This case trial reports the effects of L-carnosine supplementation on neuromuscular performance, brain metabolism, and various patient- and clinician-reported outcomes in a case series of patients with multiple sclerosis (MS). Two women (aged 37 and 48) and a man (age 48 years) who fulfilled the 2017 McDonald criteria for MS diagnosis, and were free of other major chronic diseases or acute disorders were recruited for this case study. The duration of illness was 4 years in CASE 1 (37-year old women), 5 years in CASE 2 (48-year old men), and 15 years in CASE 3 (48-year old women). L-carnosine (2 g/day) was administered orally during 8 weeks in all MS patients. The trial was registered at ClinicalTrials.gov (ID NCT03995810). The intensity of symptoms and signs of MS after L-carnosine administration diminished in 5 out of 7 domains in CASE 1, in 3 out of 7 domains in CASE 2, and one domain in CASE 3; general fatigue has been reduced in all three cases at the follow-up. The Visual Analog Scale scores for numbness, weakness, pain, and depression decreased in all MS patients at post-administration. This was accompanied by an improved walking distance to exhaustion in all patients, with values improved for 51.1% in CASE 1, 19.5% in CASE 2, and 2.1% in CASE 3 at 8-week follow-up. An increase in serum total antioxidant capacity was found at 8-week follow-up in all patients (from 4.6 to 49.6%); this was accompanied by lower blood lactates at follow-up in all cases (23.5% on average). Single-voxel 1.5 T MRS revealed an increased brain choline-contained compounds (18.9% on average), total creatine (21.2%), and myo-inositol levels (12.3%) in girus cinguli at 8-week follow; this was accompanied by a drop in brain glutamate for 22.6% on average. This case report suggests the favorable effects of medium-term L-carnosine as a possible adjuvant treatment to improve selected patient- and clinician-reported outcomes in a man and two women suffering from MS. There is a need for larger and more rigorous human intervention studies to corroborate these preliminary findings. This study was funded by the Serbian Ministry of Education, Science and Technological Development (#175,037); the Provincial Secretariat for Higher Education and Scientific Research (#114–451-710); the Faculty of Sport and Physical Education, Novi Sad; and CarnoMed LLC, Novi Sad.

Abstract A novel creatine blend (creatine nitrate mixed with creatinine, CN‐CRN) has been anecdotally suggested to be superior to traditional creatine formulations for bioavailability and performance. However, does CN‐CRN supremely affects creatine levels in the blood and skeletal muscle of healthy humans remain currently unknown. This randomized, controlled, double‐blind, crossover trial evaluated the acute effects of single‐dose CN‐CRN on serum creatine levels, and 5‐days intervention with CN‐CRN on skeletal muscle creatine and safety biomarkers in healthy men. Ten healthy young men (23.6 ± 2.9 years) were allocated to receive either CN‐CRN (3 grams of creatine nitrate mixed with 3 grams of creatinine), pure creatine nitrate (3 grams, CN), or regular creatine monohydrate (3 grams, CRM) by oral administration. We found that CN‐CRN resulted in a more powerful rise in serum creatine levels comparing to either CN or CRM after a single‐dose intervention, as evaluated with the area under the concentration–time curve calculation (701.1 ± 62.1 (µmol/L) × min versus 622.7 ± 62.9 (µmol/L) × min versus 466.3 ± 47.9 (µmol/L) × min; p < .001). The peak serum creatine levels at 60‐min sampling interval were significantly higher in CN‐CRN group (183.7 ± 15.5 µmol/L), as compared to CN group (163.8 ± 12.9 µmol/L) and CRM group (118.6 ± 12.9 µmol/L) (p < .001). This was accompanied by a significantly superior increase in muscle creatine levels after CN‐CRN administration at 5‐days follow‐up, as compared to CN and CRM, respectively (9.6% versus 8.0% versus 2.1%; p = .01). While 2 out of 10 participants were found to be nonresponsive to CN intervention (20.0%) (e.g., no amplification in muscle creatine levels found at 5‐days follow‐up), and 3 participants out of 10 were nonresponsive in CRM trial (30%), no nonresponders were found after CN‐CRN administration, with individual upswing in total muscle creatine varied in this group from 2.0% (lowest increment) to 16.8% (highest increment). Supplemental CN‐CRN significantly decreased estimated glomerular filtration rate (eGFR) at 5‐days follow‐up, as compared to other interventions (p = .004), with the average reduction was 14.8 ± 7.7% (95% confidence interval; from 9.3 to 20.3). Nevertheless, no single participant experienced a clinically relevant reduction in eGFR (< 60 ml/min/1.73 m2) throughout the course of the trial. Liver enzymes remained in reference ranges throughout the study, with no participant experienced high liver blood tests (e.g., AST > 40 units per L or ALT >56 units per L). Besides, no participant reported any major side effects during the trial, while the odors of CN‐CRN and CN formulations were considered somewhat unpleasant in 8 out of 10 participants (80.0%). Our results suggest that CN‐CRN is a preferred and relatively safe alternative to traditional creatine formulations for improved creatine bioavailability in the blood and skeletal muscle after single‐dose and 5‐days interventions.