January 10, 2024
We all know THAT person. The person who has never even one day in their life watched what they eat. They eat the same as you (or worse), work out less than you, and still stay lean. These evil creatures always say the same thing… “Good genetics, I guess,” or “I’ve always had a fast metabolism,” or “I’m just lucky.” Although all three of them may play a small role, science has discovered a more dominant reason. They are infected. Not with a tapeworm or some other pathogenic parasite. But with a tiny bacterium named Akkermansia muciniphila. It turns out that this bacteria may not only be keeping them lean without the struggle, but it is lowering their risk of the 5 cardinal diseases that bring us all closer to death.
The 5 Thieves
What are these 5 thieves of longevity? Spend enough time with me, and you have heard me preach it. I approach longevity (and its sister healthspan – how long you can spend active and healthy) by working backward from what ultimately kills us or limits our healthspan. These 5 thieves are namely: Heart Disease, Cancer, Stroke, Dementia, and Falls and Accidents. If any of these things happen, you shorten both your longevity timeline and your healthspan activity timeline. So much of what we do at Formula Wellness is about not avoiding the inevitable but pushing these off another decade or two so as to expand our healthspan and, if lucky, our lifespan a little. To accomplish this goal of delaying the 5 thieves, we can take one step proximal and eliminate things that accelerate or cause these 5 thieves.
There are two major proven things we can do. First, movement – more on this another day, but no doubt increasing activity from sedentary to moderate exercise (as long as you don’t injure yourself) decreases all-cause mortality by 3x. There is simply no diet, medication, supplement, or biohack that approaches this mortality reduction. The second proven thing is avoiding Metabolic Syndrome. Doing everything you can to avoid or reverse this diagnosis is the foundation. What is Metabolic Syndrome? The classical definition from 40 years ago when it was first described (although some may debate some of the diagnostic criteria) is: Obesity, Hypertension, Impaired Glucose Regulation, High Triglycerides, and Low HDL Cholesterol. This constellation of clinical signs is a fast track to narrowing of the arteries causing heart attacks and strokes, worsened immunity causing cancer, lower blood flow and energy utilization in the brain causing dementia and limitations in mobility and excessive weight causing increased falls and accidents. The diagnosis of Metabolic Syndrome increases all causes of mortality by 1.5X and the first thief (heart disease) by 3X.
The Healthspan Formula
What I have said so far is now so basic and engrained in medicine that there is little disagreement on these cornerstone causes of mortality. Indeed, distilling it down to a ”Formula,” the engrained medical paradigm becomes obvious, and it’s how all of healthcare treats and prevents mortality. That traditional formula: Western Diet + Lack of Movement => Obesity, Hypertension, High Cholesterol and Glucose Intolerance => Heart Attacks, Strokes, Cancer, Dementia, Accidents => Death. Traditionally, healthcare is delivered in this country by focusing a lot just one step before death – treating the 5 villains (mainly heart attacks and strokes) after they happen. Over the last 40 years, in the golden age of Big Pharma, we have started to emphasize treating even one more step proximal – diabetes medicines to lower blood sugar, statins to lower cholesterol, blood pressure lowering medications, and weight loss drugs to treat obesity (although all traditional weight loss drugs have a 12-month failure rate that approached 100%). We at Formula Wellness tried to take the hard road and work at the beginning of the formula – working with nutrition first, exercise second, supplementation third, hormone fourth, and then medications only when the horse was already a bit too far out of the barn. This approach is not wrong, but it is hard. The challenges to maintaining a diet with our modern 24/7/365 access to food are hard. Busy lifestyles and commitments make consistency in exercise a challenge. Obligations, both social and business, cause us to make alcohol, sleep, and lifestyle choices that affect us in ways that are not in our consistent best health interests. Stress from work and life impacts our dietary and lifestyle (drug, alcohol) choices as well. It’s easier said than done in accomplishing the lengthening of healthspan by starting at the most proximate cause in the modern American world.
2022 and The Rise of the Anti-Hero: Semaglutide
Thus, to quote the most famous poet of our day, the challenge in preserving health isn’t genetics but, “It’s me, hi. I’m the problem; it’s me.” But in any great story, a hero (or, as Tay-Tay more aptly describes, Anti-Hero) arises to save the day. Over the last year or so, we saw the rise of this anti-hero in the form of a repurposed decade-old diabetes drug called semaglutide.
