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 Table of Contents  
REVIEW ARTICLES
Year : 2022  |  Volume : 13  |  Issue : 3  |  Page : 199-209

Effect of L-carnitine on the lipid profile, glycemic control, oxidative stress, and anthropometric indices of individuals with type 2 diabetes: A systematic review


1 Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Nutrition, Electronic Health and Statistics Surveillance Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran

Date of Submission06-May-2022
Date of Decision13-Jul-2022
Date of Acceptance27-Jul-2022
Date of Web Publication26-Sep-2022

Correspondence Address:
Dr. Behnood Abbasi
Department of Nutrition, Science and Research Branch, Islamic Azad University, 275 Daneshgah Boulevard, Simon Bolivar Street, Tehran 1477893855
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_50_22

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  Abstract 

Diabetes mellitus is one of the most prevalent metabolic diseases in existence. With more than 536.6 million cases having been diagnosed globally, its prevalence is reported to be 10.5% in 2021. In individuals with diabetes, plasma L-carnitine is low and metabolized abnormally. In this review, we aimed to assess whether L-carnitine supplementation is correlated with a reduction of the risk of cardiovascular diseases in individuals with diabetes by improving the compositions of lipid profiles, indicators of oxidative stress, glycemic control, and anthropometric indices. A literature search in major databases such as Web of Science, PubMed, Google Scholar, Scopus, and Scientific Information Database was conducted until November 2021. This was done in conjunction with a search in Elsevier and SpringerLink databases, resulting in the inclusion of relevant articles in this review. To construct the search strategy, “Carnitine” OR “glycine propionyl carnitine” OR “Acetylcarnitine” in combination with “Diabetes Mellitus” OR “Diabetes Complications” OR “Lipid Profile” and all of its components were used to search for and within the articles and databases. After screening, 10 articles published between 1998 and 2017 were identified. They evaluated the effect of L-carnitine on lipid profile metabolism, glycemic control, anthropometric indices, and oxidative stress markers in individuals with diabetes. In this systematic review, we concluded that L-carnitine had no notable effect on lipid profile as well as glycemic control and anthropometric indices. Therefore, using L-carnitine probably has no notable effect on metabolic status in individuals with diabetes. Meanwhile, some articles suggested that L-carnitine may have positive effects on some oxidative stress indicators.

Keywords: Carnitine, diabetes mellitus, glycemic control, lipid metabolism, metabolic parameters


How to cite this article:
Khodadadi N, Abbasi B. Effect of L-carnitine on the lipid profile, glycemic control, oxidative stress, and anthropometric indices of individuals with type 2 diabetes: A systematic review. J Diabetol 2022;13:199-209

How to cite this URL:
Khodadadi N, Abbasi B. Effect of L-carnitine on the lipid profile, glycemic control, oxidative stress, and anthropometric indices of individuals with type 2 diabetes: A systematic review. J Diabetol [serial online] 2022 [cited 2022 Dec 7];13:199-209. Available from: https://www.journalofdiabetology.org/text.asp?2022/13/3/199/357131




  Introduction and Aim Top


Diabetes mellitus (DM) is one of the metabolic disorders with high prevalence.[1] With more than 536.6 million cases in 20–79-year-olds having been diagnosed, diabetes prevalence is reported to be 10.5% in 2021 globally and it is estimated that the number will rise to 783.2 million in 2045.[2] Complications of DM are rising all over the world[3],[4] and are accounting for 5–20% of healthcare budgets in most countries and even in some developing countries.[5] DM remains one of the main causes of myocardial infarction.[3],[4] Recent studies have shown a direct connection between levels of some plasma lipid profiles such as HDL cholesterol (HDL-C) level and apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), and some cardiovascular complications such as thoracic aortic atherosclerosis.[6] These studies emphasize the importance of total cholesterol (TC) or LDL cholesterol (LDL-C) in raising the risk of cardiovascular disease in individuals with diabetes, which support the current recommendation to reduce LDL-C to prevent the onset of atherothrombotic vascular events in them.[7],[8] In patients with type 2 diabetes, the LDL-C catabolism is significantly reduced,[9] resulting in an increase of the duration of the presence of LDL-C in the plasma, which itself may increase lipid deposition in the arterial wall. Moreover, the number of LDL-C B/E receptors on the cell surface is considerably diminished,[10] which may be due to a decrease in the expression of insulin and can lead to disruption of LDL-C catabolism.[10],[11] Changing LDL-C compositions may cause conformational changes and probably results in higher exposure of fatty acids to oxygen-free radicals and changes in lipid peroxidation levels.[12],[13] In plasma or subendothelial arterial wall, uptake of LDL-C will increase via scavenger receptors present in macrophages, smooth muscle cells, and endothelial cells as consequences of LDL-C oxidation.[8],[14],[15],[16] The formation of foam cells as well as the alteration of monocytes and macrophages in the arterial wall to cholesterol foam cells, which are essential parts of the atherosclerosis plaque, significantly increases with the oxidative changes in LDL-C.[17],[18] Moreover, in individuals with diabetes, levels of serum lipids are often elevated and are independently related to some complications of DM.[19],[20] Higher levels of insulin in the blood, the presence of non-oxidative glycation products, and increases in levels of blood glucose[21] because of insulin resistance may increase the risk of cardiovascular morbidity in type 2 diabetes.[21] The risk of oxidative stress, which has a vital role in LDL-C oxidation and hyperglycemia, is high in individuals with diabetes.[22],[23] Many pharmacological agents, such as calcium channel antagonists and antiplatelet[24] agents, have been used in the treatment of peripheral arterial disease (PAD) in individuals with diabetes. It has been suggested that oxidative stress might worsen the complications of diabetes,[25] whereas antioxidants may alleviate and impede mechanisms that cause diabetes at an early stage.[26]

