Cardiovascular diseases are considered the leading cause of mortality among hemodialysis patients. Hypertension, advanced age, diabetes, and other systemic diseases that affect cardiac function are commonly seen in these patients. This article will examine the effects of carnitine on hemodialysis patients.

Additionally, hemodialysis patients often suffer from deficiencies in some essential substances required for the metabolic functions of myocardial cells.

Introduction to Carnitine

Carnitine is a natural substance with its primary physiological role in the body:

It facilitates the transport of long-chain fatty acids from the cytoplasm into mitochondria for their beta-oxidation.
Therefore, sufficient carnitine within cells is essential for the normal metabolism of fatty acids in the human body. This is especially important in tissues like the heart and skeletal muscles, which depend on fatty acid metabolism to produce energy.

Key Features and Roles of Carnitine

1. Fat Metabolism: Carnitine plays a role in transporting fatty acids into mitochondria for beta-oxidation (the process of producing energy from fatty acids). This process is essential for energy production in daily activities.
2. Support for the Cardiovascular System: The heart, as the main blood pump in the human body, requires a constant supply of energy. Carnitine helps by transporting fatty acids into the mitochondria of the myocardium (heart muscle), improving energy supply and potentially improving cardiovascular function.
3. Regulation of Glucose Metabolism: The breakdown of fats by carnitine can help reduce glucose utilization as an energy source, which may be beneficial in improving blood sugar control.
4. Oxidative Balance: Carnitine acts as a natural antioxidant, helping to maintain oxidative balance within cells and preventing oxidative damage.
5. Body Composition Support: Carnitine supplementation can help reduce abdominal fat and improve overall body composition.

Biological Function in Humans

In the human biological system, carnitine exists in two forms:

1. Free form
2. Esterified form

In hemodialysis patients, unlike healthy individuals, the esterified form of carnitine is more prevalent than the free form. This is due to the loss of free carnitine through the dialysis membrane. As a result, despite normal plasma levels of total carnitine, the accumulation of the esterified form and the reduction in free carnitine leads to lower carnitine levels in tissues (including the heart and skeletal muscles).

Effects of Carnitine Administration

Various studies have investigated the effects of carnitine administration (either intravenously or orally) in hemodialysis patients or those with heart failure. One such study found that carnitine had a significant effect on improving anemia in hemodialysis patients.

Effects of Low Dose Oral Carnitine Administration

A study conducted by researchers showed that administering a low dose of oral L-carnitine (500 mg per day) for six months resulted in improvement in:

• Patient symptoms
• Increased LVEF (Left Ventricular Ejection Fraction)
• Decreased left ventricular mass

Given the mixed results regarding the effects of carnitine on cardiac function, further studies are necessary to evaluate its impact on heart function.

Results on the Cardiac Systolic Function in Hemodialysis Patients with Heart Failure

This study, conducted on hemodialysis patients, examined the effect of oral carnitine administration on the systolic function of the heart in these patients with heart failure.

In addition, the impact of carnitine administration on:

• Cardiac symptoms
• Anemia
• Hyperlipidemia

was also assessed simultaneously in these patients. A total of 20 patients participated in the study, divided into control and intervention groups. They were studied for six months.

Inclusion criteria for the patients were having an LVEF (Left Ventricular Ejection Fraction) of less than 50%. Patients with heart failure due to other specific causes, such as congenital heart diseases or valvular heart disorders, were excluded from the study. After adjusting for variables such as:

• Age
• Gender
• Cause of kidney failure
• Hypertension
• Diabetes, etc.

patients were randomly assigned to the intervention and control groups.

Drug Administration to Patients

After selecting patients and dividing them into two groups (intervention and control), the intervention group was given 250 mg carnitine tablets with a dose of 1 gram per day.

The control group received a placebo in the same form as the carnitine but without carnitine.

Other medications commonly used by these patients, including:

• Rokatrol tablets
• Ferrous sulfate tablets
• Calcium carbonate tablets
• Folic acid tablets
• Eprex injections
• Antihypertensive medications

were continued, and no changes were made to the doses. Efforts were made to ensure the medication types were similar between the two groups.

Results Regarding Ejection Fraction

The results obtained regarding:

• Ejection fraction
• Left ventricular end-diastolic diameter
• The ratio of cardiac diameter to chest diameter on chest X-ray
• Hemoglobin levels
• Triglycerides
• Plasma cholesterol

were compared using repeated-measures analysis of variance and Bonferroni post-hoc tests. To compare between the two groups, Student’s t-test was used.

