Our reviewer takes the Mitopure Challenge to see if he is a urolithin A super-producer – or whether he should consider supplementation.

A year ago today, my energy levels were through the roof. Working three jobs, hard workouts every day, coming home in the evening to play with my two-year-old son – bring it on! I would go to bed at 11 pm with some energy left to spare.

Fast forward to March of this year: I caught COVID and “recovered” after a few days, experiencing nothing more than what felt like a bad cold. Little did I know that those creepy viral invaders were brewing up something within the “black box” of my body that would significantly alter my life. Sure enough, in the months that followed my COVID event I experienced a gradual, and otherwise inexplicable decline in energy.

As I write this product review for you today, I can honestly say that I am operating at 60% of my former energy level. In other words, by the time I’m done with my work day (~ 5:30 pm) and begin to spend quality time with my wife and (now) three-year-old son, my tank is nearly empty, significantly hindering my ability to be the father and husband that I strive to be.

As a researcher that studies the cellular and molecular biology of aging, as soon as I noticed my decline in energy, I couldn’t help but consider the possibility of compromised mitochondrial health. Indeed there is growing excitement among the scientific community about the importance of mitochondrial health and its potential to help people with long COVID and neurodegenerative conditions. So, when I was serendipitously offered the opportunity to review Amazentis’s Timeline® supplement Mitopure – it was a no brainer.

Mitopure Challenge in a glance

Timeline’s supplement Mitopure: boosting cellular health with precision supplementation

Mitopure contains a proprietary, highly pure form of one of the most promising longevity molecules in the market – urolithin A – which has been shown in clinical studies to improve cellular health and human performance by re-energising cells. This translates to improved strength, endurance, fitness and cellular energy.

Further, Timeline is one of the rare companies that allows you to quantify how much urolithin A your body naturally produces, and how much of a boost you get from supplementation. The value of this cannot be overstated; I’m a fairly healthy individual, and I spend a significant percentage of my paycheck on my supplement stack to make sure that I can maintain my quality of life as I get older. But I would be lying if I said that I knew for a fact that any of the things I am taking are actually getting into my body, leave alone whether it’s exerting its desired effect. The sad fact is that the majority of supplements in the market do not do what they claim on their labels. This is particularly troublesome for a blossoming longevity supplement market in which individuals are expected to take supplements for the rest of their lives to preserve their health.

With its promising preclinical and human data state-of-the-art biomarker test — Mitopure Challenge—Timeline has positioned Mitopure at the forefront of personalised and precision supplementation. This is all fantastic from my perspective as a scientist, but the most important question is yet to be answered. Could urolithin A be the answer to my energy issues?

The science of urolithin A: Re-energising the body from “the inside out”

Urolithin A is a molecule that is naturally produced by our gut microbiome (“postbiotic”), but only when we eat certain “superfoods” such as walnuts, raspberries and, most notably, pomegranates. This is because these foods contain the precursor to urolithin A, a class of molecules called ellagitannins (Figure 1)

The “healing properties” of pomegranates have been for thousands of years, but it is only recently that scientists at Timeline deconstructed the pomegranate and identified urolithin A as a geroprotective molecule (one that protects the body against the ravages of aging). Specifically, they found that urolithin A activates a key pathway that improves the health of mitochondria, but why is preserving the health of our mitochondria so important?

Our mitochondria are tasked with unlocking energy stored in food to produce a whopping ~90% of the cellular energy required to power our bodies. In this sense, mitochondria are truly the “life force” of our cells.

Studies have shown that:

1. Mitochondrial function declines with age (as early as 30 years old!), compromising the ability of our cells to generate energy required to maintain our body’s youthful function.
2. Environmental and lifestyle factors such as poor sleep and diet, exposure to toxins, and viral infections impair mitochondrial health.

Our cells possess an “in-built” mechanism to protect themselves from mitochondrial decline called mitochondrial turnover. Mitochondrial turnover involves recycling “old and damaged mitochondria” through a process called mitophagy, and replacing them with new, healthy ones through a process called mitochondrial biogenesis (Figure 2). Urolithin A is a powerful activator of mitophagy that promotes mitochondrial turnover to improve the health status of the mitochondria within our cells.

As my significant decrease in energy levels coincides with the “perfect storm” of my 35th birthday and unfortunate encounter with SARS-Cov-2, I am extremely keen to try anything that holds promise to help renew my “worn-down” mitochondria.

This review consists of two parts:

1. Mitopure Challenge biomarker kit (measures how effectively a single dose of Mitopure increases my Urolithin A levels)
2. Timeline Mitopure supplement (how 60 days of urolithin A supplementation affects my physical and mental performance, with a focus on whether it can improve my energy levels).

Mitopure Challenge: Do I need a urolithin A boost?

The Mitopure Challenge test kit is designed to help you figure out how much urolithin A your gut microbiome naturally makes, and how effective Mitopure is at boosting your levels – all with a quick and simple “finger-prick” blood draw. Timeline is conducting an ongoing clinical trial with their test kit which suggests that around 30-40% of the population possess the necessary gut microbiome to produce urolithin A from pomegranates and this capacity declines with age. Further, individuals that produced the most urolithin A had richer and more diverse gut microbiomes – a powerful metric of healthy aging.