L-carnitine is an amino acid-based substance that has an important role in the transport of long-chain fatty acids through the internal mitochondrial membrane.[4],[27],[28] In tissues such as skeletal muscle and heart, which use fatty acids as the main fuel, it can be seen in high concentrations.[29] Additionally, as literature suggests, in individuals with diabetes, plasma L-carnitine concentrations are low.[30] In addition, abnormal metabolism of carnitine has been reported in individuals with diabetes, and the higher prevalence of carnitine deficiency in muscle tissues of PAD patients has also been observed.[31],[32],[33] Carnitine deficiency has been shown to correlate with cardiomyopathy.[34] Therefore, decreased carnitine levels may impair myocardial function.[33],[35] It has been suggested that L-carnitine, especially with its antioxidant and lipid-lowering effects, may be able to reduce atherosclerotic lesions.[36],[37] Moreover, oxidation of lipids accelerates the formation of free radicals, thus carnitine may prevent oxidative stress by inhibiting the peroxidation of membranes’ fatty acids.[38] So, due to limited amounts of L-carnitine, fatty acids cannot enter the mitochondria to oxidize and produce ATP. A study that used L-carnitine supplementation showed a rapid reduction in serum levels of oxidative LDL-C (ox LDL-C), suggesting that it could possibly reduce oxidative stress, and it has been claimed that carnitine consumption may lead to change in the metabolic pathway of the liver from esterification and synthesis of triglycerides (TGs) to the production of acetyl L-carnitine (ALC). This pathway may lead to increases in mitochondrial fatty acids beta-oxidation and reduction in the synthesis of TG and very-low-density lipoprotein (VLDL) cholesterol.[39] Also, it was shown that increasing carnitine may have positive effects on body fat reduction and increment of oxidation of the fatty acids.[18] Moreover, it has been suggested that the beneficial effects of improving vascular reactivity and antioxidant activity, which can be observed during the treatment with L-carnitine, may be due to decreased plasma lipid levels; therefore, it can be used as an effective therapeutic tactic to improve diabetes vascular complications.[40],[41] Also, arterial blood pressure,[42] insulin resistance,[43],[44] impaired glucose tolerance,[45] and hypoadiponectinemia[46] in individuals with diabetes can be safely improved by ALC.[47] In this study, we aimed to summarize the results of previous studies that examined the effects of L-carnitine supplementation on lipid profiles, indicators of glycemic control and oxidative stress, and anthropometric indices, to assess the potential relationship between L-carnitine supplementation and metabolic status in individuals with diabetes.


  Materials and Methods Top


PRISMA guideline was used for completing this review which was registered with the PROSPERO database (Code: [removed for blind peer review]).

Search strategy

We used a systematic search approach to investigate electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and Scientific Information Database (SID) to retrieve articles that examine the effect of L-carnitine on lipid profile composition, indicators of oxidative stress and glycemic control, and anthropometric indices in individuals with diabetes from inception until November 2021. Our search was supplemented with the search of publisher databases Elsevier and SpringerLink. The following MeSH and non-MeSH terms were used to construct the search strategy for screening electronic papers: “Carnitine” OR “glycine propionyl carnitine” OR “Acetylcarnitine” in combination with “Diabetes Mellitus” OR “Diabetes Complications” and “Lipid Peroxides” OR “Cholesterol, LDL” OR “Cholesterol, HDL” OR “Cholesterol” OR “Triglycerides” OR “Cholesterol VLDL” OR “Apolipoprotein A-I” OR “Apolipoproteins B” OR “Lipoprotein(a)” OR “Oxidative Stress” OR “4-hydroxy-2-nonenal” OR “Nitrites” OR “Nitrates” OR “Thiobarbituric Acid Reactive Substances” OR “Malondialdehyde” OR “Glycemic Control” OR “ Insulin” OR “Glycated Hemoglobin A” OR “Blood Glucose” OR “Anthropometry” OR “Waist-Hip Ratio” OR “Body Mass Index” OR “Body Weight”. Details of the search strategy can be found in Supplementary File 1.

Inclusion and exclusion criteria

All articles addressing the effect of L-carnitine on lipid profiles components and indicators of oxidative stress, glycemic control, and anthropometry in individuals with diabetes were eligible to enter the study after screening the titles and abstracts. There were no restrictions regarding the language of publications. Also, the minimum acceptable criterion for blood glucose level was 126 mg/dL. Animal and other studies not providing our primary outcomes were excluded. Duplicated articles and studies with supplementation through injection were removed as well.

Data extraction and quality assessment

Two independent authors (NK and BA) identified articles and then extracted the following data regarding general characteristics of the study and population (study’s first author, year of publication, study design and location, number of participants and their gender and age, intervention duration, and supplement dosage); lipid metabolism such as HDL-C, LDL-C, TC, TG, VLDL, Apo A1, Apo B, lipoprotein (a) [Lp (a)]; oxidative stress markers such as 4-hydroxynonenal (4-HNE), nitric oxide (NO), nitrite/nitrate (NO2/3), glutathione peroxidase (GPx), thiobarbituric acid-reactive substances (TBAR), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), total antioxidant capacity (TAC); glycemic control index such as insulin levels, glycosylated hemoglobin A1 C (HbA1C) and levels of fasting blood sugar (FBS), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), and fasting plasma insulin (FPI); and anthropometric indices such as body mass index (BMI), waist-to-hip ratio (WHR), and percent of body fat. The adequacy of selected trials was measured by using the quantitative 5-point Jadad scale. EndNote software was used to import and classify all the articles.

