AKG supplementation improved my biological age in these three ways
IS AKG ANTI-AGING? AKG Supplement improves bio age
AKG supplementation improved three measures of biological age, and has now been permanently added to my longevity hacking stack.
AKG supplementation (also called “Alpha Keto Glutarate") caused a notable stir in the longevity community after a 2021 study in the journal Aging found it improved the biological age of 40 of 42 participants in a small study.
We recently discussed the outcomes of this study with TruMe Labs Co-Founder Yelena Budovskaya, who have now made the biological age measurement from this study available to the general public (via their “TruMe Age Explorer” test).
Naturally, this peaked my own curiosity - could I replicate these results in my own biological age?
After a bit of investigation, it became quite clear that I could. In fact, any one of you reading this could do the same. This post will show you how.
This type of self-experiment is quite straightforward. All you need is a before and after biological age test, a supply of AKG supplement (read our review here) and a scientific approach.
This is, after all, what we love to do here at Longevity Blog - guide our readers to develop their own longevity strategy through self-experimentation.
We have already posted on the reported benefits, basic science, best choice of supply for AKG supplementation in a previous post, so we will get straight into the self-experiment framework and results.
Alpha Keto Glutarate: Experimental framework
Score a 10% discount of high quality, third party tested Alpha Ketoglutarate from DoNotAge with the discount code “longevityblog”.
Dosing of Ca-AKG commenced in November 2022 at 4x capsules of DoNotAge Ca-AKG at 400mg each, for a total of 1.2 grams of Ca-AKG. This was taken with my morning supplement stack, after breakfast.
This dose amount continued for the first 3 months, before increasing the dose to 6x capsules to bring the dose to 2 grams per day.
Dosing remained at 2g/day for the remainder of the experimental period for a total 9 months.
In the 2021 Ca-AKG study from the Journal Aging, dosing was 1g/day for 7 months.
Biological Age Measurements
I measured my before and after biological age with Longevity Blog’s 3x favourite biological age tests (we tested nearly a dozen of them!):
TruDiagnostic’s TruAge (save 15% with code ‘longevityblog’)
TruMe’s TruAge Explorer (save 12% with code ‘longevityblog’)
GlycanAge (save 15% with the code ‘longevityblog’)
Biological age measurements were taken in July 2022 and July 2023, which is my regular annual biological age testing window.
This did mean that 12 months passed between biological age measurements, with only 9 months of AKG supplementation. As you’ll soon see, results were still quite clear.
Blood Measurements
Self-ordered blood tests were ordered through Australian supplier i-screen, who allow you to order and review your own bloods without visiting a doctor.
Blood tests were selected to be very comprehensive. Allowing for the review of immune, liver, kidney function, hormone balance, lipids and more. I carefully chose these tests to have all of the required parameters for the “Phenotypic Age” biological age estimate, providing a fourth type of biological age to test.
Blood tests were closely aligned with AKG supplementation start and ending dates.
A note for your own self-experimenting, you don’t need exact matching between supplement start/end and blood testing. Focus on what’s doable for you - the main thing is that you don’t change any other lifestyle or supplement factors until you’ve completed your follow-up testing.
AKG Self-experiment results
There was a clear improvement in biological age by multiple measures, we’ll work through them sequentially, and then come back for a discussion about interpreting the results.
Make it stand out
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The TruAge Explorer test kit. From only $90USD using the discount code ‘longevityblog’.
RESULT: TruMe Age
In July 2022, my TruMe biological age was 38.9 years, or 2.3 years older than my chronological age.
After 9 months of Ca-AKG supplementation, my TruMe biological age dropped to 37.9 years (-1.0 years), however during this period I aged +1 year. This result is 0.4 years older than my chronological age.
Overall, my biological age result improved by 1 year as compared to my chronological age, with an overall improvement of 2 years.
RESULT: Trudiagnostic extrinsic age
TruDiagnostic’s TruAge Complete biological age test kits provide significantly more comprehensive results than any other biological age test.
This includes estimates of both extrinsic and intrinsic biological age, and an estimate of your telomere length biological age.
You can learn more about the differences between extrinsic and intrinsic age in our interview series with Co-Founder of TruDiagnostic Ryan Smith - part 1 and part 2.
AKG supplementation did not have a significant impact on my intrinsic age, however, there was a notable change in extrinsic biological age. Which dropped from 27.56 years (-9 years from chronological age) to 25.10 years (-12 years from chronological age).
I’ve also supplemented with Nicotinamide Mononucleotide and measured biological age before and after using the Phenotypic Age method. Curious? So were we… read the post!
Again, while one year passed, my biological age actually became younger. This time, 3 years of total improvement.
This result is particularly interesting, given AKG’s known role in improving immune system health, but we’ll save that for the discussion.
RESULT: GLYCANAGE
Unfortunately our GlycanAge biological age test was lost in transit and we do not have the after results from this test.
RESULT: Phenotypic Age
In one of our first posts on biological age, we introduced three free ways to estimate your biological age.
Tabulated results across the three tests. Don’t forget that I aged one chronological year over the course of the experiment!
One of these estimates is called Phenotypic Age", and I have now been tracking mine for the past three years, and have been able to find blood tests reaching back all the way back to 2015 to re-calculate (age 30).
After 9 months of AKG supplementation, my Phenotypic Age improved from 30 years old to 27 years old (-3 years). Given that I also aged +1 year chronologically, this is a net result of -4 years.
This biological age estimate is much more sensitive to changes in diet, lifestyle and day to day ups and downs, so we need to consider this result conservatively.
Only once before have I seen a similar improvement (-3.5 years) in my biological age, which was after I self-experimented with NAD boosting supplement Nicotinamide Mononucleotide.
Selected blood results
In the following, I share all blood results that had a significant change over the experimental period, did not have other confounding factors and for which there was scientific research on AKG supplementation that supports a causal link.
All test data presented here is through self-ordered blood test provider i-screen (Australia).
Liver Function
Nov 2022 to Aug 2023 liver markers showed statistically significant improvement. Note that my liver markers are at time elevated because I am an endurance athlete.
Inflammation
Nov 2022 to Aug 2023 high sensitivity CRP, a key marker of inflammation, reached the lowest levels of all time. Even below the levels had 10+ years ago.
LDL-C
Nov 2022 to Aug 2023 saw a 10%+ drop in LDL-C, which, which is significant as it is now at the lowest level I have ever measured. Noteworthy after the March 2021 test, I eliminated dairy from my diet and LDL-C plummeted!
DHEA
Dehydroepiandrosterone sulfate (DHEA) levels are closely linked with cellular energy production, and many important bodily systems are downstream. My levels appeared to climb by 25% post AGK supplementation.
akg supplementation: DISCUSSION
You don’t have to use supplements to improve your biological age. Nick did it by adding more plants to his diet, read about it here.
Interpreting the results of a self-experiment is a very important step. It is very tempting to see rdata in results form and try to form a conclusion straight away. To bring in tools from science, we must discuss the results first!
If you’ve ready any of my previous self-experiments, you’ll know that how the self-experiment was controlled is pivotal. In essence, this means limiting as much as possible, any external factors which could ‘confuse’ the results.
When you come to complete you own self-experiments, you need to balance several factors.
First, you need to try the intervention long enough for it to have effect on the variables you are measuring.
In this example, we are looking at biological age changes, which in the case of epigenetic tests like TruMe Labs or TruDiagnostic, take around 3-6 months for effects to be observable.
AKG supplementation has an immediate on cellular energy production, but the flow on effects to the epigenome need significant time (months). In the case of the research study on Ca-AKG and biological age, the results were measured at 7 months of supplementation on average.
My selected period of 9 months allows for enough time for the AKG supplement to imprint on my epigenome and brought it into alignment with my annual biological age testing regimine.
Second, to effectively determine how long the self-experiment will run for, you need also consider controlling other variables which might effect the result.
You’ll want to run the self-experiment for long enough to impact the measurement variables you’re after, but not so long that you cannot control other variables that might impact the result.
Hear from our Founder Nick on biological age testing and how you can change diet, sleep, exercise and stress to improve yours! Read more
In the case of biological age tests, the most influential factors to control are:
diet
sleep
stress
exercise
pollution/smoking
supplements
COVID-19
Well Controlled
In my own case, I have a very regimented lifestyle. I keep to my triathlon and strength training with daily walks (exercise). I sleep a solid 7-8 hours a night, with a consistent bedtime. I live in a rural area with very low levels of air pollution and have not moved in the experimentation window.
No major changes to my exercise, sleep or environmental pollutants were observed.
My diet is a dairy-free, mediterranean-esque diet focused on plant diversity and high protein intake (meat, fish, poultry, eggs, whey protein isolate). I know that this diet works well for me based on my blood tests and biological age data, and I’ve not made any significiant changes to it.
These factors therefore can be considered to be well-controlled, for the purposes of impacting the epigenome.
Not Well Controlled
Stress however, was an unavoidable confounder.
I went through several major life changes over the self-experimentation period, and stress was at times at very high levels, often for weeks at a time. I do believe this negatively impacted by biological age results.
I also contracted COVID-19 in May 2023, which likely also negatively impacted my biological age result, with both experts - Ryan at Tru Diagnostic and Yelena at TruMe Labs suggesting I leave at least two months after my recovery before re-testing. I followed these instructions.
Conclusion: Ca-AKG positively impacted by biological age
Given that the not well controlled self-experiment results would raise by biological age, but that I measured improvements to biological age across three different tests, as well as in several important longevity blood measurements (LDL-C, DHEA, ALT/AST, hsCRP) - I believe there is a solid and clear conclusion.
Ca-AKG supplementation at 1-2g/day positively impacted by biological age.
Note that I do not say ‘reversed’ my biological age, as I do not believe that these tests are able to substantiate that claim.
However, given there was a 3.1 year mean improvement in biological age between these three tests, I can conclude that Ca-AKG will become a permanent addition to my longevity supplement stack.
And through this example, you are now empowered to run the same experiment. This is incredibly important, as if you run the math - taking 1-2g of Ca-AKG per day (using your 10% discount code ‘longevityblog’ at DoNotAge), it will cost you $630 to $1200 USD per year.
This is not a small investment - you want to know the supplement is working for you.
The method and example laid out here can help you answer that question! It did for me!
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruMe Labs, we have a negotiated an industry leading 15% off coupon code for our readers.
Use the code “LONGVITYBLOG” at CHECKOUT TO SAVE 15%!
And through continued collaboration with DoNotAge, we are offering a 10% off discount for their Calcium Alpha-Keto Glurate supplement as well!
Use the code “Longevityblog” at checkout to save 10% on AKG
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Can Tru Diagnostic Finally Answer: Why am I aging so fast? An interview with Ryan Smith
Why am I aging? Why am I aging so fast?
Why do I feel older than I am? Why am I aging suddenly?
Sometimes aging can catch up with us very quickly, leading us to ask questions like these ones.
The years add up, and we don’t feel the vigour and vitality we are used to. Most of us assume, there isn’t much we can do about it. Aging is inevitable, after all?
You may be new to the longevity technology scene, most people are. Or you may be a longevity hacking legend, who thinks they know everything about how to slow the aging process.
It doesn’t matter which side of the spectrum you find yourself on, there is an exciting new development in the field of biological age testing which can help you answer the all important question…
Why am I aging?
In this post, we are going to review recent updates to TruDiagnostic’s biological age test, which help to answer:
Why am I aging?
If you’re new to biological age testing, there a few deep dive posts you can read on Longevity Blog, perhaps start here or here.
To summarise them in one sentence, it has become possible to measure how old you are biologically over the past few years and there are now dozens of tests for doing so.
But to date, none of them could give you concrete details on the why behind your biological age score.
You might be biologically older or younger than your chronological age (connected to your birthday, the number you celebrate each year).
And beyond ‘exercise more, eat better, sleep more, stress less, don’t smoke, avoid pollution’ - there really hasn’t been much you can do about the aging process.
Until Now….
Tru Diagnostic: Getting to the “Why” behind “why AM I AGING?” (and what to do about it)
Aging is ridiculously complex. Our approach with the OMIC Age clock has been to consolidate information from the entire system and taking a more complete look at the full picture of biological aging…
One of the big things that we have shown with this new aging clock is that it is really the most predictive of every type of age related outcome.
This quote is from our interview below with Ryan Smith, Co-Founder at Tru Diagnostic. We’ve previously introduced Ryan and interviewed him in a two part review series, which you can find here - Part 1 and Part 2.
Our role here at Longevity Blog is to dive into the why and how behind such claims. We aim to dig deep and find the real answers behind the marketing slogans.
We interview founders and lead scientists at longevity tech companies and present you the raw, unfiltered conversations that get straight into the answers.
Today, we’re going to explore some of the key updates to the TruDiagnostic test kit, including the powerful new research efforts behind its development.
What just become possible is truly impressive, and may even be groundbreaking into a new era of biological age testing (namely finally answering - why am I aging so fast?).
Let’s do just that.
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Tru Diagnostic, we have a negotiated an industry leading 12% off coupon code for our readers.
Use the code ‘longevityblog’ at checkout!
This interview was conducted in October 2023 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Tru Diagnostic “OMICmAge” Update
Longevity Blog (LB):
Ryan, thanks so much for coming back to join us again on Longevity Blog, we are really excited to talk to you about some updates that Tru Diagnostic has to their biological age estimates.
The new algorithm is called “OMICmAge” which you are pronouncing as “OMIC Age”. This algorithm is multi “omic” in nature and has demonstrated some very impressive results particularly in predictive capability for mortality and health outcomes.
We are going to break it down - let's start first with what does it mean to be “multi-omic”? And what is an “omic”?
Ryan Smith (RS):
Generally, we would call these “omics” different levels of measurement that are trying to replicate what happens naturally in our body from a stepwise process.
This starts with things like genomics, everyone's familiar with the genome. That would go to the epigenome into things like transcriptomics, metabolomics, and proteomics. These are different ways to measure physical things which are happening in the body.
Bringing together data from all of your “omes” provides a more comprehensive picture of your biological age and why you are aging.
The reason that this is important for aging, is because aging is ridiculously complex. Our approach with the OMIC clock has been to consolidate information from the entire system and taking a more complete look at the full picture of biological aging.
LB: Just to make sure we get this really clear, you mentioned a few different types of “omes”. First genome and epigenome, our audience is pretty familiar with those.
You probably start to lose some readers when you mentioned proteome or metabolome. Why don't you briefly explain what either of those are just as examples?
Tru Diagnostics New Aging Clock Tests More of Your Individual Biology
RS: In the molecular biology world, we have being transcribed by the ribosome, which then create the proteins or peptides that make up the infrastructure of the body. That's what we call proteomics.
Metabolomics is the study of all the small molecules or metabolites within the body. One example of important metabolites are our hormones or neurotransmitters.
Even if you might not be familiar with proteomics and metabolomics, you are certainly familiar with the spectrum of biomarkers that influence disease progression or performance.
LB: This involvement of these different “omes”/”omics” provides a lot more information about what's happening in the body as it is aging. Including this additional information produces a great result - the predictive capability for both mortality and health outcomes.
Can you explain the significance of this development?
OMICmAge Can Predict Health Outcomes, Not Just Mortality
RS: One of the big things that we have shown with this new aging clock is that it is really the most predictive of every type of age related outcome.
More generally, if you are accelerated with this biological clock (biological age > chronological age), you are going to be at more risk of all negative health outcomes than you would be if you were accelerated with the same amount (e.g. +1 year) than any other clock (i.e. any other biological age test).
Pulling together so many sources of information, allows the new OMICmAge algorithm to be incredibly predictive of both mortality (death) and disease outcomes (what age related illnesses you are most likely to get).
LB: The last few sentences that you described are really exciting, and something we will converge in on after a few more questions here. One thing we want to go back to, in addition to this “omic” part of the clock name - we also have an “m” in there, which stands for methylation.
This part of the background development on the new clock comes from a broader collaboration, that is actually really impressive. You have pulled in some of the best researchers on this topic in the world.
We would like to just briefly hear from you about that collaboration.
Tru Diagnostic Partnered With Harvard to Bring in the Leading Science
RS: Proving outcomes about longevity and disease requires following up patients for 40 or 50 years to see what is happening to them. Are they developing disease? Are they dying? When are they dying and what are they dying of?
All that information is incredibly important, but also incredibly difficult to get because really, you had to start a lot of these studies or these data collections a long time ago. In order to do that type of analysis, which we know we needed, we had to work with a biobank.
TruDiagnostic’s dramatic leap ahead of the competition on biological age analyses has been made possible by collaboration with world class researchers and datasets.
Dr Jessica Lasky-Su ticks both of these boxes - an Associate Professor at Harvard Medical School with access to the incredible biobank data at Brigham’s Womens Hospital.
We chose to work with Brigham Women's Hospital and researchers at Harvard. Dr. Jessica Lasky , was our main collaborator on this, along with her postdoctoral student (Dr. Ching Win).
We were able to get samples that had been taken 50 to 40 years ago, and then do our analysis on those samples.
LB: An important part of which was methylation data, the “m” in the OMICmAge clock?
RS: To your point about methylation data, it actually saves greatly on costs. Biological aging is very complex and to measure all of those different “omes” in individual aging it is prohibitively expensive.
Of the 5000 patients in our cohort, costs for testing were $9,000 to $10,000 (USD), to quantify all of those different things at every single level. It's way too expensive.