According to the studies, low-dose oral carnitine (500 mg/day for six months) significantly improved cardiac symptoms and function in hemodialysis patients.

Conclusion

The difference in the results of this study compared to previous research might be due to:

• The ejection fraction level, which in our study was set to less than 50%, whereas in the Matsumoto study it was set to less than 60%. This means the cardiac function of patients in our study was lower initially.
• The carnitine dose in their study was almost half of the dose used in our study.

Another study examined the effect of intravenous carnitine on serum triglyceride levels and showed that carnitine is effective only in patients with hypertriglyceridemia.

Research Results

According to the studies, only oral carnitine has a significant and beneficial effect on improving anemia. Researchers found that carnitine helps:

• Reduce fatigue
• Increase exercise tolerance

Given the importance of cardiovascular problems in hemodialysis patients, which is the leading cause of mortality in these patients, further studies are necessary to evaluate the effect of carnitine in improving the cardiac condition of these patients.

The Effect of L-Carnitine on Improving Sperm Quality in Infertile Men

One of the major issues in medical science is infertility and reduced fertility. This article explores the effect of L-carnitine in improving sperm quality in infertile men.

Definition of Infertility Infertility refers to the inability to achieve pregnancy after one year of regular unprotected intercourse.

Overview of the Infertile Population Infertility is observed in 10% to 15% of people and constitutes a significant aspect of clinical medicine for many doctors. In 40% of infertility cases, male infertility is a key factor, and since sperm production disorders are the leading cause of male infertility, correcting these disorders is critical to helping couples achieve pregnancy.

Male Fertility Evaluation The chosen method for evaluating male fertility is sperm analysis, which should be conducted using at least two samples with a minimum gap of four weeks. Unfortunately, the cause of infertility in most men remains unknown, which is simply a reflection of the very limited understanding of the mechanisms governing testicular function and spermatozoa production. Other methods like IVF, ZIFT, and ICSI have allowed for fertilization and addressed many infertility problems, but the cost of these treatments is high.

Drug Treatments for Infertility Drug treatments are more affordable and available to a broader range of couples. Some oral treatments improve sperm count and motility. Drugs like L-carnitine, arginine, zinc, and various antioxidants such as selenium, Vitamin B12, Coenzyme Q10, glutathione, Vitamin E, and Vitamin C are known to be effective in improving sperm quality. L-carnitine is a derivative of the amino acids lysine and methionine and is found in meat and dairy products. It was first isolated from beef in 1905.

How Free L-Carnitine Works Free L-carnitine is essential for the beta-oxidation of long-chain fatty acids in mitochondria. Fatty acids must first be activated (attached to coenzyme A) before entering mitochondria. Once inside the mitochondria, beta-oxidation and adenosine triphosphate (ATP) production begin. L-carnitine also helps protect DNA and cell membranes from damage caused by free oxygen radicals. The highest concentration of carnitine in the human body is found in the epididymis, where its concentration is 2000 times higher than in blood. Several studies have shown a reduction in carnitine levels in the semen of infertile men.

Study Methodology Variables: In this study, variables were recorded in a form completed for each participant, including age, duration of infertility, semen volume, sperm concentration (count per milliliter), total motility (percentage of motile sperm), forward motility, percentage of sperm with normal morphology, and side effects such as nausea, vomiting, abdominal discomfort, and diarrhea.

Study Entry Criteria Based on WHO criteria, an abnormal spermogram was defined as follows in at least two samples taken four weeks apart:

• Sperm count less than 20 million per milliliter
• Total sperm motility less than 50%
• Forward sperm motility less than 25%
• Normal sperm morphology less than 30%
• Normal levels of gonadotropins, testosterone, and prolactin

Study Exclusion Criteria

• Underlying conditions like varicocele grades 3 and 4, testicular atrophy, ejaculation disorders
• Any medication use in the past two months
• Patients with azoospermia, endocrine or anatomical disorders, or infections
• Patients eligible for ICSI due to severe spermogram disorders and other infertility factors

Sample Size The sample size was set at 30 participants based on previous studies.

