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Hi,
I know that correlation is not causation. I do. I promise. But sometimes you experience a correlation that sells you for life.
And that’s how I feel about the performance probiotics V-Nella and Nella.
A little over a week before the 2024 Leadville 100 Mile, our entire family got a stomach bug. I’m pretty sure it wiped out my gut microbiota, along with getting rid of old Juicy Fruit I swallowed in elementary school, the entirety of my small and large intestines, and my self worth. In my depleted state, I started taking 2 x V-Nella pills daily until the race, when I had a surprise breakthrough that changed my life forever.
(Don’t play a drinking game where you take a shot every time I mention Leadville, or you will die.)
Science of Probiotics
Let’s take this out of the world of my weird superstitions, and adventure into the wild science of probiotics. Ever since I first learned about microbiome connections to basically every aspect of health and performance, it has felt like the next frontier. 10 years ago, I was saying “just wait 10 years and the world will change.”
That change hasn't happened in a major way (at least not publicly).
It feels a bit like driverless cars. I remember listening to tech evangelists saying that every long-haul truck would be driverless...by 2020. That didn't happen. But what did happen is incremental technology growth, where the biggest claims by hotshot start-ups failed, and what grew in their place were companies with a long-term vision of how to ease into a revolution. Now, in cities like San Francisco and Phoenix, there are enough Waymos to start a robot uprising if they wanted to (and they do).
I think that's the path of microbiome interventions--incremental improvements that are almost imperceptible, until we look up and there is a massive overhaul of the current paradigm.
There are two paths of research that are most interesting right now. The first is basic probiotic supplementation, which has some solid evidence but nothing earth-shaking (we'll talk about that in a second). The other is the more revolutionary approaches, like supplementing with probiotic strains that may specifically enhance performance like V Nella.
Probiotics Overview
Let's start with the basics. A 2020 review article in the Journal of the International Society of Sports Nutrition provided a great intro to the complexity of gut microbiota in athletes. The microbiome consists of thousands of bacterial groups, millions of genes, and non-bacterial cells and viruses. The microbiome is essential for “nutrient uptake, vitamin synthesis, energy harvest, inflammatory modulation, and host immune response.” There are studies where mice are conditioned to have a limited microbiome, resulting in terrible health issues, only to be rescued when the microbiome is restored.
The ever-evolving microbiome is influenced by genetics, environment, and behavior, including athletics. In the course of a hard race, the microbiome can be stressed so severely that biota prevalence shifts rapidly. Now imagine the pressure to adapt and evolve within our individual microbiomes! It’s really unprecedented in human physiology.
Put these elements together and you have the perfect storm of scientific opportunity. Thousands of variables with massive cross-population differences; an emerging understanding of interrelated physiological functions of those variables; and aggregation of health outcomes that can be correlated with individual variance. It’s overwhelmingly exciting, but also complex.
There’s a chance for astounding amounts of statistical noise, but with recent advances in sequencing and analysis, also the potential for scientific breakthroughs. Could it reshape how we think of athletic performance too?
Probiotic Research
A 2024 review study addressed that question, looking at the 13 randomized control studies from 2012-2023. That seems like a pretty low number of studies for such an important subject! Fascinatingly, “all studies found a positive correlation between taking probiotic supplementation and a reduction in fatigue, fatigue causing symptoms or perceptions of fatigue.” Some identified pathways for reducing lactate accumulation and creatine kinase concentrations. A couple others found reduction in anxiety and stress!
There seemed to be little impact on inflammation and performance, with some studies showing positive results but most neutral. The three studies on GI complaints found those were reduced.
The big problem with recommending probiotics or not is that the actual lines of causation are weakly understood.
And that leads us to the next line of study: areas where researchers have theories about direct links between specific microbiota and outcomes, and they manipulate the microbiome to express those bacteria at greater levels. A 2019 study in Nature found a post-marathon spike in Veillonella, which is known to metabolize lactate. After isolating Veillonella in a runner, the researchers inoculated mice with it, and those mice were able to run 13% farther on their adorable mice treadmills. The author of that study founded Fitbiomics, which aims to isolate what makes the world’s best athletes unique, then apply that information to develop nutrition interventions for everyone. Capitalism!
That company came out with Nella in 2021 and V-Nella in 2024, with some hopeful research but nothing definitive. Fun fact: I am writing this email today because a pre-print was just published showing that V Nella may reduce fatigue and increase voluntary physical activity. Pre-prints are not peer reviewed, so I’m not delving into major details here. The authors could say that V Nella makes you crap out platinum R+B hits, and I’d have to take them at their word.
The Future of Probiotics
In the future, it’s likely that the scientific community will develop a far more detailed understanding of how the microbiome functions, much like the human genome was unraveled with DNA sequencing technology. Honestly, it seems like the perfect application of AI, similar to how Alphafold unraveled the protein folding mystery.
For now, I personally take both Nella and V Nella. Does it do anything? I don't know. I don't think anyone really knows if the current slate of options does much at all, and if it does do something, what's the right dose and composition. I was initially motivated to make some interventions by my bad GI system (leading me to Nella), and later by the pre-Leadville sphincter exorcism (V Nella).
So that might be the best framework for thinking about it. Do you have health issues of almost any type? Well, the studies on probiotics sometimes show weird and non-linear benefits, and a good probiotic is likely neutral at worst....
...Or not. Because we don't really understand all of the arrows of causation, there could be other issues that the review study didn't see, and that applies even more with specific bacteria.
Big takeaway: stay tuned. I personally think probiotics could be the next frontier of health and performance. Or maybe it’s still 10 years away. Either way, I’m going to buy 4 packages of V Nella before this email goes out just in case, since it has become my emotional support supplement.
- David
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