Cak8.5

Calcium AKG Research

45 peer-reviewed studies · Evidence score: 8.5/10

Nutritional interventions for preventing and treating pressure ulcers

Langer G et al. • The Cochrane database of systematic reviews (2024)

The benefits of nutritional interventions with various compositions for pressure ulcer prevention and treatment are uncertain.

Compared to standard diet, protein supplements may result in little to no difference in pressure ulcer incidence (protein 21 per 1000, standard diet 28 per 1000; RR 0.75, 95% CI 0.49 to 1.14; 4 studies, 4264 participants; low-certainty evidence).
The evidence is very uncertain about the gastrointestinal side effects of these supplements (protein 109 per 1000, standard diet 155 per 1000; RR 0.70, 95% CI 0.06 to 7.96; 2 studies, 140 participants, very low-certainty evidence).
Compared to standard diet, energy, protein and micronutrient supplements may slightly increase the number of healed pressure ulcers (energy, protein and micronutrients 366 per 1000, standard diet 253 per 1000; RR 1.45, 95% CI 1.14 to 1.85; 3 studies, 577 participants, low-certainty evidence).

Meta-Analysisn=7,920

DOI

Nutritional supplementation for hip fracture aftercare in older people

Avenell A et al. • The Cochrane database of systematic reviews (2016)

There is low-quality evidence that oral multinutrient supplements started before or soon after surgery may prevent complications within the first 12 months after hip fracture, but that they have no clear effect on mortality.

There was low-quality evidence that oral feeds had little effect on mortality (24/486 versus 31/481; risk ratio (RR) 0.81 favouring supplementation, 95% confidence interval (CI) 0.49 to 1.32; 15 trials).
There was low-quality evidence that the number of participants with complications may be reduced with oral multinutrient feeds (123/370 versus 157/367; RR 0.71, 95% CI 0.59 to 0.86; 11 trials).
Based on very low-quality evidence from six studies (334 participants), oral supplements may result in lower numbers with 'unfavourable outcome' (death or complications): RR 0.67, 95% CI 0.51 to 0.89.

Meta-Analysisn=3,881

DOI

Biomarker discovery in NAFLD: insights from metabolomics and vote counting meta-analysis

Mudgal P et al. • Metabolomics : Official journal of the Metabolomic Society (2025)

This study highlighted the role of different metabolites in the progression of NAFLD condition.

This study highlighted the role of different metabolites in the progression of NAFLD condition.
However, the analysis also reveals certain limitations requiring better standardization of metabolomics investigations, signifying errors and lacunas of metabolic databases in identification and reporting.
Additionally, inadequate publicly accessible metabolomics data, limits the discovery potential of meta-analyses of clinical studies.

Meta-Analysis

DOI

Nutritional interventions in patients with burn injury: an umbrella review of systematic reviews and meta-analyses of randomised clinical trials

Naeini F et al. • The British journal of nutrition (2024)

Lower length of hospital stay was also seen in burn patients supplemented with glutamine, although the evidence was weak.

We adopted the random-effect models to determine the pooled effect sizes while employing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to examine evidence certainty.
Glutamine showed a notable decrease in the length of hospital stay (MD: -6·23, 95 % CI: -9·53, -2·94, GRADE = low certainty).
However, other nutritional interventions, including combined immunonutrition, branched-chain amino acids, fish oil, ornithine α-ketoglutarate and trace elements, did not significantly affect the assessed clinical outcomes.

Meta-Analysis

DOI

Novel circulating biomarkers for non-alcoholic fatty liver disease: A systematic review

Sahebkar A et al. • Journal of cellular physiology (2018)

However, due to methodological differences, we propose the implementation of international, multicenter, multiethnic studies with larger population size, and biopsy proven NAFLD diagnosis to analyze and compare α-ketoglutarate and CK18-F as potential biomarkers of the silent evolution of NAFLD.

The lack of a biomarker of NAFLD pushes to develop this new line of research.
The aim of the present systematic review is to clarify and update all the NAFLD biomarkers described in the literature until recently.
We highlight α-ketoglutarate and CK18-F as currently the best potential biomarker of NAFLD.

Systematic Review

DOI

Recruitment evaluation of a gerotherapeutic randomized controlled trial testing alpha-ketoglutarate in biologically older, middle-aged adults (ABLE)

Lim ZM et al. • Experimental gerontology (2025)

ABLE demonstrated the feasibility of recruiting biologically older yet generally healthy middle-aged adults for gerotherapeutic interventions.

Eligibility rates were 80.3 % at pre-screening and 67.3 % at screening, with a consent rate of 66.1 %.
Conversion rates were 25.7 % and 48.4 % from pre-screening and screening to enrolment, respectively.
The biological age was exceeding the chronological age in 80.2 % of participants and 54.3 % reported no pre-existing health conditions.

RCTn=120

DOI

Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial

Kacerova T et al. • Alzheimer's & dementia : the journal of the Alzheimer's Association (2025)

B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, α-ketoglutarate, α-ketobutyrate, glucose, and glutamate.