Quality assessment of included studies

The risk of bias in the eligible included studies was assessed using the Cochrane criteria.[48] The quality of all studies was assessed by two different authors (NK and BA) for following items: sequence generation, allocation sequence concealment, blinding of participants and researchers, and outcomes reporting to evaluate possible sources of bias [Figure 1].
Figure 1: Summary of the risk of bias for individual studies

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  Results Top


From the 22 eligible studies, 10 articles were selected for studying after checking the full text carefully [Figure 2].
Figure 2: Flow diagram of the included studies

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These articles were conducted from 1998 to 2017. The size of target groups ranged from 12 (in which 3 men and 3 women received L-carnitine)[49] to 94 (in which 24 men and 22 women were in the L-carnitine group)[3] patients. The longest period of the study was 12 months,[26],[32] and the minimum length of the study was 4 weeks.[49],[50] In these 10 articles, the lowest dose of L-carnitine was 500 mg[50],[51] and the highest dose was 3 g/day.[31],[49],[52] Studies were conducted in five countries: Iran,[31],[50],[51],[53] Italy,[3],[18],[26],[32] Mexico,[49] Iraq,[54] and China.[52] One study did not mention the gender of participants[26],[32] and two studies were done exclusively on women[51],[53]: one on men[50] and the other study included both genders. In two of the studies, patients were taking oral antidiabetic drugs in addition to L-carnitine treatment, glyburide, and metformin in one paper,[31] the results of which indicated an increment in TG, Apo A, and Apo B and no changes in LDL-C, HDL-C, and TC, and metformin and sulfonylurea in another study,[54] the results of which showed significant reductions in FBS levels. The relevant factors to the title of this article, which have been reviewed in those 10 papers, are LDL-C, HDL-C, TC, TG, VLDL, and Lp (a). In addition, factors such as Apo B, Apo A1, HbA1C, and levels of FBS, FPG, PPG, and FPI and 4-HNE, MDA, insulin levels, NO2, NO3, and TBARs, BMI, WHR, body weight, and fat were also reviewed [Table 1].
Table 1: Characteristics of included publications

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Lipid panel parameters

In nine articles, it was shown that the levels of HDL-C did not significantly change with L-carnitine treatment when compared with the placebo group.[3],[18],[26],[31],[32],[49],[50],[52],[53],[54] Based on these results, the consumption of L-carnitine may not have a significant effect on HDL-C levels. In nine articles that measured TC levels, there was no significant change via L-carnitine treatment in the TC levels in comparison with the placebo group.[3],[18],[26],[31],[32],[49],[50],[52],[53],[54] Likely, L-carnitine has not affected the TC levels. In five assessed papers, treatment with L-carnitine did not result in significant changes in TG levels when compared with the placebo group.[3],[26],[32],[49],[50],[52],[53] Two studies found that TG levels were notably lowered in comparison with the placebo group,[18] but another study showed that TG levels significantly increased by 3 g of L-carnitine daily when compared with the placebo group.[31] Therefore, according to the results; it seems that the use of L-carnitine does not affect TG levels. In seven studies that measured LDL-C level, it was shown that L-carnitine consumption could not change LDL-C level[3],[26],[31],[32],[49],[50],[53],[54]; one paper found that levels of LDL-C were significantly decreased when compared with the placebo group.[18] Based on these results, the use of L-carnitine does not affect LDL-C levels. Levels of VLDL cholesterol were investigated in one study and no significant relevance was found.[49] So, further studies are necessary to reach a definitive conclusion. In one paper, concentration of the plasma Lp (a) was significantly reduced with the consumption of L-carnitine after 6 months compared with the placebo group,[3] but two studies did not find any significant decrease compared with the placebo group.[31],[54] Because of the inconsistency of the findings, further studies are necessary to reach a conclusive result. Apo A and Apo B were discussed in four papers; one of the studies showed a significant effect of L-carnitine on the reduction of Apo A1 and Apo B100 levels when compared with the placebo group.[18] Two studies found no significant change in L-carnitine compared with the placebo group after 6 months,[3],[52] and one study showed that Apo B100 and Apo A1 levels significantly increased after intervention in comparison with the placebo group.[31] Due to these contradictory findings, further studies with different durations of intervention, and doses, are necessary to reach a conclusive result.

Glycemic control

Ten studies evaluated glucose levels. In four of them, compared with the placebo group, a significant decrease in glucose levels was observed after L-carnitine administration.[31],[50],[53],[54] Moreover, six studies indicated a contrast reporting no significant change in glucose levels compared with the placebo group.[3],[18],[26],[32],[49],[51],[52] Also, one paper indicated no statistically notable change in PPG and FPI in comparison to the placebo group after 6 months.[3] Moreover, all of the eight studies that evaluated the HbA1C level showed that it did not have any significant change after the intervention when compared with the placebo group.[3],[18],[26],[31],[32],[49],[51],[52],[54] Therefore, according to our results, supplementation of L-carnitine does not have any short-term or long-term effects on glycemic control.

Oxidative stress profile

Some studies investigated oxidative stress factors such as ox LDL-C, 4-HNE, NO2/NO3, TBARs, and MDA. One study found that levels of ox-LDL-C, TBARs, and conjugated dienes decreased compared with the placebo group.[18] In addition, a paper observed a significant change in the LDL-C oxidation time in patients who were treated with 2 g/day propionyl L-carnitine (PLC). They showed that 4-HNE, MDA, and NO2/NO3 ratio (nitrite/nitrate) levels significantly decreased in the PLC-treated group when compared with the placebo group.[26],[32]

Anthropometric indices

In all nine articles that measured BMI,[3],[18],[26],[31],[32],[49],[51],[52],[53] in three articles that measured WHR,[31],[51],[53] in two articles that measured body fat,[51],[53] and in all three articles that measured body weight,[3],[52],[53] there was no significant decrease after L-carnitine treatment when compared with the placebo group, but Liang et al.[52] detected a significant diminishment in WHR and body fat. Based on these results, L-carnitine treatment in diabetes probably does not correlate with anthropometric indices.