Placebo Characteristics The placebo was identical to the carnitine in terms of color, smell, taste, and appearance. Carnitine itself has no significant side effects, but previous studies have noted the possibility of side effects like nausea, vomiting, abdominal discomfort, and diarrhea. Patients were fully informed about these potential side effects.

Patient Grouping and Treatment Procedure Patients were randomly divided into two groups, A and B. Grouping and drug or placebo administration were done by one of the nurses, and other team members were unaware. Group A received L-carnitine tablets at a daily dose of 2 grams, while group B received the placebo. Treatment continued for two months, followed by a two-month break. After the break, the treatment was switched, and the groups continued for another two months. For each patient, a spermogram sample was taken before entering the study and at the end of every two-month period, making a total of four spermogram samples.

Male Reproductive Function Over the past decade, there has been significant progress in understanding male reproductive function and the importance of male factors in infertility.

Treatable Disorders by Medication Many infertile men have treatable disorders that can be addressed with proper diagnosis and drug treatment, leading to natural fertilization. The current study found that carnitine had a positive effect on improving abnormal sperm analysis parameters, especially in sperm motility and forward motility.

Study Results (2003 Cross-over Method) A similar study in 2003 used a cross-over method and involved 86 patients with spermogram disorders. This study found that carnitine had a positive effect on sperm count and motility, especially in patients with more severe disorders. The study concluded that in cases with more severe spermatozoa production disorders and mitochondrial metabolism defects, increasing intracellular carnitine levels is beneficial. However, no significant change was observed in sperm morphology.

Study Findings The study showed that L-carnitine treatment did not cause a significant increase in carnitine levels in semen, as carnitine acts intracellularly, and its concentration is already high in the epididymis. A minor increase in carnitine in the semen might not be statistically significant, but biologically it could have a significant impact.

Comparison Between Two Groups Comparison of the two groups showed that those receiving the drug (who initially received placebo) experienced an increase in sperm count and motility, which was statistically significant.

Conclusion of Current Study The current study showed that the most noticeable effect of carnitine was on sperm motility, likely due to its known mechanisms in energy production and antioxidant activity. This effect was particularly clear during the drug withdrawal period, where a decrease in motility was evident. In the group that initially received carnitine, a decrease in sperm count and motility was observed during the placebo period.

Spermatogenesis Cycle Since the spermatogenesis cycle lasts 74 days, a two-month break was sufficient to clear the effects of the drug and placebo and allow for re-evaluation of the spermogram. The mechanism of carnitine’s effect is not fully understood, but it might relate to its impact on epididymal conditions, reducing gamete phagocytosis and increasing sperm count. Further studies are needed to explore its role in the spermatogenesis process.

Conclusion L-carnitine has a beneficial effect in increasing sperm count and motility, especially forward motility, in patients with unexplained spermogram abnormalities. However, further studies with a larger sample size and varying motility levels are needed.

References: Amiri I, Mahmodi R, Babalhavaeji H, Sheikh N, Najafi R. Effects of Carnitine on Sperm Parameters of Infertile Males with Idiopathic Asthenospermia. Armaghan J 2008; 12(4):65-7

Diabetes and Impaired Glucose Tolerance in Liver Patients

Disruption in carbohydrate metabolism is quite common in patients with cirrhosis. Disturbances in glucose metabolism in cirrhotic patients have been frequently discussed in references and articles, particularly regarding fasting and food consumption.

Prevalence of Diabetes and Glucose Tolerance Disorders: The prevalence of diabetes and glucose intolerance in these patients varies widely. In fact, laboratory methods and diagnostic criteria for glucose metabolism disorders in various studies have not been uniform, and these criteria have been revised several times in recent decades. This article examines diabetes and glucose disorders in liver patients.

Liver Disease and Glucose Tolerance: Many studies examining the relationship between liver disease and glucose tolerance have noted that several potential factors influencing the onset of diabetes, which could be considered intervening factors, have not been addressed. In this study, we examine the prevalence of diabetes and glucose intolerance in patients with chronic liver disease using the latest diagnostic criteria. The independent relationship between chronic liver disease and diabetes, considering other potential risk factors for diabetes, is also explored. Additionally, this study investigates factors specifically related to the onset of diabetes in liver patients.

Onset of Diabetes: Before or After Liver Disease? Since both diabetes and chronic liver disease are often asymptomatic until advanced stages, it is generally difficult to determine whether:

• Diabetes onset occurs before or after liver disease?

