Sergej Ostojic

• Baltic, Sonja; Nedeljkovic, David; Todorovic, Nikola; Ranisavljev, Marijana; Korovljev, Darinka & Cvejic, Jelena [Show all 11 contributors for this article] (2024). The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 28(8). doi: 10.1016/j.jnha.2024.100287.
• Ostojic, Sergej; Grasaas, Erik; Baltic, Sonja & Cvejic, Jelena (2024). Dietary creatine is associated with lower serum neurofilament light chain levels. Applied Physiology, Nutrition and Metabolism. ISSN 1715-5312. doi: 10.1139/apnm-2024-0064.
• Ostojic, Sergej; Slankamenac, Jelena; Ranisavljev, Marijana; Todorovic, Nikola; Stajer, Valdemar & Candow, Darren G [Show all 9 contributors for this article] (2024). Eight-week creatine-glucose supplementation alleviates clinical features of long COVID. Journal of Nutritional Science and Vitaminology. ISSN 0301-4800. 70(2), p. 174–178. doi: 10.3177/jnsv.70.174.
• Kurniawan, Adi; Ostojic, Sergej; Shinde, Sachin; Laxy, Michael; Neumann, Christine & Berhane, H. [Show all 13 contributors for this article] (2024). Enhancing adolescent and youth health through nutrition fluency in Sub-Saharan Africa: ARISE-NUTRINT initiative. Perspectives in Public Health. ISSN 1757-9139. doi: 10.1177/17579139241251636.
• Ostojic, Sergej; Stea, Tonje Holte; Ellery, Stacey & Smith-Ryan, Abbey (2024). Association between dietary intake of creatine and female reproductive health: Evidence from NHANES 2017–2020. Food Science & Nutrition. ISSN 2048-7177. doi: 10.1002/fsn3.4135.
• Ostojic, Sergej & Vranes, Milan (2024). Molecular hydrogen content of different dietary supplements. Czech Journal of Food Sciences. ISSN 1212-1800. 42(2), p. 136–140. doi: 10.17221/16/2024-CJFS.
• Grasaas, Erik; Ostojic, Sergej & Jahre, Henriette (2024). Adherence to sleep recommendations is associated with higher satisfaction with life among Norwegian adolescents. BMC Public Health. ISSN 1471-2458. 24(1). doi: 10.1186/s12889-024-18725-1.
• Kurniawan, Adi Lukas; Ranisavljev, Marijana; Partap, Uttara; Shinde, Sachin; Ferrero, Elisabetta & Ostojic, Sergej [Show all 12 contributors for this article] (2024). Community-based interventions targeting multiple forms of malnutrition among adolescents in low-income and middle-income countries: protocol for a scoping review. BMJ Open. ISSN 2044-6055. 14(3). doi: 10.1136/bmjopen-2023-078969.
• Fernández-Landa, Julen; Todorovic, Nikola; Santibañez-Gutierrez, Asier; Ostojic, Sergej; Calleja-González, Julio & Sekulic, Djordje [Show all 7 contributors for this article] (2024). Effects of HMB on Endurance Performance in a Healthy Population: A Systematic Review and Meta-Analysis. Journal of Strength and Conditioning Research. ISSN 1064-8011. 38(4), p. E202–E210. doi: 10.1519/JSC.0000000000004690.
• Andjelic, Bogdan; Todorovic, Nikola; Panic, Jovana; Vranes, Milan & Ostojic, Sergej (2024). Video Gaming Reduces Circulating Creatine Levels in Young Male E-Gamers. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 14(1), p. 59–62. doi: 10.14740/jem923.
• Ostojic, Sergej; Ratgeber, Laszlo; Trunic, Nenad & Rajkovic, Sava (2023). Cataloguing guanidinoacetic acid content in nutritional supplements. Food Science & Nutrition. ISSN 2048-7177. 11(4), p. 1603–1605. doi: 10.1002/FSN3.3206. Full text in Research Archive
• Candow, Darren G.; Prokopidis, Konstantinos; Forbes, Scott C.; Rusterholz, Flavia; Campbell, Bill I. & Ostojic, Sergej (2023). Resistance Exercise and Creatine Supplementation on Fat Mass in Adults < 50 Years of Age: A Systematic Review and Meta-Analysis. Nutrients. ISSN 2072-6643. 15(20). doi: 10.3390/nu15204343. Full text in Research Archive Show summary

  The combination of resistance exercise and creatine supplementation has been shown to decrease body fat percentage in adults ≥ 50 years of age. However, the effect on adults < 50 years of age is currently unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo on fat mass and body fat percentage Twelve studies were included, involving 266 participants. Adults (<50 years of age) who supplemented with creatine and performed resistance exercise experienced a very small, yet significant reduction in body fat percentage (−1.19%, p = 0.006); however, no difference was found in absolute fat mass (−0.18 kg, p = 0.76). Collectively, in adults < 50 years of age, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat percentage without a corresponding decrease in absolute fat mass.