These results were particularly striking to me as they emphasise that eating healthy foods isn’t enough to reap the benefits of a healthy diet – you need the right microbiome in place as well. In a sense, our microbial denizens are our own personal drug factories. So, how much urolithin A do my microbial pharmacies need to produce to boost health and even treat disease?

The scientists at Timeline have found the optimal dose to be between 500-1000 mg of urolithin A a day. To put this into perspective, that would require the average “urolithin A producer” to drink at least 6 glasses of pomegranate juice a day. The amount of sugar that would have to be ingested in the process could place even the healthiest individual on the fast-track to diabetes and fatty liver disease. To make matters more complex, 6 glasses is just the average. Data suggests that there’s substantial differences in the amount of ellagitannin containing fruits/nuts that need to be eaten to hit that therapeutic dose – both between individuals and as one ages.

So I was really excited to take the Mitopure Challenge to see where I fall on the urolithin A spectrum and assess the likelihood that Mitopure could be the answer to my early evening exhaustion.

Taking the Mitopure Challenge

I applied for (through a simple online form), received, and registered my Mitopure Challenge kit – all within 10 days. I was very impressed with how smooth the process was considering that Timeline’s scientists are based in Switzerland and I’m situated thousands of miles away in New Jersey.

The packaging of the kit consisted of a well-organised box with a sleek design and clearly distinct compartments for instructions, return UPS envelope, components for blood sample collection, Mitopure sample sachet, etc.

Every aspect of the packaging felt elegantly presented, cleanly designed and straightforward to use – it reminded me of the first time I saw the packaging of an Apple iPhone. Although packaging may not seem like a huge deal, it plays an absolutely essential role for kits with multiple steps and components. I find it especially impactful (at least psychologically) for those kits that require collecting biological samples, and it is a great way to flex their brand.

I found the overall protocol to be time-intensive, so it required some planning. This was likely due to the challenge of squeezing a multi-step protocol, spread across several hours, into a busy schedule which includes work and a 3-year-old.

The protocol:

1. Drink a glass of pomegranate juice in the morning, wait 24 hours and then use a simple finger prick device to collect 4 drops of blood on a measurement card (measures natural urolithin A production).
2. Consume Mitopure mixed with your favourite yoghurt (urolithin A is fat soluble), wait 8 hours and then repeat blood collection (measures Mitopure-boosted urolithin A levels).
3. Once the collection cards are dried, send them back to Amazentis using the postage-paid UPS shipping envelope provided. This must be done within 24 hours after the last blood collection.

The intensive protocol was unavoidable, but the great instruction manual and video tutorial left minimal room for error and hiccups along the way.

My results

About a week after I sent my samples back, I received the much-anticipated email that my results were ready! Deep breath. I entered my login email and Kit ID, heart thumping harder as I waited for the page to load with my results and:

My heart dropped when I saw how much urolithin A my body naturally produces. Not 100 (high producer), not 30 (low producer), not even a measly 5 ng/mL – 0 ng/mL. Here I was expecting a “dopamine ping” from finding out my microbiome was one of the minority “super-producers” and I couldn’t be further from the truth. But there is a bright side. Supplementation with Mitopure brought my levels up to 161. A ray of hope. Being at “rock bottom” means that there’s plenty of room for improvement and an increased chance that boosting my depleted urolithin A levels could significantly improve my mitochondrial health and energy levels.

Verdict

Seeing my results from the Mitopure Challenge was the decisive factor that convinced me to give Amazentis’s Mitopure supplement a try. Yes, the scientific data is robust and includes human safety and efficacy data from individuals across the age and health spectrum, but I rarely make decisions based on scientific research alone. We are transitioning into a new era of healthcare that has realised the central importance of personalised and precision therapeutics – of validating research with “me-search”. This requires acknowledging that a supplement that is effective in one individual, may not be effective when interacting with my unique physiology. And this is where companion diagnostic tests can be extremely powerful tools to guide effective screening of supplements and is indeed, the future of next gen supplementation.

On a personal level, there are only so many supplements I can afford to take and I want to make sure that I am getting the most “bang for my buck” from my significant supplement stack. This is hard to do without a window into what is going on inside my body. The Mitopure Challenge gave me the opportunity to evaluate the potential benefit I could get from supplementing with Mitopure, as well as validate that it is being effectively absorbed into my body.

I have started supplementing with Mitopure every day and will continue for 3 months. My regimen involves supplementing with 500 mg in the first month and increasing my dose to 1000 mg in the second month.

I chose this hybrid regimen based on Amazentis’s human clinical data which suggests that:

1. 500 mg is the minimum dose for benefits and the commercially recommended dose. As a rule of thumb, I always start supplementing with the minimum viable dose and monitor how I feel.
2. 1000 mg is the optimal therapeutic dose where individual’s experienced the most significant benefits and within the shortest time frame.

Throughout the 3 month period, I will be tracking various metrics that reflect both physical and cognitive health which I will describe in further detail in my next review. Metrics include: exercise performance, recovery, sleep quality, resilience (various stress tests), immune health and overall physical and mental energy levels.

I am optimistic that Mitopure will help me get my mitochondrial health and overall energy levels back on track! Stay tuned for my 2-month evaluation at the end of January!