Dave Asprey – author, founder of BulletProof Coffee and all-round father of biohacking – recently interviewed Nuchido founder Dr Nichola Conlon on his #1 biohacking podcast, BulletProof Radio. In the episode they discuss the role of NAD+ and Nuchido's NAD+ supplement, Nuchido TIME+, in taking control of the aging process and optimizing health. Dave and Dr Conlon go deep into the biology to find the most meaningful insights and practical solutions.
Here we describe the key highlights from the discussion and their findings that:
- NAD+ is critical to cellular health – but it declines with age
- You can address falling NAD+ levels – but you need a multitargeted approach because of the way NAD+ is made in the body
- Nuchido TIME+ enables this multitargeted approach, improving the cell’s ability to make and recycle NAD+
- The ingredients in the Nuchido TIME+ supplement enhance other approaches to health optimization such as fasting and IV NAD+
Dave is also offering the discount code DAVE10 for the Nuchido TIME+ NAD+ supplement which you can enter at checkout in the summary box.
NAD+ is critical to cellular health – but declines with age
NAD+ is a compound Dave Asprey has written about extensively in his antiaging book Superhuman. As molecular biologist Dr Nichola Conlon explained, NAD+ is a natural molecule found in every cell in your body and is fundamental to energy production in the mitochondria. However, more recently it’s become apparent that NAD+ is not just involved in energy production.
It is now well established that NAD+ also acts as an activator of cellular repair pathways. A key example of this is DNA repair. DNA damage is one of the major causes of aging. Every day, UV light and oxidative stress from our own metabolism is damaging our DNA. Our body has to continually repair the daily damage and it has DNA repair enzymes that do this. NAD+ is critical in activating these DNA repair mechanisms and ensuring the repair enzymes get to damaged sites and do the job that’s required.
But NAD+ levels fall significantly with age (Dave cited data that describes a 90% decline between the age of 0 and 90 years). As Dr Conlon says in the podcast,
"This exponential decline in NAD+ with age is not good for cellular health when you consider the important jobs it’s responsible for in the body."
Dr Conlon explains that to understand why NAD+ declines with age you need to understand how the body makes NAD+ when we’re young. When NAD+ is used to activate multiple different pathways and enzymes it gets broken down and a by-product of this is nicotinamide. That nicotinamide can, in fact, act as a precursor for NAD+ production via a salvage pathway; the cell recycles nicotinamide back into NAD+. This is how youthful cells operate.
The problem is, the main enzyme that enables this recycling (salvage) pathway, NAMPT, declines as we get older. This means as our body is using up NAD+ and breaking it down into the precursor nicotinamide, it can’t be recycled back into NAD+. Nicotinamide therefore builds up and the cell has to find a way to get rid of it. It upregulates a methylation pathway to excrete this precious ingredient that could have been turned into NAD+.
This is problematic and knocks the whole system out of balance with a net decline in NAD+.
However, we now know that this imbalance can be addressed and NAD+ levels can be increased.
Biohack your NAD+ levels
The biohacking approach to health optimization made popular by Dave Asprey appreciates the complexity of biology and therefore utilizes many different approaches to a specific health issue. Dave has been doing this for years with a ‘home-brew’ version of a systems pharmacology approach - taking many supplements to solve key issues with his health.
NAD+ requires this type of multitargeted approach because it is made within the cell through several different pathways, each one associated with different enzymes, ingredients and proteins. And more specifically, as we age, there are a number of factors responsible for the reduced supply of NAD+ such as the enzyme that powers the cell’s recycling mechanism, NAMPT. Furthermore, there are a number of factors that create a higher demand for NAD+ as we age such as the protein CD38 which consumes vast amounts of NAD+.
This is where the area of Systems Pharmacology comes in. Systems Pharmacology is the area of expertise that identifies all the main players in a biological system and deeply understands the interactions between them. Dr Nichola Conlon described to Dave how, earlier in her career, she was part of a team that applies this area of expertise to the field of drug discovery. The team was approached by a thought leader in the field of longevity science suggesting that this approach would add great value to the field of aging and, as a result, Nuchido was founded and Nuchido TIME+ was created.
Nuchido TIME+ is an NAD+ supplement - a combination of evidence-based ingredients specifically selected to address each of the factors involved in the falling levels of NAD+ with age. This avoids the need to identify separate methods or supplements to target each relevant part of the pathway.