• Øverby, Nina Cecilie; Hillesund, Elisabet Rudjord; Medin, Anine Christine; Vik, Frøydis Nordgård & Ostojic, Sergej (2023). Nutrition in a lifecourse perspective: From molecular aspects to public health approaches. Maternal & Child Nutrition. ISSN 1740-8695. 20(S2). doi: 10.1111/mcn.13582. Full text in Research Archive
• Korovljev, Darinka; Javorac, Dejan; Todorovic, Nikola; Ranisavljev, Marijana; Engeset, Dagrun & Stea, Tonje Holte [Show all 15 contributors for this article] (2023). The Effects of 12-Week Hydrogen-Rich Water Intake on Body Composition, Short-Chain Fatty Acids Turnover, and Brain Metabolism in Overweight Adults: A Randomized Controlled Trial. Current Topics in Nutraceuticals Research. ISSN 1540-7535. 21(3), p. 235–241. doi: 10.37290/ctnr2641-452X.21:235-241. Full text in Research Archive Show summary

  The aim of this randomized controlled trial was to analyze the effects of medium-term supplementation with hydrogen-rich water on brain metabolism, appetite-regulating hormones, body composition, and safety biomarkers in overweight adults. Twenty (n = 20, 10 females) apparently healthy adults with a body mass index >24.9 kg/m2 were assigned to receive 0.5 L per day of hydrogen-rich water (7.5 mg of hydrogen) or hydrogen-free water (tap water) for 12 weeks. Two-way analysis of variance with repeated measures revealed a significant difference between the two interventions in several body composition indices (P ≤ 0.05), with hydrogen-rich water superior to placebo to reduce waist circumference and mid-upper arm circumference by 1.31 cm (95% confidence interval, from –0.23 to 2.85) and 0.65 cm (95% confidence interval, from –0.10 to 1.40), respectively. Hydrogen-rich water outcompeted placebo to raise serum ghrelin levels, as the mean difference from the placebo group was 17.28 pmol/L (95% confidence interval, from 1.81 to 32.75) (P = 0.02). A non-significant strong positive trend (P = 0.10) was reported toward hydrogen-rich water being superior to placebo in augmenting total serum short-chain fatty acid levels, with a mean difference from the control group of 195.6 μmol/L (95% confidence interval, from –64.55 to 275.85). The mean fecal calprotectin levels were significantly reduced after hydrogen-rich water intervention for 19.7 μg/mg (95% confidence interval, from 0.31 to 39.09) (P = 0.03). Our findings advance hydrogen-rich water as a promising metabolic intervention in overweight adults, but further validation via multicentric longitudinal randomized controlled trials in metabolic and nutritional disorders is required.

• Korovljev, Darinka; Todorovic, Nikola; Ranisavljev, Marijana; Andjelic, Bogdan; Kladar, Nebojsa & Stajer, Valdemar [Show all 7 contributors for this article] (2023). Hydrogen-rich water upregulates fecal propionic acid levels in overweight adults. Nutrition - The International Journal of Applied and Basic Nutritional Sciences. ISSN 0899-9007. 116. doi: 10.1016/j.nut.2023.112200.
• Slankamenac, Jelena; Ranisavljev, Marijana; Todorovic, Nikola; Ostojic, Jelena; Stajer, Valdemar & Ostojic, Sergej (2023). Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome. Food Science & Nutrition. ISSN 2048-7177. doi: 10.1002/fsn3.3597. Full text in Research Archive Show summary

  Dietary creatine has been recently put forward as a possible intervention strategy to reduce post-COVID-19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel-group, randomized placebo-controlled double-blind trial, we analyzed the effects of 6-month creatine supplementation (4 g of creatine monohydrate per day) on various patient- and clinician-reported outcomes, and tissue creatine levels in 12 patients with post-COVID-19 fatigue syndrome. Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3-month and 6-month follow-ups (p < .05). Two-way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels (p < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter. Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values (p = .04), and significantly improved scores for several post-COVID-19 fatigue syndrome-related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6-month follow-up (p < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post-COVID-19 fatigue syndrome; additional studies are warranted to confirm our findings in various post-COVID-19 cohorts.

