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 Dr. Frank Lipman sits on a chair, cross-legged, arm resting on the back of the chair, lightly touching his other hand that is resting on his thigh. He is wearing blue denim, a blue dress shirt and a navy textured blazer and black glasses. He is smiling, showing his front teeth looking off to the side.

Dr. Frank Lipman

Chief Medical Officer at THE WELL

Updated: 02/23/2024

There are some basic facts that just about all of us can agree on, and one of them is that modern Western medicine is dominated by pharmaceutical drugs. They are, for better or worse, just about everywhere these days, and while they have their place, they’re also wildly over-prescribed – blunt instruments that can sometimes create more problems than they solve. That’s why I’m always curious about promising alternatives and excited by the growing research into natural compounds – some which come from the food we eat, some are synthesized versions of what our own bodies make – which can help the body restore itself when it begins to run down.

You may ask, why take a supplement to boost levels of a natural compound beyond normal physiological levels? Doesn’t Mother Nature know best? Well, in the first decades of our life, She certainly does, but as we age, key chunks of our cellular machinery begin to wear down, and evolution doesn’t much care. It’s driven by natural selection — passing on our genes to the next generation – and as we pass through our 40s, our prime reproductive years are in the rear view mirror. So, there is a strong argument for shoring up key body molecules we’ve got, and nudging them back up to more youthful levels, in order to live as healthfully and robustly as we possibly can. One candidate that may be able to keep health moving in a positive direction is something called ‘alpha-ketoglutarate’ or ‘AKG’. At age 80, our levels are one-tenth of what they were at 40, so a little nudging may be in order as time marches on.

Supplementing with AKG has been shown to do a bunch of helpful things as a complementary surgical therapy. But it’s probably generated the most excitement as a potential all-purpose anti-aging supplement. In one notable mouse study, it extended healthspan by more than 40%. You may want to explore AKG with a knowledgeable integrative practitioner. You certainly should follow the news as more human research unfolds (admittedly a slow process without Big Pharma bucks behind it). In the meantime though, here’s what you need to know about this versatile compound:

AKG: what is it?

You’ve probably heard this one before: food molecules are turned into energy inside the “power plants” of the cells, the mitochondria. The chain of those biochemical reactions is, take my word for it, complicated. But what’s important here is that AKG is continually being produced and consumed in the process. What’s really interesting is that AKG plays a key helper role in all sorts of essential physiological processes both inside and outside the mitochondria. It’s a busybody molecule (in a good way), for instance, inside the body, it converts into the amino acid glutamine which helps regulate a host of body businesses, from the immune system to metabolism (burning sugar and fat for energy) to the musculoskeletal system. Consequently, AKG shows promise as an energy-enhancer, an anti-inflammatory and as all-round protection against disease.

What does AKG supplementation mean for us humans?

Most of the AKG anti-aging studies have been done in animals. But we do have good evidence that adding supplemental AKG to the mix may improve human health outcomes, especially in the surgical realm. Studies have shown that intravenous AKG limited muscle wasting after abdominal surgeries, a major post-surgery problem. Several studies have shown that AKG delivered to patients undergoing heart surgery was likely beneficial, boosting the amount of energy the heart cells could generate, thereby improving blood flow throughout the body.

Younger, More Resilient Skin and Bones — Yes, Please

We know that AKG boosts collagen – the essential building block of bone and connective tissue, two types of tissues that become more fragile with age. No surprise, manufacturers have begun adding it to some of their skin care products. As for bone, AKG boosts glutamine which in turn boosts bone formation, good evidence that it may prove valuable in the fight against serious bone thinning, or osteoporosis, which often leads to disabling falls and fractures. In hospital settings, AKG has shown promise as a complementary therapy for burn victims and wound healing. 

Out With Cobwebs, Out With Toxins

AKG not only helps our bodies produce the proteins it needs to keep us up and running, it helps clean up the waste products. Building protein generates ammonia which, above certain levels, is severely toxic. But when AKG converts into glutamine, it burns up excess ammonia and in so doing performs for us a valuable detox function. Because ammonia is especially toxic to the brain, that makes AKG a good candidate to help us fend off common, and dreaded, neurological conditions like dementia that so often accompany old age. Another villain in the aging brain story? Oxidative stress (that is, those free radicals spun out by our energy production system). And AKG has a good lab track record of tamping excess oxidative stress by pumping up our antioxidant enzymes.

Anti-Inflammatory, Anti-Cancer, Take Your Pick

Some of you probably remember the discussion about “cytokine storms,” how an over-excited immune system can overdo its attack on the COVID 19 virus and cause more damage than the virus itself. Well, it turns out the body produces anti-inflammatory cytokines as well, and AKG lends a helping hand here. And we know, inflammation is a root cause of most, if not all, of our most serious chronic diseases, including cancer. But AKG possesses potentially cancer-fighting properties of another sort as well. It acts as a kind of “good cop” helping to police our DNA, specifically the system that determines which genes should be turned on and off, and when (the epigenome, to get technical). As we get older, the on/off desk makes more mistakes and consequently, our risk of cancer goes up. AKG looks to help keep our DNA behaving the way it was designed to.

AKG Could Help Your Gut Stay Strong and Leak-Free

The animal research gives us strong reason to think that AKG is an ally in the gut. Working through glutamine, it helps maintain a healthy balance of bacteria in microbiome which, in turn, protects the lining of the gut wall and helps maintain overall good gut function. The hoped-for net result: less “leaky-gut”-driven systemic inflammation and better absorption of nutrients and vitamins, often a problem in the elder years. 

But ‘weight’ — there’s more: Some intriguing research on mice suggests that AKG can keep weight down, keep blood sugar under control, and promote the formation of calorie-burning brown fat.

Adding more AKG to your life?

Again, we’re early days when it comes to clinical proof that oral supplements will make a positive difference in your life. But if you’re working with an integrative health doc (especially important for pregnant or nursing women and children) and you follow the recommended dosages, then the risks and side-effects seem to be virtually non-existent. But again, work with a practitioner – no freestyling! You can also increase your natural AKG production with good old-fashioned exercise and fasting, so you and your practitioner can tailor a program that works for you.

Know that AKG works as an energy donor and cellular signaling molecule and is involved in several metabolic and cellular pathways that decline with age. As such, it is often combined with other anti-aging ingredients in supplement form, and sometimes with calcium, as supposedly the mineral enhances the body’s ability to make use of the compound.

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