physiol. Rev. 1983;63:1420–80.

(2) Jacob C, Belleville F.   L-carnitine: metabolism, functions and value in pathology.  Pathol Biol (Paris). 1992 Nov;40(9):910-9.

Pistone G, Marino A, Leotta C, Dell'Arte S, Finocchiaro G, Malaguarnera M. Levocarnitine administration in elderly subjects with rapid muscle fatigue: effect on body composition, lipid profile and fatigue. Drugs Aging. 2003;20(10):761-7. doi: 10.2165/00002512-200320100-00004.

Abstract. Aim: Levocarnitine is an important contributor to cellular energy metabolism. This study aims to evaluate the effects of levocarnitine supplementation on body composition, lipid profile and fatigue in elderly subjects with rapid muscle fatigue. Method: This was a placebo-controlled, randomised, double-blind, two-phase study. Eighty-four elderly subjects with onset of fatigue following slight physical activity were recruited to the study. Prior to randomisation all patients entered a 2-week normalisation phase where they were given an 'ad libitum'diet, according to the National Cholesterol Education Program (Step 2). Subjects were asked to record their daily food intake every 2 days. Before the 30-day treatment phase, subjects were randomly assigned to two groups (matched for male/female ratio, age and body mass index). One group received levocarnitine 2g twice daily (n = 42) and the other placebo (n = 42). Efficacy measures included changes in total fat mass, total muscle mass, serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein (apo)A1, and apoB levels. The Wessely and Powell scale was used to evaluate physical and mental fatigue. Subjects were assessed at the beginning and end of the study period. Results: At the end of the study, compared with placebo, the levocarnitine-treated patients showed significant improvements in the following parameters: total fat mass (-3.1 vs -0.5 kg), total muscle mass (+2.1 vs +0.2 kg), total cholesterol (-1.2 vs +0.1 mmol/L), LDL-C (-1.1 vs -0.2 mmol/L), HDL-C (+0.2 vs +0.01 mmol/L), triglycerides (-0.3 vs 0.0 mmol/L), apoA1 (-0.2 vs 0.0 g/L), and apoB (-0.3 vs -0.1 g/L). Wessely and Powell scores decreased significantly by 40% (physical fatigue) and 45% (mental fatigue) in subjects taking levocarnitine, compared with 11% and 8%, respectively, in the placebo group (p < 0.001 vs placebo for both parameters). No adverse events were reported in any treatment group. Conclusion: Administration of levocarnitine to healthy elderly subjects resulted in a reduction of total fat mass, an increase of total muscle mass, and appeared to exert a favourable effect on fatigue and serum lipids.

Takashima H, Maruyama T, Abe M. Significance of Levocarnitine Treatment in Dialysis Patients. Nutrients. 2021 Apr 7;13(4):1219. doi: 10.3390/nu13041219.

Abstract. Carnitine is a naturally occurring amino acid derivative that is involved in the transport of long-chain fatty acids to the mitochondrial matrix. There, these substrates undergo β-oxidation, producing energy. The major sources of carnitine are dietary intake, although carnitine is also endogenously synthesized in the liver and kidney. However, in patients on dialysis, serum carnitine levels progressively fall due to restricted dietary intake and deprivation of endogenous synthesis in the kidney. Furthermore, serum-free carnitine is removed by hemodialysis treatment because the molecular weight of carnitine is small (161 Da) and its protein binding rates are very low. Therefore, the dialysis procedure is a major cause of carnitine deficiency in patients undergoing hemodialysis. This deficiency may contribute to several clinical disorders in such patients. Symptoms of dialysis-related carnitine deficiency include erythropoiesis-stimulating agent-resistant anemia, myopathy, muscle weakness, and intradialytic muscle cramps and hypotension. However, levocarnitine administration might replenish the free carnitine and help to increase carnitine levels in muscle. This article reviews the previous research into levocarnitine therapy in patients on maintenance dialysis for the treatment of renal anemia, cardiac dysfunction, dyslipidemia, and muscle and dialytic symptoms, and it examines the efficacy of the therapeutic approach and related issues.

Pekala J, Patkowska-Sokoła B, Bodkowski R, Jamroz D, Nowakowski P, Lochyński S, Librowski T. L-carnitine--metabolic functions and meaning in humans life. Curr Drug Metab. 2011 Sep;12(7):667-78. doi: 10.2174/138920011796504536. 

Abstract. L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects.

Mao CY, Lu HB, Kong N, Li JY, Liu M, Yang CY, Yang P. Levocarnitine protects H9c2 rat cardiomyocytes from H2O2-induced mitochondrial dysfunction and apoptosis. Int J Med Sci. 2014 Aug 15;11(11):1107-15. doi: 10.7150/ijms.9153. 