We knew we had to consolidate data from all those ‘omics’ into a single test which can be done at a much lower price and at scale.
With DNA methylation we can actually predict the “omic” data. Meaning we can quantify things that previously you could only do through advanced proteomics and metabolomics.
OMICMAGE Uses Methylation Data to Predict Biomarkers of Aging
Through measuring your DNA methylation (epigenome), TruDiagnostic can now reveal how different systems in your body are contributing to your biological age.
In short, the “why” behind why you as an individual are aging is starting to be revealed.
LB: Let us jump in there and just break down some really important parts of what you just said.
The omic data you were describing at the opening of the interview is a rich source of information from all different systems in the body. However, it is very expensive to measure those things directly, but they are very indicative of aging outcomes. So we want that information.
Now, what Tru Diagnostic and your research collaborators have made possible, is using the DNA methylation data to make estimates or predictions of omic information that is driving aging - this is a really big advancement.
RS: That is exactly it. We are starting to understand the why of biological aging by incorporating more detail about the things that are driving the process. In our study we used methylation to predict other values.
Right now we can use methylation to predict things you would get at a typical doctor's visit, things like your HbA1c for blood sugar management, your fasting insulin, fasting glucose, or even your creatinine.
Now we can use DNA methylation to output the things that previously were things you had to go get a blood draw at your physician's office to actually quantify.
See Why You are Aging So Fast (Or Not!)
An excerpt from a sample report from TruDiagnostic. Your DNA methylation data can now reveal the status of key blood markers and how they are contributing to your biological age.
LB: To that point, this ability to use the methylation data to predict different biomarkers and provide information about the “why” behind individual aging - there are new reports that are going to be accessible to Tru Diagnostic customers on the 12th of October (2023).
Moving ahead, OMICmAge is going to become your primary biological age clock and this information about these biomarkers will be in the TruDiagnostic reports made available to your customers.
You have offered to show us a sample report with some of this information. Let's pull that up now and walk through some specifics of what information we are able to predict about different OMIC areas of the body with his DNA methylation data.
RS: This is a very robust report, I won't take you through everything. We have about 10 clinical biomarkers, 12 different proteins and 12 different metabolites which we can connect to impacting your epigenetic age.
For instance, we might give you your haemoglobin or your creatinine results, much like you might see on a blood based lab. The real important part here is that we can also tell you how it is contributing to either helping or hurting your biological aging process.
For instance, probably the most protective factor in this particular individual (see image) is serum albumin. Serum albumin is a protein which can bind a lot of other things in your body and for people who are very interested in aging, this is one of those factors, which tends to decrease in decline with age.
We also know that red cell distribution width (RDW) and HbA1c are probably the factors in this particular patient, which are driving their aging process the most.
Another excerpt from a TruDiagnostic OMIC Age test report. Key blood markers which are contributing to an individual’s aging. Here, low blood Albumin is a key target for intervention. Low levels are making this individual biologically older than the would otherwise be. Red cell distribution width (RDW) on the other hand, is looking healthy.
Why I am Aging? Then, What do I do about it?
LB: This seems to be directly related to the term precision aging - we have heard it in a few other places.
That concept is broadly representing what you just said - namely personalised outcomes and understanding aging for the individual.
Carotenediol also goes into the name Lutein, which people already often take as a supplement.
Through the work on the OMICmAge clock, its importance in aging has been even further emphasised. It is a key metabolite for biological age.
You have shown some examples there. Let's talk in a little bit more detail about what this means for an individual's longevity strategy for their own effort to stay helpful and youthful for longer.
You mentioned that we can use that report to find targeted opportunities for improving biological age. Could you give an example from this report that reveals a marker that is very important for that individual and what action would they take to improve their biological age?
RS: I think that one great example is a metabolite. These are really good examples because a lot of the metabolites in your body are based off of things you eat or supplement. Carotenediol also goes into the name Lutein, which people already often take as a supplement. People might be familiar with it for some of its eye health benefits, which is probably most common for.
Lutein and other Carotenoids are a pillar of longevity. With the OMIC Age test from TruDiagnostic, you can understand how your diet (and supplement) strategy are working (or aren’t working) to improve your biological age.
We included Lutein in our OMIC Age prediction through algorithmic selection. We find that if we wanted to predict death accurately, that Lutein (carotenediol) was one of those metabolites which was highly influential in terms of predicting longevity as an outcome.
This is a really good case example because we also know that if you supplement with carotenoids, you start eating more things like leafy green vegetables like spinach, or kale or, or carrots or yellow peppers, you can actually increase that carotenediol level within your plasma.
And that will actually change our biological age prediction through changes in DNA methylation. That will then take your overall biological age down.
OMIC Age and Self-Experimentation
LB: What is the sensitivity in or I should say, responsiveness of the algorithm to change that you just mentioned? How long do you think a user would have to run that self experiment? They are going to measure with a Tru Diagnostic test, they are going to make a dietary or supplement change, maybe both and test again. What does that testing protocol look like?
RS: That is a really good question, and to be honest with you, we are not quite sure yet.
I think quite frankly, it might be different for many of those different predictors. For instance, your HbA1c is a really good example, because it behaves a little bit like methylation biomarkers behave, which is sort of a three month running average.
Traditionally, we only recommend testing every six months. But we've seen even some of these epigenetic biomarkers change effectively, in as little as eight weeks.
LB: So we are still looking at six months as the approximate timeline for self experimentation, that could change because there is a lot here that is new and unknown.
Just come back to that example, if somebody wanted to make a dietary shift or dietary change, or supplementation change, and then measure before and after, we are going to still go with the guidance of approximately six months at this time for measuring before and after. Do you agree with that summarization?
RS: I think on a casual basis that is what I would recommend. In shorter periods of time, you might have some transient changes that don't reflect the true biological aging changes and so the longer period of time that you are doing intervention, the more confident we can be that the result is correct, and that you are moving in the right direction.
DISCOVERING NEW FACTORS DRIVING AGING
Before you go! Why not dive deeper on biological age testing with TruDiagnostic? Our two part interview with Ryan Smith covers many important basics.
LB: One other thing I wanted to explore before we close off, Ryan - You have actually been discovering new influential factors in aging through this research that were not previously known - please give us an example?
RS: As our ability to predict other things with epigenetic methylation become even more powerful we are going to have even more insights. The metabolite ribitol is one of those examples.
This is a metabolite that is influential in creating the baseline molecules we use to regulate DNA, RNA, or even some of those sugar based pathways.
If you look this up in the literature, you find only two examples about this in PubMed. Although there were very few references to it, we are seeing that it seems to be a very good predictor of mortality.
LB: That's really fascinating Ryan, and we have walked through a great update of what is coming out with this new clock. Soon, we are going to be able to look at some examples from our Founder Nick’s results after the OMIC Age clock comes out.
In closing, we just would like to say that this is really exciting and congratulations to TruDiagnostic and your collaborators for bringing such an advancement to the field!
RS: It is always a pleasure to talk with Longevity Blog. We always have some elevated conversations, which probably yield a lot of questions. If anyone has any questions, feel free to reach out to us directly at TruDiagnostic.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
AKG supplement benefits your biological age? An Interview with Dr. Yelena Budovskaya of TruMe Labs
AKG Supplement benefits - A Younger YOU?
The AKG supplement has many benefits. However, the most powerful of them might just be making you biologically younger!
The AKG supplement “Alpha Keto Glutarate" has a wide array of benefits:
It improves muscle growth and athletic recovery
Delays fatigue in sport performance
Reduces muscle breakdown during exercise
Improves the health of skin by increasing collagen production
May improve bone density
Appears to improve immune function
Scavenges excess blood nitrogen and ammonia, improving detoxification
But perhaps most excitingly, recent evidence shows that it just might make you younger.
For many, this is a startling claim, so let us explain it in more detail.
First, as we will explore in our expert interview today, we can now measure biological age - meaning how old your body is, biologically (rather than just chronologically) - at home for only $100.
And second, in both animal models and in humans, AKG supplementation has been found to:
Improve the biological age of 40 humans by a median of 8+ years (clinical trial)
Change gene expression (epigenetics) to a younger state
Alter cellular signalling to be more youthful
Possibly be reducing wrinkles
May be reversing or delaying hair greying (in mice evidence is strong, in humans, anectdotal)
This is nothing short of groundbreaking information for wellness enthusiasts and longevity hackers everywhere.
If we’ve managed to catch your attention, please keep reading!
Alpha Keto Glutarate Supplement Benefits - The Why and How
Alpha Keto Glutarate is a pivotal molecule for your energy metabolism (interacts with the Krebs cycle).
The TruAge Explorer test kit. From only $100USD using the discount code ‘longevityblog’.
It is produced in your skeletal muscle and is involved in the balance of many key processes that regulate levels of carbon, ammonia and nitrogen across the body.
The reason that the AKG supplement seems to be involved with regulating aging is that the levels of Alpha Keto Glutarate decrease with age. This means that many cellular functions do not perform optimally, with many knock-on effects.
By supplementing with AKG, we may be delaying these effects significantly.
We’ve recently composed a more thorough review of AKG supplementation which you can read here.
As we move ahead, we are going to focus on the technology you can use to test whether or not AKG improves your own biological age and understand in a bit more detail why AKG supplementation might be one of the most powerful longevity interventions you can try at home.
AKG Supplementation and Biological Age - From Expert Dr Yelena Budovskaya
“AKG is actually balancing a basic metabolic process within your body, specifically the Krebs cycle...
What we see with alpha ketoglutarate is it influencing not just the methylation process, but also the methylation of certain sites associated with younger age.
Another example are the molecules called integrins that are key parts of our skin health... People do report less wrinkles and much better quality of skin.”
At Longevity Blog, we are fascinated by all things related to longevity technology. We define this sector as anything tech that is helping you stay healthier for longer.
In our post today, we are focusing on the intersection between two such technologies.
Calcium Alpha-Ketoglutarate - a longevity supplement, which we source from DoNotAge.
And, biological age testing, specifically the most affordable high quality offering on the market - the TruAge Explorer from TruMe Labs.
The unique nature and power of this combination cannot be understated. Here we have two technologies which together have been shown in clinical research, to improve the youthfulness of 40 (out of 42) human subjects.
The question is then of course - could it do the same for you?
The fantastic news is that both of these technologies are available to you in the safety and comfort of your own home.
With a bit of careful forethought, you can run your own self-experiment to see if AKG can improve your biological age for only a few hundred dollars (with our unique discount codes).
To understand how this all works in more detail, we reached out to CEO and Co-Founder of TrueMe Labs, Dr Yelena Budovskaya to learn about how biological age testing works and why Alpha Keto Glutarate appears to be so powerful for maintaining your health as you age.
Let’s hear what she has to say…
NOVEMBER 2023 UPDATE:
Nick has now completed his 9 month self-experiment with Ca-AKG. Read the results here!
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with TruMe Labs, we have a negotiated an industry leading 15% off coupon code for our readers.
Use the code “LONGVITYBLOG” at CHECKOUT TO SAVE 15%!
And through continued collaboration with DoNotAge, we are offering a 10% off discount for their Calcium Alpha-Keto Glurate supplement as well!
Use the code “Longevityblog” at checkout to save 10% on AKG
This interview was conducted in November 2022 over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Alpha Keto-Glutarte, biological age & More
Longevity Blog (LB):
Yelena, thank you so much for joining us today, we're really excited to talk with you about biological age testing. You've co-founded TruMe Labs and you offer the TruAge Explorer test kit.
We might hear about biological age testing all of the time, but it's still a new concept to most people. And it's fundamental for the rest of this discussion.
An important important place to start: how do we determine biological age?
Yelena Budovskaya (YB): Biological age is the age an individual would be if they lived a perfectly healthy life, and did not take any anti aging supplements. His physiology will be representative of that generic age group. Your biological age is the physiological state of your body, not the years by calendar.
Interview excerpt: Biological age testing - how it works, what it means (in three minutes)
Biological age - How young you are on the inside
“Your true biological age... might be a little bit behind... or it might be faster than your chronological age. But in any case, it is more representative of your health...”
LB: In that way, we're looking at an age that tells you what you “look like” biologically, not necessarily what the clock says. But instead, comparing you to other people than other populations saying, do you look older or younger at a cellular level?
What would you add to that?
YB: We look at how your cells and in particular how your DNA looks after all you put it through over the years. How that information is written on your DNA is reflecting your physiological state.
This physiological state is your true biological age. So it might be a little bit behind your chronological age. It might be faster than your chronological age. But in any case, it's more representative of your health rather than your calendar years.
Biological Age Reveals How Old You Really Are - for ONLY $100USD
Nick with an AKG supplement from DoNotAge
LB: So ‘biological age’ is comparing your biology with other healthy individuals in your age group to see how you stack up in terms of biological years accumulated or not accumulated.
In this space, we've had biological age testing for a few years now, but they've traditionally been quite expensive, costing $400-$500 US dollars per kit. One of the most attractive aspects of the TruAge Explorer biological age test kit is that it's very affordable.
Talk to us about the innovations that are occurring at TruMe Labs in terms of biological age testing. How can you offer a biological age kit for only $100 US dollars?
Speaking of supplements - Our Founder Nick tried the supplement Nicotinamide Mononucleotide and measured biological age before and after. Curious? So were we… read the post!
YB: Our journey actually started quite a while ago. I spent so many years studying the natural genetics of the aging process.
One of the things that I noticed is that we cannot stop human beings from aging. But nor can we stop them from trying to extend their lifespan - people are always going to be searching for the answer to their aging process.
With the expansion of internet and social media what's happened is more individuals are reading new innovative science in longevity and they think “Okay, I'm gonna start taking that supplement tomorrow. If it works on mice, it should work on me”.
When I first started in this field, it shocked me to see a lot of people who take a lot of supplements without really checking whether or not it's actually working for them.
self-experiments & biological age tests
LB: It is so refreshing to hear you say this. Part of our philosophy at Longevity Blog is to guide people to know the answer to what works for them! Go on.
“When I first started in this field, it shocked me to see a lot of people who take a lot of supplements without really checking whether or not it’s actually working for them. ”
YB: Then we start thinking - how can we measure if these interventions works? And of course that means we needed a biomarker of aging. Today, we know many companies are spending the time looking at biomarkers of aging.
I really liked what Steve Horvath, Hanham and other centers in genetics were doing, because it looks like that biomarker was actually very simple to adapt to home testing.
LB: This is referring directly to epigenetic biological age clocks, based on DNA methylation data.
YB: Yes, but DNA methylation is a very dynamic process. We started the development of our test kit with several basic requirements in mind.
Firstly, how can we make our test very accurate. So deviation from the number that we predict, should not be more than five years.
Second, it should be affordable - no more than $120. About the cost of three months worth of vitamins.
Feeling impatient and just want to learn about Alpha Keto-GluTArate and biological age? Just Scroll down a few sections!
Third, it should be fast, because the tests that we've previously done take 8 to 10 weeks to complete. We wanted to have a two week turnaround time. And no needles!
LB: That’s a great answer, we can see that affordability was actually just one part of your holistic thinking about how you might produce a quality and low cost kit.
Does the AKG supplement actually work? What about other longevity supplements?
We love the part of the story where you referred to how others were taking supplements without knowing if the are actually working for them. This is precisely one of the things we talk about on Longevity Blog, repeatedly.
In your answer you mentioned accuracy - we want to get into some of the details around the accuracy and precision of your test. But first, we’ve just introduced the concept of “epigenetic” age testing where the test is looking at the epigenome and particularly these sites called CpG islands.
These locations control turning the genetic code on or off in our bodies. Please briefly tell our audience a bit about that process of on/off in the epigenome.
If you want to go deeper on biological age clocks, epigenetic aging and what all of these terms mean, check out our interview with Ryan Lewis, Founder at TruDiagnostic.
YB: Even at birth, we already have some level of methylation happening in the body. And as you mentioned, this is the CpG sites on our genome. These CpG sites are located all throughout genome.
In some cases they are in the “promoter region” of the gene. Methylation at these locations prevents the cellular machinery from binding this region before the gene and expressing it.
In some way, epigenetics is a dynamic mechanism instructing the cell to turn on and off genes to fine tune how the genes are working together.
DNA Methylation and Biological Aging
LB: Why is this turning on/off of genes important for aging/longevity?
You don’t have to use supplements to improve your biological age. Nick did it by adding more plants to his diet, read about it here.
YB: DNA methylation is happening all the time. DNA is methylated and demethylated. Certain genes activate expression and other genes repress the expression.
This is how the body is fine tuning its function throughout life. It can be associated with the biomarkers for almost every single physiological process with the body.
LB: With aging, tracking this process is incredibly complex. Some of the other technologies we looked at for biological age testing might look at hundreds of thousands to millions of points in the epigenome.
However, your biological age test kit has actually boiled it down to looking at just nine locations in the epigenome. Clearly those are very closely related to aging.
Can you help our readers understand how there could be this reduction from millions of points in the epigenome in some of the fancier, more expensive test kits down to just nine points in your TruAge Explorer test?
Low Cost Biological Age Testing: How TruMe Labs Made it Happen
Test your biological age for $100USD with TruMe Labs and our discount code “longevityblog”
YB: When we first studied epigenetic connections to aging, we looked at the whole genome, because we didn't know much. We didn't know where this information was actually kept.
Any model that uses epigenetics to calculate biological age is a statistical mathematical model. It converts DNA methylation data into the number that corresponds to the biological age.