Multivariate modeling distinguished treated from placebo groups with 91.2 ± 1.8% accuracy.
Further research warranted to confirm findings

RCTn=173

DOI

Urine tricarboxylic acid cycle signatures of early-stage diabetic kidney disease

Lunyera J et al. • Metabolomics : Official journal of the Metabolomic Society (2021)

Thus, lower urine TCA cycle OAs, most notably lower methylmalonate, ethylmalonate and citrate/isocitrate, are potential indicators of kidney impairment in early stage DKD.

Among 132 participants with 24 h urine samples (50% men; 58% Black; mean age 64 years [SD 9]; mean eGFR 74 ml/min/1.73m2 [SD 21] and median urine albumin-to-creatinine [UACR] 20 mg/g [IQR 8-95]), PCA identified 3 OA metabolite PCs.
Thus, lower urine TCA cycle OAs, most notably lower methylmalonate, ethylmalonate and citrate/isocitrate, are potential indicators of kidney impairment in early stage DKD.
Further research warranted to confirm findings

RCTn=132

DOI

Olaparib in treatment-refractory isocitrate dehydrogenase 1 (IDH1)- and IDH2-mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial

Cecchini M et al. • Cancer (2025)

Olaparib does not have sufficient single-agent activity to warrant further development in IDH-mutant CCA.

Median progression-free survival (PFS) was 2.4 months (95% CI, 1.9 to 6.5 months) and median overall survival was 12.9 months (95% CI, 6.3 months to not reached).
Eight patients (27%) had clinical benefit (CB), with a PFS of ≥6 months.
Olaparib does not have sufficient single-agent activity to warrant further development in IDH-mutant CCA.

RCTn=30

DOI

Proton-Nuclear Magnetic Resonance Metabolomics of Gingival Crevicular Fluid During Orthodontic Tooth Movement With Aligners

Domini MC et al. • Orthodontics & craniofacial research (2025)

High values of Glutamine and low values of Uracil, N-Acetylneurinamate and alpha-ketoglutarate could be utilised to predict the progress of orthodontic tooth movement over time.

VIP-score values showed statistically significant differences between the metabolites involved in moving and stationary molars (p < 0.05).
High values of Glutamine and low values of Uracil, N-Acetylneurinamate and alpha-ketoglutarate could be utilised to predict the progress of orthodontic tooth movement over time.
Knowledge of metabolites predictive of tooth movement could contribute to the design of tailored orthodontic treatment planning, reducing time, costs and side-effects.

RCTn=24

DOI

Effects of Co-Ingestion of β-Hydroxy-β-Methylbutyrate and L-Arginine α-Ketoglutarate on Jump Performance in Young Track and Field Athletes

Kaczka P et al. • Nutrients (2021)

The results of this study indicate that the daily co-supplementation with calcium salt of β-hydroxy-β-methylbutyrate (7.5 g) and L-Arginine α-ketoglutarate (10 g) during training might help to prevent decline in jump performance.

At the end of the training cycle, a significant (p = 0.002) decrease in the countermovement jump (CMJ) height was found in the placebo group when compared to the baseline.
In contrast to the supplements group, in the placebo group, the CMJ changes were statistically significant: a noticeable (p = 0.002) decrease in CMJ was noted between the baseline measurement and the 6th measurement.
The well-being of the subjects from both groups changed significantly during the training period, and the intergroup differences in the mood level were similar and not statistically significant.

RCTn=40

DOI

Exercise increases TCA intermediate concentrations during low-calorie diet independent of insulin resistance among women with obesity

Ragland TJ et al. • Physiological reports (2024)

Physiological Reports

Treatments increased FFA tAUC180min (p = 0.005), cis-aconitate, isocitrate, and succinate (p ≤ 0.02), as well as reduced phenylalanine and tryptophan, cysteine (p ≤ 0.005).
However, LCD + INT increased malate, citrate, α-ketoglutarate, and alanine more than LCD (p ≤ 0.04).
Thus, INT enhanced LCD effects on some TCAi in women with obesity independent of IR.

RCTn=23

DOI

Myocardial Protecting Role of Glutamine in Patients with Low Ejection Fraction Undergoing Elective On-Pump Coronary Artery Bypass Graft Surgery

Parmana IMA et al. • Vascular health and risk management (2022)

Perioperative administration of 0.5 g/kg intravenous glutamine solution over the period of 24 hours has myocardial protection effect in patients with low EF who undergo elective on-pump CABG.

Plasma glutamine levels at 24 hours after CPB were significantly higher in the glutamine than the control group (mean 935.42 ± 319.10 μmol/L vs mean 634.79 ± 243.89 μmol/L, p = 0.001).
Plasma lactate levels at 6 and 24 hours after CPB were significantly lower in the glutamine than the control group (median 5.30 mmol/L [min-max: 1.20-9.50] vs median 5.70 mmol/L [min-max: 2.80-11.30], p = 0.042; mean 2.08 ± 0.67 mmol/L vs mean 2.46 ± 0.69 mmol/L, p = 0.044, respectively).
Myocardial injury score was significantly lower in the glutamine than the control group (mean 1.30 ± 0.24 vs mean 1.48 ± 0.26, p = 0.011).