Abstract. Background: Although the protective effects of levocarnitine in patients with ischemic heart disease are related to the attenuation of oxidative stress injury, the exact mechanisms involved have yet to be fully understood. Our aim was to investigate the potential protective effects of levocarnitine pretreatment against oxidative stress in rat H9c2 cardiomyocytes. Methods: Cardiomyocytes were exposed to H2O2 to create an oxidative stress model. The cells were pretreated with 50, 100, or 200 μM levocarnitine for 1 hour before H2O2 exposure. Results: H2O2 exposure led to significant activation of oxidative stress in the cells, characterized by reduced viability, increased intracellular reactive oxygen species, lipid peroxidation, and reduced intracellular antioxidant activity. Mitochondrial dysfunction was also observed following H2O2 exposure, reflected by the loss of mitochondrial transmembrane potential and intracellular adenosine triphosphate. These pathophysiological processes led to cardiomyocyte apoptosis through activation of the intrinsic apoptotic pathway. More importantly, the levocarnitine pretreatment attenuated the H2O2-induced oxidative injury significantly, preserved mitochondrial function, and partially prevented cardiomyocyte apoptosis during the oxidative stress reaction. Western blotting analyses suggested that levocarnitine pretreatment increased plasma protein levels of Bcl-2, reduced Bax, and attenuated cytochrome C leakage from the mitochondria in the cells. Conclusion: Our in vitro study indicated that levocarnitine pretreatment may protect cardiomyocytes from oxidative stress-related damage.

Jones AE, Puskarich MA, Shapiro NI, Guirgis FW, Runyon M, Adams JY, Sherwin R, Arnold R, Roberts BW, Kurz MC, Wang HE, Kline JA, Courtney DM, Trzeciak S, Sterling SA, Nandi U, Patki D, Viele K. Effect of Levocarnitine vs Placebo as an Adjunctive Treatment for Septic Shock: The Rapid Administration of Carnitine in Sepsis (RACE) Randomized Clinical Trial. JAMA Netw Open. 2018 Dec 7;1(8):e186076. doi: 10.1001/jamanetworkopen.2018.6076. 

Abstract Importance: Sepsis induces profound metabolic derangements, while exogenous levocarnitine mitigates metabolic dysfunction by enhancing glucose and lactate oxidation and increasing fatty acid shuttling. Previous trials in sepsis suggest beneficial effects of levocarnitine on patient-centered outcomes. Objectives: To test the hypothesis that levocarnitine reduces cumulative organ failure in patients with septic shock at 48 hours and, if present, to estimate the probability that the most efficacious dose will decrease 28-day mortality in a pivotal phase 3 clinical trial. Design, setting, and participants: Multicenter adaptive, randomized, blinded, dose-finding, phase 2 clinical trial (Rapid Administration of Carnitine in Sepsis [RACE]). The setting was 16 urban US medical centers. Participants were patients aged 18 years or older admitted from March 5, 2013, to February 5, 2018, with septic shock and moderate organ dysfunction. Interventions: Within 24 hours of identification, patients were assigned to 1 of the following 4 treatments: low (6 g), medium (12 g), or high (18 g) doses of levocarnitine or an equivalent volume of saline placebo administered as a 12-hour infusion. Main outcomes and measures: The primary outcome required, first, a greater than 90% posterior probability that the most promising levocarnitine dose decreases the Sequential Organ Failure Assessment (SOFA) score at 48 hours and, second (given having met the first condition), at least a 30% predictive probability of success in reducing 28-day mortality in a subsequent traditional superiority trial to test efficacy. Results: Of the 250 enrolled participants (mean [SD] age, 61.7 [14.8] years; 56.8% male), 35, 34, and 106 patients were adaptively randomized to the low, medium, and high levocarnitine doses, respectively, while 75 patients were randomized to placebo. In the intent-to-treat analysis, the fitted mean (SD) changes in the SOFA score for the low, medium, and high levocarnitine groups were -1.27 (0.49), -1.66 (0.38), and -1.97 (0.32), respectively, vs -1.63 (0.35) in the placebo group. The posterior probability that the 18-g dose is superior to placebo was 0.78, which did not meet the a priori threshold of 0.90. Mortality at 28 days was 45.9% (34 of 74) in the placebo group compared with 43.3% (45 of 104) for the most promising levocarnitine dose (18 g). Similar findings were noted in the per-protocol analysis. Conclusions and relevance: In this dose-finding, phase 2 adaptive randomized trial, the most efficacious dose of levocarnitine (18 g) did not meaningfully reduce cumulative organ failure at 48 hours.