As we have studied this more we have realised that not all the biomarkers are the same. Some of them actually influence and can predict your biological age more. Most others have a miniscule influence on the equation.
We have identified the methylation markers that change with age, which are promoters of those genes. These markers should also be age regulated (changing its expression with age).
When we put these constraints over our algorithm development, we end up only with 30 CpG sites. But still, 30 was too many sites for the affordability and scalability of the process that we were developing.
So we distilled it to the best performers (9 of them). Afters some early testing and improvements, we validated it within a clinical trial setting and we saw that our deviation from the chronological age of the healthy individual was only 3.8 years, which met our accuracy target.
How does TruAge Explorer Compare to More Expensive Biological Age Tests?
LB: What an interesting story to follow. You've described this process of thinking about how to constrain a very complicated problem through the lens of affordability and the very dynamic relationship between gene expression and aging.
You’ve mentioned accuracy again, so let’s discuss this in more detail. You've done a comparison with your kit to the MyDNAge test. That test kit uses a much larger portion of the epigenome (approximately two thousand CpG data points). And yet there's a really strong correlation between the outputs from your algorithm and theirs.
Tell us what that reveals about these nine CpG sites and the way you've just constructed the test?
YB: Well, of course I think it tells you that we're probably found the CpG sites that are more dynamically changing with age and that methylation within those sites is clearly important for measuring a normal natural aging process.
The main reason our accuracy is comparable to another test in the market is because we are actually using different technology.
We don't use next generation sequencing (NGS), because we wanted to keep the cost down. NGS is quite expensive unless you sequence hundreds of patient samples at the same time.
We are instead using single sequencing, which allows us to sequence at a greater depth. In other words we sequence the same region many, many, many times over.
Low Cost Biological Age Test, the Makings Of
LB: Let's help our readers understand in a bit more detail. Just so it's nice and clear.
You've described Next Generation Sequencing, which enables many samples to be computed in parallel. However this is not the route that you've chosen, as you’ve pursued affordability. Explain to us again, what the difference in your single sequencing approach means for the consumer.
YB: What we do is sequence only one sample at a time. From this one sample, one fragment at a time.
Altering CpG sites in action. By sleeping better, Stacey improved her biological age from TruMe Labs. Read their female biohacking guide here!
Let's say we are sequencing nine fragments, the nine CpG sites. This means we sequence each of the CpG sites separately.
For each of the sites, we look separately at all the messages we get to calculate the percentage of methylation at that particular site.
This means we get thousands to tens of thousands of messages that we aggregate together to calculate the percentage over one CpG site.
As a result, we can use statistics over these many messages to see how clean the sample was.
There's one positive side and one negative side of this approach. The positive side is, because we sequence it so deeply, it means that we can actually capture miniscule changes of methylation, which can have acute effects on your biological age.
The negative part is that our test is much more sensitive to your lifestyle changes than tests using the NGS approach.
Is the TruMe Age Explorer Precise? Repeatable results are key for self-experimentation
LB: Both the price point and the sensitivity to lifestyle changes make the TruAge Explorer a very nice tool for self experimentation.
Read our interview with Ryan Smith at TruDiagnostic to understand the importance of accuracy and precision for biological age testing.
Let's talk a little bit about error and precision in the test kit. We recently discussed these concepts with Ryan Smith of TruDiagnostic. Talk about your test through the lens of accuracy and precision.
YB: Yeah, so we actually tested two aspects of precision and accuracy.
The first was precision. Let's say, I give you five tests today and you collect your saliva across five samples. So the sample is the same, right? It was put in the paper at the same time, and was sent to us in the same envelope. So what is the result is going to be?
We actually tested this quite a bit and the result is that we predict biological age from these five samples to within 3 to 4 months of each other.
Then a second aspect of this is actually a bit tricky but super important to understand. And I'm not sure very many people actually understand it.
LB: Our audience will! Give it to us.
YB: Every single biological age algorithm, including ours, uses the chronological age to standardize your biological age number. This presents an issue - why is the chronological age the standard?
Well, we don't have any other markers right now that reliably would predict that. So that's why we still use it. And this is why I keep bringing up this healthy individual who does not take any anti-aging therapies, who would live a healthy life and overall being healthy in perfect health today. What is their biological age?
We make the assumption that their biological age is equal to their current chronological age.
Then we took individuals between ages 40 to 75 that were absolutely healthy. No chronic diseases, no big problems. When measured the biological age of these individuals (150 of them) we realised that were within plus or minus 3.8 years of that person's chronological age.
This is why we know that even with multiple repeats of the same test, we can say that we can predict person chronological age plus minus 3.8 years.
“We get biological age as a starting point, do something to change the biological age and then compare follow-up results to your first biological age test.
The goal is to make that number smaller (“younger”).”
TruMe AGe Explorer: Precise to within 3 months, accurate to within 4 years
LB: This is a really fascinating point that you're making. We are going to try to say it back to you in different terms.
You're saying here is that to know how “accurate” a biological age test result, we have to find a compare that to a source of truth. When we consider “what is the right answer?” or what is the “true age” of a given person, TrueMe Labs construct this by looking at both the biological age and chronological age of many healthy individuals across different ages, statistically.
Here, you found an accuracy of plus or minus 3.8 years.
YB: Exactly. But I want to add to that.
If you personally are taking a biological age test, the most important thing is actually comparing your own results after an intervention. We get biological age as a starting point, do something to change the biological age and then compare follow-up results to your first biological age test.
The goal is to make that number smaller (“younger”).
AKG Supplement BenefitS Video: Reducing Biological Age
AKG supplement benefits for biological age with Dr Yelena Budovskaya of TruMe Labs.
LB: This is great, because you're coming back around to the concept of self experimentation.
We believe this is true value of biological age tests. They are giving you a reference point from which to improve.
This is why it's so important to pick a kit that you can afford that you have confidence in, and to keep using it. Because you get your baseline result and then try to improve and see what works for you.
We have a really great example in the literature of this - your company the TruMe Labs technology worked participated in a clinical study published in the journal Aging back in 2021.
November 2023 Update: Nick’s 9 month self-experiment with Ca-AKG results are in! See how much his biological age improved.
There were 42 participants self-experimenting with an alpha ketoglutarate supplement (AKG), which we've just recently written about on the blog. Your TruMe Explorer test kit had an important role in that study.
Can you tell us about this study?
YB: This study was done in collaboration with Ponce de Leon Health, who are producing the akg supplement. They wanted to give their clients the opportunity to be sure that their product works.
In this study, the result showed that so many of the participants actually decreased their biological age significantly. They also reported that they don’t have gray hair anymore and that their skin health improved.
We saw that on average there was 8.8 years of healthy lifespan reversal. Only two people actually did not improve their biological age.
AKG Supplement Benefits: Why it Works on Biological Age
LB: We love this. We think this is the longevity science of the future, particularly as longevity technologies move faster and faster.
This is why finding a kit that we can use for self experimentation is so important.
Score a 10% discount of high quality, third party tested Alpha Ketoglutarate from DoNotAge.
How do you think the alpha ketoglutarate supplement is working on these nine CPG sites in a way that improves biological age? What’s happening here?
YB: I think the AKG supplement is actually balancing a basic metabolic process within your body, specifically the Krebs cycle. AKG is also important for increasing the activity of demethylase, which is the enzyme that the methylate the genome.
What we see with alpha ketoglutarate is it influencing not just the methylation process, but also the methylation of certain sites associated with younger age.
Another example are the molecules called integrins that are key parts of our skin health. They are important for wound repair and skin elasticity. We observed that some of those markers actually methylated more with alpha ketoglutarate.
Maybe that's why there's such a great effect on skin. People do report less wrinkles and much better quality of skin.
The Future of Biological Age Testing
LB: Thank you for diving into that. Our audience loves looking after their skin health!
As we move to close the interview, can you share us your your vision for biological age testing? Where is it going over the next five years? What will become possible?
YB: We think that the most important thing right now is not actually making more precise biological age measurements.
Instead, we intend to expand our portfolio with genetic tests which give you information is how your DNA by drivers of aging. For example, how you are are affected by your diet taken or by the air you breathe, or your stress levels, or level of inflammation in your body. This could also included your hormone status.
We are going to be combining epigenetic and genetic tests together to deliver this information. So this is where we're heading next.
Dr Yelena Budovskaya’s Longevity Strategy
“I also finally tested alpha ketoglutarate on myself. It actually did work and I love it! ”
LB: That's an exciting vision. We love that you have this idea of combining different types of data in practical way for people to influence their longevity, at ho
We're going to wrap up the interview here. But before we go, we'd like to ask every guest to just share one or two things that they do to look out for their longevity each day.
Hear from our Founder Nick on biological age testing and how you can change diet, sleep, exercise and stress to improve yours! Read more
YB: Personally, I have always been fighting with weight loss. I was also guilty of taking too many supplements.
Now I practice intermittent fasting and am trying to get my feeding window to just six hours a day. It seems to work great for me. I like the effect this is having on my body.
I also finally tested alpha ketoglutarate on myself. It actually did work and I love it!
Everything else I am trying, I aim to be very thoughtful and self-experimenting with one intervention at a time.
LB: Thank you for your answer Yelena, and thank you again for joining us on Longevity Blog today. It was a pleasure.
YB: Thank you. I'm looking forward to see what result you get from your AKG self-experiment!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Mitopure Review - Does this Urolithin A supplement actually work?
Reviewing Mitopure Before and After - Urolithin A Supplement Self-Experiment
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We review the Urolithin A supplement Mitopure. We review Mitopure through our favourite approach - self-experimentation to answer - does Mitopure actually work?
Urolithin A supplementation is grabbing some serious attention in the longevity technology space. With its purported benefits in mitochondrial rejuvenation, it appears to be a promising intervention into the known age-related decay of mitochondrial health over time.
Beyond its proven positive impacts on mitochondria, Urolithin A is showing promise in reducing the incidence and intensity of several types of cancer, including prostate, pancreatic and colon cancers. It also appears to have powerful effects in healing the gut barrier and may help support a healthy immune system.
Urolithin A is a by-product of the digestion of ellagitannins, which are found in certain foods, including raspberries, walnuts and pomegranate. However, only 20% of people have the right gut flora to covert ellagitannins into urolithins (more on this shortly).
This is why there are likely many benefits to Urolithin A supplementation.
In this post we’ll review:
what is the best source of Urolithin A?
who makes Mitopure and is it legit?
how can you know if Mitopure will work for you?
our Founder Nick runs a self-experiment with Mitopure
The Best Urolithin A Supplement is Mitopure
If you’re interested in self-experimenting with Urolithin A, don’t go searching for “Urolithin A supplement Amazon” hoping for an alternative to Mitopure.
Mitopure is currently the *only* and *best* Urolithin A supplement available. Putting your hard earned cash anywhere else at this stage will only lead to disappointment, as our review of the alternatives has not found anything else worth mentioning (as of late 2022).
Why is this the case? Simply put - no other supplement is actually isolating Urolithin A. What you are getting instead are pomegranate extracts. However, if you do not have the correct gut flora, pomegranate extracts will not convert to Urolithin A in your digestive tract. That’s your hard-earned money wasted!
If another source of Urolithin A supplement becomes available, we’ll be sure to share it with you.
Over the course of the next few paragraphs, we’ll explain to you in additional detail why Mitopure is your best Urolithin A supplement option (and how to know if it will work for you).
Who Makes Mitopure?
First, if you would like to understand the history behind this Urolithin A supplement and its path to becoming a consumer product, you can check out our interview with Amazentis CMO Federico Luna. He details the decade long research effort that Amazentis put into dicovering and developing a Urolithin A supplement.
Who are Amazentis? They are a Swiss pharmaceutical company that was founded by scientists, doctors and entrepreneurs who wanted to create a new class of nutrition supported by the rigor of research you typically only find in biotechs that are solely developing drugs.
To bring Urolithin A to market, they founded Timeline Nutrition, who are the makers of Mitopure.
Is Mitopure Legitimate?
Yes! Mitopure is about as legitimate as it can possibly get in the supplementation space.
Timeline Nutrition was founded by a highly respected phamarceutical company that needs to be ensure its reputation is spotless. They then branded the Urolithin A supplement used in their research studies under the brand name “Mitopure”.
Now consumers have access to the exact formulation of Urolithin A which has been producing impressive results in clinical research studies and has proven safety and efficacy.
Furthermore, Amazentis are now putting millions of additional dollars into research efforts to study and better understand the impacts of Mitopure in humans, particularly in age related decline of muscle quality and into its benefits for sport performance (for example, their collaborative relationship with the American College of Sports Medicine).
You’d be hard pressed to find another longevity supplement with such a reputable background.
How much does Mitopure cost?
Mitopure Urolithin A supplement in sachet form. It is also available as a softgel.
You won’t find a better deal on Mitopure than through our 5% discount code (‘longevityblog’) and purchasing directly from Timeline Nutrition on a subscription. That’s the most cost effective way to get your own supply for self-experimentation.
In part two of our interview with Amazentis CMO Federico Luna, we worked with him to break down the costs of Urolithin A supplementation.
We found that Mitopure costs about 50-60% of what it would cost to get an equivalent amount of Urolithin A from pomegranate juice (you’d also have to drink 1.3L of it each day).
The cost of Mitopure is between $2.50 to $4.00 per day, dropping to $2.35 to $3.80 per day with our discount code ‘longevityblog’. The lower cost options are for longer term subscriptions (up to 12 month supply), which save you progressively more as you extend your supply.
We have found that 1-2 months supply is effective for testing before and after to see if Mitopure works for you (read on for those details).
Once you have decided on your volume of supply. You’ll of course want to be able to test and see - does Mitopure actually work? This is where Longevity Blog content really starts to shine! It is self-experiment time!
PARTNER Discount Code!
A part of our mission is to make your longevity budget stretch further.
Through our collaboration with Timeline Nutrition we have secured you a 5% off discount code!
Use the code longevityblog at checkout to save!
Mitopure review - is it worth it? We self-experimented to find out
In this self-experimentation, as per usual we had our Founder Nick set off on a detailed self-experiment to test Mitopure before and after.
However, in a Longevity Blog first, we have also invited members of our readership to participate in self-experimentation as well!
In an upcoming post, we’ll also share the results from both a high performing amateur cyclist (Aaron) and an ironman triathlete (Claire). Be sure to subscribe to get notified when we post their results!
Starting Point: Do your gut flora produce Urolithin A?
The answer to this question is paramount. If you are one of the 20-30% of individuals who can produce Urolithin A from the ellagitannins in foods (pomegranate, walnuts, berries, etc), then you are much less likely to have a measurable response from supplementing Urolithin A.
Nick takes the “Mitopure Challenge” to see if he produces Urolithin A from Pomegranates
Nick undertook the ‘Mitopure Challenge’ to see if he was a natural producer of Urolithin A (no need to supplement) or if he would benefit from taking a Urolithin A supplement.
In this experiment, Nick drank 300ml (11oz) of fresh pomegranate juice and then gave a few drops of blood via finger prick the next morning.
On the following day, he took 500mg of Urolithin A supplement Mitopure and repeated the blood test process. This blood was sent back to Timeline where they analysed it to see the concentration of Urolithin A Glucuronide.
The result? Nick was not a producer of Urolithin A (at left in image). His gut flora did not produce Urolithin A after drinking pomegranate juice.
However, there was a significant increase in Urolithin A in his bloodstream after taking 500mg of Mitopure.
At left (zero), Nick’s Urolithin A Glucuronide levels after drinking 300ml of pomegranate juice (11oz). At right, after 500mg of Mitopure. This result shows that Nick was not naturally producing Urolithin A through his diet and that supplementing with Urolithin A would be likely to provide him with measurable benefit.
Measuring Urolithin A Supplement Benefits
As we look at the research into Urolithin A, most of the results thus far have focused on muscle strength as the primary measure of performance improvement. However, several studies are underway to look at Urolithin A benefits and safety in athletes.
While the results from these works have not yet been published, we can expect them quite soon. Naturally, given the exceptional role of mitochondria in athletic performance and the primary mechanism for Urolithin A’s health benefits being mitophagy, we can expect that athletic performance is an excellent data point for establishing the efficacy of Mitopure.
“What we’ve shown is Urolithin A acts on the mitophagy pathway... a natural cleansing and renewal process whereby damaged and inefficient mitochondria are identified and cleared away.
This makes room for new healthy mitochondria, a process known as [mitochondrial] biogenesis to kick in and help create and rejuvenate the mitochondria ”
But not just any exercise - we need to look to specific types of exercise which are repeatable, well controlled and which place significant demand on mitochondria.
Given these requirements, Nick decided to use running interval workouts as his primary before and after data point.
This type of exercise is energetically demanding, repeatable and relatively well controlled (if we use the same workout).
It entails running at a very high intensity, where mitochondria are under very high demand for energy production.
If Urolithin A really does trigger mitophagy, then Nick’s older less functional mitochondria should be recycled into new more efficient mitochondria, and this should be observable as an improvement in his athletic performance.
In addition to running data collected from Nick’s Garmin Fenix 6 and HRM Pro (Chest-strap heart-rate monitor), Additionally, a detailed blood panel was collected using the i-Screen Sport Hormone Check (self-ordered blood tests available in Australia).
Mitopure Before and After Results
Nick’s training load from mid-June to mid-July. Relatively light and recovery focused.