In the studies reviewed in this paper, some side effects were also observed. In one of the studies, one patient complains of nausea, which was resolved after 3 days of treatment.[3] In another study, several cases of nausea, headache, and abdominal pain were observed in the L-carnitine-treated group. In the placebo group, several cases of diarrhea and nausea and headache were also observed.[18] In addition to the aforementioned side effects, in one study, one subject from L-carnitine and one subject from the placebo group were excluded due to facial flushing and skin rash after 5 days and 4 weeks, respectively.[52]


  Discussion Top


A former review[55] evaluated the metabolic effect of L-carnitine in individuals with diabetes. The present systematic review by providing additional evidence intends to update the previous results and to evaluate more parameters.

Lipid panel parameters

Based on the fact that Apo A1 has significantly increased whereas the HDL-C level remained unaffected, it seems that there is no correlation between L-carnitine and HDL-C levels. One possible hypothesis leading to this observation could be related to the increasing concentration of TG in the remaining VLDL and rising of TG antiport with HDL-C at the same time.[31] One study showed a contrasting result by reporting the effect of carnitine on the HDL-C level; it found that ALC may increase the HDL-C levels probably via reducing HDL-C clearance and also by increasing the activity of lipoprotein lipase (LPL).[56] The difference in results may be due to the type of the study conducted and/or the increase of dosage and duration of the intervention.[57] L-carnitine may have cholesterol-lowering effects. This may be due to its effect on lowering TG as a result of changes in lipoprotein composition, which is damaged in diabetes.[58] These different results may be caused by the difference in the types of studies conducted,[4],[57] the way in which they were designed, and the duration of intervention applied.[59] Also, TG levels may increase due to an elevated amount of fatty acids and Apo B100 that can lead to increased VLDL production.[60] However, L-carnitine may in fact decrease TG levels. This may be based on the hypothesis that changes in the liver metabolic pathways of esterification and synthesis of TGs to ALC could reduce the production of TG.[18] The LDL-C level may not decrease because cholesterol is not decreasing and also the Apo B100 level is increasing at the same time. In addition, the LDL-C receptor saturation and its regulatory reduction increase TG and abnormal VLDL that enriches in TG. Moreover, based on the Friedwald–Fredrickson formula [LDL-C= TC-(HDL-C+TG/5)], the levels of LDL-C depend on TC, HDL-C, and TG levels. If there is no significant change in cholesterol, TG, and HDL-C levels, there will not be any changes in the LDL-C level.[61],[62] However, supplementation with L-carnitine could probably decrease the LDL-C and TG levels by increasing the expression of the LDL-C receptor and LPL genes.[63] The observed reduction in LDL-C levels may be due to the consumption of low-calorie diet and aerobic exercise along with the supplementation.[64] González-Ortiz et al. assess the effect of L-carnitine on VLDL cholesterol level and no significant correlation was found.[49] However, L-carnitine may change metabolic pathways from esterification in the liver and change TG synthesis to ALC, which can reduce the synthesis of TG and VLDL cholesterol.[39] Also, catabolism of VLDL is reduced in individuals with diabetes, which is due to decreased activity of LPL in adipose tissue leading to augmented levels of TG in individuals with diabetes. Since insulin activates LPL, insulin resistance reduces the LPL activity. In addition, increasing plasma levels of Apo C-III, which inhibits the activity of LPL in individuals with diabetes, can reduce the catabolism of VLDL.[10] Additionally, increasing the transfer of fatty acids to the liver, a common disorder in insulin-resistant diabetes, may increase the secretion of VLDL,[65],[66] and also its concentration may rise by higher amounts of fatty acids and Apo B100.[60] By stimulating and contributing to the decomposition of fatty acids in the mitochondria, L-carnitine can probably reduce the number of fatty acids to produce Lp (a) in patients who are likely to have high atherogenic lipoprotein production. In addition, it has been shown that strong inhibitory acyl cholesterol acyltransferase may be able to reduce plasma Lp (a) levels.[3] Moreover, some studies measured the effect of L-carnitine on Apo B and Apo A1 levels, and their results were inconsistent.[3],[18],[31],[52] This may be because apolipoproteins are genetically determined and dietary supplements are unlikely to have a significant effect on them.[67] L-carnitine may affect Apo levels via its effect on oxidative stress. Apo A1 and Apo B100 levels may decrease because of the fact that L-carnitine reduces and inhibits oxidative stress. It also regulates cellular respiration, nitric oxidative stress, and nitric oxide and defends enzymes against oxidative damage. It also protects the enzymes catalase, succinate dehydrogenase, and superoxide dismutase and antioxidant enzymes.[68] However, it has been proposed that high levels of carnitine may possibly induce fatty acids synthesis rather than their oxidation. Therefore, high doses of L-carnitine or its prolonged intake could probably play a role in increasing Apo B in a period of more than 3 months.[69]

Glycemic control

Most studies suggested that L-carnitine supplementation probably did not have any beneficial effect on the short-term depletion of glucose. In addition, there was no evidence of the ability of L-carnitine to regulate long-term hyperglycemia based on the HbA1C factor. L-carnitine may raise the hepatic homogenate glucose levels possibly by increasing beta-oxidation and producing excess hepatic glucose via gluconeogenesis.[70] However, some studies indicated that carnitine could have a positive effect on glucose metabolism via modifying and altering the genes expression that contributes to its metabolism such as enzymes of gluconeogenic, glycolytic, and insulin signaling pathway, and also by increasing the activity of pyruvate dehydrogenase, producing more acetyl-CoA and stimulating the Krebs cycle.[71]