• Korovljev, Darinka; Ostojic, Jelena; Todorovic, Nikola & Ostojic, Sergej (2023). Molecular hydrogen modulates brain glutamate/ GABA-glutamine cycle in overweight humans. Archives of Medical Science. ISSN 1734-1922. 19(4), p. 1151–1153. doi: 10.5114/aoms/162938. Full text in Research Archive Show summary

  Introduction: We evaluated whether 12-week intake of molecular hydrogen (H2 ) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2 ) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods: A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results: The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2 ) followed-up in the past without this treatment. Conclusions: We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

• Ranisavljev, Marijana; Todorovic, Nikola; Panic, Jovana; Andjelic, Bogdan; Vranes, Milan & Ostojic, Sergej (2023). Short-term fasting affects biomarkers of creatine metabolism in healthy men and women. Human Nutrition & Metabolism. ISSN 2666-1497. 34. doi: 10.1016/j.hnm.2023.200217.
• Todorovic, Nikola & Ostojic, Sergej (2023). Reconsidering molecular hydrogen deficits: A potential target for intervention? Medical Hypotheses. ISSN 0306-9877. 177. doi: 10.1016/j.mehy.2023.111116. Show summary

  Molecular hydrogen (H2, dihydrogen) is considered an antioxidant and signaling molecule that possesses potent antioxidative, antiapoptotic, and anti-inflammatory properties. Despite the growing interest in H2 as a potential therapeutic agent, there is a scarcity of fundamental studies on dihydrogen and limited knowledge regarding its effects on cellular health and function. In this paper, we propose a hypothesis concerning the potential link between H2 shortage and overall health status. The primary objective is to address two critical questions: first, what is the overall significance of H2 levels in maintaining optimal cellular function, and second, whether specific health conditions are associated with H2 deficiencies. Further validation is necessary to establish the relationship between H2 levels and health, yet the growing body of evidence indicates that disturbances in H2 turnover may have a modulatory effect on immune function, homeostasis, and the development of neurodegenerative diseases.

• Ostojic, Sergej; Grasaas, Erik & Jelena, Cvejic (2023). Dietary creatine and cancer risk in the U.S. population: NHANES 2017–2020. Journal of Functional Foods. ISSN 1756-4646. 108. doi: 10.1016/j.jff.2023.105733. Full text in Research Archive Show summary

  While creatine is generally considered a safe dietary compound, there have been concerns about excessive creatine intake and its possible link to cancer. The main of this study was to examine the relationship between dietary creatine intake and cancer risk in the general US population using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset that included information on medical conditions and dietary intake from 7,344 NHANES respondents. We used individual data files containing detailed information about each food and beverage item consumed to calculate creatine intake from meat- and milk-based food sources. In a subset of NHANES respondents who reported their cancer status, the average daily creatine intake was 11.6 ± 11.5 mg per kg body mass (95 % CI, 11.3 to 11.8); all participants in the subset were 20 years or older. Cancer-free individuals consumed significantly more creatine per day than those with cancer (11.7 ± 11.6 mg/kg body mass vs. 10.6 ± 10.2 mg/kg body mass; P = 0.01). The odds ratio for having cancer in the subset of participants consuming < 10.5 mg of creatine per kg body mass daily (the 50th percentile of consumption) compared to those with higher intake (≥10.5 mg) was 1.18 (95 % CI, from 1.01 to 1.37), indicating a significant association between lower dietary creatine intake and increased cancer risk (P = 0.03). Our findings suggest that consuming a diet that includes more creatine may be associated with a reduced risk of cancer or malignancy in U.S. adults aged 20 years and over, with the average difference in creatine intake between cancer-free individuals and cancer groups was relatively small (1.1 mg/kg body mass). Further studies are necessary to confirm the potential benefits of creatine-rich foods or dietary supplements in the management of cancer.

• Candow, Darren G.; Forbes, Scott C.; Ostojic, Sergej; Prokopidis, Konstantinos; Stock, Matt S. & Harmon, Kylie K. [Show all 7 contributors for this article] (2023). “Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function. Sports Medicine. ISSN 0112-1642. doi: 10.1007/s40279-023-01870-9. Full text in Research Archive Show summary

  There is emerging interest regarding the potential beneficial effects of creatine supplementation on indices of brain health and function. Creatine supplementation can increase brain creatine stores, which may help explain some of the positive effects on measures of cognition and memory, especially in aging adults or during times of metabolic stress (i.e., sleep deprivation). Furthermore, creatine has shown promise for improving health outcome measures associated with muscular dystrophy, traumatic brain injury (including concussions in children), depression, and anxiety. However, whether any sex- or age-related differences exist in regard to creatine and indices of brain health and function is relatively unknown. The purpose of this narrative review is to: (1) provide an up-to-date summary and discussion of the current body of research focusing on creatine and indices of brain health and function and (2) discuss possible sex- and age-related differences in response to creatine supplementation on brain bioenergetics, measures of brain health and function, and neurological diseases.