The self-experiment begins as Nick enters the triathlon ‘off season’ where he is not running interval workouts. He travels to the United States for 6 weeks starting in mid-June 2022 and has only intermittent training opportunities; while he is consistent with training his volume/load is much lower (see image) than it was in the preceding 6 months.
Nick’s training load from mid-August to mid-September. It was gradually picking back up, but consisted mostly of ‘base training’ in August and did not train running intervals in August (leading up to the test date).
Nick begins Urolithin A supplementation at the start of July (training load remains low) at 500mg/day and returns to Australia and regular triathlon training at the start of August. At the end of August, he re-tests the VO2 max pyramid workout.
As his first proper interval workout in nearly three months his expectations were low. However, as he began the workout, he was very surprised by how he felt.
Let’s take a look at the data and let it do the talking.
Before - Interval Run
Data from Nick’s ‘Before’ running interval workout. Click to zoom. Blue is running speed and red is heart-rate.
The before and after running test are a VO2 max pyramid. This type of workout is structured such that you add one minute at your target pace for each interval.
There are 7 intervals. The first is 1-minute, the second is 2-minutes, then 3-minute, 4-minutes and then back down the pyramid (3min, 2min, 1min) each with two minutes of recovery in between.
There is also a warm-up with some 30 second ‘builds’ at the beginning where your work up to your target pace to get your body ready to perform.
In the ‘Before’ test, Nick had a target pace of 4:10-4:15/km, which he was able to hold for the first 3 intervals, but not for the fourth interval.
His heart-rate peaked at 187bpm (Nick’s maximum HR is 210bpm) on the third interval. Nick reported that he was unable to finish the full pyramid after failing to complete the fourth interval at pace. Simply put, he ran too fast and built up too much lactate and couldn’t hold the target pace.
After - Matched Interval Run
Data from Nick’s ‘After’ running workout. Click to zoom.
At the end of August, Nick completes the ‘After’ test, which is the same structure as the first.
This time he was able to complete the work out at the target pace of 4:10-4:15/km. Additionally, he did so at 5-7% lower heart-rate than in the ‘before’ test, running at 175-180bpm.
He also found he had to moderate his pace as he was running the intervals too quickly at the start (3:50/km pace).
This was due to a change in relative perceived effort (RPE) where faster speeds felt easier than they did previously.
There certainly appears to be a significant change in Nick’s performance. So let’s discuss.
Discussion: Does Mitopure Urolithin A Supplement Work?
Before we jump to any conclusions at Longevity Blog - we have a thorough discussion. Sure, the numbers appear convincing, but let’s make sure we consider the results carefully (and scientifically).
There are some potential confounding factors to consider in answering the question, did Urolithin A supplementation boost Nick’s athletic performance?
First - training. It would be expected that Nick’s ability to hold a given running pace would improve over time as he is training. Could he have simply gotten 5-7% faster from his off-season training?
As we mentioned already, Nick wasn’t running any interval workouts during the intervening period. In fact, he had much lower training load while he was travelling.
In run training, it is generally accepted that if you want to run faster, you have to train by… running faster. This is what running intervals are for, they allow you to accumulate training time at a faster pace so that you can hold that pace for longer.
Nick was not doing this. It is safe to say that training was not a factor.
Second - reduced training load; could it be a factor?
It is possible that the several weeks off provide Nick with ample recovery time and that he was able to re-engage the interval workout with ‘fresh legs’ and hence why he was able to perform so well.
However, Nick reports that his ability to run these interval workouts has been sustained as he picked back up his training load in September and October. As he has again become fatigued and picked his training load back up by 3-4x what is was in June, he can still run at this pace for his running interval workouts.
It does not appear that being ‘fresh’ and well rested is why Nick was able to run faster for longer in the ‘After’ workout.
Third - the one off nature of the analysis; Nick could have had a bad day in the ‘before’ workout and a ‘great day’ in the ‘after’. Was this the case?
Our response to the ‘second issue’ about re: training load addresses the latter. Nick’s performance gains have been sustained as he has continued with Urolithin A supplementation. In fact, he can now run 3:50/km intervals for 4-5 minutes at a time and is running a 20-minute 5km race time (that’s 4:00/km for 20 minutes).
As for the ‘before’ data having been a ‘bad day’ as a one off, we searched through the Strava and Garmin case files. We found two matched workout runs of Nick’s from before Mitopure supplementation. In each, we observed the same inability to hold the target pace across the whole workout.
Nick at the Byron Bay triathlon in May 2022. He loves the run leg… is Mitopure helping him improve his times? Evidence suggests - Yes!
Mitopure Review - Conclusion: Nick is running faster after Urolithin A supplementation
In our view, the data support a significant improvement in Nick’s interval run times after supplementing 500mg of Mitopure Urolithin A.
This improvement has not only been sustained, but Nick’s running times continue to quicken as he continues supplementing with Urolithin A.
Anecdotally, Nick reports lower heart-rate at equal pace on his easier runs as well. He has also seen a 20% improvement in his cycling FTP (functional threshold power), but none of these results have been well controlled or directly verified.
His fellow triathlon club teammates have also noted his rapid improvement!
Will Mitopure Work For You?
So, will Mitopure work for you? We can’t tell you the answer. There is only one way to find out! Run your own-self experiment!
Use “longevityblog” at checkout to save 5%
We have two Longevity Blog readers who are trying their own Mitopure self-experiment (Aaron and Claire). Will you join them? Let us know, you just might be featured in the next Longevity Blog post!
Until then, Live Long!
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Increasing Plant Diversity Improves GlycanAge Significantly - A Self-Experiment
First things first - we have a 15% discount code available for the GlycanAge test - ‘LONGEVITYBLOG’.
Now go run your own self-experiment!
Glycan Age Test Self-experiment Results
In a series of recent posts, Longevity Blog has been investigating glycans and their many important roles in the body.
There is much to learn, but the key takeaway is that they play an informative role to the immune system by ‘tagging’ which of the many foreign molecules in the both are friend and which are foe.
We’ve some ideas on how you might improve your GlycanAge - by eating more types of plants! Read on for more!
If you’re across the basics of how the immune system works, you’ll be aware that inflammation is a sign that the immune systems is activated.
And while this can be highly valuable for enacting repair of specific areas of the body (e.g. damaged tissue), it is also a destructive process (e.g. tear down and rebuild that tissue).
As we age, levels of chronic inflammation rise, both as a result of and a cause of the aging process.
In your quest to maintain your ‘youthfulness’ and achieve longevity, monitoring and improving levels of inflammation in your body is highly important!
However this has not always been easy. There are many ways to measure inflammation in the body - which to choose? How to improve it?
It turns out, there is a simpler answer - don’t track the result of inflammation, instead track the molecules which signal - should inflammation be ‘on’ or ‘off’?
That line of thinking brings us to glycans and specifically the GlycanAge biological age testing kit.
In this post, we’ll review the results from our Founder Nick’s GlycanAge self-experiment. For the nitty-gritty details on the how & why the experiment was conducted, including the hypothesis and scientific framework, be sure to read that post first!
Read on for a few basics, and then a deep dive into the results.
Self-experimenting with diet to inform the immune system
Hey everyone, Nick here! I’m excited to share with you that I was able to improve my GlycanAge by 6 years in just 3 months, with a specific dietary change.
That change? Eating at least 30 different plants per week.
This self-experiment was completed in effort to improve a GlycanAge that was already quite favourable (30 yrs for a 35 yr old) in an individual who was already ‘doing all of the right things’ with diet, exercise, sleep and stress.
From my perspective, -5 years just wasn’t quite good enough. I was convinced I could improve further, as I’d achieved much younger biological age by other measures, and I like a good challenge!
To complete this self-experiment I dutifully designed and tested a specific hypothesis, which was:
“By programming the immune system with a diversity of plant information (local & organic where possible), chronic inflammation will be reduced as the immune system learns more about what is friend and what is foe, leading to an improvement in the Glycan Age”
Let’s briefly talk about why adding more plants to the diet could be reasonably expected to improve GlycanAge and then take a look at the evidence which shows it worked.
Why would 30 plants per week improve glycanAge? The basics
Of course I suggest you read the introductory post, which will offer you much more detail, but here is the main line of reasoning why eating a diversity of plants is likely to improve your GlycanAge.
Delicious veggies from our local farmers market. Full of environmental information just waiting to program your immune system. Eat me!
The immune system is constantly monitoring what you eat - deciding what should and should not be allowed into the bloodstream.
This surveillance occurs in the small intestine at your “intestinal epithelial cells” (IECs) which act as a filter, whereby nutrients, electrolytes, water and beneficial bacteria are allowed into the bloodstream (while the ‘baddies’ are not)
The immune system that is supporting the IECs with this ‘filtering' step is learning what is good and what is bad through the diet you eat
This effectively means that your diet is information about your environment
The diet is then responsible for telling the body, through a diversity of food and organisms, what is ‘friend’ and what is ‘foe’ - and it does this through partnership with glycans
Thus the hypothesis:
When you don’t eat a diverse diet your immune system receives less information = more inflammation (and higher GlycanAge)
However, the opposite is also hypothesised to be true: more information = less inflammation (and lower GlycanAge)
Did it work? Experimental results
The results from this self experiment are provided through the GlycanAge online dashboard, which delivers a biological age result, but more importantly, a breakdown of the three most important glycan indices.
These indices summarise the 24 glycan types which regulate inflammation in the body, and are broken down in GlycanAge test results as follows:
G0 are glycans without galactose, which are the most proinflammatory. These are represented by the Mature Index.
G2 are glycans with two galactoses, which are suppressing inflammation. These are represented by the Health Index.
GS are glycans with sialic acid, which also suppress inflammation. These are represented by the Youth Index.
Result: GlycanAge improves by 6 years
I am presently 35 years old. My GlycanAge at the start of the self-experiment was 30, an encouraging result. After eating 30+ plants per week for 3 months, my GlycanAge further improved by 6 years, to a value of 24.
If you’re interested to understand a bit more about how this biological age estimate works, you can read our interview with glycan expert Prof. Gordan Lauc.
One very important question that we asked Prof. Lauc was about the importance of the absolute value of biological age versus the relative changes that occur over time.
“It’s also important to not worry about the absolute number, because the absolute number is also strongly affected by genetics. Approximately 30-50% of the GlycanAge is determined by your genes, you cannot fix it.
It is the relative number, the pace of changes in biological age which are important. If your GlycanAge is increasing more slowly than your chronological age, then that’s good. ”
My GlycanAge at the start of the self-experiment.
My GlycanAge at the end of the 3 month experiment.
Result: glycan indices improve across the board
One aspect of the GlycanAge test kit that I really like is that they give me direct access to raw data, a summary PDF report and insightful indices which breakdown the biological age estimate further.
Not many biological age test kits will offer you this level of detail, and it provides an important layer of additional insight into why a given self-experiment worked/didn’t work for improving biological age.
Intriguingly, the self-experiment resulted in across the board improvements in these indices. The changes in the % relative to my peers (percentiles) reveal this in a straightforward way.
For example, the ‘Health - G2’ index improved by 0.11. What does that mean? My result is now better than 60% of others in my age group, whereas before it was only 49% (a below average result).
The three major glycan indices at the start of the self-experiment.
The three major glycan indices at the end of the self-experiment.
Improving GlycanAge with diet: Discussion
Interpreting the results of a self-experiment is very important. We cannot simply look at the data in results form and make a conclusion. In the spirit of science, we must discuss them!
The most important aspect to discuss here, is how the self-experiment was controlled. In essence, this means limiting as much as possible, any external factors which could ‘confuse’ the results.
Importantly, we need to examine any changes in the four main drivers of GlycanAge results. As Professor Lauc outlined for us in his in-depth Longevity Blog interview, these are: stress, sleep, exercise and diet.
Let’s briefly review each.
Controlling Diet
I kept a simple list organising plants I ate into groups of 10 for each week of the self-experiment. This was done in the ‘notes’ app on my iPhone and was very easy to manage.
In our experiment we turned the ‘diet knob’ in a very specific way. By introducing the primary experimental change of eating 30+ plants per week.
First of all - compliance. I can confidently report that I was fully compliant over the 12 week period of experimentation.
In no week did I eat less than 30 different plants. I ate as many as 40 different plants and as few as 31 different plants.
I did not change my dietary protein, carbohydrate or fat ratios or overall intake of calories.
Inevitably, I did eat more soluble fibre due to increased plant diversity, however, I was already eating many organic vegetables and select fruits to begin with.
I just was not eating many different types, instead favouring about 10-15 different plants which I ate repeatedly.
It was as a fun challenge to find new plant foods to try! It resulted in my whole family eating more plants as well - an added bonus.
Controlling Sleep
As any good longevity focussed biohacker, I’m quite religious with my sleep schedule.
During the experiment, I did not change my bedtime or my wake-up time. There was no significant changes in sleep duration or quality. I also did not change any sleep-related supplements.
As monitored by Oura Ring, sleep time was between 7.5 - 8 hours per day with a sleep score of 80 on average.
The below is a gallery of images you can click through (4 in total) showing the sleep score and total sleep from early and late in the self-experiment.
Controlling Exercise
As set out in the opening post for this self-experiment, I maintained a consistent exercise load to within 10% on average (in a given month) as measured by my Garmin smartwatch and heart-rate monitor.
No significant changes were made to total time exercising, exercise intensity or the type of exercise I was completing.
I kept up my routine of 4 weeks of triathlon training with a one week de-load. Average load over the period was unchanged at around ~750-800.
Controlling Stress
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This aspect of the self-experiment was more interesting! I’d originally set out to complete this experiment over 6 months with two GlycanAge tests. However I cut it off at 3 months. Why?
Australia went into a sudden COVID lockdown, upending my life routine and introducing significant additional stress (homeschooling in and of itself would confound the results, haha!).
I simply could not continue the self-experiment for the additional 3 months and maintain good control over the experiment.
Thankfully, I was able to complete the 3 month self-experiment with no significant lifestyle or stress related changes. So this was well-controlled overall.
Conclusion: Eating a diversity of plants significantly improved my GlycanAge
To design this self-experiment, I used Dr Jenna Macciochi’s suggestion to eat 30+ plants per week to boost the immune system.
Immunity: The Science of Staying Well is one of the most up to date, accessible and helpful books out there on building a healthy immune system. Check it out! (Amazon Affiliate link)
We are fortunate to have a pretty clear cut result in this self-experiment.
It was well-controlled and occurred over a short-time frame, with very limited opportunity for external factors to confuse the result.
Moreover, the magnitude of the change in GlycanAge was significant. A 6 year improvement is well outside the measurement error.
Had my GlycanAge improved by only 1-2 years, we would not be able to make such a strong conclusion.
In addition to the size of the change in GlycanAge, there was significant improvement in all three of the glycan indices, where I improved by ~10% in age group relative terms.
This firmly suggests hypothesis looks to have been ‘proven’, with the expressly limited scope of this being an ‘n of one’’ dataset.
Conclusion: Eating more plants improves GlycanAge (for me, and maybe you as well!)
Practically, what does this mean?
For one, I know that I should most definitely keep eating 30+ plants/week! I now consider this part of my longevity strategy.
This is in addition to other tactics like supplementing with NMN, which I also determined to improve my biological age through a seperate self-experiment.
This is precisely how we should use these types of tests. In an intentional and controlled way to test a change and see if it helps you in your longevity journey.
While the ‘conclusion’ is only applicable to myself, this design of this self-experiment provides the opportunity for other wellness and longevity enthusiasts (that’s you!) to use this approach to improve their biological age.
However, if you do not already have healthy diet, exercise, sleep or stress habits - start with those first! Don’t forget that losing weight is the surest path to reducing inflammation and improving your GlycanAge (we asked Gordan!)
If you plan to give it a try, be sure to reach out on Twitter or Instagram and let me know!
You can check out GlycanAge test kits here, and don’t forget to use the code “LONGEVITYBLOG” to save 15% on your order!
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Self-experimenting with GlycanAge - Before and After Diet Changes
We’re glad you’re here! How about a 15% discount code available for the GlycanAge test?
Simply use the code “LONGEVITYBLOG” at checkout
Glycan Age Test review & Self-experiment
As we’ve learnt over the past few posts, glycans are incredible molecules with many important roles in the body.
Perhaps the most important of which is providing information to our immune system about what foreign molecules (i.e. diet, dust particles, bacteria, etc!) are friend and which are foe.
My GlycanAge biological age test kit - just a few drops of blood, drop it in the envelope & it’s ready to go!
As such, they strongly regulate inflammation in to the body, and as we’ve learnt - they are impressively capable of predicting age-related disease onset.
Also, their ‘youthfulness’ can maintained by paying attention to certain lifestyle factors - chiefly diet, exercise, stress and sleep - monitoring them can help us track how we’re doing as we biohack our way to long & healthy lives.
In this post we’ll cover:
The role of glycans in immunity
How glycans are involved in the digestive system
How to use diet to improve GlycanAge
Why food is information for the immune system
Setting up a self-experiment for improving GlycanAge
Plus - snippets from our interview with world expert on glycans - Professor Gordan Lauc
Glycans Regulate Immunity
It is the role of glycans in immunity and disease related processes which makes them so important with respect to the aging process.
Such is their potential impact, that any personalised longevity strategy should likely include an effort to maintain youthful glycan characteristics.
