Alpha-ketoglutarate (Ca-AKG): Better Than NMN and NAD+ Precursors?

From Mental Health to Longevity: The Wide-Ranging Benefits of Calcium Alpha-ketoglutarate (Ca-AKG)

For a technical version of this post click here.

As we age, our body's energy production declines, and we become more susceptible to diseases such as cancer, diabetes, and neurodegeneration. In the world of health and wellness, there is no shortage of buzzworthy supplements promising to unlock the secrets to longevity and vitality. Among the most popular in recent years are NAD+ precursors, such as NMN and NR, which have gained widespread attention for their potential to speed up metabolism and increase energy. However, there's a lesser-known molecule that could hold even more promise: AKG and its more stomach friendly supplement form Ca-AKG.

Metabolism is a fundamental process that keeps us alive. One of the most important metabolic processes is called the TCA cycle. Why is an efficient and well-oiled TCA cycle important to longevity? This is because the TCA cycle is responsible for energy production in cells, which is used by numerous other processes in our cells such as converting amino acids into peptides and proteins. 

AKG and NAD+ precursors are both heavily involved in the TCA cycle – NAD+ feeds into three of the eight steps in the TCA cycle, while AKG production is the rate-limiting step of the TCA cycle. Therefore, boosting NAD+ and AKG are thought to boost the TCA cycle and thus metabolism.

This highlights the importance of AKG in facilitating metabolic processes, which control thousands of genes and reactions per second in every cell. In fact, toxins that target metabolism can quickly prove fatal - cyanide, for instance, kills by halting metabolic processes. Interestingly, AKG is used as a treatment for cyanide poisoning (Bhattacharya and Tulsawani 2009), underscoring its importance in maintaining healthy metabolic function.

What's more, AKG has been identified as a potential key to unlocking the mysteries of aging. As mitochondrial TCA cycle metabolites have become an increasingly popular target for anti-aging research (Martínez-Reyes 2020), AKG's role in facilitating these processes is gaining attention as well. In short, while NAD+ precursors may be the current darlings of the supplement world, AKG's potential benefits cannot be overlooked.

Exploring Ca-AKG's Unique Pathways for Increased Lifespan and Healthspan

While Ca-AKG's potential benefits are still being explored, early research suggests that it may offer some unique advantages over popular supplements like NMN when it comes to promoting longevity and healthy aging.

One key area where Ca-AKG stands out is in its ability to increase lifespan. In a study conducted on mice, Ca-AKG was found to increase lifespan by a remarkable 17% - even when administered later in life, at the age of 60 human years. In comparison, NMN only resulted in a 5% increase in lifespan. This significant difference suggests that Ca-AKG may be capable of promoting healthy aging through pathways that are not targeted by NMN.

One possible explanation for Ca-AKG's superior performance is its ability to increase the activity of AMPK, an energy sensor that regulates cellular metabolism, while simultaneously inhibiting mTOR, a protein that regulates cell growth and metabolism. By inhibiting mTOR, AKG may be able to activate autophagy - a process by which cells break down and recycle damaged proteins and other cellular components. This can help to keep cells healthy and functional, which in turn may contribute to improved healthspan and longevity.

In addition to its potential benefits for metabolic function and autophagy, Ca-AKG may also activate certain longevity genes that are not targeted by NAD+ precursors like NMN. For example, David Sinclair's lab recently used OSK Yamanaka factors (OCT4, SOX2, and KLF4) to completely reverse blindness in mice and extend lifespan without cancer risks. Ca-AKG has been found to activate these same longevity genes, suggesting that it may have unique potential for promoting healthy aging.

Unlocking Longevity without Compromising Vitality: The Unique Benefits of Ca-AKG

Many interventions that have been shown to increase lifespan come at the expense of energy and vitality, making them less attractive options for individuals seeking to promote healthy aging.

For example, calorie restriction combined with fasting has been shown to increase lifespan by a remarkable 35% in mice, while the drug rapamycin increases lifespan by 15%. However, both of these interventions work by slowing cellular growth and metabolism by inhibiting mTOR - a protein that regulates cell growth and metabolism. Unfortunately, this can also inhibit the immune system, which can have negative implications for overall health and vitality.

Metformin, a drug commonly used to treat type 2 diabetes, has also been found to increase lifespan in mice by 6%. However, it does so by starving the body of glucose and increasing sugar metabolism via AMPK activation. This can compromise athletic performance, which requires glucose as fuel.