Oxidative stress profile

Oxidative stress is caused by an imbalance in the production of reactive oxygen species and the cell’s own antioxidant defense, which may contribute to a number of diseases.[72] Some studies showed that L-carnitine may be able to improve oxidative stress via affecting factors such as ox LDL-C, 4-HNE, NO2/NO3, TBARS, and MDA. A study[26],[32] indicated that PLC could change the oxidative profile, as one of the roles of carnitine is facilitating the passage of fatty acids from cytosol to the matrix of mitochondria. Beta-oxidation of these fatty acids produces ATP, and any alteration in this pathway changes the oxidative metabolism. Also, in non-insulin-dependent diabetes mellitus (NIDDM) patients, increased blood glucose level and decreased insulin sensitivity lead to some changes in oxidative metabolism at the cellular level and endothelial dysfunction, which plays an important role in maintaining the balance of the circulatory system. L-carnitine is likely to improve oxidative-negative conditions in individuals with diabetes, as well as peripheral use of oxygen. A study[18] indicated a notable decrease in ox LDL-C, which may be due to lower oxidative stress by the ability of L-carnitine to increase the mitochondria-mediated uptake of fatty acids to produce ATP.[73] Additionally, this could be due to vasodilation of vessels that is related to the activity of acetylcholine, which is disrupted in NIDDM. By increasing the release of relaxation factors such as NO, acetylcholine induces vasodilation of the endothelium. Disturbance in NO production or response leads to the vascular and endothelium complications. Some studies showed that superoxide, hydroxyl, and free radicals can interact with NO. They produce weaker vasodilators such as peroxynitrite NO2 and NO3, which may interfere with endothelium-dependent vasodilators. L-carnitine improved acetylcholine and its response.[4] However, in practice, a diet rich in nitrate can achieve the same plasma nitrate concentration as supplements.[74] Also, another study[26],[32] showed that the 4-HNE level significantly decreased in the PLC-treated group when compared with the placebo group. At a very low concentration, 4-HNE, which is the production of lipid peroxidation of unsaturated fatty acid on the cell membrane, can participate in the normal physiological cell functions. When its concentration is higher than normal, it can stimulate cell apoptosis, affecting cell signal transduction and creating a cytotoxic influence. Lipid peroxidation, created by free radicals attacking cell membranes, results in the production of lipid peroxidation derivatives, including 4-HNE, MDA, and many other toxic aldehydes.[75] HNE can damage beta cells of the pancreas and impair the ability of muscle and the liver cells to respond to insulin. HNE may elevate the risk of atherosclerosis by altering lipoproteins. By impairing the metabolic enzymes, it can also damage the cardiac cells.[76] Another study[18] found that in hyperlipidemic individuals with diabetes, reducing antioxidants or improving their defensive function may correlate with a decrease in TBARs and conjugated dienes as lipid peroxidation indicators. The interaction between fatty acids and free radicals and, finally, changes in lipid peroxidation levels, could be altered by changes in LDL-C compounds. Hypertriglyceridemic and hypercholesterolemic individuals with diabetes are associated with protein glucose and glucose autoxidation and changes in the oxidative LDL-C, which increase lipid peroxidation. As a result, the amount of TBARs and conjugated dienes increases and, ultimately, elevates oxidative stress. Ox LDL-C is likely to cause atherogenesis by altering the TBARS level.[13],[18] Also, the results of one study indicated[77] that L-carnitine could decrease MDA levels. MDA is an important indicator of lipid peroxidation and its increase in the liver may be the result of the stimulating effect of L-carnitine in the oxidation of fatty acids in mitochondria to produce ATP.

Anthropometric indices

We could not find a significant correlation between L-carnitine and the reduction of anthropometric indices in individuals with diabetes, and also a recent systematic review did not support consumption of alternative dietary supplementation for weight loss.[78] However, some studies showed that L-carnitine may reduce body weight through insulin resistance, appetite reduction, and food digestion by affecting the hypothalamus directly, for instance, Askarpour et al. found that L-carnitine could decrease body weight and BMI because the end product of beta-oxidation, acetyl coenzyme A, can be increased by L-carnitine, which can affect the supply of glucose to brain, thereby regulating energy expenditure and suppressing appetite and could effect on body weight; this different result may be due to that they consider weight as a secondary outcome variable in their study.[53],[79],[80]


  Conclusion Top


This systematic review concluded that the intake of L-carnitine had no significant effect on the lipid profile composition, glycemic control, and anthropometric indices in individuals with diabetes. However, it identified a significant enhancement in some oxidative stress indicators. It seems that the use of L-carnitine may not significantly affect metabolic status in individuals with diabetes. However, as only the intermediate parameters were evaluated in the papers reviewed in this study, further research is needed to recommend the use of L-carnitine in individuals with diabetes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Avilés-Santa ML, Monroig-Rivera A, Soto-Soto A, Lindberg NM Current state of diabetes mellitus prevalence, awareness, treatment, and control in Latin America: Challenges and innovative solutions to improve health outcomes across the continent. Curr Diab Rep 2020;20:62.  Back to cited text no. 1
    
2.
Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022;183:109119.  Back to cited text no. 2
    
3.
Derosa G, Cicero AF, Gaddi A, Mugellini A, Ciccarelli L, Fogari R The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. Clin Ther 2003;25:1429-39.  Back to cited text no. 3
    
4.
Salmanoglu DS, Gurpinar T, Vural K, Ekerbicer N, Darıverenli E, Var A Melatonin and L-carnitine improves endothelial disfunction and oxidative stress in type 2 diabetic rats. Redox Biol 2016;8:199-204.  Back to cited text no. 4
    
5.
Abbasi B, Mirlohi M, Daniali M, Ghiasvand R Effects of probiotic soymilk on lipid panel in type 2 diabetic patients with nephropathy: A double-blind randomized clinical trial. Prog Nutr 2018;20:70-8.  Back to cited text no. 5
    
6.
Kohsaka S, Jin Z, Rundek T, Homma S, Sacco RL, Di Tullio MR Relationship between serum lipid values and atherosclerotic burden in the proximal thoracic aorta. Int J Stroke 2010;5:257-63.  Back to cited text no. 6
    