A tumour cell being tagged with 'bad guy’ glycans (represented by the squares, circles, diamonds on cell membrane). Image credit: Gly-tech
“Youthful” in this context essentially means ‘anti-inflammatory’, meaning:
the immune system is not overactive
chronic inflammation is not present (or in advanced age, well managed)
the ravages of inflammaging (the negative feedback cycle of inflammation creating more damage & inflammation) are avoided
How Glycans Impact the Immune System
As we learned in our exclusive interview with world expert in all things glycans, Professor Gordan Lauc, glycans keep track of foreign materials in the body, tagging them as ‘friend’ or ‘enemy’ so that our antibodies know whether to activate inflammation (attack) or suppress inflammation (don’t attack).
“When antibodies are developed, they do not know whether a given foreign object will be an enemy, like a bacteria or a virus, or if it is friendly, such as food or a dust or something else they should ignore.
After the antibody binds to this foreign object, what happens next is determined by glycans. This very complicated process (glycosylation) is regulated by least 40 different genes.
These glycans decide whether antibody will kill a target cell (activate inflammation) or will it suppress inflammation”
Glycans, Immunity and Digestion
A major role of this immune surveillance process is centred on digestion. This is because the process of taking what we eat, and turning it into our own cells or energy requires active decision making on what should be allowed into the bloodstream.
Ultimately, food is “a foreign object” (using Prof. Lauc’s words above) that has entered the body.
This is clearly done for the purposes of providing fuel and supplying important nutrients, such as vitamins and minerals. However, much more than simple nutrition comes along for the ride.
This includes a host of ‘commensal’ (friendly) bacteria, and sometimes, bad ones, along with the occasional plant compounds that may stress the body (such as glycoalkaloids in the ‘nightshade’ family of veggies).
Our immune system has an important role to play in screening which of these compounds should be permitted to pass through the wall of the small intestine and into the blood stream.
We’ll revisit this in detail later in the post!
Using Diet to Self-Experiment with GlycanAge
I (Nick here! Founder at Longevity Blog) am currently experimenting with improving my GlycanAge through a change in my diet, and in this post, I’ll explain what changes I am making, why and how to make this self-experiment an effective one.
Changing diet to improve my GlycanAge - can it be done? Certainly - the question is - for relatively health people, how?
This self-experiment will explore a hypothesis related to increasing the diversity of plants in my diet and potential improvement in my GlycanAge.
However, before we get into the specifics on how this experiment will work, let’s introduce some important background knowledge to support the approach.
Improving GlycanAge with Diet
Improving GlycanAge through changes in your diet can be either quite easy or mysteriously challenging.
If you’re someone who needs to lose some weight - you’re in luck. You can very likely improve you GlycanAge by simply losing weight. Look no further than our interview with Professor Lauc for the reasons why:
“Longevity Blog: Could you point to a successful model for testing and improving your GlycanAge in a way that you can say, I know what did improved it, it was _____ ?
Gordan Lauc: One good example is weight loss. Losing extra weight helps the vast majority of people, because obesity is a big driver of inflammation.”
However, if you’re already at healthy weight, how to use your diet to improve GlycanAge is not immediately obvious. In fact, clinical research with GlycanAge and diet has shown this to be quite challenging (see below tweet & follow me on Twitter for more!).
1000 people were divided into groups eating very different diets
— Nick Engerer (@nickengerer) July 16, 2021
The outcome? It was impossible to predict which diet was best for whom
However, by monitoring glycans, that became possible. Their role in inflammation signalling can reveal - what diet works best for you? pic.twitter.com/D7AyNlzVfp
Improving GlycanAge with Diet by Eating More Plants
Despite this challenge, I believer I have developed a solid hypothesis for testing how people at a healthy weight may be able to reliably improve their GlycanAge.
Through some serious homework, I also believe that this proposed change in diet that would also have relevance to other self-experimenters, and it could be replicated reliably.
This approach will leverage the sub-process of our immune system screening food particles and non-human organisms (i.e. bacteria) as they are processed in the duodenum (small intestine).
This critical step occurs before entering food materials and/or friendly bacteria are permitted to enter the bloodstream and intimately involves - you guessed it, glycans!
Food as Information for the Immune System
To continue down this line of reasoning, you need to adapt your thinking of the small intestine. Stop thinking of it as ‘inside’ your body, and start thinking of it as ‘outside’.
It is within the small intestine where a critical decisions is made - namely, what foreign materials from the diet are permitted to enter the blood stream.
Pictured: Intestinal villae, lines with intestinal epithelial cells (IECs) along with several other functional cells include macrophages (immune surveillance cells). Image Credit: Nature Reviews: Immunology
The small intestine is lined with “intestinal epithelial cells” or IECs for short. IECs are a single layer of cells with two key functions:
1) be a barrier to anything harmful - toxins, bad bacteria, viruses or antigens
2) act as a filter, whereby nutrients, electrolytes, water and beneficial bacteria are allowed into the bloodstream.
In this secondary function of ‘filtering’ where a detailed and highly important involvement of the immune surveillance system takes place.
The details are vastly complicated, but we can afford a useful simplification here.
Assuming you have tight junctions between the epithelial cells of the small intestine, only the foreign material ‘accepted’ by your immune system is permitted to pass through.
Anything else - and your immune system signals ‘attack’ - producing inflammatory signals.
IGG glycolisation (that’s science talk for how glycans are being used within the body - read more about this in the interview with Prof. Gordan Lauc) plays a critical roles in this screening process, and the ‘tagging’ of foreign material as friend or foe is at its peak level of activity at this epithelial junction.
Critically - this highly complex process includes many trillions of bacteria, which participate in the breakdown and processing of food materials by the body.
These so called ‘commensal’ bacteria are actually actively recruited and ‘pulled through’ the epithelial junctions by the immune system.
The commensal bacteria are pivotal to your broader bodily health, with your overall wellbeing depending on a vibrant and diverse population of these friendly bacteria in the gut.
Food as Information
Local organic root vegetables from our weekly farmers market. Covered in healthy soil based commensal bacteria - just waiting to program your immune system.
The activities of food screening and bacterial populations in the gut are tremendously influential on inflammation in the body.
To better illustrate this, we’ll adopt a basic framework - where our diet is information about our environment.
This is the case because the food we eat, the bacterial populations in that food, as well as ‘antigens’ (‘bad things for us’) effectively ‘program’ our immune system.
In prehistoric times, this information was often life-saving, as it was critical for our bodies to become well adapted to the organisms, toxins and food sources around us in order to survive.
In this way, we evolved for our diet to signal “this is what your environment is like and thus how you should adapt to prepare for it”.
Now consider the modern environment, where food is sterilised and our environment is kept much cleaner than ‘nature’ could ever be. Your immune surveillance system is now cut-off from this critical source of information!
Why does this matter? Well, because in a relatively sterile environment, your body lacks enough exposure to healthy bacteria and the wide variety of food it needs to know when or when not to attack.
What does that mean? A sterile diet effectively means your immune system’s default mode is ‘attack’. The immune system, out of interest in self-preservation, will work to eliminate a foreign material it is not comfortable with (used to seeing).
Add it all up and you get - you guessed, more inflammation.
Eating a Diversity of Plants Programs Immunity
In viewing food and organisms from the environment as information, we can begin to build up our glycan self-experiment in the following way.
If your body is not provided a diverse amount of information about the environment through a diversity of food and organisms through the diet, it will tend to react with ‘attack’ more often.
Through our framework: less information = more inflammation.
On the flip side the pathway to reconciling the overactive immune system is through providing ample information about the environment through the diet.
Dr Jenna Macciochi’s Immunity: The Science of Staying Well is one of the most up to date, accessible and helpful books out there on building a healthy immune system. (Amazon Affiliate link)
This will then support the immune system with a more comprehensive view of what foreign materials are ‘friendly’ and which are not.
This conceptual framework is precisely what Dr Jenna Macciochi lays out in her book Immunity: Science of Staying Well.
One of the key recommendations from this exceptionally insightful book is to eat a diversity of plants regularly, preferably local and organic ones.
The result will be a stronger immune system, which Dr Macciochi argues, is one of the only *real* ways to “boost your immunity”.
In her book, immunity expert Dr Macciochi says there is a valuable ‘rule of thumb’ for improving your immune system with diet.
What’s the rule? We’re glad you asked..
“A good rule of thumb for the biggest impact on health is to aim for over 30 different plants per week.
Whereas the opposite is also true. Eating 10 or few has a potentially damaging effect on the microbiota”
Why is this the case? It’s all about diversity of information about the environment.
And that information is programmed in the body via your glycans.
GlycanAge Self-experiment: A Diet with Diversity of Plants
My GlycanAge as of April 2021 is already ‘favourable’. But that’s not good enough for a longevity focussed biohacker now is it?
How low can we go?!
Coming full circle, this logic leads naturally to the experimental hypothesis:
“By programming the immune system with a diversity of plant information (local & organic where possible), chronic inflammation will be reduced as the immune system learns more about what is friend and what is foe, leading to an improvement in the Glycan Age”
The is precisely the hypothesis that this self-experiment will evaluate. So let’s get down to it!
My GlycanAge was first measured in April 2021.
My GlycanAge is 30, whereas my chronological age is 35.
According to Prof. Gordan Lauc, this is a great result.
“Longevity Blog: What is a “good” GlycanAge result Gordan?
Gordan Lauc: Anything which is younger than your chronological age, I would say it’s good.
It’s also important to not worry about the absolute number, because the absolute number is also strongly affected by genetics.
Approximately 30-50% of the GlycanAge is determined by your genes, you cannot fix it.””
Self-experiment: Starting Conditions & Control
This result does make sense. In the 6 months leading up to this test, I maintained optimal levels of physical activity (training for sprint triathlons), a healthy balanced diet (eating small meals across the day, mostly vegetarian but with animal protein 3-5x/week), sleeping fairly well (Oura ring sleep scores at 75-85 on average) and well managed stress levels.
So in each of the four levy lifestyle factors (diet, exercise, sleep, stress) for my GlycanAge, things were in tip-top shape.
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In this self-experiment, beginning from 1 May, I will eat 30+ plants per week.
Where possible, this will be from local and organic sources (of which we have plenty in the Byron Bay Area!).
Experimental Control
As discussed in my previous foray into self-experimentation with the NAD precursor NMN, it is challenging, but not impossible, to perform a well controlled self-experiment.
We approach this by keeping lifestyle factors as constant as we can, not changing any other key variables, and running the self-experiment for as short a time as possible.
For the GlycanAge self-experiment I will:
maintain a consistent exercise load to within 10% on average (as measured by my Garmin smartwatch and heart-rate monitor)
keep my same sleep schedule (7-8 hours a night)
not make any large lifestyle changes that might negatively impact my stress
not make any other changes to my diet (we’ll have to keep in mind that my diet will also have a reduction in non plant foods - to make room for all of the plants!)
Experimental Test Period
The experiment, according to advice from Prof Lauc will be run for a minimum of 3 months and maximum of 6 months.
This means I will re-test date on 1 August and again on 1 November.
I asked @GordanLauc - how often should we test @GlycanAge?
— Nick Engerer (@nickengerer) July 20, 2021
⁰⁰The half life of IGG glycolisation is ~3 weeks. 1 month would be the shortest period for re-testing
Lifestyle change effects take a bit longer. Modify diet, sleep, stress or exercise?
Recheck every 3 to 6 months pic.twitter.com/hjuVEdWIBo
Other Relevant Items
To keep track of my plant intake, and ensure that eat enough plants, I am keeping a weekly record of all of the plants that I eat.
I keep this pretty simple, recording them in the iOS notes app - presumably you could do this just about anyway that you please.
There is of course an important question - what is a ‘plant’? What counts as 1x plant?
I will only be counting whole food plant sources which equate to at least one serving of that food.
So for example, I would not count ‘bread’ to be a plant, although it comes from wheat flour at it is quite refined/processed (not a whole food). I would however count rolled oats as a 1x plant (limited processing, effectively a whole food item).
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
How GlycanAge Biological Age Testing Works - An Interview with Glycan Expert Gordan Lauc
Glycans Can Be Used to Estimate Biological Age
In our most recent post, we explored the basics behind biological age testing with glycans.
Working up from the basics (what are glycans?) through to how glycans interact with inflammation in the body, and ultimately are a signal of the aging process itself.
We also heard from Nikolina Lauc, CEO at GlycanAge, a longevity technology company based in the United Kingdom, whose mission is to “bring glycoscience into the hands of both clinicians and consumers to inform, guide and preserve your future health”.
GlycanAge has recently made it possible to purchase a direct to consumer kit to assess your ‘glycome’, which as we will learn in this follow-up post, is a powerful indicator of your future health and longevity.
Today, we’re publishing an exclusive interview with glycan expert and GlycanAge Director Gordan Lauc.
Gordan is not just a glycan expert, he is THE global authority on all things glycans.
As a Professor of Biochemistry and Molecular Biology at the University of Zagreb, he kicked off the Human Glycome Project in 2017 and has built the world’s largest human glycome database.
Through this effort, he has built an entire research team who have pioneered the glycomic analysis technology required to inspect glycans quickly and efficiently.
It is this technology which has made consumer testing of biological age and personal health status through glycans possible.
Our interview subject, and global glycan leader, Professor Gordan Lauc.
While an impressive figure of great reputation, Gordan is also a great conversationalist, amateur gardener and all around collaborative and friendly bloke who is passionate about helping people lead healthier lives.
Through collaboration with GlycanAge, we sat down with Gordan for a 1-on-1 interview, diving into the details behind how the human glycome works, and how to use it to assess biological age.
We even documented Gordan’s input on how you can run your own self-experiment with GlycanAge, to improve your health and overall longevity.
Let’s get into it!
GlycanAge Discount Code!
As a part of our mission, we are working to make your longevity budget stretch further!
Through our collaboration with GlycanAge, we have a 15% off coupon code, which you can use on their biological age test kits.
Use the code “longevityblog” to save 15% on GlycanAge
This interview was conducted on 20 May 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
Screen capture from Gordan’s YouTube video where he briefly tours his state of the art glycan laboratory.
How does the GlycanAge test work?
Longevity Blog (LB): Gordan. We recently checked out a video that is uploaded to YouTube. It was from an Instagram Live video with longevity doctor. Dr Joseph Raffaele.
In this video, you briefly toured your glycan laboratory. We found that absolutely fascinating.
You had a few generations of machines that were in place, and it made us naturally quite curious.
Could you explain what happens when a GlycanAge sample comes into your lab?
Tell us about the process of going from blood sample to glycan analysis!
Gordan Lauc (GL): Glycans are very complicated molecules. You cannot just read the letters in the way you read DNA or protein, they're branched. They're chemically very similar, but in the same way very diverse. Analyzing glycans is a challenge. This is why we need so many fancy machines.
When we do the GlycanAge test, it focuses on the glycan immunoglobulins. First, we have to fish out immunoglobulins (IGG) from the blood sample (a dried blood stain collected by fingerprick),
We have a special technology to get just IGG out of all other proteins in the sample. From the IGG, we remove the glycans, using a special enzyme which acts like a pair of scissors. It removes the one group of glycans called N glycans from the IGG.
After this, we have to dye them to make them visible in our machines. These machines use capillary electrophoresis, or chromatography, which separates glycans based on their chemical structure. Then we quantify the amount of each of them.
For the GlycanAge, we focus on glycans which change with age.
LB: There's around 2,000 to 3,000 types of glycans, is that right?
GL: When we talk about the total 'glycome', there are approximately 2000 different glycan blocks. For IGG, there are 24 major structures, so this “fishing out” process of the immunoglobulin reduces the number of glycans significantly. Using these individual structures we calculate the changes which happen with age.
Biological Aging and Glycan Immunoglobulins
Pictured: A 3D model of an human immunoglobulin
LB: In this biological age analysis, there is a close link between the IGG N glycans you're analysing as age markers and inflammation.
Can you can you explain that connection between these immunoglobulins and inflammation in the body.
GL: Immunoglobulins are the main weapons of our immune system. They are made to recognize any foreign object (bacteria, virus food, any foreign molecules) which comes into the body. They do this by a relatively complex genetic process to make a hypervariable domain to bind to this foreign object.
LB: A complex process certainly - give us the simplified explanation.
GL: When antibodies are developed, they do not know whether a given foreign object will be an enemy, like a bacteria or a virus, or if it is friendly, such as food or a dust or something else they should ignore.
After the antibody binds to this foreign object, what happens next is determined by glycans. This very complicated process (glycosylation) is regulated by least 40 different genes. These glycans decide whether antibody will kill a target cell (activate inflammation) or will it suppress inflammation.
Inflammation and Glycans
LB: And it is this increasing level of inflammation across the body which is tied to aging. What does a youthful version of this process look like?
GL: What we see in young people is that the majority of immunoglobulins have these anti inflammatory glycans. But when there is an attack by a foreign invader, like a bacteria or virus, then you need inflammation.
The problem is that as we live longer. We are genetically not made to live over 40. Once you stop making children, your genes don't work for you anymore, they work against you!
As we're getting older, this process gets disturbed, and immunoglobulins become more and more pro inflammatory. And actually, what we are measuring in the GlycaAge test are these molecules which regulate inflammation.
GlycanAge Biological Age Estimate
LB: This is how you can produce a biological age estimate, right? If you know what the glycome of an old person would look like versus a young one, you can make a prediction. Talk about how you create a biological age assessment using this information?
Pictured: A GlycanAge biological age testing kit. We discussed some of the basics on these kits in a recent post.
