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Cak3.5
Calcium AKG Research
Likely helps
23 peer-reviewed studies
What the evidence says
Likely helps
Calcium AKG appears to help in 4 of 5 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality randomised trials published 2006–2026 with a typical study size of 40 participants.
Based on 23 studies · 13 RCTs · 731 total participants
Confidence
Moderate confidence
What the studies found
4helped1unclear· 18 more without graded effect data
By outcome
Longevity & agingLifespan benefits shown in animals only; no completed human outcomes · 4-6 months
Likely helps14 studies
Muscle strength & power
Mostly mechanism / observational7 studies
Endurance & exercise performance
Mostly mechanism / observational6 studies
Cognitive function
Mostly mechanism / observational4 studies
Safety profile
Mostly mechanism / observational3 studies
Therapeutic & clinical
Too few graded studies2 studies
Bone health
Too few graded studies2 studies
Lean body mass & muscle growth
Too few graded studies2 studies
Heart & blood pressure
Too few graded studies2 studies
Inflammation
Too few graded studies2 studies
Recovery
Too few graded studies1 study
Energy & fatigueMechanistic role only; no human energy outcomes · 4-8 weeks
Too few graded studies1 study
Glucose & metabolicMechanistic TCA-cycle role; no human metabolic outcomes · 8-12 weeks
Too few graded studies1 study
Neuroprotection & brain aging
Too few graded studies1 study
Women's health
Too few graded studies1 study
By the numbers
Pulled from 18 studies with measurable effects
Likely real effects
100%
across studies
People studied
731
typical study: 40 people
Strongest designs
13
0 pooled, 13 randomised
Showed benefit
80%
4/5 studies
How long studies ran
Under a week
1
1–3 months
1
3+ months
3
Populations Studied
metabolic syndrome patients1
middle-aged adults1
Biologically older, middle-aged adults1
Young track and field athletes1
Active research area
12 studies in the last 5 years
200620162026
1metabolic syndrome parametersReview2024
For the next step, researchers may focus on the co-pathogenesis of metabolic syndrome and investigate whether α-KG can be used to achieve the therapeutic goal of "homotherapy for heteropathy" in the treatment of metabolic syndrome.
Li Y, Wang Y, Yuan Q. · Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition (2024)
Exogenous supplementation of α-KG improves obesity, blood glucose levels, and cardiovascular disease risks associated with metabolic syndrome.
Furthermore, α-KG regulates the common pathological mechanisms of metabolic syndrome, suggesting the potential application prospect of α-KG in metabolic syndrome.
For the next step, researchers may focus on the co-pathogenesis of metabolic syndrome and investigate whether α-KG can be used to achieve the therapeutic goal of "homotherapy for heteropathy" in the treatment of metabolic syndrome.
This review aims to provide a comprehensive overview of AKG's benefits and identify future directions for research in both clinical and sports settings.
Xu M, Zhang Q, Liu X, Lu L, Li Z. · Nutrients (2024)
For athletes and active individuals, AKG supplementation has enhanced endurance, reduced fatigue, and supported faster post-exercise recovery.
Despite promising preliminary findings, research gaps remain in understanding AKG's long-term effects, optimal dosage, and specific pathways, particularly across diverse populations.
Further research, including large-scale clinical trials, is essential to clarify AKG's role in muscle health and to optimize its application as a therapeutic agent for skeletal muscle diseases and an enhancer of physical performance.
5Jump performanceRCTCited 3×n=40 · small study2021
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.
Kaczka P et al. · Nutrients (2021)
Likely real
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.
6Brain perfusion improvementRCTCited 9×n=27 · very small study2018
Isoleucine supplementation achieved a better impact on brain perfusion restoration in HE.
Romeiro FG et al. · NeuroImage. Clinical (2018)
Likely real
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).
These results indicate that MIPS supplementation is less ergogenic and cost effective than caffeine alone.
Kruszewski M et al. · Nutrients (2022)
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.
8Shoulder post-operative pain and repair integrityRCTCited 24×n=90 · small study2012
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.
Gumina S et al. · Current medical research and opinion (2012)
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.
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.
Jung YP et al. · Journal of the International Society of Sports Nutrition (2017)
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.
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.
Jung YP et al. · Journal of the International Society of Sports Nutrition (2017)
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.
11Plasma L-arginine levelsRCTCited 22×n=24 · very small study2011
NO(2) Platinum increased plasma L-arginine levels; however, the effects observed in hemodynamics, brachial-artery blood flow, and NOx can only be attributed to the resistance exercise.
Willoughby DS et al. · International journal of sport nutrition and exercise metabolism (2011)
NO(2) Platinum increased plasma L-arginine levels; however, the effects observed in hemodynamics, brachial-artery blood flow, and NOx can only be attributed to the resistance exercise.
Because AAKG supplementation may hinder muscular endurance, the use of these supplements before resistance training should be questioned.