• Ostojic, Sergej; Ratgeber, Laszlo; Betlehem, Jozsef & Acs, Pongrac (2023). Molecular nutrition in life course perspective: Pinpointing metabolic pathways to target during periconception. Maternal & Child Nutrition. ISSN 1740-8695. 20(52). doi: 10.1111/mcn.13474. Full text in Research Archive Show summary

  Lifecourse nutrition encompasses nourishment from early development into parenthood. From preconception and pregnancy to childhood, late adolescence, and reproductive years, life course nutrition explores links between dietary exposures and health outcomes in current and future generations from a public health perspective, usually addressing lifestyle behaviours, reproductive well-being and maternal-child health strategies. However, nutritional factors that play a role in conceiving and sustaining new life might also require a molecular perspective and recognition of critical interactions between specific nutrients and relevant biochemical pathways. The present perspective summarises evidence about the links between diet during periconception and next-generation health and outlines the main metabolic networks involved in nutritional biology of this sensitive time frame.

• Todorovic, Nikola; Fernández-Landa, Julen; Santibañez, Asier; Kura, Branislav; Stajer, Valdemar & Korovljev, Darinka [Show all 7 contributors for this article] (2023). The Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis. Pharmaceuticals. ISSN 1424-8247. 16(2). doi: 10.3390/ph16020142. Full text in Research Archive Show summary

  Over the last two decades, a plethora of disease models and human studies have confirmed the beneficial effects of molecular hydrogen (H2), a simple biotherapeutic gas. Recent small-scale studies evaluating the effects of hydrogen-rich water (HRW) on various metabolic conditions pointed to advantageous effects of HRW in regulating blood lipid profiles. However, to the best of the authors’ knowledge, no systematic review and/or meta-analysis (SRMA) were published considering HRW consumption and lipid/lipoprotein status. Therefore, the aim of this SRMA was to assess the effects of HRW consumption on blood lipid panel in clinical populations. The search strategy was designed using PRISMA guidelines, and the databases PubMed/Medline, Web of Science, and Scopus were explored from inception until 4 October 2022. A total of seven studies satisfied all the eligibility criteria and were included in SRMA. The results for the pooled meta-analysis showed a significant reduction in total cholesterol, low-density lipoprotein, and triglycerides after HRW intake (p = 0.01), with small to moderate effects (pooled SMD = −0.23 (from −0.40 to 0.05); pooled SMD = −0.22 (from −0.39 to 0.04); pooled SMD = −0.38 (from −0.59 to 0.18), respectively). Our findings indicate that drinking HRW can significantly improve lipid status in the clinical populations. Additional studies are warranted to further validate this connection.

• Fernández-Landa, Julen; Santibañez-Gutierrez, Asier; Todorovic, Nikola; Stajer, Valdemar & Ostojic, Sergej (2023). Effects of Creatine Monohydrate on Endurance Performance in a Trained Population: A Systematic Review and Meta-analysis. Sports Medicine. ISSN 0112-1642. 53(5), p. 1017–1027. doi: 10.1007/s40279-023-01823-2.
• Stajer, Valdemar; Todorovic, Nikola; Conic, Branislava Srdenovic; Kladar, Nebojsa; Engeset, Dagrun & Stea, Tonje Holte [Show all 12 contributors for this article] (2023). The Effects of Medium-Term Intake of Hydrogen-Rich Water on Sperm Quality Biomarkers in Normospermic and Oligospermic Men: A Randomized Controlled Pilot Trial. Current Topics in Nutraceuticals Research. ISSN 1540-7535. 21(2), p. 182–186. doi: 10.37290/ctnr2641-452X.21:182-186.
• Momtazmanesh, Sara; Moghaddam, Sahar Saeedi; Ghamari, Seyyed-Hadi; Rad, Elaheh Malakan; Rezaei, Negar & Shobeiri, Parnian [Show all 50 contributors for this article] (2023). Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019. EClinicalMedicine. ISSN 2589-5370. 59. doi: 10.1016/j.eclinm.2023.101936. Full text in Research Archive
• Ostojic, Sergej & Jorga, Jagoda (2023). Guanidinoacetic acid in human nutrition: Beyond creatine synthesis. Food Science & Nutrition. ISSN 2048-7177. 11(4), p. 1606–1611. doi: 10.1002/fsn3.3201. Full text in Research Archive Show summary

  Guanidinoacetic acid (GAA) is a nutrient that has been used in human nutrition since the early 1950s. Recommended for its role in creatine biosynthesis, GAA demonstrated beneficial energy-boosting effects in various clinical conditions. Dietary GAA has also been suggested to trigger several creatine-independent mechanisms. Besides acting as a direct precursor of high-energy phosphagen creatine, dietary GAA is suggested to reduce blood glucose concentration by acting as an insulinotropic food compound, spare amino acid arginine for other metabolic purposes (including protein synthesis), modulate taste, and perhaps alter methylation and fat deposition in various organs including the liver. GAA as a food component can have several important metabolic roles beyond creatine biosynthesis; future studies are highly warranted to address GAA overall role in human nutrition.