GL: Initially when we developed the DNA typing, we noticed that glycans correlate with age. At the time, we were thinking to use this information to determine the age of a person who left a blood stain at a crime scene.
This is relevant information for police investigation, whether this was a young guy or experienced criminal.
We tried to correlate the glycans with chronological age, and this was reasonably successful.
When we did this, approximately a decade ago, this was one of the most accurate ways to determine the chronological age of a person. Subsequently methylation test was developed, which was way more accurate in predicting chronological age.
LB: But there is still unique value in the GlycanAge test, particularly in assessing lifestyle factors?
GL: What we have learned is that our test deviates from the chronological age, approximately nine years. But not in a random way! But in a way which associates with lifestyle.
On our GlycanAge test, people living healthy lifestyle will always be younger, while people living an unhealthy lifestyle will be older. Also, people with different diseases will generally look older too.
What is Biological Age?
GL: We realized that the GlycanAge is not a good test of chronological age, so we can't use it in forensics, but it is very informative about something we call biological age. Although biological age is a very tricky word, because there is no golden standard.
Learn more about assessing your biological age in our interview with Chronomics CSO Dani
There is no universal unit of measure of biological age. And so someone can give you any kind of number and you cannot say whether it's right or wrong.
LB: Let us ask you about that, Gordan. What do you think about this term biological age? Is “age” the right term? Or is it more of a “biological score” or a “health score”?
Why do you think the industry has chosen the term “biological age”? It sounds nice. But we’re hearing from you that that term is a bit squishy.
What Health Information Does GlycanAge Provide?
An example of the ‘indices’ for the G0 (top) and G2 (bottom) IGG glycans. A GlycanAge test gives you access to this information as well as your biological age.
GL: When we do research, we report 24 directly measured glycans and maybe additional 50 different scores.
But the problem is that this is too complicated for people to understand. So then we made two levels of simplification.
One level is that we have three key indexes or scores, which is G0, G2, and GS.
G0 are glycans without galactose, which are the most proinflammatory.
G2 are glycans with two galactoses, which are suppressing inflammation.
GS are glycans with sialic acid, which also suppress inflammation.
LB: These three indices are reported to users when they complete the GlycanAge test.
This ‘first level’ of simplification provides direct insight into the levels of inflammation driven by or suppressed by each group.
How are these indices useful for the user?
GL: These three indexes are something which one can use to quantify three different aspects of regulation of inflammation. These three indices are exactly measured from the blood sample. This means, anybody in the world who has the right equipment can take the same blood sample and they should get the similar number.
LB: From there, biological age is the next level of simplification?
GL: The ultimate simplification is the biological age, but that's just the name, you can also call it a score. This is the model number. It is not a number which has an absolute meaning.
Screenshot from one of Gordan’s presentations on the GlycanAge biological age clock. Source: YouTube and also this pubmed article.
However, we know that the higher biological age number means more inflammatory glycans, and that means more low grade chronic inflammation.
This chronic inflammation is something which happens with aging and with disease. A smaller number of the GlycanAge means more immune suppressive glycans, less low grade chronic inflammation.
This is a number which is modeled. We use 1000s of people (over 150k) to build a model and compare an individual to this model to determine their GlycanAge.
Of course, it's not absolutely “accurate”, because there is no golden standard of accuracy. But what makes GlycanAge different from other indexes of biological age, which are being used is that we know that glycans which we measure are functional effectors of inflammation. They're molecules which do the damage.
Improving Your GlycanAge Biological Age
LB: Gordan - let's talk about improving our biological age. In other interviews, we've heard you talk about four key factors: sleep, diet, exercise, and managing stress. Making postiive changes in these lifestyle can help change the glycan based biological age estimate.
Can you can you explain why that's the case? Why are those four factors driving the GlycanAge?
GL: These four factors are the key factors of healthy life. Now, we all know, we need enough sleep, we need healthy diet, we need a moderate amount of exercise, and we don't need too much stress. There is no magic in that.
The problem is that this is extremely difficult. We cannot do it all. It simply is not possible in a modern society.
Could GlycanAge testing help identify the most optimal diet for YOU?
The other important thing is that we are all very different. The more research we do, we are learning this.
For example, we did recently cohort of 1000 people on five different diets. And each diet is good for somebody and bad for somebody else, so there is no universal diet, which will help everybody.
LB: Fascinating! Could you share what some of those diets were?
GL: This is still unpublished. I cannot go into details. This was a large European project. But these diets were generally high and low protein and high and low glycemic index and different combinations.
High glycemic index is not bad for some people. It is bad for perhaps most people, but some people cope with glucose better than others.
What we are hoping that the GlycanAge can do is help people to focus on one of the four aspects which is dominant in them.
Gordan is actively collaborating with Dr Joseph Raffaele to explore using GlycanAge on his patients at his longevity clinic in New York. Image Source: LinkedIn
For example, for some people, it could be only a few extra hours of sleep, and then they don't have to spend an hour day in a gym.
For other people, it could be just less carbohydrates. And then maybe they don't have to sleep that much.
GlycanAge is a kind of objective tool to evaluate what works and what does not work for us.
You earlier mentioned this Instagram Live video Dr Raffaele and I did. He has an anti aging clinic in New York where they are testing these ideas.
GlycanAge and Hormone Optimisation
LB: Let's talk about that. Dr Raffaele specifically talks about hormone optimisation.
We know that there's a real strong relationship between hormone balance in women, for example, and menopause and perimenopause.
Research with GlycanAge is finding a close link in aging and hormone levels. You also just mentioned diet.
So here’s our next question: How do we create understanding on what an individual needs in terms of their own personalised approach to improving their GlycanAge?
GL: This is exactly what we're trying to do at the moment. We started to work with Joseph to test his patients, and they all turned out younger. His average patient is 20 years younger, for male and I think 15 for a female patient, which is unbelievable.
Estrogen levels change significantly over the course of a woman’s life. GlycanAge is closely correlated with these changes.
I asked him - what are you doing to your patients? What are you giving to them? He's giving them more or less everything one can do.
We decided to dissect what works in which patient, and are now trying to do proper, placebo controlled randomized trials to see which of the approaches work.
What we know is that estrogen is a very dominant factor in woman.
We had, we got samples from one very interesting study where menopause was chemically induced in young women. In a half of the group, the estrogen was returned with estrogen patch, and the other half of the woman received a placebo.
Estrogen supplementation completely prevented the change in the IGG glycome while the woman who were on placebo aged nine years in a few months on average. Some women going through menopause age as much as 20 - 30 years within a year (on average, this number is only 7-9 years)
This loss of estrogen is extremely strong regulator of IGG glycosylation. The problem is when these women lose their good glycans, its promoting low grade chronic inflammation.
We know for example, from animal models that this is causative of hypertension. The increased risk of cardiovascular diseases known to occur with menopause could be partly caused by the wrong balance in IGG glycans.
LB: Clearly the estrogen balance and associated with changes that occur in menopause are very important for aging in women.
What about hormone levels in men? Is it a drop in testosterone which drives the changes?
GL: Interestingly in men it is also estrogen which regulates IGG glycosylation. In the same study, they also had a group of men where the gonadal hormones were blocked. When the testosterone was returned, it saved the glycome from changing.
Pictured: Testosterone, which plays a secondary role in GlycanAge. It is the change in conversion of testosterone into estrogen, which is altered in ageing in men.
But if the testosterone was added back in combination with another drug which is blocking conversion of testosterone to estrogen, this (the glycome remaining stable) the protective effect did not happen.
So in men, it's not testosterone which regulates IGG glycosylation - it's estrogen.
Hormones are very important regulators. But it's not only hormones, and it does not work to the same extent, in everybody.
So we definitely need to do more research to understand it.
Self-Experimenting with GlycanAge
LB: Hormone optimisation is clearly a really interesting topic area. Here, you've highlighted how it works for women, how it could work for men in the estrogen sense, which is fascinating.
Let’s talk about isolating specific changes one could make using GlycanAge test results. On Longevity Blog, we focus on helping our readers conduct self experiments to find out what works for them.
Want to see an example of using GlycanAge to try to improve your biological age? Our Founder Nick is kicking off his own self-experiment, and wants to take you along for the journey. Subscribe to content notifications to learn how to do this yourself!
For GlycanAge, what does this process look like? Could you point to a successful model for testing and improving your GlycanAge in a way that you can say, I know what did improved it, it was _____ ?
GL: One good example is weight loss. Losing extra weight helps the vast majority of people, because obesity is a big driver of inflammation.
However, when trying to lose weight, people often make a mistake. I personally did the same mistake when I realised my GlycanAge was not ideal. I decided to sweat it out. I was hiking in mountains, three, four hours a day, for the whole summer.
While some aspects of my health did improve, my GlycanAge did not improve much. This is because overtraining is also causing inflammation. Usually people think more is better, but for physical activity, it is not!
What is a “Good” GlycanAge Result?
LB: How can users of the GlycanAge test use that information to strike the right balance?
GL: There is no magic coach who will tell you what to do. Even the best coach can only know what is good for an average person. But there is no average person in the world! We're all different.
Pictured: Our Founder Nick’s GlycanAge from April 2021. This is a ‘good’ age for him, as it is 5 years younger than his chronological age.
He will of course be trying to get it even lower!
What people have seen with our tests, and this is what makes me happy, is that, often they get a poor GlycanAge result.
At first, they're angry, they claim the test is not good. This is why we also offer a free consultation with some of our nutrition and lifestyle experts to help them identify the problem.
Soon, they find the problem.
Maybe I'm overworked. Maybe I'm not sleeping enough. Maybe it is too much stress, I have family issues.
But when people resolve these problems, GlycanAge improves! This is a fantastic motivator.
You know you did something right when you turn out now 5-10 years younger on the scale.
Elevated GlycanAge and Disease Risk
LB: And as you mentioned before, that reduced GlycanAge comes with reduced disease risk and many other health benefits.
“This is the process I like to see - when people get the bad result, improve and get a better result”
GL: Pro-inflammatory markers usually change up to decade before people become ill. Disease onset is usually like this - you work normally, live your life and at one point you feel pain.
Because of that pain, you go to the hospital, and then you do all the checkups. Then the doctor says - you have inflammation in your guts, this is Crohn's disease, or you have inflammation in your joints, this is arthritis.
This is the end stage, when all the compensatory mechanisms have failed. All the ways your body tried to fix the problem have failed, then you have pain, and then you get the disease.
The problem with most of these chronic diseases, they are irreversible. This is why we call them chronic, you get some medicine, you feel better, you don't have the pain anymore, but you are stuck to these medicines for the rest of your life or the disease returns.
But if you identity and fix inflammation early, often simple lifestyle changes or an early pharmacological intervention can prevent disease.
This is the process I like to see - when people get the bad result, improve and get a better result.
“Approximately half of the GlycanAge is determined by your genes, you cannot fix it. ”
Something which is not so satisfactory for the user is when they are already good. Because then they ask - “what should I do now?” I say nothing, you're good. Just come in a year or two and do it again to see whether you're still good.
LB: What is “good” Gordan? Is it 5 years younger? 10 years younger? Exactly your age?
How does somebody know that they're doing “good”? What says - keep going, stay the course, this lifestyle approach is working for you?
GL: Anything which is younger than your chronological age, I would say it's good. It’s also important to not worry about the absolute number, because the absolute number is also strongly affected by genetics. Approximately 30-50% of the GlycanAge is determined by your genes, you cannot fix it.
It is the relative number, the pace of changes in biological age which are important. If your GlycanAge is increasing more slowly than your chronological age, then that’s good.
I recommend starting to do this relatively early, maybe even at 20 to 30 years old, initially once every few years. Maybe if you make a change in lifestyle, then you do it every few months to see whether something works or not. This is the most informative.
How Often Should You Test Your GlycanAge?
LB: Talk about that part. If one of our readers takes a GlycanAge test, and runs a self-experiment, they’ll be thinking about how to control the experiment. Here, the shorter the time-period, the more likely they are to keep it well controlled.
What is the timescale on which our GlycanAge is changing? Is it 3 months? 6 months? Does it depend on what one is changing? Give us a sense for how often we could retest if we wanted to say test, reducing our stress, for example, or changing our diet.
GL: Glycans change relatively slowly. The half life of IGG is approximately three weeks. I think the shortest period to see something would be maybe a month. But this is for a really radical change. If you start taking a drug, or really changed lifestyle factors a lot, such as completely changing diet, starting to exercise much more.
Normally, we see things changing after three or four months. If you slightly change your diet today, it first takes some some time to manifest in the glycans. Normally, we recommend people when they change a lifestyle, re-test after three months and then six months again. If what you are doing is working, you will see the result.
LB: That's a very clear answer. Thank you. We didn't find a good answer for this out there, and our readers are quite curious!
GlycanAge and the future of longevity?
LB: We are going to move toward the close here.
What do you think the role of testing glycans and GlycanAge is going to be as we transition into a future where more of these interventions are possible to slow, halt or possibly reverse our biological age? Where is the GlycanAge test going to fit in the next five to 10 years?
GL: I think the GlycanAge will be one of the tools to evaluate different types of therapies and interventions. It will also not be the only one. GlycanAge is primarily measuring the pro and anti inflammatory arms of the immune system, and there are many other aspects of aging.
If you’re interested in biohacking your biological age - so are we. We recently published results on using NAD booster NMN for improving you biological age
For example, cellular aging is something completely different. Something that happens within a cell, like telomeres or energy metabolism (NAD boosters) and so on.
GlycanAge is looking at the organism as a whole. I think this will be a very good tool for people to just monitor the way they are consuming their body.
In a reasonable timeframe, this will become a regular medical test, like testing the HbA1c for diabetes. We will soon be testing the IGG glycans for a low grade chronic inflammation as part of inflammaging.
Gordan’s Personal Longevity Journey with GlycanAge
LB: In your own personal longevity journey, you you've openly shared that you've tested you GlycanAge fairly frequently. You’ve learned that you go through phases, right?
For example, stress increases when there is extra work to be done, you start enjoying food a bit more and it worsens. However, then you get on to a new training regime or new diet, and your GlycanAge improves.
“Even now I’m losing weight again, and my GlycanAge is going down again. It’s a marathon. It’s not a sprint”
Is regular GlycanAge testing almost encouraging you to lead a more healthy lifestyle for your personally? Is that accurate to say?
GL: Definitely it's an indicator, which helped me to identify some of the problems I had. I don't have a magic solution for myself, my GlycanAge is still not ideal. But I have learned that my key problem is food. I like to eat too much, I should eat less.
So yes, when it GlycanAge gets too high, then I am motivated to fix it. For example, even now I'm losing weight again, and my GlycanAge is going down again. It's a marathon. It's not a sprint.
How Can You Use GlycanAge Testing?
LB: And what would you say as a closing statement for others who are out there in that same up and down? Those who are really trying to make a health lifestyle change and curious to test their GlycanAge?
What is the takeaway from your personal journey that you’d take the chance to share with them?
GL: I think the most important value in the GlycanAge test is it gives us opportunity to focus on the changes which are effective for us, because there is no standard human. For me, I have that I can occasionally have that extra cake. The cakes are not that bad for me. It's more the fruit which is not so good for me.
GlycanAge can help you customise your longevity strategy. Should you walk more? Sleep more? Eat less?
Not everything which is considered to be “healthy”, is healthy for you. So the key thing we can get from the GlycanAge test, is information about ourselves.
It's revealing the hidden secrets of our body, which we can modify, which we can change.
This allows you to see what works and what does not work for you. So whether we are going to live 50, 70, 90, 120 or 150, it doesn't really matter.
What matters is that for longest we live, we should be healthy and enjoy our lives and not suffering from different type of pain or diseases.
LB: That's a lovely place to close that off Gordan, and thank you so much for chatting with Longevity Blog today.
GL: My pleasure! Thank you for your time.
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN Nicotinamide Mononucleotide Before and After
NMN Before and After with Biological Age
In mid 2020, I set out on a self-experiment with NMN. The purpose of this experiment was three-fold
First - my primary intention was to lay out some suggestions for how you could structure your own self-experiments, and not just for NMN
Second - I of course was quite curious what my own results would be, and wanted to have a well-controlled self-experiment to answer the question: should I continue to invest in NMN as part of my longevity supplement stack?
Third - to raise awareness of NMN, biological age testing and encourage more of you to join in on being a biohacker!
Designing a self-experiment with NMN in mid 2020 was a unique challenge, as at the time, there was no direct way to test intracellular NAD levels.
That has however changed, and in upcoming posts, I am going to show you how to test your NAD levels directly. If that sounds interesting, be sure to subscribe below!
Takeaway: Over 6 months, a combination of 500mg NMN, 500mg TMG and 500mg resveratrol improved my biological age by 3.5 years. Read on to learn more!
Use the code ‘longevityblog’ to save 10%.
Looking for an NMN supplier? I recommend DoNotAge, who:
offer a third party tested product
have a bulk supply option (100g)
offer further savings when you subscribe to regular shipments
plus I can get you a discount: Use the code ‘longevityblog’ to save 10%!
Self-Experimenting With NMN
It is not easy to run a self-experiment. To review, all self-experiments are:
Difficult to control
Often hard to measure directly
Prone to bias and placebo effect
Even when well-controlled, don’t necessarily provide clear insights
Let’s take a minute to address each of these, how this particular self-experiment addressed each over the course of the 6-months of NMN supplementation.
