role of micronutrients in infertility, role of carnitine by dr shashwat jani

Micronutrients In Infertility( Role Of Carnitine )

Dr. Shashwat Jani.M. S. ( Obs – Gyn )

Diploma in Advance Laparoscopy.

Consultant Assistant Professor,Smt. N.H.L. Municipal Medical College.

Sheth V. S. General Hospital , Ahmedabad.Mobile : 99099 44160.

E-mail : [email protected]

May 3, 2023 Dr Shashwat Jani 99099 44160. 2

Introduction Many studies and researches have proved that there is a strong positive relationship between Micronutrients & fertility.


• In order to examine the association between micronutrients and infertility, articles with case-control, descriptive, cohort, and interventional (clinical trials) design, published between 1984 and 2014, were accessed through PubMed and Embase databases, using keywords such as “micronutrients “ , "oxidative stress", "antioxidant", "vitamins", "minerals", and "infertility“….


Male Infertility

Nutritional Considerations

• Various micronutrients are

associated with male fertility.

• Deficiency of these

micronutrients may result in

infertility.

Nutritional Factors

Free radical scavengers

L-Carnitine Lycopene

Coenzyme Q10

Vitamin C

Zinc Vitamin E

Arginine Glutathione

Vitamin B12

Selenium

Altern Med Rev. 2000;5(1):28-38.

Role of Micronutrients in Male Fertility

Nutrition plays vital role in maintaining male fertility:

Involved in the successful maturation of sperm

Provides nutrition for motility of sperm

Improvement in sperm count and motility

Helps in production of sex hormones

Prevents sperm damageAltern Med Rev. 2000;5(1):28-38.

L-carnitine

Improves sperm motility by providing energy to the sperm cell through fatty acid metabolism

ZincPromotes sperm production & maturation testosterone synthesis & improves sperm morphology

Ideal Nutraceutical for Male Infertility

Coenzyme Q10Improves sperm motility by providing energy through ATP generation in mitochondrion

LycopeneIncreases sperm count and improves morphology by reducing oxidative damage to sperm DNA and lipids


Female Infertility


Many studies have shown that micronutrient supplements users have higher pregnancy rates even if they have fertility disorders.

It has been suggested that oxidative stress plays a role in the pathophysiology of unexplained infertility, endometriosis, polycystic ovarian syndrome (PCOS), and tubal and peritoneal factor infertility .


Moreover , there is some evidence of micronutrients role in ovarian hormones secretion and uterus structure .

Micronutrients useful in female infertility :Iron Folic acidVit. B Complex, CarnitineVitamins A, D, E, CSelenium , ArginineMagnesium & Zinc


Role Magnesium and Selenium supplementation resulted

in increased levels of RBC-Mg and serum glutathione peroxidase and hence, improved fertility rates .

Vitamin E supplement associated with increase endometrial thickness .

Total iron intake and intake of non-heme iron as well as multivitamin consumption are associated with lower risk of ovulatory infertility.

Furthermore, sufficient levels of vitamin D as well as folic acid supplement had resulted in increased clinical pregnancy rate.


L - Carnitine


Carnitine Trimethylated aminoacid -esterSynthesized in liver, brain, and kidney from

dietary amino acids-methylation of lysine .Most derived from diet: red meat, fish and dairy

productsL-carnitine is concentrated in high energy

demanding tissues such as skeletal and cardiac muscles and in a specialized reproductive tract organ.


L-carnitine is biologically important for mitochondrial beta-oxidation of long-chain fatty acids and thus for energy generation in the form of ATP.


Pharmacokinetics• Absorbed in the intestine by a combination of active

transport and passive dilution.• Mucosal absorption is saturated at about a 2 g dose.

• Max blood concentrations are reached approximately 3.5 hrs after an oral dose, with a half-life of about 15 hrs.

• Stored in skeletal muscles, myocardium, epididymis, liver and adrenal glands.

• Eliminated by kidneys• Bioavailability varied 54-87%


L – Carnitine in Male Infertility


Three compartments of the male genital tract :• Epididymal tissue, • Seminal plasma, and • Spermatozoa maintain the highest free L-carnitine concentrations in the body.


The main function of L-Carnitine in the epididymis is to provide an energetic substrate for spermatozoa.

May be involved in the successful maturation of sperm.

L-Carnitine is necessary for transport of fatty acids into the mitochondria to produce energy.

Low levels of L-Carnitine reduces fatty acid concentrations within the mitochondria, leading to decreased sperm motility

May 3, 2023 20

• Significantly high levels of free L-Carnitine is

observed in the seminal plasma of the fertile men

compared to the infertile men.

• The level of free L-Carnitine in the semen has

positive correlation with sperm concentration, sperm

motility and vitality of sperm cells

• L-Carnitine provides readily available energy for

use by spermatozoa, which positively affects sperm

motility, maturation and the spermatogenesis process.

Dr Shashwat Jani 99099 44160.