7.
Asia Pacific Cohort Studies Collaboration. Cholesterol, diabetes and major cardiovascular diseases in the Asia-Pacific region. Diabetologia 2007;50:2289-97.  Back to cited text no. 7
    
8.
Hoogeveen RC, Ballantyne CM, Bang H, Heiss G, Duncan BB, Folsom AR, et al. Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: The Atherosclerosis Risk in Communities study. Diabetologia 2007;50:36-42.  Back to cited text no. 8
    
9.
Stolinski M, Alam S, Jackson NC, Shojaee-Moradie F, Pentecost C, Jefferson W, et al. Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus. Metabolism 2008;57:1608-14.  Back to cited text no. 9
    
10.
Vergès B Pathophysiology of diabetic dyslipidaemia: Where are we? Diabetologia 2015;58:886-99.  Back to cited text no. 10
    
11.
Duvillard L, Florentin E, Lizard G, Petit JM, Galland F, Monier S, et al. Cell surface expression of LDL receptor is decreased in type 2 diabetic patients and is normalized by insulin therapy. Diabetes Care 2003;26:1540-4.  Back to cited text no. 11
    
12.
Zhong S, Li L, Shen X, Li Q, Xu W, Wang X, et al. An update on lipid oxidation and inflammation in cardiovascular diseases. Free Radic Biol Med 2019;144:266-78.  Back to cited text no. 12
    
13.
Regnström J, Nilsson J, Tornvall P, Landou C, Hamsten A Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 1992;339:1183-6.  Back to cited text no. 13
    
14.
Steinberg D Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997;272:20963-6.  Back to cited text no. 14
    
15.
Grundy SM Atherogenic dyslipidemia: Lipoprotein abnormalities and implications for therapy. Am J Cardiol 1995;75:45B-52B.  Back to cited text no. 15
    
16.
Parthasarathy S, Rankin SM Role of oxidized low density lipoprotein in atherogenesis. Prog Lipid Res 1992;31:127-43.  Back to cited text no. 16
    
17.
Boullier A, Bird DA, Chang MK, Dennis EA, Friedman P, Gillotre-Taylor K, et al. Scavenger receptors, oxidized LDL, and atherosclerosis. Ann N Y Acad Sci 2001;947:214-22; discussion 222-3.  Back to cited text no. 17
    
18.
Malaguarnera M, Vacante M, Avitabile T, Malaguarnera M, Cammalleri L, Motta M L-carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin Nutr 2009;89:71-6.  Back to cited text no. 18
    
19.
Einarson TR, Acs A, Ludwig C, Panton UH Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol 2018;17:1-19.  Back to cited text no. 19
    
20.
Bhowmik B, Siddiquee T, Mujumder A, Afsana F, Ahmed T, Mdala IA, et al. Serum lipid profile and its association with diabetes and prediabetes in a rural Bangladeshi population. Int J Environ Res Public Health 2018;15:1944.  Back to cited text no. 20
    
21.
Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuñiga FA Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol 2018;17:122.  Back to cited text no. 21
    
22.
Motta M, Bennati E, Ferlito L, Malaguarnera M Diabetes mellitus in the elderly: Diagnostic features. Arch Gerontol Geriatr 2006;42:101-6.  Back to cited text no. 22
    
23.
De Rijke YB, Verwey HF, Vogelezang CJ, Van Der Velde EA, Princen HM, Van Der Laarse A, et al. Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis. Clin Chim Acta 1995;243:137-49.  Back to cited text no. 23
    
24.
Tsigkou V, Siasos G, Rovos K, Tripyla N, Tousoulis D Peripheral artery disease and antiplatelet treatment. Curr Opin Pharmacol 2018;39:43-52.  Back to cited text no. 24
    
25.
Baynes JW Role of oxidative stress in development of complications in diabetes. Diabetes 1991;40:405-12.  Back to cited text no. 25
    
26.
Santo SS, Sergio N, Luigi DP, Giuseppe M, Margherita F, Gea OC, et al. Effect of PLC on functional parameters and oxidative profile in type 2 diabetes-associated PAD. Diabetes Res Clin Pract 2006;72:231-7.  Back to cited text no. 26
    
27.
Carter AL, Abney TO, Lapp DF Biosynthesis and metabolism of carnitine. J Child Neurol 1995;10(Suppl. 2):S3-7.  Back to cited text no. 27
    
28.
Bene J, Hadzsiev K, Melegh B Role of carnitine and its derivatives in the development and management of type 2 diabetes. Nutr Diabetes 2018;8:8.  Back to cited text no. 28
    
29.
Brass EP Pivalate-generating prodrugs and carnitine homeostasis in man. Pharmacol Rev 2002;54:589-98.  Back to cited text no. 29
    
30.
Ramazani M, Qujeq D, Moazezi Z Assessing the levels of L-carnitine and total antioxidant capacity in adults with newly diagnosed and long-standing type 2 diabetes. Can J Diabetes 2019;43:46-50.e1.  Back to cited text no. 30
    
31.
Rahbar AR, Shakerhosseini R, Saadat N, Taleban F, Pordal A, Gollestan B Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus. Eur J Clin Nutr 2005;59:592-6.  Back to cited text no. 31
    
32.
Signorelli SS, Fatuzzo P, Rapisarda F, Neri S, Ferrante M, Oliveri Conti G, et al. A randomised, controlled clinical trial evaluating changes in therapeutic efficacy and oxidative parameters after treatment with propionyl L-carnitine in patients with peripheral arterial disease requiring haemodialysis. Drugs Aging 2006;23:263-70.  Back to cited text no. 32
    
33.
Poorabbas A, Fallah F, Bagdadchi J, Mahdavi R, Aliasgarzadeh A, Asadi Y, et al. Determination of free L-carnitine levels in type II diabetic women with and without complications. Eur J Clin Nutr 2007;61:892-5.  Back to cited text no. 33
    