Greer BK et al. · Journal of strength and conditioning research (2011)
The AAKG supplementation did not improve muscle endurance or significantly affect the BP response to anaerobic work.
Subjects performed fewer total chin-ups (23.75 ± 6.38 vs. 25.58 ± 7.18) and total trial repetitions (137.92 ± 28.18 vs. 141.08 ± 28.57) in the supplement trial (p ≤ 0.05).
Subjects executed fewer reverse chin-ups (5.83 ± 1.85 vs. 6.75 ± 2.09) during set 2 after receiving the supplement as compared to the placebo (p < 0.05).
This systematic-review examined the effects of Calcium AKG.
Wei F, Liu Z, Yu X, Sun Y, Zhao Y, Wang Y, Feng Z, Zhao X, Ke X, Yang A, Cui H. · Autophagy (2026)
Dysregulation of this network contributes broadly to human diseases including inflammatory bowel disease, cancer, and neurodegenerative disorders.
Notably, the functional impact of specific regulatory events is highly context dependent, a principle exemplified by the Crohn disease-associated T300A polymorphism.
Deciphering this regulatory landscape and its crosstalk with both autophagy-dependent and autophagy-independent functions positions ATG16L1 as a pivotal node in cellular homeostasis and as an emerging therapeutic target.
This review systematically proposes an integrated theoretical framework of "aging metabolic memory", explaining the persistence, transmissibility, and potential heritability of aging from a systems biology perspective.
This review summarizes the spatiotemporal dynamic characteristics of aging and may provide multi-dimensional intervention pathways for the precise prevention and treatment of age-related diseases and the promotion of healthy aging.
16Metabolic and immunomodulatory effectsSystematic Review2026
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Niederegger T et al. · Journal of burn care & research : official publication of the American Burn Association (2026)
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The goal of this review is to critically examine the current mechanistic knowledge related to AKG biosynthesis and breakdown and its future implications in maintaining cellular homeostasis and controlling chronic inflammation.
Devulapalli V, Sathiyamurthi A, Gautam S, Bhattaram P. · Biomedicines (2026)
Additionally, because endogenous AKG levels decrease with age, oral supplementation of AKG, especially with calcium and arginine, has drawn attention to its potential benefits in longevity and metabolic health.
Thus, AKG is versatile and has encouraging therapeutic promise for cancer, aging, and inflammatory illnesses.
However, a lack of human clinical evidence prompts further research to determine ideal dosage, tissue selectivity, and long-term safety.
Therefore, alpha-ketoglutarate is linked to improving reproductive performance, but further studies are needed due to a lack of studies on humans.
Doroftei B, Ilie OD, Timofeiov S, Dabuleanu AM, Scripcariu IS, Micu R, Tataranu E. · Reproduction (Cambridge, England) (2024)
This metabolite modulates the expression of pluripotency genes, thus controlling stem cells' self-renewal, differentiation, and reprogramming dynamics, while also alleviating structural transformations induced by exposure to heavy metals and other inhibitors.
This significantly demonstrated a direct influence of alpha-ketoglutarate in mitigating oxidative stress and prolonging the lifespan, consequently supporting metabolic and endocrine adjustments.
It influences oocyte quality and quantity, delays reproductive aging, and establishes an optimal competence framework for development with minimal risk of failure.
19Wound closure rateRCTCited 10×n=160 · medium study2009
This clinical trial supports a potential benefit of OKG 10g daily in the subgroup of patients with pressure ulcers <or= 8 cm2 surface area in elderly population when associated with debridement together with wound management according to pressure ulcer guidelines.
Meaume S et al. · The journal of nutrition, health & aging (2009)
Noticeable benefit
← WorseNo effectBetter →
Likely real
At inclusion, ulcer area distribution deviated from normal distribution (median ulcer area OKG 6.6 cm(2), placebo 3.9 cm2, p=0.044, Mann-Whitney test).
The mean wound area reduction for baseline area <or= 8 cm2 are -59.5 +/- 71.4% and -54.0 +/- 69.0% for the OKG group and placebo groups respectively (p=0.477, Mann-Whitney test).
When closure rate is considered, a significant difference in favor of OKG group is observed (- 0.07 cm2/day in the OKG group and - 0.04 cm2/day in the placebo groups respectively p=0.007, Mann-Whitney test).
20Serum CTX levelsRCTCited 34×n=76 · small study2007
AKG-Ca induced beneficial changes in serum CTX, which was consistent with preserving the bone mass in the lumbar spine; however, the long-term effect needs to be further investigated.
Filip RS et al. · International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition (2007)
Huge benefit
← WorseNo effectBetter →
Likely real
The maximum decrease of the mean CTX level in the AKG-Ca group was observed after 24 weeks (37.0%, p = 0.006).
The differences in CTX between study groups were statistically significant after 12 and 24 weeks.
The BMD of the AKG-Ca group increased by 1.6% from baseline; however, the difference between treatment groups was estimated as 0.9% (non-significant).