• Ostojic, Sergej; Hillesund, Elisabet Rudjord; Øverby, Nina Cecilie; Vik, Frøydis Nordgård & Medin, Anine Christine (2023). Individual nutrients and serum klotho levels in adults aged 40–79 years. Food Science & Nutrition. ISSN 2048-7177. 11(6), p. 3279–3286. doi: 10.1002/fsn3.3310. Full text in Research Archive Show summary

  Several dietary factors (including adherence to the Mediterranean diet or higher nut intake) seem to positively affect circulating antiaging Klotho protein levels; yet, a description of possible relationships between individual nutrients and Klotho activity has not been evaluated. We analyzed the association of dietary intake of individual macro- and micronutrients and nonnutritive food components with circulating Klotho levels in a sample of 40- to 79-year-old US adults. Data from the 2015–2016 National Health and Nutrition Examination Survey were analyzed. Nutrient/food component intakes were calculated in relation to total energy intake using the nutrient density method, and available pristine serum samples were analyzed for serum Klotho concentrations. The final study sample consisted of 2637 participants (mean age 59.0 ± 10.7 years; 52% women). Higher Klotho concentrations were found with higher intake of carbohydrates (p < .001), total sugars (p < .001), dietary fibers (p < .001), vitamin D (p = .05), total folates (p = .015), and copper (p = .018). The results of the regression analysis with a crude model showed significant associations among five nutrients/food components (carbohydrates, alcohol, total sugars, dietary fibers, and niacin) and soluble Klotho levels across the sample. After adjusting the models for age and gender, the nutrient/food component–Klotho association remained significant for carbohydrates, total sugars, and alcohol (p < .05). Dietary exposure to individual nutrients and nonnutritive food components appears to be associated with Klotho activity; however, additional research is needed to investigate the relationship between cause and effect in diet composition–Klotho interplay.

• Todorovic, Nikola; Santibañez-Gutierrez, Asier; Milovanov, Djordje; Stajer, Valdemar; Ostojic, Sergej & Fernández-Landa, Julen (2022). EFFECTS OF ACUTE Β-ALANINE SUPPLEMENTATION ON COUNTERMOVEMENT JUMP PERFORMANCE AFTER A 4X400 M RUNNING FATIGUE PROTOCOL: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. Kinesiology. ISSN 1331-1441. 54(2), p. 201–207. doi: 10.26582/k.54.2.1. Full text in Research Archive Show summary

  This study aimed to examine the effect of acute beta-alanine (β-alanine) supplementation on jump performance after a strenuous fatigue protocol. Twelve healthy young men (age 21.4±0.5 years, body height 180.2±5.8 cm, body mass 76.6±9.2 kg) volunteered to participate in this randomized, double-blind, placebocontrolled trial. The experimental group ingested 3.2 g of β-alanine (separated into two 1.6 g dosages) mixed with 23 g of glucose, whereas the placebo group ingested two dosages containing 23 g of glucose. Following the supplementation intake, participants completed a jump protocol involving countermovement jump (CMJ) and four consecutive countermovement jumps (CMJ-4). Subsequently, a 4x400 m running fatigue protocol was carried out to produce fatigue. After the fatigue protocol, the same jumping tests were repeated, CMJ and CMJ-4, to evaluate the loss in jump height. The Mann-Whitney U test was used to analyze differences between the groups, whereas Wilcoxon signed-rank test was conducted to analyze differences within the groups with statistical significance set at p<.05. After β-alanine supplementation, no significant decrease in jump height was found in the experimental group in none of the tests after the fatigue protocol. Conversely, a significant decrease was noticed in the placebo group in CMJ but not in the CMJ-4 test. In conclusion, an acute β-alanine supplementation could attenuate jump height loss after the fatigue protocol. Therefore, athletes and coaches should consider acute β-alanine supplementation to attenuate sports performance decrease after high-intensity exercises in which muscle acidosis is highly increased.

• Todorovic, Nikola; Korovljev, Darinka; Stajer, Valdemar; Jorga, Jagoda & Ostojic, Sergej (2022). Creatine consumption and liver disease manifestations in individuals aged 12 years and over. Food Science & Nutrition. ISSN 2048-7177. doi: 10.1002/fsn3.3151. Full text in Research Archive
• Giannos, Panagiotis; Prokopidis, Konstantinos; Lidoriki, Irene; Triantafyllidis, Konstantinos K.; Kechagias, Konstantinos S. & Celoch, Kamil [Show all 9 contributors for this article] (2022). Medium-chain triglycerides may improve memory in non-demented older adults: a systematic review of randomized controlled trials. BMC Geriatrics. ISSN 1471-2318. 22. doi: 10.1186/s12877-022-03521-6. Full text in Research Archive Show summary

  Background: Ketosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT) supplementation may induce nutritional ketosis. The aim of this systematic review is to explore the efects of MCTs on memory function in older adults without cognitive impairment. Methods: A systematic literature search of PubMed, Cochrane Library, Scopus, and Web of Science was employed from inception until April 2022 for randomized controlled trials (RCTs) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, investigating the impact of MCT oils on components of memory. Risk of bias (RoB2) tool was utilized for quality assessment. Results: Six trials were included for qualitative synthesis, in which two studies examined the efect of MCTs through a ketogenic meal. MCT supplementation compared to controls was associated with improved indices of memory function in 4 out of 6 studies, particularly working memory. A meta-analysis was not employed due to the low number of studies, therefore, a true efect measure of MCT supplementation was not explored. Conclusions: MCT supplementation may enhance working memory in non-demented older adults. These efects may be more prominent in individuals with lower baseline scores, from short and long-term supplementation. Further studies are warranted to confrm these fndings in terms of optimal dose and MCTs composition, which may protect from memory decline during aging.