34.
Pekala J, Patkowska-Sokoła B, Bodkowski R, Jamroz D, Nowakowski P, Lochyński S, et al. L-carnitine-metabolic functions and meaning in humans life. Curr Drug Metab 2011;12:667-78.  Back to cited text no. 34
    
35.
Akisu M, Kultursay N, Coker I, Huseyinov A Myocardial and hepatic free carnitine concentrations in pups of diabetic female rats. Ann Nutr Metab 2002;46:45-8.  Back to cited text no. 35
    
36.
Sayed-Ahmed MM, Khattab MM, Gad MZ, Mostafa N L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits. Pharmacol Res 2001;44:235-42.  Back to cited text no. 36
    
37.
Wang S, Xu J, Zheng J, Zhang X, Shao J, Zhao L, et al. Anti-inflammatory and antioxidant effects of acetyl-L-carnitine on atherosclerotic rats. Med Sci Monit 2020;26:e920250.  Back to cited text no. 37
    
38.
Binienda ZK Neuroprotective effects of L-carnitine in induced mitochondrial dysfunction. Ann N Y Acad Sci 2003;993:289-95; discussion 345-9.  Back to cited text no. 38
    
39.
Casciani CU, Caruso U, Cravotto E, Corsi M, Pola P, Savi L, et al. Effect of L-carnitine on lipid pattern in haemodialysis. Lancet 1980;2:1309-10.  Back to cited text no. 39
    
40.
Ragozzino G, Mattera E, Madrid E, Salomone P, Fasano C, Gioia F, et al. Effects of propionyl-carnitine in patients with type 2 diabetes and peripheral vascular disease: Results of a pilot trial. Drugs R D 2004;5:185-90.  Back to cited text no. 40
    
41.
Irat AM, Aktan F, Ozansoy G Effects of L-carnitine treatment on oxidant/antioxidant state and vascular reactivity of streptozotocin-diabetic rat aorta. J Pharm Pharmacol 2003;55:1389-95.  Back to cited text no. 41
    
42.
Digiesi V, Palchetti R, Cantini F [The benefits of L-carnitine therapy in essential arterial hypertension with diabetes mellitus type II]. Minerva Med 1989;80:227-31.  Back to cited text no. 42
    
43.
Ringseis R, Keller J, Eder K Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: Evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. Eur J Nutr 2012;51:1-18.  Back to cited text no. 43
    
44.
Capaldo B, Napoli R, Di Bonito P, Albano G, Saccà L Carnitine improves peripheral glucose disposal in non-insulin-dependent diabetic patients. Diabetes Res Clin Pract 1991;14:191-5.  Back to cited text no. 44
    
45.
Molfino A, Cascino A, Conte C, Ramaccini C, Rossi Fanelli F, Laviano A Caloric restriction and L-carnitine administration improves insulin sensitivity in patients with impaired glucose metabolism. J Parenter Enteral Nutr 2010;34:295-9.  Back to cited text no. 45
    
46.
Derosa G, Maffioli P, Ferrari I, D’Angelo A, Fogari E, Palumbo I, et al. Comparison between orlistat plus l-carnitine and orlistat alone on inflammation parameters in obese diabetic patients. Fundam Clin Pharmacol 2011;25:642-51.  Back to cited text no. 46
    
47.
Salama RH Hypoglycemic effect of lipoic acid, carnitine and Nigella sativa in diabetic rat model. Int J Health Sci (Qassim) 2011;5:126-34.  Back to cited text no. 47
    
48.
Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions. 2nd ed. Chichester: John Wiley & Sons; 2019.  Back to cited text no. 48
    
49.
González-Ortiz M, Hernández-González SO, Hernández-Salazar E, Martínez-Abundis E Effect of oral L-carnitine administration on insulin sensitivity and lipid profile in type 2 diabetes mellitus patients. Ann Nutr Metab 2008;52:335-8.  Back to cited text no. 49
    
50.
Ramezanpour M, Matboo M, Hejazi EM The effect of four weeks aerobic training with using L-carnitine supplement on lipid profile and blood glucose in diabetic men. Med J Mashhad Univ Med Sci 2015;58:316-21.  Back to cited text no. 50
    
51.
Hassani A, Ghorbani M Comparison of the effects of omega-3 supplements and L-carnitine with the combination exercise on hematological parameters of type 2 diabetic women. Sci J Iran Blood Transf Organ 2017;14:140-6.  Back to cited text no. 51
    
52.
Liang Y, Li Y, Shan J, Yu B, Ho Z The effects of oral L-carnitine treatment on blood lipid metabolism and the body fat content in the diabetic patient. Asia Pac J Clin Nutr 1998;7:192-5.  Back to cited text no. 52
    
53.
Alipour B, Barzegar A, Panahi F, Safaeian A, Eshaghi M Effect of L-carnitine supplementation on metabolic status in obese diabetic women with hypocaloric diet. Health Scope 2014;3:e14615.  Back to cited text no. 53
    
54.
Mohammed-Jawad NK, Sabbagh MA, AL-Jezaeri KA Role of L-carnitine and coenzyme Q10 as adjuvant therapy in patients with type 2 diabetes mellitus. Am J Pharmacol Sci 2014;2:82-6.  Back to cited text no. 54
    
55.
Vidal-Casariego A, Burgos-Peláez R, Martínez-Faedo C, Calvo-Gracia F, Valero-Zanuy MÁ, Luengo-Pérez LM, et al. Metabolic effects of L-carnitine on type 2 diabetes mellitus: Systematic review and meta-analysis. Exp Clin Endocrinol Diabetes 2013;121:234-8.  Back to cited text no. 55
    