Control
Over the course of my 6-month experiment, I made several efforts to control the experiment:
My exercise ‘Load’ as per my Garmin Fenix 6 Pro, which I use to track all of my workouts. At top, near the start, at bottom, near the end of the 6 month period.
I did not change my exercise load or volume
I did not change my diet
I did not start taking any other supplements
I did not make any other major lifestyle changes
It is of course not possible to completely control your life! However this does not mean you should not try.
Of these items, I would suggest that consistency in diet and supplementation are of paramount importance.
You can find many “NMN before and after” testimonials on YouTube, for example, but each of these has many problems with control.
The most common issue is making too many changes, mostly around supplementation protocol, during the ‘before’ and ‘after’ period.
Your chief goal here is to decide: is taking NMN worth my hard earned cash?
You can’t make that call if you’re also introducing many other longevity supplements at the same time! You’d be surprised how often this is the case! Be patient and be consistent.
Measurement
In the absence of a direct NAD test, the decided measurements before & after were set according to the 2x clinical NMN trials which were ongoing at the time, as well as adding biological age:
Lipid profile
Blood pressure
Biological age
Epigenetic age (Saliva Test via Chronomics)
Phenotypic age (Blood Test)
Bias & Placebo
I put serious thought into how to conduct a double-blind experiment, but ultimately elected not to.
Given the objective measurements we could draw from the above, and the ‘n of one’ experimental design, this was not practical to implement.
It also reduced the likelihood that everyday folks like yourself would be able to repeat the experiment effectively.
In the effort to minimise placebo effect, I made it my mindful intention to not overhype my personal attitude toward the experiment.
To be quite honest - I adopted quite a sceptical attitude.
Personally, I was unconvinced that NMN would make much of a difference in my day-to-day experience, as there was relatively little science in human subjects & most of these ‘hot trends’ turn out to be over-hyped!
NMN
NMN Self-experimentation Protocol
The supplement protocol for this self-experiment was designed to match the widely used combination of NMN, Resveratrol and TMG:
NMN at 250mg/day (first two months), 500mg (following four months)
For risk management, 1:1 dosage of Tri-Methyl Glycine (TMG)
Resveratrol at 500mg/day, taken with a high fat meal
Note: this was not a change for me, I’d been taking it for 2+ years, and therefore did not interfere with the need for supplemental control
NMN Before & After: Our Hypothesis
This experiment was undertaken to test the following hypothesis (all self-experiments should have one!):
NMN supplementation will boost intracellular NAD+ levels
Boosting NAD+ levels with NMN will measurably improve select characteristics of youthfulness
Combining boosted NAD+ with a sirtuin activator (resveratrol) will enhance DNA repair
Combined, these effects are hypothesised to be likely to:
change blood lipid profile (as per clinical trial designs)
change blood pressure (as per clinical trial designs)
slow or reverse biological age (Longevity Blog hypothesis)
NMN Before & After: Results
The self-experiment was run from 1 August 2020 for 6 months until 31 January 2021.
What follows are the results, including both hard data points and anecdotal observations.
Blood Lipid Profile:
Blood lipids refer to the commonly assessed HDL, LDL and Total Cholesterol measurements. These are also joined by Triglycerides to form the ‘Blood Lipid Panel’ of tests.
As you can see in the provided image, there was no significant change in any of these parameters over the course of my NMN self-experiment.
Blood Pressure
Blood pressure measurements at the start of the experiment were ~125/85.
At the end of the experiment, 126/84.
There was no significant change in blood pressure from the NMN self-experiment.
Biological Age: Phenotypic Age
Phenotypic age is calculated using 9 blood based biomarkers, to calculate a biological age.
This is based on work led by Yale researcher and longevity thought-leader Dr. Morgan Levine (whom we hope to interview on the blog in the future!).
We’ve previously reviewed this test, including providing information on how you can use it yourself here (its free!).
Blood markers in this test include:
White Blood Cell Count (WBC)
Red Cell Distribution Width (RDW)
Mean Corpuscular Volume (MCV)
Fasting Blood Glucose
Lymphocyte %
Creatinine
Albumin
Alkaline Phosphatase (ALP)
C-reactive protein (CRP)
If you’d like to learn more about any of these blood markers, checkout Lab Tests Online.
Pictured: My Phenotypic Age (Biological Age measure #1) over time.
At the start of the self-experiment, my Phenotypic Age was 28 (Chronological Age 34).
At the end of the self-experiment, my Phenotypic Age was 25 (Chronological Age 35).
Given that 6 months passed, this equates to a total change of -3.5 years of Biological Age.
Did I reverse my biological age with NMN?
Now - the key question is, was this change significant? Was it due to the NMN based protocol?
This comes back around to one of my initial opening points about self-experiments: “Even when well-controlled, they don’t necessarily provide clear insights”
For our analysis, we should extrapolate from the baseline measurements a bit further.
Over the preceding 3 years, my Phenotypic Age was an average of 25.7 years old. It was as high as 28 and as low as 23.
More importantly, we need to consider the difference between biological age and chronological age.
My average difference between biological age and chronological age over the preceding 3 years was -7.7 years. This was as high a -10 years and as low as -5 years.
At the start of the NMN self-experiment, this difference was -7 years (below the average), whereas at the end, it was -10 years (at the previous extreme).
There is a degree of subjective interpretation which must occur here, as the data volume does not lend itself to statistical analysis.
Based on the data and trends, there is sufficient evidence to suggest that this NMN based protocol reversed my biological age.
It is however is not conclusive evidence, and as a scientist, I choose to approach that statement conservatively.
There is a bit more to explore however, to let’s continue.
Biological Age: Epigenetic Age
This one was a real bummer. My follow-up test with Chronomics failed their quality control step, meaning the biological age result was not valid.
This was a crushing blow, as it was the chief data point, in my opinion.
However, I have re-tested it, but it was not in-line within the 6-month period self-experimentation period.
Due to my choice to begin another 6-month self-experiment immediately following this one, the next biological age result will not be valid for this experiment.
I’ve since dramatically increased my exercise routine (I’m now training for triathlons), made major dietary changes and increased my NMN supplementation to 1000mg/day in a separate 6-month self-experiment aimed a direct feedback from Chronomics on how to reverse my biological age.
I will update this post with those results, when they are returned, however they will not be well-controlled for NMN experimental purposes.
I know - major bummer! 😔
Such is self-experimenting life!
NMN Before and After: Anecdotal Observations
SF-36 Questionnaire
My results from the SF-36 questionnaire before & after did show a slight change in a few key areas.
While I did not experience any changes in general health, physical health problems or limitation of activities, I did have interesting results in the energy & emotions section.
Excerpt from my SF-36 questionnaire, before and after the NMN self-experiment.
At the start of the self-experiment, I think I was feeling many of the things that folks in their mid-30s start to feel. Notably less energy than in their 20s, less upbeat and more likely to feel worn out at the end of a long day.
Over the course of the self-experiment, this changed in notable ways, in a sustained way that continues to today.
You can see for yourself the meaningful parts of the questionnaire that changed for me in the following image.
I have to add - it is completely possible that these results are placebo based. I was taking NMN, most folks who supplement with NMN boast ‘increased energy levels’.
But of course, since NMN is hypothesised to impact intracellular energy, this is what we expect to happen.
When it comes to ‘energy levels’, NMN is a prime placebo influence candidate.
Nicotinamide Mononucleotide Before and After Conclusions
To summarise, I was able to run a well-controlled self-experiment with NMN supplementation at 500mg/day.
I recorded before and after blood tests, blood pressure and detailed subjective experience related data.
Initial results do indicate improvement in my Biological Age (as per the Phenotypic Age) by approximately 3.5 years.
Subjective data (qualitative data) support this quantitative data, and therefore the conclusion is: NMN left me both feeling younger and perhaps biologically younger.
However, this cannot be placebo controlled, and warrants further testing. In particular, direct testing of NAD levels is now available, and that is what I will be testing next!
Also, we have not been able to test the much more robust and accurate epigenetic age via Chronomics, which was unable to be measured. Ultimately, this was the most powerful data point, and though disappointing - we will revisit it.
Coming soon, I will review the results from testing intracellular NAD levels directly, before and after 1000mg of NMN.
Follow NICK on Twitter for the latest #Longevity news!
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RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
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My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
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It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
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“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
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I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
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Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
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RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
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Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Choosing an NMN Supplier for Self-Experimentation
What is the Best NMN Supplement?
Who should you choose for your NMN supplement?
Fast-take: I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments. Use the code ‘longevityblog’ to save a further 10%!
Want the details and the ‘why’ I make this recommendation? Do read on!
Today on Longevity Blog, I wrap up my three part series on self-experimenting with Nicotinamide Mononucleotide. Complete with NMN before and after testing.
As discussed in the first post of the series on NMN risk management, there are three key questions that Longevity Blog will engage with on the topic of NMN. These are:
What NMN supplement should I use?
In this third post of the three-part series, we’re going to zoom right in on the question - how do I choose a high quality NMN supplier?
Choosing the best NMN supplement: Potential Pitfalls
NMN is a supplement, meaning its production and distribution are largely unregulated. As such, this potentially exposes the self-experimenter to several potential pitfalls when purchasing.
The most important of which are:
Imposters (i.e. not actually NMN)
Contaminants (e.g. heavy metals)
Impurities (e.g. fillers, extras)
Unnecessarily high cost per dose (e.g. low potency)
Naturally this raises the question - How can we avoid these potential disruptors to our self-experimentation?
For those currently searching for their own NMN supplier, I personally understand where you are coming from.
First up - you are aiming to purchase a product with confidence in knowing it is NMN, but fake supplements are common and are lurking amongst in the available NMN suppliers on the web right now.
Even if you can become confident the product in question is NMN (not an imposter), you still must consider the risk of contaminants such as heavy metals showing up in your supply.
Furthermore, we don’t want to waste our money on a product that has low potency and/or uses fillers to push more product (impurities).
And then there is cost. Once satisfied on the above three - imposters, contaminants, impurities - we still need an NMN supply that fits our budget. This is complicated by varying levels of potency across the options:
what is a ‘dose’?
how much NMN per dose?
how many doses per container?
shipping costs?
The above long list of factors can make selecting an NMN supplier quite daunting, and perhaps overwhelming!
No one individual can take on the challenge of sorting through these points on their own. Thankfully, the NMN self-experimentation community is working together on this one…
NMN Supplement Review Useful Sources
One of my favourite aspects of the self-experimentation community, is the collective spirit of sharing knowledge and helping each other navigate the pitfalls of sourcing supplements.
Despite its relative novelty, NMN suppliers have been usefully reviewed in several formats - the most valuable of which, at this stage, are two YouTube videos.
In the first, we find that once again, my mate Dr. Brad Stanfield continues to be one of the top sources of information on NMN.
In his videos, he reviews several brands - and parallels my above selection criteria - analysing imposters, impurities, contaminants and cost per dose.
Dr. Stanfield’s endeavour to find 3rd party testing data reveals a key resource in our journey to select our NMN supplier.
The second YouTube video is from Vince and his channel “My NMN Experiment”.
Vince has several relevant videos for the NMN self-experimenter on the topic of NMN sourcing, self-experimentation and review of available third party testing.
Of particular use is his video on ‘Testing Heavy Metals” which you can view below:
Choosing the Best NMN Supplier
Use the code ‘longevityblog’ to save 10% on any order with DoNotAge
Amongst the growing number of choices for supplying NMN, is UK based company DoNotAge.
I recently became a strategic advisor to this company, owing to our shared interest in making longevity supplements like NMN widely available.
Simply put, if NMN can deliver even a fraction of the longevity benefits to humans that are observed in mice, then I firmly believe in the democratisation of access to the molecule.
By democratisation, I mean - making it widely available in both supply and cost. Quality is of course pre-requisite.
Before we move on, it is important to disclose that I stand to benefit from the sales of NMN by DoNotAge due to my advisory role.
However, this monetary benefit is modest and frankly, is not part of what motivates me to self-experiment with NMN, nor to recommend the company to you personally.
Instead, what my position as an advisor has allowed me to do is more clearly understand the NMN global supply chain and access certain confidential information about its production, proprietary competitor testing, distribution and profit margin.
Many NMN options are low quality
Through the clarity this position has provided me, I have a heightened level of concern on the practices of many of the other NMN suppliers.
The issues I am now privy to are numerous and commonplace. I am aware of products sold on Amazon, claiming to be NMN, which contain nicotinamide instead (imposters).
Suppliers who claim to be ‘manufactured in the USA’, source their products from China (lack of integrity) and package it in the United States in order to ‘cheat’ their way to this label.
Others have degradation of the product due to poor packaging and storage practices (potency), while many others provide no third party certification regarding heavy metals (contaminants).
Moreover, many sell NMN at low potency, including doses at 50 - 150mg, which are well below even the conservative doses being used in early clinical trials.
DoNotAge is a High Quality Supplier of NMN
In addition to the “insider scoop” on the NMN supply landscape, my advisory position has also provided me with a high degree of confidence on DoNotAge’s Pure NMN product.
I know with certainty it is NMN (not an imposter), is appropriately free of contaminants or impurities, and it is amongst the highest potency options available on the market (500g NMN per capsule).
This combination of factors given me the confidence to personally consume the DoNotAge product, using it in my current NMN self-experiment, selecting it from the ‘Wild West’ of NMN suppliers.
Despite the potential conflict of interest I hold in monetarily benefiting from the sales of this product, it is my hope that this vote of confidence may contribute to your own decision making process.
Simply put - in my longevity journey, I am very disciplined in choosing the supplements I consume! DoNotAge passes all my checkpoints.
Reviewing NMN for Self-experimentation Protocol:
Use the code ‘longevityblog’ to save 10% on any order with DoNotAge
Zooming out from the details of choosing the best NMN supplier, let’s come back to my NMN self-experiment.
I am presently wrapping up week 4 of the protocol, which will run for a total of 6 months.
The experiment will rely on several different data points, one of which is before & after biological age tests from Chronomics, and will wrap up at the end of February.
Unlike many of the other self-experimenters out there, I am holding constant my daily habits, diet and supplement routine, in the interest of generating the most robust scientific outcome.
When complete, I will finalise the results and protocol, in order to support the self-experimentation community.
The self-experimentation protocol is as follows:
NMN 500mg per day (updated)
TMG 500mg, every day (1:1 ratio to support methylation)
All of which is being supplied by DoNotAge.
You can find the relevant DoNotAge products in each of the above hyperlinks.
Use the discount code ‘longevityblog’ to save 5%!
Follow Longevity Blog on Twitter for the latest #Longevity news!
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RT @nickengerer: Join a team, do a sport. Staying fit is easier with a clear purpose Bonus: you just might live longer Pic: Byro… https://t.co/L5yHxHJXas -
Calcium AKG Alpha Keto Glutarate Supplement Review https://t.co/K7keDM3Lyn
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Mitopure Review - Does this Urolithin A supplement actually work? https://t.co/0Y6Bx4yA7h
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How Fast are You Aging? A Biological Age Test for Rate of Ageing with Ryan Smith of Trudiagnostic (Part 2) https://t.co/5SZW3Or6JJ
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What is the Most Accurate Biological Age Test? An Interview with Ryan Smith of Trudiagnostic (Part 1) https://t.co/wdIxtTVeq0
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One Skin Review - Self-Experiment Before and After Results with OS-01 https://t.co/3hqzLtfVa3
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Regrowing Knee Cartilage and Restoring Joint Health Naturally. An Interview with Reviiv Light CEO Forrest Smith - P… https://t.co/O671LROvzw
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I post related #Longevity content to Instagram as well, follow me @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
Self Experimentation with NMN Nicotinamide Mononucleotide
NMN Before and After with Biological Age
Given the introduction of nicotinamide riboside (NR) and more recently nicotinamide mononucleotide (NMN) as supplements over the past four years, many in the longevity community are self-experimenting with these molecules which boost NAD+ levels.
Looking for an NMN supplier? I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments. Use the code ‘longevityblog’ to save a further 10%.
Get the details in Part 3 of this NMN self experiment series
As discussed in the previous post on NMN risk management, there are three key questions that Longevity Blog will engage with on the topic of NMN. These are:
NMN
How can we self-experiment to determine efficacy?
In this post, I’ll discuss how we can self-experiment to determine the efficacy of NMN supplementation. Let’s do it!
NMN Self-experimentation: A first draft “how to” guide
Let’s science this and see what happens
As with any good self-experiment, we should design a solid experimental framework based on the principles of the scientific method.
This has caveats however, owing to our inherent complexity as a biological system.
As you up your self-experimentation game (what a biohacker you are!), you’ll find out that self experiments are:
Difficult to control
Often hard to measure directly
Prone to bias and placebo effect
Important to make repeatable
Through this post and others that follow, we will do our best to continually consider these issues with self-experimentation (an example of this can type of thinking can be seen in previous posts).
In your endeavour to self-experiment with NMN, getting the experiment right is particularly important.
It should be our goal to provide insight to the broader self-experimentation community, and facilitate others to effectively self-experiment so we can benefit from collective knowledge sharing.
So let’s aim to get this right, in the name of science!
NMN Before and After, Our Hypothesis: What are we testing?