RCTn=30

DOI

A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial

Chashmniam S et al. • European journal of clinical nutrition (2019)

Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.

Characterizing the serum metabolic profile of the patients with NAFLD at the end of the intervention using NMR-based metabolomics method indicated that the targets of curcumin treatment included some amino acids, TCA cycle, bile acids, and gut microbiota.
Further research warranted to confirm findings

RCTn=90

DOI

Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial

Romeiro FG et al. • NeuroImage. Clinical (2018)

Isoleucine supplementation achieved a better impact on brain perfusion restoration in HE.

Brain single Photon Emission Computed Tomography (SPECT) and dynamic brain scintigraphy (DBS) were performed pretreatment and at 1, 8 and 12 months of supplementation.
Brain perfusion was increased only in the isoleucine group at 8 months of treatment by both SPECT and DBS (p < 0.001 and p = 0.05, respectively) and by SPECT at the 12th month (p < 0.05).
This was associated with hepatic encephalopathy improvement at 8 and 12 months (p = 0.008 and 0.004, respectively), which was not observed in the leucine group (p = 0.313 and 0.055, respectively).

RCTn=27

DOI

Effects of Multi-Ingredient Pre-Workout Supplement and Caffeine on Bench Press Performance: A Single-Blind Cross-Over Study

Kruszewski M et al. • Nutrients (2022)

These results indicate that MIPS supplementation is less ergogenic and cost effective than caffeine alone.

In a cross-over manner, they participated in two sessions where they were blinded to the order of supplementation they were given: either a MIPS including caffeine or caffeine alone.
They completed the bench press strength endurance test with pre- and post-training psychological assessments containing FS, FAS and sRPE.
Bench press repetition volume was greater after anhydrous caffeine than MIPS supplementation with no difference in psychological measures.

Crossovern=15

DOI

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism

Op den Kamp YJM et al. • Molecular metabolism (2022)

Dapagliflozin treatment for 5 weeks leads to adaptive changes in skeletal muscle substrate metabolism favoring metabolism of fatty acid and ketone bodies and reduced glycolytic flux.

Dapagliflozin treatment increased intramyocellular lipid content (0.060 (0.011, 0.110) %, p = 0.019).
Dapagliflozin treatment for 5 weeks leads to adaptive changes in skeletal muscle substrate metabolism favoring metabolism of fatty acid and ketone bodies and reduced glycolytic flux.
The trial is registered with ClinicalTrials.gov, number NCT03338855.

RCTn=26

DOI

Arginine L-alpha-ketoglutarate, methylsulfonylmethane, hydrolyzed type I collagen and bromelain in rotator cuff tear repair: a prospective randomized study

Gumina S et al. • Current medical research and opinion (2012)

The use of the supplement for 3 months after cuff repair decreases shoulder post-operative pain and leads to a slight improvement in repair integrity.

No statistically significant differences were identified between the two groups for each considered variable, except for shoulder pain (follow-up: 6 months) and repair integrity (final follow-up).
Analogously, in Group I, the percentage of patients with a better repair integrity result was significantly higher than Group II.
The use of the supplement for 3 months after cuff repair decreases shoulder post-operative pain and leads to a slight improvement in repair integrity.

RCTn=90

DOI

Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males

Jung YP et al. • Journal of the International Society of Sports Nutrition (2017)

Results provide some evidence that 4-weeks of PWS and/or PWS + S supplementation can improve some indices of cognitive function and exercise performance during resistance-training without significant side effects in apparently health males.

Although significant time effects were seen, no statistically significant overall MANOVA Wilks' Lambda interactions were observed among groups for body composition, resting heart and blood pressure, readiness to perform questions, 1RM strength, anaerobic sprint capacity, or blood chemistry panels.
MANOVA univariate analysis and analysis of changes from baseline with 95% CI revealed some evidence that cognitive function and 1RM strength were increased to a greater degree in the PWS and/or PWS + S groups after 4- and/or 8-weeks compared to PLA responses.
Results provide some evidence that 4-weeks of PWS and/or PWS + S supplementation can improve some indices of cognitive function and exercise performance during resistance-training without significant side effects in apparently health males.

RCTn=80

DOI

Effects of acute ingestion of a pre-workout dietary supplement with and without p-synephrine on resting energy expenditure, cognitive function and exercise performance

Jung YP et al. • Journal of the International Society of Sports Nutrition (2017)

Within the confines of this study, ingestion of PWS and/or PWS + S prior to exercise appears to be well-tolerated when consumed by young, healthy individuals.

No statistically significant differences were observed among treatments in total bench press lifting volume, leg press lifting volume or WAC sprint performance.
Within the confines of this study, ingestion of PWS and/or PWS + S prior to exercise appears to be well-tolerated when consumed by young, healthy individuals.
The primary effects appear to be to increase REE responses and improve perceptions about readiness to perform and cognitive function with limited to no effects on muscular endurance and WAC.

RCTn=25

DOI

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