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Table 1 Human and animal studies involving carnitine supplementation to improve female fertility/reproductive status

From: Role of L-carnitine in female infertility

Study aim Carnitine(s) supplementation (dose and duration) Study design/Subjects Outcomes relevant to reproduction Reference
Human Studies
Single center, prospective study to evaluate whether ALC modulates opiatergic pathway in a group of patients with stress-induced amenorrhea 1 g/day ALC orally for 16 weeks 24 patients (aged 21–32 years) with FHA for the last 6 months were subdivided into 2 groups:
Group A (hypogonadotropic patients, plasma LH levels ≤3 mIU/ml, n = 16)
Group B (normogonadotropic patients, plasma LH levels > 3 mIU/ml, n = 8)
• ALC administration significantly modulates GnRH and LH secretion in hypothalamic amenorrhea in hypogonadotropic patients
• ALC probably affects neuroendocrine control of gonadotropin secretion by modulating opiatergic control of GnRH-LH secretion
• Data support the use of ALC as a therapeutic drug for stress-induced reproductive disorders with low LH levels or hypogonadotropic condition
[17]
Single center, double blinded, randomized controlled clinical trial to evaluate the effectiveness of LC on improving the ovulation and pregnancy rates as well as adverse metabolic indices in clomiphene-resistant PCOS women 3 g/day LC orally from day three until day seven of the cycle 170 clomiphene resistant PCOS women (aged less than 35 years) were randomly allocated into 2 groups:
Group A (n = 85) received 250 mg clomiphene citrate plus LC
Group B (n = 85) received 250 mg clomiphene citrate with placebo
• The combination of LC and CC significantly improved both the ovulation and the pregnancy rates in clomiphene-resistant PCOS women
• The number of stimulated follicles reaching ≥17 mm diameter was significantly higher in Group A as compared to Group B
• Endometrium at the time of hCG administration was significantly thicker in Group A
• Serum E2, on the day of hCG administration, was significantly higher in the LC group
• Pregnancy occurred in 42/85 cycles in Group A (54.5%) and 5/85 cycles in Group B (5.8%) and the difference was statistically significant.
• The miscarriage rate was lower in Group A (2/85; 2.3%) than in Group B (4/85; 4.7%) (p = 0.67)
[11]
Before-after clinical trial to examine the effect of adding LC to PCOS patients who were resistant to clomiphene citrate and gonadotropin 2 g LC orally every 12 h, given from the third day of treatment with clomiphene citrate and gonadotropin until the hCG injection 50 PCOS patients (aged 20–35 years) either received LC or did not receive LC • LC-treated women experienced the growth of dominant follicles (64%, 32/50 therapeutic cycles) and displayed a positive pregnancy test (20%, 10/50 therapeutic cycles)
• LC-supplemented women had increased left ovarian follicle size compared to those without LC, however right ovarian follicle size was not significantly different between both groups
• LC supplementation increased the mean endometrial thickness compared to those without LC.
[18]
Prospective, randomized, double-blind, placebo-controlled trial to determine the effects of oral LC supplementation on weight loss, and glycemic and lipid profiles in women with PCOS 250 mg LC orally for 12 weeks 60 overweight PCOS (aged 18–40 years) were randomized to receive either LC (n = 30) or placebo (n = 30) • LC supplementation reduced body weight, body mass index, waist circumference and hip circumference and improved glycemic control in PCOS patients compared with placebo.
• LC supplementation did not affect lipid profiles or free testosterone levels compared with placebo
[12]
Oral LC supplementation on mental health and biomarkers of OS in women with PCOS 250 mg LC for 12 weeks 60 patients: randomized, double-blind, placebo-controlled study • LC supplementation improved general and mental health parameters
• LC supplementation improved TAC, MDA/TAC ratio and decreased lipid peroxidation
[40]
Animal Studies
LC supplementation on endometriosis in BALB/c mice 25 mg/ml/d LC for 7 days Young female BALB/c mice of 4–8 weeks of age • Increased concentration of LC in serum
• Decreased levels of IFN-γ, TNF-α, IL-6, IL-2
[19]
LC on reproductive hormones and organs of pregnant mice 0.5 and 1.0 mg/kg LC from day-1 until parturition Female Swiss albino mice of 12–14 weeks of age • Significantly increased FSH, LH and estradiol levels
• Increased litter size, weight of reproductive organs and thickness of endometrium
[42]
ALC on HPG axis of female Sprague-Dawley rats 50 mg/kg/d ALC for 2 consecutive estrous cycles Female Sprague-Dawley rats of 3 months of age Improved hormonal secretions through HPG axis: increased GnRH, LH, estradiol and progesterone levels [16]
LC on OS parameters in oophorectomized rats 100 mg/kg/d LC during post-castration day-21 to -35 (14 consecutive days) Female adult Wistar rats Decreased MDA, and NO levels, and improved TAC and OS index [49]
Reproductive performance of sows on LC-supplementation 125 mg/d LC (pregnancy), 250 mg/d LC (lactation) 300 sows (Leicoma) Improved litter size and piglets' body weight gain, decreased number of stillborn piglets [51]
LC in gestating sow diet on fetal development 50 ppm in diet for 3 reproductive cycles, until day-110 of gestation 232 gestating sows Increased leanness and muscle density in offspring [52]
Dietary LC on laying hen performance and egg quality 500 mg/kg LC diet for 84 days 180 Isabrown laying hens of 27-weeks of age Improved egg quality parameters including albumin content [50]
LC on reproductive traits of white leghorns 125 ppm LC until 37-week of age 720 White leghorns Improved total lipid and LC content in yolk [43]
LC in cows during transition and high lactation period 2 g/d LC for 5 weeks 262 dairy cows (German Holstein) Improved metabolic status during lactation period, increased milk protein content [53]
  1. ALC, Acetyl-L-carnitine, FHA, Functional hypothalamic amenorrhea, HPG Hypothalamo-pituitary-gonadal axis, LC L-Carnitine, MDA Malondialdehyde, NO Nitric oxide, OS Oxidative stress, PCOS Polycystic ovary syndrome, SCC Somatic cell count, TAC Total antioxidant capacity