Similarly, 17-alpha-estradiol - a form of estrogen - has been found to increase lifespan in male mice by 12% by suppressing testosterone production. While this may be a viable option for male mice, it's important to note that lowering testosterone can have negative implications for men's physical, sexual, and emotional health.

In contrast, Ca-AKG was found to increase female mice lifespan by 17% (10% in males) even when started late in life at the age of 60 human years. By improving metabolism and simultaneously activating Yamanaka longevity genes, Ca-AKG can boost energy levels and support immune function, while also promoting healthy aging and longevity. This makes it a truly unique and promising option among current longevity interventions.

Ca-AKG's Potential Benefits for Mental Health, Muscle, Immunity, and Fertility

Ca-AKG's potential benefits on various aspects of health and well-being are becoming increasingly apparent. Beyond its anti-aging effects and positive impact on metabolism, one study published in the journal Aging Cell found that Ca-AKG can delay age-related fertility decline in mammals. The study, which was conducted on female mice, found that supplementing with AKG improved fertility and increased the number of healthy offspring produced by the mice. The researchers believe that this effect may be due to AKG's ability to activate autophagy, which is a process that helps to clear damaged cells from the body and promote the growth of healthy cells.

Another study, published in the journal Trends in Endocrinology & Metabolism, found that dietary supplementation with Ca-AKG could improve health in humans. The study reviewed a number of previous studies on Ca-AKG and found that it had a number of beneficial effects on the body, including improving insulin sensitivity, reducing inflammation, and improving overall metabolic function. The authors of the study believe that Ca-AKG could be a promising tool for preventing and treating a wide range of metabolic disorders, including diabetes and obesity.

Perhaps most impressively, a study published in the journal Aging found that a compound containing Ca-AKG and vitamins, called Rejuvant®, could confer an average 8-year reduction in biological aging after an average of just 7 months of use, as measured by the TruAge DNA methylation test. This study demonstrates the significant impact that Ca-AKG can have on the aging process and suggests that it may be a powerful tool for improving overall health and longevity.

Additionally, research has suggested that Ca-AKG may have anti-cancer properties, and could be beneficial in supporting the immune system, maintaining muscle and bone health, and improving mental health outcomes.

Regarding the immune system, AKG has been shown to increase the production of white blood cells, which play a critical role in fighting off infections and diseases. Furthermore, AKG has been found to stimulate the growth of muscle and bone, which is particularly important for athletes and the elderly.

The positive effects of Ca-AKG on mental health are particularly intriguing. In one study, Ca-AKG was able to completely reverse depression in mice. The study monitored the level of physical and social activities of mice and introduced stressors over the course of nine days. The stressed group of mice experienced a near complete collapse in physical and social activities, while the Ca-AKG-supplemented group not only was unaffected by stress and moved about and socialized like normal mice, but became even more resilient than normal mice, with increased numbers of neurons.

Exploring the Future of Ca-AKG and Longevity Interventions

In conclusion, Ca-AKG stands out among the many interventions aimed at increasing lifespan and improving healthspan due to its unique ability to increase longevity without compromising vitality. The molecule not only improves metabolism, but also boosts the immune system and enhances mental health and physical performance. In contrast, other interventions such as calorie restriction, fasting, and drug treatments like rapamycin and metformin, come at the cost of energy and vitality.

The potential of Ca-AKG goes beyond anti-aging effects as it has shown promise in various fields such as cardiovascular disease, cancer, and neurodegenerative diseases. Scientists are actively exploring combination treatments of Ca-AKG with other molecules, blood factors, and genetic targets to uncover the next breakthrough in improving health and aging.

It's important to note that while Ca-AKG shows great promise as a health supplement, more research is needed to fully understand its benefits and potential side effects. As with any supplement or medication, it's important to consult with a healthcare provider before starting to use Ca-AKG. Additionally, the quality and source of the supplement should be thoroughly researched to ensure its safety and effectiveness.

In summary, Ca-AKG is a molecule with vast potential to improve health and extend lifespan without sacrificing vitality. Its unique ability to increase longevity and enhance physical and mental performance makes it a promising candidate for further research and development in the field of anti-aging.

If you found value in today's discussion, please take a moment to like, subscribe, comment, and share. Your engagement helps me to continue creating content that matters to you. As always, our topics are chosen by you, our readers. So if you have an idea or topic you'd like to see covered, let me know in the comments below. Until next time, stay healthy, be kind, and know that your support is deeply appreciated.