• Ostojic, Sergej (2022). Malproduction of endogenous hydrogen gas in COVID-19. Frontiers in Cellular and Infection Microbiology. ISSN 2235-2988. 12. doi: 10.3389/fcimb.2022.924832.
• Todorovic, Nikola; Stajer, Valdemar; Milovancev, Aleksandra; Banjanin, Danijela; Celarevic, Milijana & Ratgeber, Laszlo [Show all 13 contributors for this article] (2022). The Effects of Nitrate-Based Nutritional Formula on Oxygen Saturation and Patient-Reported Outcomes in COVID-19 Patients: A Randomized Controlled Trial. Current Topics in Nutraceuticals Research. ISSN 1540-7535. 20(4), p. 720–724. doi: 10.37290/ctnr2641-452X.20:720-724.
• Ostojic, Sergej; Korovljev, Darinka; Stajer, Valdemar & Todorovic, Nikola (2022). Food Creatine and Head Circumference Among Children Aged 0–2 Years. Current Developments in Nutrition (CDN). ISSN 2475-2991. 6(Supplement 1), p. 699–699. doi: 10.1093/cdn/nzac061.083. Show summary

  Objectives Several small-scalle studies demonstrated an association between dietary creatine intake and body size in school-aged children and adolescents, yet no such connection has been evaluated in very young children at the populational level. We conducted a secondary analysis of previously completed cross-sectional study, and determined an association between food creatine and body measures in 597 U.S children aged 0 to 2 years, using the 2017–2018 National Health and Nutrition Examination Survey database. Methods Total grams of creatine consumed per day were computed using the average amount of creatine (e.g., 0.20 g/kg for milk-based foods and 3.88 g/kg for meat-based sources) across all creatine-containing food sources. Results Dietary creatine intake was positively correlated with head circumference (r = 0.184; P = 0.031) when controlled for age at screening, while no link was found between creatine consumption and recumbent length (r = - 0.003; P = 0.955) or body weight (r = 0.048; P = 0.317). A multiple regression analysis revealed a significant relationship between food creatine and head circumference (P < 0.001) when adjusted for the effects of selected dietary variables (e.g., weight of food consumed, total caloric content, protein intake). Conclusions Our findings indicate a relationship between food creatine and head circumference as a surrogate marker of brain size in early childhood; further pediatric studies should appraise the role of dietary creatine in neurodevelopment.

• Todorovic, Nikola; Korovljev, Darinka; Stajer, Valdemar; Maksimovic, Nebojsa; Ratgeber, Laszlo & Betlehem, Jozsef [Show all 8 contributors for this article] (2022). Effects of 6-Month Supplementation with Multi-Component Herbal Supplement PhytodynamicTM on Mitochondrial Function, Telomere Length, and Chronic Inflammation in Adults Aged 65 Years and Older: A Pilot Trial. Current Topics in Nutraceuticals Research. ISSN 1540-7535. 20(3), p. 594–597. doi: 10.37290/ctnr2641-452X.20:594-597.
• Ostojic, Sergej (2022). Guanidinoacetic Acid as a Nutritional Adjuvant to Multiple Sclerosis Therapy. Frontiers in Human Neuroscience. ISSN 1662-5161. 16. doi: 10.3389/fnhum.2022.871535. Full text in Research Archive
• Milovancev, Aleksandra; Avakumovic, Jovana; Drid, Patrik; Todorovic, Nikola; Stajer, Valdemar & Ostojic, Sergej (2022). Hydrogen-rich water alleviates inflammation and fatigue in COVID-19: A pilot study. European Journal of Inflammation. ISSN 1721-727X. 20. doi: 10.1177/1721727X221094197.
• Ostojic, Sergej; Stea, Tonje Holte & Engeset, Dagrun (2022). Creatine as a Promising Component of Paternal Preconception Diet. Nutrients. ISSN 2072-6643. 14(3). doi: 10.3390/nu14030586. Full text in Research Archive Show summary

  Abstract: Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertilitypromoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.