The ingredients in Nuchido TIME+ create a whole system approach that:
- Increases the cell’s production of NAD+ by increasing enzymes NAMPT and AMPK that power the recycling of nicotinamide into NAD+ via the salvage pathway
- Provides more of the precursor nicotinamide for recycling into NAD+, nicotinamide
- Promotes the conversion of NADH into NAD+
- Reduces NAD+ waste – by inhibiting the excretion of the valuable precursor nicotinamide from the cell so it can be recycled into fresh NAD+
- Reduces NAD+ consumption – by inhibiting the largest consumer of NAD+, CD38 which increases with age and drives inflammation.
Our study showed that Nuchido TIME+ increased NAD+ by an average of 242%.
NAD+ levels were measured in the blood cells of two human volunteers before, during and after taking Nuchido TIME+ for 16 days. The full scientific study was presented on stage at the International Conference Undoing Ageing in Berlin and can be viewed here.
Dave Asprey described Nuchido’s product Nuchido TIME+ as “a groundbreaking NAD+ systems management supplement”.
“You can pour more NAD+ into the system but this idea of increasing the efficiency of reuse just seems more elegant from a biohacking perspective.”
Remember to use your DAVE10 discount code at checkout in the summary box.
Enhance your fasting regime
Fasting is a great tool to boost your health and no matter the type of fast there are a multitude of benefits. Having recently published a whole book on the topic, Dave was particularly interested to discuss the link between fasting and NAD+.
Fasting increases NAD+ because it activates the key energy sensor AMPK in the cell, which lies at the heart of many anti-ageing pathways.
This is relevant because higher levels of NAD+ will enable a higher activation of a group of proteins called sirtuins. These proteins are responsible for the mechanisms in our cells which repair the damage Dr Conlon described earlier and maintain cellular health. These roles have been so closely linked to cell health and aging that they are often referred to as the longevity genes.
As part of its multitargeted approach to boosting cellular NAD+ levels, Nuchido TIME+ contains the ingredient Alpha Lipoic Acid (ALA) which activates AMPK. Given Nuchido TIME+ is taken with food, this means it can extend the activation of AMPK and, therefore, the benefits of fasting into your feeding window. Dr Conlon recommends taking your TIME+ when you break our fast to gain maximum benefits.
Get the most out of your NAD IV
Intravenous infusions of NAD+ are becoming increasingly popular as a quick method to boost cellular NAD+ levels and this is something Dave himself has tried before. Dave and Dr Conlon looked into what happens inside the cell after an IV infusion and how this expensive treatment can be enhanced by improving the cell’s ability to recycle the NAD+ it receives intravenously.
When NAD+ enters the cell, it is quickly used up by the various NAD+ consuming proteins such as PARPs (DNA repair proteins), CD38 (inflammatory protein) and sirtuins. Once it has been used it is broken down into nicotinamide. However, as Dave and Dr Conlon discussed before, the cell’s ability to recycle this nicotinamide into fresh NAD+ is increasingly reduced with age due to falling levels of NAMPT – the enzyme that powers this recycling (salvage) pathway. This means the nicotinamide is likely to be methylated and excreted. Indeed, Dave described his own experience of methylation and the need to take a methyl donor alongside IV NAD+ to counteract the symptoms. Either way, the cell’s recycling capability has not been addressed with IV NAD+ and the nicotinamide is wasted.
Nuchido TIME+ was designed to increase the activity of the salvage pathway and improve the recycling of NAD+ and contains evidence-based ingredients that increase NAMPT and activate AMPK – both of which promote this recycling mechanism. This helps the cells ability to recycle that nicotinamide back into fresh NAD which can be used again and again - extending the benefits of your IV infusion, sustaining your cellular NAD+ levels and preventing methyl donor depletion. Dr Conlon recommended taking Nuchido TIME+ in advance of and in combination with an NAD+ infusion to maximise the long-term benefits of this expensive treatment.
Buy Nuchido TIME+ with DAVE10
Dave offered all his listeners a discount on Nuchido TIME+ using the code DAVE10 at checkout.
Simply add the code where prompted in the Summary Box on the Order page (just to the right of where you enter your shipping address). Maintaining NAD+ levels is a long term strategy so you get an additional $10 off when you select the 90 day subscription.
Three capsules of Nuchido TIME+ are taken twice a day with food (remember – you get a lot of ingredients in Nuchido TIME+!) and this can be aligned to your intermittent fasting regime.