56.
Fernandez IC, del Carmen Camberos M, Passicot GA, Martucci LC, Cresto JC Children at risk of diabetes type 1. Treatment with acetyl-L-carnitine plus nicotinamide—Case reports. J Pediatr Endocrinol Metab 2013;26:347-55.  Back to cited text no. 56
    
57.
Hajinezhad MR, Hajian S, Saghayei S, Samzadeh-Kermani AR, Nabavi R Comparison of the protective effects of L-carnitine and acetyl L-carnitine on blood glucose and lipid peroxidation level in diabetic rats. Quart Horizon Med Sci 2016;22:229-35.  Back to cited text no. 57
    
58.
Lofgren IE, Herron KL, West KL, Zern TL, Brownbill RA, Ilich JZ, et al. Weight loss favorably modifies anthropometrics and reverses the metabolic syndrome in premenopausal women. J Am Coll Nutr 2005;24:486-93.  Back to cited text no. 58
    
59.
Malaguarnera M, Vacante M, Motta M, Malaguarnera M, Li Volti G, Galvano F Effect of L-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin. Metabolism 2009;58:1618-23.  Back to cited text no. 59
    
60.
Davis RA, Hui TY 2000 George Lyman Duff Memorial Lecture: Atherosclerosis is a liver disease of the heart. Arterioscler Thromb Vasc Biol 2001;21:887-98.  Back to cited text no. 60
    
61.
Ezedi M, Nazem F, Zarifian A, Eghdami A, KHorshidi D The effect of chronic intake of L-carnitine L-tartrate on lipid metabolism during aerobic exercise. J Kerman Univ Med Sci 2010;17:113-20.  Back to cited text no. 61
    
62.
Cristiana P L-carnitine. Health and disease. Am Rev Respir Dis 2004;112:219-49.  Back to cited text no. 62
    
63.
Haghighi A, Foroughian M, Hamedinia M, Ch M The effect of 6 weeks of aerobic training and L-carnitine supplement on body fat percent and serum lipid profiles in active men. J Sport Biosci 2010;2:41-58.  Back to cited text no. 63
    
64.
Patalay M, Lofgren IE, Freake HC, Koo SI, Fernandez ML The lowering of plasma lipids following a weight reduction program is related to increased expression of the LDL receptor and lipoprotein lipase. J Nutr 2005;135:735-9.  Back to cited text no. 64
    
65.
Ginsberg HN, Fisher EA The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism. J Lipid Res 2009;50(Suppl):S162-6.  Back to cited text no. 65
    
66.
Goldberg IJ Clinical review 124: Diabetic dyslipidemia: Causes and consequences. J Clin Endocrinol Metab 2001;86:965-71.  Back to cited text no. 66
    
67.
Sheikhi A, Djafarian K, Askarpour M, Shab-Bidar S The effects of supplementation with L-carnitine on apolipoproteins: A systematic review and meta-analysis of randomized trials. Eur J Pharmacol 2019;858:172493.  Back to cited text no. 67
    
68.
Kremser K, Stangl H, Pahan K, Singh I Nitric oxide regulates peroxisomal enzyme activities. Eur J Clin Chem Clin Biochem 1995;33:763-74.  Back to cited text no. 68
    
69.
Golper TA, Wolfson M, Ahmad S, Hirschberg R, Kurtin P, Katz LA, et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects. Kidney Int 1990;38:904-11.  Back to cited text no. 69
    
70.
Nagashima T, Shigematsu N, Maruki R, Urano Y, Tanaka H, Shimaya A, et al. Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: Improvement of fasting glycemia in diabetic db/db mice. Mol Pharmacol 2010;78:961-70.  Back to cited text no. 70
    
71.
Sugden MC, Holness MJ Therapeutic potential of the mammalian pyruvate dehydrogenase kinases in the prevention of hyperglycaemia. Curr Drug Targets Immune Endocr Metabol Disord 2002; 2:151-65.  Back to cited text no. 71
    
72.
Azimi P, Ghiasvand R, Feizi A, Hariri M, Abbasi B Effects of cinnamon, cardamom, saffron, and ginger consumption on markers of glycemic control, lipid profile, oxidative stress, and inflammation in type 2 diabetes patients. Rev Diabet Stud 2014;11:258-66.  Back to cited text no. 72
    
73.
Hongu N, Sachan DS Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise. J Nutr 2000;130:152-7.  Back to cited text no. 73
    
74.
Chantler S, Griffiths A, Matu J, Davison G, Holliday A, Jones B A systematic review: Role of dietary supplements on markers of exercise-associated gut damage and permeability. PLoS One 2022;17:e0266379.  Back to cited text no. 74
    
75.
Fritz KS, Galligan JJ, Smathers RL, Roede JR, Shearn CT, Reigan P, et al. 4-hydroxynonenal inhibits SIRT3 via thiol-specific modification. Chem Res Toxicol 2011;24:651-62.  Back to cited text no. 75
    
76.
Mattson MP Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol 2009;44:625-33.  Back to cited text no. 76
    
77.
ElGendy AA, Abbas AM Effects of warfarin and L-carnitine on hemostatic function and oxidative stress in streptozotocin-induced diabetic rats. J Physiol Biochem 2014;70:535-46.  Back to cited text no. 77
    
78.
Batsis JA, Apolzan JW, Bagley PJ, Blunt HB, Divan V, Gill S, et al. A systematic review of dietary supplements and alternative therapies for weight loss. Obesity (Silver Spring) 2021;29:1102-13.  Back to cited text no. 78
    
79.
Askarpour M, Hadi A, Miraghajani M, Symonds ME, Sheikhi A, Ghaedi E Beneficial effects of L-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose–response meta-analysis of randomized controlled trials. Pharmacol Res 2020;151:104554.  Back to cited text no. 79
    
80.
Obici S, Feng Z, Arduini A, Conti R, Rossetti L Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 2003;9:756-61.  Back to cited text no. 80
    


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