• Ostojic, Sergej (2022). Low tissue creatine: a therapeutic target in clinical nutrition. Nutrients. ISSN 2072-6643. 14(6). doi: 10.3390/nu14061230. Full text in Research Archive Show summary

  Low tissue creatine characterizes many conditions, including neurodegenerative, cardiopulmonary, and metabolic diseases, with a magnitude of creatine shortfall often corresponds well to a disorder’s severity. A non-invasive monitoring of tissue metabolism with magnetic resonance spectroscopy (MRS) might be a feasible tool to evaluate suboptimal levels of creatine for both predictive, diagnostic, and therapeutic purposes. This mini-review paper summarizes disorders with deficient creatine levels, and provides arguments for assessing and employing tissue creatine as a relevant target in clinical nutrition.

• Ostojic, Sergej (2022). Cataloguing guanidinoacetic acid content in various foods. International Journal for Vitamin and Nutrition Research. ISSN 0300-9831. doi: 10.1024/0300-9831/a000753. Show summary

  Guanidinoacetic acid (GAA) is a natural amino acid derivative involved in several metabolic pathways across the human body, including creatine biosynthesis, arginine utilization, and neuromodulation. Apart from GAA synthesized internally from glycine and arginine, a total daily exposure to GAA also involves exogenous dietary sources. However, a majority of food databases provide no comprehensive data about the amount of GAA available from various foods. In this report, we summarize information for GAA levels in different food groups, as extracted from the available scientific literature. The content of GAA appears to vary across different foods, with meat-based products contain the highest relative amount of GAA (~ 50 mg per kg), followed by a dairy group (~ 0.3 mg per kg), and plant-based foods (~ 1 µg per kg), with the latter considered to be almost negligible. Although no data are currently available about its requirements in humans, cataloguing GAA amount in various foods could help in more accurate quantification of GAA provision via regular diet in the future.

• Forbes, Scott C; Cordingley, Dean; Cornish, Stephen; Gualano, Bruno; Roschel, Hamilton & Ostojic, Sergej [Show all 11 contributors for this article] (2022). Effects of Creatine Supplementation on Brain Function and Health. Nutrients. ISSN 2072-6643. 14(5). doi: 10.3390/nu14050921. Full text in Research Archive Show summary

  While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research which has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Further, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussions.

• Ostojic, Sergej; Ostojic, Jelena; Zanini, Dragana; Jezdimirovic, Tatjana & Stajer, Valdemar (2022). Guanidinoacetate–creatine in secondary progressive multiple sclerosis: a case report. Journal of International Medical Research. ISSN 0300-0605. 50(1), p. 1–5. doi: 10.1177/03000605211073305. Full text in Research Archive Show summary

  Acute secondary progressive multiple sclerosis (SPMS) is characterized by escalating neurological disability, with limited disease-modifying therapeutic options. A 48-year-old woman with acute SPMS being treated with interferon beta-1a and oral corticosteroids presented as a clinical out- patient with no disease-modifying effects after treatment. A decision was made to treat her with a combination of guanidinoacetate and creatine for 21 days. She had made clinical progress at follow-up, with the intensity of fatigue dropping from severe to mild. Magnetic resonance spec- troscopy revealed increased brain choline, creatine, N-acetylaspartate, and glutathione. Patients with SPMS may benefit from guanidinoacetate–creatine treatment in terms of patient- and clinician-reported outcomes; this requires additional study.

• Ostojic, Sergej (2021). Safety of dietary guanidinoacetic acid: a villain of a good guy? Nutrients. ISSN 2072-6643. 14(1). doi: 10.3390/nu14010075. Full text in Research Archive Show summary

  Guanidinoacetic acid (GAA) is a natural amino acid derivative that is well-recognized for its central role in the biosynthesis of creatine, an essential compound involved in cellular energy me-tabolism. GAA (also known as glycocyamine or betacyamine) has been investigated as an ener-gy-boosting dietary supplement in humans for more than 70 years. GAA is suggested to effective-ly increase low levels of tissue creatine and improve clinical features of cardiometabolic and neurological diseases, with GAA often outcompetes traditional bioenergetics agents in maintain-ing ATP status druing stress. This perhaps happens due to a favorable delivery of GAA through specific membrane transporters (such as SLC6A6 and SLC6A13), previously dismissed as un-targetable carriers by other therapeutics, including creatine. The promising effects of dietary GAA might be countered by side-effects and possible toxicity. Animal studies reported neurotoxic and pro-oxidant effects of GAA accumulation, with exogenous GAA also appears to increase methylation demand and circulating homocysteine, implying a possible metabolic burden of GAA intervention. This mini-review summarizes GAA toxicity evidence in human nutrition, and outlines functional GAA safety through benefit-risk assessment and multi-criteria decision anal-ysis

• Ostojic, Sergej & Engeset, Dagrun (2021). Improving brain creatine uptake by Klotho protein stimulation: can diet hit the big time? Frontiers in Nutrition. ISSN 2296-861X. 8. doi: 10.3389/fnut.2021.795599. Full text in Research Archive Show summary