Researchers have gathered information showing that, in some patients, diabetes is diagnosed either simultaneously with or after cirrhosis.

Importance and Necessity of Screening: The prevalence of diabetes in cirrhosis and chronic hepatitis groups is significantly related to the severity of liver disease. This finding suggests that liver fibrosis, rather than necessarily cirrhosis, may initiate the process of glucose intolerance. It’s interesting to note that although the exact mechanism of glucose intolerance in cirrhosis is not yet fully understood, insulin resistance and reduced receptor sensitivity have been observed.

Insulin Resistance: Insulin resistance is observed in the early stages of chronic hepatitis. Another study examining chronic hepatitis patients with normal glucose tolerance showed a strong correlation between insulin resistance and the degree of fibrosis.

Chronic Hepatitis as an Independent Factor for Diabetes: All these findings confirm that chronic hepatitis is an independent factor for diabetes, and the development of diabetes in these patients is related to the severity of liver disease.

Diabetes and Liver Disease: This study did not find a relationship between diabetes and the cause of liver disease. Some studies have reported a correlation between Hepatitis C infection and higher rates of diabetes, but these findings are not yet definitive. A retrospective study involving 1,117 patients with chronic HCV hepatitis found a relatively strong relationship between diabetes and HCV infection. This study suggested that, independent of its role in chronic liver disease, HCV may play an important role in the onset of diabetes. However, there are also studies presenting findings contrary to this conclusion.

Development of Diabetes in Cirrhotic Patients: The prevalence of diabetes in cirrhosis patients caused by Hepatitis C was significantly higher than in those with cholestatic liver disease. However, there was no significant difference in the rate of diabetes in Hepatitis C cirrhosis patients compared to alcohol-related cirrhosis patients. This suggests that the development of diabetes in cirrhotic patients is closely related to the underlying cause of liver disease. A study did not find a correlation between the cause of liver disease and diabetes in either the cirrhosis or chronic hepatitis groups. However, future studies will likely provide more insights into the relationship between diabetes and the underlying liver disease.

BMI as an Independent Variable: In patients with chronic hepatitis, BMI was identified as an independent variable related to diabetes. Some studies have shown that obesity may be a potential risk factor for liver fibrosis in chronic hepatitis. However, our study found that high BMI may play a distinct role in the pathogenesis of diabetes in chronic hepatitis, independent of liver fibrosis. Furthermore, serum lipids, including plasma free fatty acids and glycerol concentrations, were found to be higher in diabetic cirrhotic patients.

Family History as a Factor in Diabetes: Family history of diabetes is a well-known risk factor. Our study showed that even when the variable of family history of diabetes was included in the regression model, the relationship between cirrhosis and chronic hepatitis with diabetes remained significant. Other studies have confirmed this result, suggesting that liver injury in chronic liver disease is an independent risk factor for diabetes, with family history only acting as a secondary factor.

Age as a Risk Factor for Type 2 Diabetes: Age is a well-known risk factor for Type 2 diabetes, and it was expected that this would also be true for chronic liver disease patients. However, the relative risk of cirrhosis and chronic hepatitis was found to be higher than that of age, indicating a stronger relationship between liver disease and diabetes.

Onset of Diabetes During Interferon Treatment: Some studies have previously reported the onset of diabetes during interferon treatment, but evidence is still lacking. In our study, interferon treatment did not significantly affect the prevalence of diabetes.

Conclusion: Overall, the results indicate a relatively high prevalence of diabetes in patients with chronic liver disease. Given that a significant number of these patients are unaware of their condition, regular screening is highly recommended. For advanced cases, shorter intervals for screening should be considered due to the higher risk of developing diabetes. Weight reduction in chronic hepatitis patients could potentially prevent the onset of diabetes, and doctors should advise these patients to engage in continuous weight reduction measures. Based on the findings of this study, further research should focus on identifying the pathophysiology of diabetes in chronic liver disease patients and the role of viral hepatitis and liver disease severity in the development of diabetes and possibly insulin resistance.

References:

• Alavian S M, Hajarezadeh B, Nematizadeh F, Larijani B. DIABETES AND IMPAIRED GLUCOSE TOLERANCE IN CHRONIC LIVER DISEASE. ijdld 2004; 3 (1): 57-70.