Newsletter Monday
Hello Reader,
I was going to make a social media post about NAD+ and NMN last week.
Then I got a puppy.
So absolutely nothing happened.
But perhaps Peggy did me a favour, because the more I thought about this subject, the more I realised it was bigger than a post.
If you’ve spent any time in the longevity corners of the internet, you will probably have come across NAD+.
In fact, if your algorithm senses you're looking at health supplements, you'll definitely have seen it.
What actually is it?
NAD+ is a molecule involved in cellular energy metabolism and lots of other important biological processes. As we age, aspects of NAD biology change, and this has led to a very appealing hypothesis:
If we can increase NAD+, perhaps we can slow down some of the effects of ageing.
Enter supplements such as NMN and NR, which are precursors that the body can use to make NAD+.
And here’s the thing.
It’s not a stupid idea.
There is a perfectly plausible biological mechanism behind it. Give NAD-boosting compounds to mice and some genuinely interesting things happen.
Unfortunately, you are not a mouse 🐭.
And this is where the story becomes considerably less exciting.
Human trials show that NMN and NR can alter NAD-related biomarkers.
In other words, you can take the supplement and demonstrate that it has done something.
What we haven’t convincingly demonstrated is that the something translates into meaningful improvements in human health or ageing.
A systematic review published this year found 80 rodent studies and 33 human intervention studies. The animal findings were frequently impressive. Human outcomes were inconsistent and often null.
A more recent meta-analysis of 15 NMN trials found no significant improvement in things such as body weight, blood glucose, HbA1c, cholesterol or systolic blood pressure.
That’s not the same as proving NMN does nothing.
It means we don’t currently have good evidence that taking it produces the anti-ageing health benefits being claimed for it.
There is quite a large gap between those two statements.
I think of it a bit like an old car.
Imagine you discover that the engine oil in your ageing car isn’t in the same condition it was when the car was new.
So you change the oil.
Have you now got a new car?
No.
You’ve got an old car with new oil.
You haven't even changed the engine, just the oil.
And before somebody emails me to explain that NAD+ isn’t literally engine oil, I know.
Because there’s an even bigger problem with the analogy:
Your body isn’t a car.
It’s not a collection of independent components that can simply be replaced one by one until everything is new again.
It’s a living, dynamic system. Thousands of processes are interacting with each other constantly. We adapt to our environment, our behaviour, illness, stress, food and exercise. Genes switch on and off. Hormones change. Cells communicate. Our immune system reacts.
Ageing isn’t one broken pathway waiting for us to discover the correct spanner.
And yet I completely understand why we want it to be.
Humans LOVE a shortcut.
In fact, you could argue that much of human progress has been about shifting the effort/reward seesaw.
We invented machinery because doing everything by hand was exhausting.
Then came the Industrial Revolution.
Cars.
Washing machines.
Computers.
And now AI.
Again and again we’ve found ways of getting more output for less effort.
So perhaps it’s unsurprising that we approach our bodies with the same question.
Isn’t there an easier way?
Could I take something that makes my cells behave as though they’re younger?
Could I swallow the exercise benefits?
Could I optimise the ageing out of myself?
And there is an enormous industry very happy to tell us that perhaps we can.
Meanwhile, the things for which we have considerably better evidence remain spectacularly unexciting.
Move your body.
Get reasonably fit.
Keep your muscles strong.
Don’t smoke.
Eat mostly decent food.
Keep an eye on your blood pressure, cholesterol and other cardiovascular risk factors.
Sleep as well as life allows.
Maintain relationships.
Manage stress.
Go outside occasionally.
None of this comes in an expensive frosted bottle with CELLULAR LONGEVITY written on the side.
Worse still, it requires us to keep doing it.
Which brings me to Bryan Johnson.
If you don’t know who he is, he’s a tech millionaire who has turned trying to slow his own ageing into an extraordinarily detailed public experiment. His diet, exercise, sleep, supplements, blood tests, scans and countless other biological measurements are tracked to a degree that makes your Garmin look positively lackadaisical.
And recently he revealed that he has been diagnosed with autoimmune gastritis, a condition in which the immune system attacks cells in the stomach.
This doesn’t mean his lifestyle caused it.
And it certainly doesn’t mean that looking after yourself doesn’t matter.
Quite the opposite. Being fit, strong and metabolically healthy is generally a pretty good position from which to encounter illness.
But I was struck by something Johnson said when talking about his diagnosis:
“I eat whole foods. I exercise every day, and I don’t do bad things.”
There it is.
That deeply human expectation that if we do everything correctly, biology should uphold its end of the bargain.
Unfortunately, there is no bargain.
We can influence our risk of disease enormously.
We can improve our physical capacity.
We can maintain muscle, fitness and independence for longer.
We can detect and treat risk factors.
We can give ourselves better odds.
But we cannot guarantee the outcome.
Genetics still exists.
Autoimmune disease still exists.
Cancer still exists.
Infections still exist.
Chance still exists.
And ageing, inconveniently, still exists.
Perhaps one day NAD research will lead somewhere genuinely important. That’s how science works. Interesting biological mechanisms are investigated, evidence accumulates, hypotheses are discarded or refined, and occasionally something genuinely transformative emerges.
But we’re not there yet.
For now, if someone tells you that they’ve found a molecule that can turn back your biological clock, remember the old car.
Changing the oil might be useful.
But it doesn’t make the car new.
And you aren’t a car anyway.
