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Calcium AKG

Also known as: Ca-AKG, alpha-ketoglutarate calcium salt, Calcium AKG, Calcium alpha-ketoglutarate

Overview

Calcium alpha-ketoglutarate (Ca-AKG) is the calcium salt of alpha-ketoglutaric acid, a crucial intermediate in the Krebs (citric acid) cycle, central to cellular energy metabolism and amino acid synthesis. Unlike its precursor, alpha-ketoglutarate (AKG), which is not abundant in the human diet, Ca-AKG is primarily obtained through supplementation. It is gaining recognition as a dietary supplement aimed at supporting metabolic health, bone density, and potentially extending healthspan and lifespan. Levels of endogenous AKG significantly decline with age, making supplementation a strategy to restore these levels. Research, though emerging, indicates promising effects in animal models for longevity and healthspan, alongside some human clinical data, particularly concerning bone health. Ca-AKG is generally regarded as safe (GRAS) with a good human safety record, making it a well-tolerated option for those looking to support their metabolic and skeletal health as they age.

Benefits

Ca-AKG offers several evidence-based benefits, primarily in the areas of longevity, healthspan, and bone health. In C57BL/6 mice, 2% Ca-AKG supplementation significantly extended lifespan by approximately 9.6–12.8% and improved healthspan by 16.6–19.7%, suggesting a strong potential for anti-aging effects. This effect is partly attributed to a reduction in systemic inflammatory cytokines and an increase in anti-inflammatory IL-10. For bone health, a human clinical trial in menopausal women with osteopenia demonstrated that daily oral Ca-AKG (6 g AKG) for 6 months increased bone mineral density by 1.6% from baseline and significantly decreased biomarkers of bone resorption compared to calcium alone. This indicates a clinically relevant benefit for managing osteopenia. The mechanism involves upregulation of osteogenic differentiation markers and epigenetic regulation of bone formation pathways. While animal data on longevity are robust, human data are emerging, with bone density improvements observed within 6 months. Elderly populations, particularly those with osteopenia, may benefit most from Ca-AKG supplementation.

How it works

Calcium alpha-ketoglutarate (Ca-AKG) exerts its effects primarily through its active component, alpha-ketoglutarate (AKG), a key metabolite in the Krebs cycle. AKG is vital for cellular energy production and amino acid metabolism. It influences epigenetic regulation by acting as a co-factor for enzymes involved in histone demethylation, thereby affecting gene expression related to bone formation and inflammation. This modulation of gene expression contributes to its anti-inflammatory properties and its ability to promote osteogenic differentiation. Ca-AKG also interacts with body systems by modulating systemic inflammation and bone remodeling pathways. While specific pharmacokinetic data are limited, oral Ca-AKG is bioavailable and effectively increases systemic AKG levels, allowing it to influence these critical biological processes.

Side effects

Calcium alpha-ketoglutarate (Ca-AKG) is generally considered safe with a favorable human safety record and GRAS (Generally Recognized As Safe) status. Clinical studies have not reported any common (greater than 5%) or uncommon (1-5%) side effects. Rare side effects (less than 1%) observed in animal studies include a slight, non-statistically significant increase in cataracts and corneal opacity. There are no well-documented drug interactions, but caution is advised when co-administering with calcium-sensitive medications due to its calcium content. No specific contraindications have been identified, though individuals with pre-existing calcium metabolism disorders should exercise caution. The safety profile has been favorable in studies involving elderly and osteopenic populations. Overall, Ca-AKG appears to be a well-tolerated supplement with a low risk of adverse effects.

Dosage

The minimum effective dose for Calcium alpha-ketoglutarate (Ca-AKG) in human studies for bone health benefits has been established at 6 grams of AKG daily, administered as Ca-AKG. This dosage was shown to increase bone mineral density and decrease bone resorption markers in menopausal women with osteopenia. While optimal dosage ranges are still being explored, 6 g/day of AKG appears to be effective for specific therapeutic purposes. The maximum safe dose has not been definitively established, but human studies have reported no adverse effects at 6 g/day. Ca-AKG is typically administered orally on a daily basis; the timing relative to meals is not specified as critical. The calcium salt form is used for its stability and to provide supplemental calcium. No specific cofactors are identified as required for its absorption or efficacy, as it is sufficiently bioavailable to achieve systemic effects.

FAQs

Is Ca-AKG safe for long-term use?

Current evidence from both human and animal studies supports the long-term safety of Ca-AKG, with no significant adverse effects reported even with prolonged use.

How soon can benefits be expected?

Bone density improvements have been observed after 6 months of consistent supplementation. Longevity and healthspan benefits, as seen in animal models, would require long-term, consistent use over an extended period.

Does Ca-AKG interact with other supplements?

There are no known significant interactions with other supplements. However, due to its calcium content, it's advisable to consider your total daily calcium intake from all sources.

Can Ca-AKG replace calcium supplements?

While Ca-AKG provides calcium, its primary purpose is to deliver alpha-ketoglutarate. It should not be considered a direct replacement for calcium supplements, especially if you have a diagnosed calcium deficiency.

Is it effective for athletic performance?

Current research on Ca-AKG primarily focuses on aging, longevity, and bone health. There is limited evidence to suggest its direct effectiveness for enhancing athletic performance.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC8508957/ – This animal randomized controlled trial (RCT) in C57BL/6 mice demonstrated that 2% Ca-AKG supplementation extended lifespan by approximately 10-13% and improved healthspan. The study also noted a reduction in systemic inflammation and no significant adverse effects, providing strong evidence for Ca-AKG's potential in longevity. Limitations included the lack of a calcium-only control group.
https://pubmed.ncbi.nlm.nih.gov/34952764/ – This systematic review summarizes the effects of AKG supplementation in both human and animal studies. It highlights the benefits for bone health, discusses the underlying epigenetic mechanisms, and confirms the safety profile of AKG. The review emphasizes the need for more extensive human RCTs to further validate the promising healthspan benefits observed in animal models.
https://research.vu.nl/files/160079366/AlphaKetoglutarate_dietary_supplementation_to_improve_health_in_humans.pdf – This human randomized controlled trial (RCT) involving menopausal women with osteopenia (n≥30) showed that 6 g/day of Ca-AKG for 6 months significantly increased bone mineral density by 1.6% and decreased biomarkers of bone resorption compared to a calcium-only control group. The study provides clinical evidence for Ca-AKG's benefit in bone health, supported by a plausible mechanism involving epigenetic regulation.