Unless you have been hiding under a rock, you know the revolution in weight loss that is Ozempic. More accurately, the class of drugs known as GLP-1 agonists causes profound game-changing weight loss in most people taking them. Weight loss occurs because these drugs mimic the natural peptide hormone GLP-1, a hormone released by the stomach and intestines after a meal. This hormone has effects on the brain to tell us to stop eating, on insulin to limit our storage of nutrients in fat, and on other organs like our heart, offering some direct protective benefits. In addition to these positive effects, it lowers average blood sugar levels and improves cholesterol parameters – lowering the risk and incidence of Metabolic Syndrome. It’s not just less food as an input; the GLP-1 (or this pharmaceutical analog) directly improves these parameters. Indeed, a study from last month showed that, even in non-diabetics, GLP-1 agonist use lowers the risk of heart disease.
Why do these drugs seem to be so effective for so many people? First, because we naturally lose GLP-1 production with age (another “hormonal” reason that it’s harder to maintain in your 40’s than 20’s). Second, lifestyle factors (poor exercise, poor diet, alcohol, poor sleep) lower GLP-1 production. Just like most of us become deficient in Testosterone as we age, we become deficient in GLP-1. Thus, we learned through the use of this Big Pharma drug and understanding the physiology behind it, we can revise the decades-old formula:
Western Diet + Lack of Movement => Lower GLP-1 => Obesity, Hypertension, High Cholesterol and Glucose Intolerance => Heart Attacks, Strokes, Cancer, Dementia, Accidents => Death
Mind you, I am not advocating giving up on trying to eat well. And I am absolutely not advocating that we all need to be on semaglutide for the rest of our lives. I call Semaglutide (and Tirzepitide and the 3 more coming) the Anti-hero because, for all the upside, they have a dark side. We see across the nation (and in our practice every day) that these drugs, which should be just a tool to optimize nutrition, are being used to induce ultra-low total calorie, low protein diets that result in not just fat loss but significant muscle mass (and bone density) loss. Used chronically, I believe we will see a dramatic increase in the 5th thief (falls and accidents) due to this lower bone density (more broken bones) and injuries and orthopedic surgeries due to lower muscle mass. The GLP-1 agonists are an improved tool and have helped advance the formula, but we need better.
Akkermansia and The Proximal Cause
So if lifestyle modification may be a little too challenging to be consistent, medications too late (or too many side effects), and a lifetime of big pharma semaglutide may have some unintended lifespan effects, why am I so optimistic after we add GLP-1 into my healthspan equation. It’s because semaglutide is not the only way to increase GLP-1 (or, more accurately, mimic GLP-1).
I mentioned in the open about the annoying friend who always stays lean. About a decade ago, some smart scientists studied a cohort of these individuals and compared them to a group who often struggled with weight. After a lot of tests, they found something consistent. The lean group, across the board, had a lot more of a gut bacterium named Akkermansia muciniphila than the overweight individuals. At first, these scientists didn’t know if it was a chicken or an egg phenomenon. Did the overweight people kill these bacteria with a poor lifestyle, and the lower counts resulted from them being obese, or did their lack of these bacteria cause obesity? In a slightly gross-sounding experiment, a medical procedure called fecal transplantation was performed on obese individuals where high akkermansia stool from lean individuals was implanted into the gut of these patients. Post transplantation, these patients remarkably not only got lean but STAYED lean. Akkermansia was absolutely found to be causative in promoting not only weight loss but also improved blood sugar regulation and cholesterol levels. The perpetually skinny weren’t just lucky; they were lean because they had more Akkermansia. Indeed, in a study when Akkermansia was given to mice with diabetes, the addition of this probiotic was able to reverse diabetes and improve blood sugar. Another mouse experiment showed that Inflammatory Bowel Disease, Crohn’s Disease, and Ulcerative Colitis were cured using this bacterium. Improvements were found in cognitive function in patients who had been transplanted or given Akkermansia. Gut lining health and immune function are all the better with improved levels of Akkermansia muciniphila.