Folia Med (Plovdiv). 2005;47(1):26–30. . Zhonghua Nan Ke Xue. 2007;13(2):143–146.

L-Carnitine: Clinical Trials

According to a study conducted by Costa et al. L-carnitine increased the sperm parameters drastically

10.8

28.43.73.1

142.4

1832.5

4.120.3

163.3

020406080

100120140160180

Baseline At 4 months

Motile spermatozoa (%)

Mean velocity (microns)

Linearity index

Spermatozoa with rapidlinear progression (%)Number of ejaculatedspermatozoa

Andrologia.1994;26:155-159.

L- Carnitine for asthenospermia with varicocele

Carnitine

Placebo

Zhonghua Nan Ke Xue. 2004;10(9):671–672.

There was significant improvement in sperm count,motility and pregnancy rates in infertility due to varicocele.

Use of Carnitine therapy in selected cases of male factor infertility: A double-blind

crossover trial

• Patient(s): One hundred infertile patients (ages 20–40 years) with the following baseline sperm selection criteria: concentration, 10–20 X 106/mL; total motility, 10%–30%; forward motility, <15%; atypical forms, <70%; velocity, 10–30 µ/s;

• Interventions : L-Carnitine therapy 2 g/day or placebo;

• Duration : 4 monthsFERTILITY AND STERILITY VOL. 79, NO. 2, FEBRUARY 2003

Total motile sperm/mL

Carnitine

Placebo

FERTILITY AND STERILITY VOL. 79, NO. 2, FEBRUARY 2003

Forward motile sperm/mL

Carnitine

Placebo

FERTILITY AND STERILITY VOL. 79, NO. 2, FEBRUARY 2003

L- Carnitine in idiopathic asthenozoospermia: a multicenter study.

Italian Study Group on Carnitine and Male Infertility.

Andrologia 1994;26:155-159

N = 100 patients L-carnitine - 3 g/day Duration - 4 months. Percentage of motile spermatozoa increased from 26.9 ± 1.1 to 37.7 ± 1.1 %. Total number of spermatozoa per ejaculate also increased

Conclusion - Oral administration of L-Carnitine improves sperm quality


• Mazzilli et al, established strict correlation between intrasperm L-carnitine content and sperm motility survival in bovine cervical mucus. This is possibly due to the fact that lipids are an important energy source for sperm in cervical mucus and to metabolize these lipids intrasperm Lcarnitine is essential.

• L-carnitine not only helps in lipid metabolism but also it modulates the reserves of free CoA, essential for tricarboxylic acid ( TCA ) cycle regulation.

• Therefore, L carnitine content can be considered as an indicator of sperm motility life span in cervical mucus.


Anti Oxidant Property

It is also proposed that carnitine exerts antioxidant properties as a result of repairing mechanism by which elevated intracellular toxic acetyl-CoA is removed and fatty acids in membrane phospholipids are replaced.


Carnitine exerts its anti-apoptotic effects in diverse tissues :• Does carnitine exert anti-apoptotic

effects in the testis?• Which step(s) of apoptosis does

carnitine influence?

Anti-apoptotic effects


Carnitine in irradiated testes

• L- Carnitine enhanced the recovery of spermatogonial cells after X ray damage.

( AmendolaR et al. Andrologia. 1989 Nov.-Dec; (6):568-75. )


Carnitine in heated testis•More rapid recovery of

spermatogenesis after heat treatment with L-ACAR administration.


L – Carnitine in Female Infertility


Polycystic ovary syndrome (PCOS) is often characterized by obesity and impaired insulin function and affects about 7–10% of women during reproductive age.


Obesity may play a role in the aetiology of PCOS, and weight loss has been found to improve some of the clinical aspects of PCOS including menses regularity and fertility, as well as many cardiovascular (CV) risk markers associated with PCOS such as insulin resistance (IR) and dyslipidaemia.

IR affects approximately 65% of women with PCOS and can potentially increase the prevalence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS ).


• L - Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism.

• The potential mechanisms include increasing mitochondrial efflux of excess acyl groups from insulin responsive tissues and facilitating transportation of the long chain free fatty acids into the mitochondrial matrix.


• Some studies have reported that circulating levels of free and total L carnitine were significantly lower in PCOS women.

• In addition, in a study by Ismail et al…. Combined L – carnitine and clomiphene citrate significantly improved both ovulation and cumulative pregnancy rates in patients with clomiphene resistant PCOS.


Intravenous L - Carnitine (4 g/day) among patients with MetS for 7 days resulted in weight loss, improved fasting induced hunger and cholesterol abnormalities.


It’s proven that…12 weeks of L - Carnitine

administration among women diagnosed with PCOS had beneficial

effects on weight, BMI, Waist Circum, Hip Circum. and glycemic control; however, it does not affect lipid

profiles or free testosterone.

Thank you

role of micronutrients in infertility, role of carnitine by dr shashwat jani

Health & Medicine