After thorough consideration, I believe our hypothesis for NMN supplementation can be summarised as follows:
NMN supplementation will boost intracellular NAD+ levels
Boosting NAD+ levels with NMN will measurably improve select characteristics of youthfulness
This hypothesis is formed upon on a large volume of work around NAD+ boosting supplements such as Nicotinamide, Nicotinamide Riboside (NR) and NMN (nicotinamide mononucleotide), which indicate 1) the importance of NAD+ levels on a plethora of cellular processes, 2) the known decline of NAD+ levels with age and 3) the apparently causal relationship in this drop in NAD+ levels with a wide array of age-related diseases.
It also formulated in such a way that we can test it, by gathering related data and analysing them to draw conclusions.
Does NMN Work in Humans? How We Can Test the Hypothesis:
In order to test our hypothesis, we need to determine:
An appropriate NMN dose for raising NAD+ levels
How we will measure the NAD+ levels
What controls we can apply, and adopt defensive positions against bias/placebo
How much NMN should you take?
In order to determine the appropriate dose for the experiment, I suggest we look to the two FDA approved clinical trials which are currently evaluating NMN safety and efficacy:
You can search for clinical trials on any topic you like at clinicaltrials.gov
Clinical Trial #1: Dosing for participants 40-65 years olds set at 300mg/day
Clinical Trial #2: Dosing for post-menopausal women set at 250mg/day
Anecdotes from elsewhere suggest this a good level for supplementation. Consider this 27 year old who was totally ‘buzzed’ on 500mg/day and this discussion thread for a 34 year old (same age as me at the time of writing) settling on ~250mg day.
Setting the NMN supplementation level should be done based on age and moderated based on one’s experience with the dose (e.g. insomnia, flushing, etc can be inferred to mean one should titrate downwards).
Measure: Data Collection for the NMN Self-Experimenter
From first principles, our goal here will be to measure related biometrics before NMN supplementation, and then again after sustained NMN supplementation. However, the details here are challenging. As, unfortunately sampling intracellular NAD+/NADH levels presents a few issues.
So for widespread, democratised access to NAD+/NADH testing, we face these two barriers:
First, direct testing of NAD+/NADH is limited to professional assay test kits (like this one)
This violates our goal to make the experiment repeatable for other self-experimenters.
Secondly, it turns out they are fairly ‘noisy’ data anyway, making interpretation difficult and making representativeness of the measurement problematic
NAD+/NADH levels change dramatically across the day with activity, eating, circadian rhythm (Interestingly, blood glucose exhibits these same characteristics; which is perhaps unsurprising as they are both part of our body’s ‘energy system’ );
even if we could test it directly, we would also need to sample it semi-continuously (many measurements)
However, given the widespread interest, research funding and commercial development of NAD+ boosters, measuring NAD+/NADH is likely to become more widely available in the near future. My research found at least two promising options,:
Liquid chromatography - “high-performance liquid chromatography (HPLC) to accurately measure the levels of NAD+ in cells and tissues”
A bioluminescent biosensor - “for the rapid quantification of NAD+ levels in biological samples, which can be used either in laboratories or at the point of care”
Establishing an NAD+ Proxy
In science, where we can’t measure something directly, we use a suitable proxy. In atmospheric science, to study the past climate, we can use bubbles captured in glacial ice cores to estimate past CO2 concentrations and global temperatures.
Climate researchers do this because they inconveniently didn’t have thermometers sampling the atmosphere 100,000 years ago. Here, our issue is we don't have the ‘thermometer’ for NAD+/NADH levels yet. So what’s our proxy?
I have spent many hours researching and considering this. It is my suggestion is that we leverage several different biomarkers that are representative of youthfulness as our proxies. The reasoning for this reaches back to the hypothesis and the purpose of boosting NAD+ : to restore youthfulness.
There are a few proxies we can draw from the clinical trials mentioned above, these are:
Walking speed tests
Blood pressure
Lipid profile
I suggest we eliminate the walking speed test, as it is really only valuable in advancing aging or for sedentary individuals. The latter three are widely accessible, so we’ll adopt them.
But I suggest we go a bit further in our assessment of expressing a youthful phenotype, and adopt measurements of biological aging. My reasoning for using biological age (BA) is the following:
BA is our target for longevity optimisation
BA measurement and calculation is accessible to others, therefore can be repeated
BA is a wide reaching measurement of overall bodily youthfulness (that is its purpose)
BA has multiple modes of testing available to us; so we can work with more than one
Epigenetic test kits for before and after the Longevity Blog NMN based planned biological age reversal experiment. Read about what I made this choice!
For the NMN self-experimenter, I suggest the following two biological age computation methods.
The first is the Phenotypic Age test, which I cover in this post.
The second is a biological age test based on measurement of DNA methylation (aka epigenetic age)
While the prior test is a blood test, the latter is direct measurement of methylation at CpG sites in the epigenome.
There is a fundamental connection here between NAD+ levels, which are the ‘fuel’ for the SIRT enzymes which repair DNA and regulate expression of the genome.
In theory, increasing NAD+ levels could improve our bodily ability to regulate the epigenome, so potential improvements could be realised in the epigenetic age.
Epigenetic age kits are also becoming widely accessible very quickly, and therefore are repeatable.
Analysis: How should the self-experimenter analyse their data?
At the most fundamental level, at the very least, one should statistically compare the before & after measurements of our proxy measurements.
An added benefit would be the inclusion of additional baseline measurements from before the experiment begins.
This inherently needs to include some basic corrections for the non-stationary nature of the data. In layperson terms - chronological time is passing over our measurement period.
So the ‘after’ measurements should be corrected in our analysis, considering the amount of time that has passed over the course of the experiment.
Lastly, and perhaps more importantly, we must employ purposeful management of potential confirmation bias.
Anyone who is running an NMN self-experiment and is looking after their longevity wants and likely expects the supplement to work.
Since we know the result we want, therefore we need to be defensive against our bias when we draw conclusions based on this result.
This is particularly relevant for bloggers and social media focussed folks - we inherently want the Ben Greenfield headline to draw clicks and eyeballs.
I refuse to do that to you, and will revisit these issues when we analyse the data and draw our conclusions.
NMN Self-experimentation: What’s Next for Longevity Blog?
We’ve nearly designed our experimental framework, but we’ve not yet discussed the dosing protocol. So here’s what I personally plan to do:
Baseline
Measurements of:
Blood lipids
Blood pressure
Estimation of:
Phenotypic Age (established here)
Epigenetic Age (via Chronomics)
Complete the SF-36 questionnaire
Post Protocol
Measurements of:
Blood lipids
Blood pressure
Estimation of:
Phenotypic Age (established here)
Epigenetic Age (via Chronomics)
Complete the SF-36 questionnaire
So, what will the exact dosing protocol be? It is still in draft form, as I am awaiting potential additional insights from first Chronomics test.
These may provide additional insights on what to add to the protocol to further improve my biological age.
This does step outside of the experimental design for NMN self-experimentation, but let’s delay that discussion until further posts.
NMN Self-experimentation Protocol (DRAFT):
NMN dose will be set at 250mg per day (based on clinical trial dosing levels)
Update: Two months into the protocol, I raised to 500mg per professional advice from a knowledgeable third-party
For risk management, we’ll include 1:1 TMG (as discussed in my last post)
Resveratrol at 500mg/day, taken with a high fat meal (I’ve been doing this for 2+ years)
Inclusion of Resveratrol is based on its role as a SIRTuin activator, which pairs well with NAD+ boosting and potential benefits to the ‘health’ of the epigenome
Will you experiment with NMN? You’ll need a trusted supplier - I recommend DoNotAge, who offer a third party tested pure product, have a bulk supply option (100g) with further savings when you subscribe to regular shipments.
Use the code ‘longevityblog’ to save a further 10%.
Get the details in Part 3 of this NMN self experiment series
Follow me on Twitter for the latest #Longevity news!
-
RT @rebeccavziegler: The cryonics payoff matrix. Choose wisely my friends. https://t.co/l1rzsmOC2w
-
My rate of aging: 0.79 It’s the new street cred What you got? https://t.co/aHzWHAfCnD https://t.co/L3rZC4QFN2
-
It’s official - I’m co-producing and hosting a new #longevity docuseries, and will begin shooting in a few months… https://t.co/wLGqRrBfbp
-
“The #longevity segment opened my eyes to the groundbreaking advances in biotechnology, health, and wellness. The i… https://t.co/F8YB7PAeMW
-
I’m completely mindblown by what AI has done over the past 3-6 months, and it continues to accelerate… https://t.co/hh0JslucRg
-
Longevity legends take on many shapes and sizes https://t.co/X9vGa7gvOe
-
RT @BradStanfieldMD: Avoid These Popular Supplements (shout out to Professor Matt Kaeberlein @mkaeberlein & Professor Brian Kennedy… https://t.co/cy9CXldgUS
-
Who are influential persons in #longevity who are of Asian, African American or other “minority” group in the US?
I post related #Longevity content to Instagram as well, follow me @nickengerer
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
NMN - Nicotinamide Mononucleotide Safety and Risk Management
NAD boosters are a HOT topic. NMN is the hottest 🔥
One of my favourite ways to analyse the latest health action in longevity technologies is to use Google’s keyword planner and trends tools. They form a great way to track the ‘pulse’ of human interest on healthspan. And as I planned my next upcoming series of blog posts on NAD boosting with NMN and diving deep into epigenetics and biological age, I certainly found plenty of evidence of our collective curiosity on the topic.
Given the introduction of nicotinamide riboside (NR) and more recently nicotinamide mononucleotide (NMN) as supplements over the past four years, many in the longevity community are self-experimenting with these molecules. And while the requisite clinical trials (those in humans which reveal their effectiveness) are still ongoing, it is clear from the data and trends I analysed that these molecules, particularly NMN, are moving into the mainstream. Heck, I’ve even run into many folks in the energy sector (where I run my day job - Solcast), taking NR and/or NMN!
Trends in NMN and NR over time
Here is a great illustration on how the search analysis for NR and NMN have changed over time. While NR got an early boost with the launch of Elysium Health and their product “Basis”, searches quickly returned to baseline within a matter of weeks.
NMN however, after an outstanding boost from David Sinclair’s appearance on the Joe Rogan Experience podcast, and likely supported by Dr. Sinclair’s impressively wide-reaching Lifespan book launch tour, has clearly achieved a wider and more sustained appeal. NMN is clearly the hottest topic in the world of NAD+ boosters, and this is supported further by the search results present in many English speaking countries, with thousands of searches for NMN and related topics each month (and growing steadily).
What is NMN? What are its benefits?
It is hardly my role to explain the basics of NMN and NAD+ boosting supplementation, as that is not the focus of the Longevity Blog (here we focus on decision making, actionable insights). Thankfully however, my mate from across the pond Dr Brad Stanfield (New Zealand) runs a fantastic and educational YouTube channel covering these topics. You should be able to find the resources you need to become more familiar with NAD+ boosting supplementation by watching his videos (be sure to SMASH that like button 😂).
NMN Supplementation: Safety, Strategy, Sourcing
There are however three key questions that Longevity Blog will engage with on the topic of NMN. These are:
Is NMN safe for self-experimentation?
How can we self-experiment to determine efficacy?
What NMN supplement should I use?
In this post, we’re looking into NMN safety and risk management. We’ll come back to #2 and #3 in future posts.
NMN Supplementation: Is it safe? (Key Question #1)
When exploring NMN supplementation safety, there are two important sub-questions to explore:
1) Has the molecule been found to be safe by reputable third-parties?
2) Are there known risks with supplementing the molecule?
NMN Safety
Perhaps the most compelling safety certifications a molecule can receive is the GRAS accreditation from the FDA. GRAS - Generally Regarded As Safe status has been awarded to NR, as well as other forms of Vitamin B3 such as Niacin and Nicotinamide. NMN however has not yet reached this hurdle as of mid 2020.
However, in my opinion, this is inevitable, will arrive soon, and there are currently no reasons other than timing and resourcing as to why this has not yet occurred. NMN supplements are just entering the market en masse (see the above analysis!), and the FDA will be certain to react to this. To be clear, I am not asserting its safety independently, this is the role of the FDA. What I am saying is that closely related molecules have received GRAS status, and the lack of GRAS status for NMN is related to its relative newness in the world of supplementation not due to any known risks.
In summary, NMN is likely to become Generally Recognized as Safe (GRAS), and the other members of the Nicotinamide family (NR, Niacin) have GRAS status. We presently have no reasons to doubt it is a safe molecule to ingest.
NMN Supplementation Risks
However, GRAS status doesn’t ensure it will yield us a positive longevity based outcome. It more or less means it won’t poison us. Safety in this context does not mean there are not risks.
Nicotinamide. Source: Wikipedia
I have spent many tens of hours studying scientific publications available on the topic of Vitamin B3 supplementation and other closely related molecules to NMN (NR, Nicotinamide). What I have found clearly suggests supplementation of Vitamin B3 and its related molecules at high doses. At the most fundamental level, NAD booster supplementation of any form, results in adding significantly higher amounts of B vitamins into the body than it is prepared to metabolise. This is what I would refer to as ‘high doses’ in this context - specifically, consuming 1, 2 or even 3 orders of magnitude greater than the RDA for the vitamin group.
NMN! Source: Wikipedia
Conversely, my research also cemented the claims behind high dose supplementation, as there are a wide array of purported benefits for NMN (limited to mouse studies at the time of writing) and even greater supporting evidence for the benefits of NR (which NMN is converted into prior to entering cells) including early studies in humans. I won’t delve into all of these benefits - if you’re reading this post, you’re likely already sold on the benefits!
In making a judgment call, one is left with a risk management scenario. The possible benefits are significant. However, there are risks associated with high doses of B vitamin intake. To gauge how we make a decision, we turn to the fundamentals of risk management. Understand the motivations for the activity, diagnose the risks of the activity, apply a risk management strategy, and make a decision based on the residual risk.
This means, we next need to understand the risk better, after which we look at the options to managing the risk.
From the abstract:
“However, possible adverse effects and their mechanisms are poorly understood. High-level NAM (Nicotinamide) administration can exert negative effects through multiple routes. For example, NAM by itself inhibits poly(ADP-ribose) polymerases (PARPs), which protect genome integrity. Elevation of the NAD+ pool alters cellular energy metabolism. Meanwhile, high-level NAM alters cellular methyl metabolism and affects methylation of DNA and proteins, leading to changes in cellular transcriptome and proteome. Also, methyl metabolites of NAM, namely methylnicotinamide, are predicted to play roles in certain diseases and conditions.”
NMN Supplementation Primary Risk - Depletion of Methyl Pool
In my review, the primary risk of NMN supplementation (or NR), is the depletion of the methyl group ‘pool’ on which many aspects of your metabolism interact and modulating your DNA expression depend.
A recent study in the journal Biomolecules shares the work of South Korean duo Eun Seong Hwang & Seon Beom Song, who approach this topic from the same place that we opened this blog post - Vitamin B supplementation is growing dramatically in all forms, what are the possible consequences?
Of the many possible negative effects of NMN supplementation, only one of these has been determined to be highly probable. In fact, based on the fundamentals of organic chemistry, it is nearly certain to occur.
Taking high doses of Vitamin B3 (NAM, NMN or NR) will increase the demand on your available methyl pool. This means there are reduced methyl groups available for the methylation of DNA (which, for example, operates in the epigenetic expression of DNA via histones). This could have the deleterious effect of altering your patterns of gene expression and thereby impacting the supply of proteins your cells need to encode for important processes such as cellular repair or replication.
I have adapted the below image from the Biomolecules paper in order to add a bit of clarifying sign-posting on the diagram. From left to right, we have the flow of potential consequences of elevated NAM intake. At far left, the methylation cycle is represented, and at the nexus of it and the NAM cycle, we can see the methylation of NAM (to metNAM) occur. This is what will need to occur in high doses of Vitamin B (NR, NMN or any other form of NAM).
NMN Supplementation Risk Management
Having understood the risk, analysis reveals a critical system (DNA expression, protein encoding) depends on the methyl groups which high doses of Vitamin B are likely to deplete.
So now the question is, can we employ a risk management strategy to minimise this risk?
I believe the answer is yes. Thankfully, it is possible to replenish the cellular methyl pool exogenously via supplementation. Allow me to explain a bit further.
At left in the above image, is an input to the methylation cycle via betaine. Betaine is a metabolite of choline (note how the methylation cycle flows from betaine to choline) and is one of the most important methyl ‘donors’ (another being folate). Betaine can also be called ‘Trimethylglycine’ (TMG). More broadly betaine actually refers to a class of molecules, but in the context of metabolism TMG and betaine are used interchangeably.
TMG is our risk management strategy when it comes to high dose NAM supplementation (including NR and NMN). This molecule is formed of an amino acid (glycine) that has three methyl groups attached to it. It is these three methyl groups that provide the extra inputs we need to support our ramped up methylation cycle when supplementing with NAM. It is possible that different forms of methyl groups, not provided by TMG, could also be required. This will be the subject of future research and updates to featured on the Longevity Blog.
nmn and nr Supplementation gets the green light
Based on the deep dive of research I have been completing on the topics of NAD+ boosters and epigenetics + biological age, I believe NMN supplementation to be risk-appropriate and a potentially effective tool in my longevity supplement stack.
I will soon be embarking upon my own NMN self-experimentation, and as I do so, I will be supplementing with Tri-methyl glycine (TMG) on a 1:1 basis with my NMN intake. In my view, the supplementation of TMG provides self-experimenters with an appropriate risk management strategy for long-term (i.e. more than 1-2 months) NMN (or NR) supplementation.
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FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.