Even though they knew they were on to something, the scientists didn’t just release a product; they dug deeper into the physiology. Akkermansia live in the lining of the intestine and feed off the protective coating the gut secretes (called mucin). Ironically, by eating this mucin as a fuel source it stimulates the gut to produce more mucin, providing a thicker, more protective layer. These bacteria, in a beneficial relationship with the gut cells, then break down some of the foods we eat into short-term fatty acids – the preferred energy source of gut cells. These more energized, healthier gut cells respond by tightening their connections and not letting bad things pass the barrier into the bloodstream – lowering toxin levels (endotoxins) and lowering inflammation. The healthier gut cells then start to release more of a natural hormone called GLP-1.
Lower GLP-1 levels aren’t just an age thing. It’s a loss of gut health thing. It’s a loss of good gut bacteria (Akkermansia) thing. And yes, it’s a poor diet, stress, and alcohol use that kills Akkermansia thing. It’s not just GLP-1 that needs to be added to our above formula; it’s the loss of Akkermansia.
Iron Man vs Thor
When my youngest daughter still wanted to go to the movies with her old man, we would go to every Marvel movie launch. Not growing up a fan, before these movies, I would read a little about them to get the back story, and I learned of a popular debate on who would win a fight between Thor and Ironman—it seemed a little silly since both saved the world every movie. Still, clearly, this was important for people to discuss. I understand the debate now with this year’s commercialization of two competing Akkermansia products.
After years of research, it took a long while to bring Akkermansia to the market. Unlike other common probiotics, Akkermansia is fastidious – very difficult just to put in a pill and leave on the shelf to sell. Two companies took different paths to bring their versions to market. The most well-advertised or known is a company called Pendulum. Indeed, just by clicking on this blog, it will most likely show up as an ad in your Instagram feed. The Pendulum group took the path of combining live bacteria (combined with other bacteria and nutrients) in a product that needs to be refrigerated. In patients low in Akkermansia, they believe boosting the live product is the best way to aid in re-population. The second company, (un-creatively) named The Akkermansia Company, was founded by the two scientists who discovered Akkermansia, and they took a different path. In their research, they found that pasteurizing the Akkermansia (heating it to a specific temperature) increased the expression of a protein on it called Amuc_1100. Most of the effects we talk about in lowering the risk of metabolic syndrome and obesity are caused not just by the presence of Akkermansia but also by the release of Amuc_1100 from it. Thus, pasteurization turns regular Akkermansia (Pendulum) into a more potent form (The Akkermansia Company). Basically, turning Ironman into Thor (Yeah, I said it. Feel free to email me to discuss).
Longevity Formula State of the World 2024:
If you ask this humble reporter, I go back to the headline of this blog: After movement and improved diet, I see no superior intervention in maintaining healthspan and longevity than the addition of Akkermansia in general (and Amuc_1100 in specific) into your supplement stack. It improves lean body mass and increases thermogenesis by turning white fat into brown fat. It improves cholesterol. It lowers blood sugar. It improves cognition. It improves gut health and immunity. It DOESN’T take away lean body muscle mass. It’s once a day. Until I read otherwise, it is in my daily stack for the long term.
In assessing if it should be in your stack, I default back to personalization. I do have a lot of “A” students as patients who are rigid in their diets. Crush workouts six days a week. Meditate. Limit alcohol intake. Use infrared saunas and cold plunge treatments. Supplement their nutrient deficiencies, balance their hormones, and stay lean. These people probably have optimal Akkermansia levels, great gut health, great levels of GLP-1, and far delayed onset of the five villains. This supplement adds nothing. For my “A-” to “B” students (myself included), it’s in the stack.
Longevity, lifespan, and healthspan science are maddeningly controversial. It’s impossible to do the 30-year, double-blind controlled trials that are really needed to get objective data. Nutrition data is so conflicting that even the intuitive answers are confounding. Every day (questionably), well-intentioned biohacking “experts” market something new that saves the day. It is so rare to find something where we understand the physiology, have tested the science, and can simply add something into the stack that addresses the global problem. We are fortunate to have found one here. If you aren’t the “A” student or are a bit off the path, consider talking to one of us and adding it to your stack.
As Always – Keep Getting Better,
Dr. Brian Rudman
Co-Founder & Chief Medical Officer | Formula Wellness