  Creatine plays a pivotal role in cellular bioenergetics, acting as a temporal and spatial energy buffer in cells with high and fluctuating energy requirements (1). Jeopardizing delicate creatine homeostasis can be detrimental to many energy-demanding tissues, including the brain. For instance, cerebral creatine hypometabolism accompanies various neurological conditions, including a number of developmental disorders (2, 3), neurodegenerative and cerebrovascular diseases (4, 5), and brain cancer (6). A reduced creatine availability in the brain has been thus recognized as an apposite therapeutic target, and supplying exogenous creatine to compensate for a disease-driven shortfall emerged as a first possible approach. However, early success in animal models of neurological diseases was not corroborated in human trials, with the use of creatine supplementation proved largely disappointing in clinical studies with a number of symptomatic neurological disorders [for a detailed review, see (7)]. A meager delivery of creatine to the brain could be partly due to a low activity/density of creatine transporter (CT1 or SLC6A8), a transmembrane sodium- and chloride-dependent protein that mediates creatine uptake into the target cells (8). For that reason, the upregulation of CT1 function has been identified as an innovative course of action to facilitate creatine uptake, with several exotic agents and routes were cataloged so far, including glucocorticoid-regulated kinases, mammalian target of rapamycin, ammonia, and Klotho protein (9).

• Korovljev, Darinka; Todorovic, Nikola; Stajer, Valdemar & Ostojic, Sergej (2021). Food Creatine and DXA-Derived Body Composition in Boys and Girls Aged 8 to 19 Years. Nutrition and Metabolic Insights. ISSN 1178-6388. 14, p. 1–5. doi: 10.1177/11786388211059368.

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• Ostojic, Sergej (2024). Preterm Babies: Predicting the Consequences. Journal of Pediatric Neurology. ISSN 1304-2580. 22(1), p. 85–85. doi: 10.1055/s-0043-1761933.
• Ostojic, Sergej (2024). Creatine metabolism during pregnancy: advancing toward understanding. American Journal of Clinical Nutrition. ISSN 0002-9165. doi: 10.1016/j.ajcnut.2023.12.026.
• Ostojic, Sergej; Korovljev, Darinka; Todorovic, Nikola & Stajer, Valdemar (2023). Dietary creatine intake and head circumference among very young U.S. children. Progress in Nutrition. ISSN 1129-8723. 25(1). doi: 10.23751/pn.v25i1.11595.
• Ostojic, Sergej & Øverby, Nina Cecilie (2023). Editorial: Scientific integrity in nutritional research. Frontiers in Nutrition. ISSN 2296-861X. 10. doi: 10.3389/fnut.2023.1323265.
• Todorovic, Nikola & Ostojic, Sergej (2023). Molecular hydrogen as a potential adjuvant therapy for alleviating long COVID. Medical Hypotheses. ISSN 0306-9877. 180. doi: 10.1016/j.mehy.2023.111188.
• Candow, Darren G.; Forbes, Scott C.; Ostojic, Sergej; Prokopidis, Konstantinos; Stock, Matt S. & Harmon, Kylie K. [Show all 7 contributors for this article] (2023). Correction to: “Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function (Sports Medicine, (2023), 10.1007/s40279-023-01870-9). Sports Medicine. ISSN 0112-1642. doi: 10.1007/s40279-023-01888-z.
• Ostojic, Sergej (2022). Hydrogen-Rich Water as a Dietary Activator of Brown Adipose Tissue and UCP1? Annals of Nutrition and Metabolism. ISSN 0250-6807. 78(4), p. 242–243. doi: 10.1159/000525175.
• Ostojic, Sergej (2022). Relationship between dietary creatine and growth indicators in children and adolescents aged 2-19 years.
• Ostojic, Sergej (2022). Creatine and post-viral fatigue syndrome: an overview. .
• Forbes, Scott; Ostojic, Sergej; Souza-Junior, Tacito & Candow, Darren G (2021). A High Dose of Creatine Combined with Resistance Training Appears to Be Required to Augment Indices of Bone Health in Older Adults. Annals of Nutrition and Metabolism. ISSN 0250-6807. 78(3), p. 183–186. doi: 10.1159/000520967.
• Ostojic, Sergej; Stajer, Valdemar; Ratgeber, Laszlo; Betlehem, Jozsef & Acs, Pongrac (2021). Guanidinoacetic Acid Consumption via Regular Diet in Adults. Annals of Nutrition and Metabolism. ISSN 0250-6807. doi: 10.1159/000520550.
• Ostojic, Sergej; Forbes, Scott C & Candow, Darren G (2021). Do Pregnant Women Consume Enough Creatine? Evidence from NHANES 2011-2018. Annals of Nutrition and Metabolism. ISSN 0250-6807. 78(2), p. 114–116. doi: 10.1159/000520818.

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