We can all see the bewildering array of products from the supplement industry. There can often be a lack of solid scientific evidence, along with health claims that can seem a little far fetched. This has tended to put me off paying too much attention, but since listening to a particular podcast (Joe Rogan with guest David Sinclair, see link below), I've researched into some of the substances mentioned, which are said to improve mitochondrial health (organelles in each cell that produce energy).

                                                                                                               

These are NAD (Nicotinamide Adenine Dinucleotide) precursors, principally Nicotinamide Riboside (NR) and compounds that can activate or ‘up-regulate’ the Sirtuin genes (producing enzymes that support efficient mitochondrial function)

 

Here are some sources that I’ve found very interesting, especially in regard to ‘slowing down ageing’ and ‘restoring the body to youthful energy levels’!

It seems too good to be true, but there may be some truth to it, at least in part :-

 

Interview with Leonard Guarente, (1st researcher into the Sirtuin protein (1991) and its role in longevity.

Here he discusses the link between Sirtuin genes, diet, NAD and life extension.

2013 interview with David Sinclair (professor of medical genetics at Harvard university and longevity researcher)

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Extended interview with David Sinclair on Joe Rogan podcast (#1234) he discusses Sirtuin genes, the biochemistry of aging, and molecules that might help treat aging itself eg Nicotinamide Riboside (NR), Resveratrol and Metformin.

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Here is a more recent interview with David Sinclair (19/9/19) in which he discusses the science of longevity. He discusses the details of Nicotinamide Riboside from 37 minutes.

 

Interview with Charles Brenner, (Professor of Biochemistry and Internal Medicine) and discoverer of the NR to NAD pathway, (podcast #81 STEM-Talk @TuneIn) Discusses the importance of NAD, it’s decline with aging, and the unique properties of NR, making it the most effective precursor to elevate tissue levels of NAD throughout the body.

 

Sirtuin genes and their role in metabolic health

 

General information on Nicotinamide Riboside with research links

 

General information on Resveratrol, which was discovered to exist in red wine (grape skins) in 1992

However, Pterostilbene (found in blueberries) would seem to be a better compound in terms of its stability, bioavailability, and half-life in the body.

General information and research on Pterostilbene

Human research trial of combination Pterostilbene + NR - effects on human blood NAD and biomarkers of health. Blood levels of NAD is considered to be a proxy for tissue levels.

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Human research trial on NR to show that it is an especially good precursor to raise cellular NAD levels in middle age and older patients, and that this improves a number of biomarkers for health.

 

Detailed paper on mitochondrial sirtuin genes 2010

As anticipated in their concluding remarks; it does now seem as if these genes can be targeted in ways that are promising for general health and longevity in humans. For a number of reasons, NR is the best precursor molecule for increasing NAD in a compromised system. And Pterostilbene is the most promising supplement for up-regulation of these Sirtuin genes. When taken together these compounds have a synergistic effect.

 

Some have speculated that NR excretion may deplete methyl donors but this does not seem to be the case: link

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Summary points

NAD is a key and ubiquitous molecule in liberating food energy for all cellular functions and metabolism.

Brain and tissue levels of NAD decline with age.

This can be up-to 50% from the ages of 20-50.

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Pterostilbene (natural extract from blueberries) appears to be the best up-regulator of Sirtuin genes. Sirtuin proteins work in biochemical feedback with metabolites, principally NAD, for optimising mitochondrial health and function. When NAD declines over time (for various reasons associated with age and/or episodic stressors to the NAD system) the feedback communication between the nuclear and mitochondrial DNA becomes dis-regulated/declines.

 

When NAD is raised to more youthful levels, the NAD-Sirtuin communication pathway is re- established. This can increase mitochondrial health and push cellular metabolism back towards optimum healthy levels.

 

Nicotinamide riboside is uniquely suited as a precursor molecule to safely and significantly raise tissue levels of NAD throughout the body, and in doses that are practical to take in supplement form.

It is not actually possible to consume NR or Pterostilbene from natural food sources in the doses that are relevant to these physiological effects.

 

Research over the last 2 decades into a range of model organisms has shown that age related diseases can be mitigated through supplementation with these products. These effects relate to their ability to improve mitochondrial health. In a growing number of human trials, it would appear that these animal studies do indeed extrapolate to illnesses in humans and age related processes. These beneficial effects can occur in doses that are practical to take 😊.

 

A side note - you may remember the ‘Midi-chlorians’ from Star Wars? - tiny entities producing ‘the Force’. Am thinking the idea probably came from Mitochondria - very similar sounding and the spelling can’t be a coincidence.

 

I look forward to seeing more research into these fascinating supplements, but personally I’ve seen enough already to want to have some of this myself!

Typically one might take 250-500mg per day. Possibly more if one were treating specific ailments eg heart failure or diabetes, or less if one were using it intermittently as a kind of tonic for when NAD is depleted eg late night, jetlag, stress etc.

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I have made up my own capsules (vegetarian) using raw powder (99.5% Nicotinamide Riboside) and also blueberry extract (20% Pterostilbene), so will have some available for those who may wish to try it.

Having recently bought some ready-made pterostilbene capsules, I believe there to be some kidology going on (conflating blueberry extract with total pterostilbene content). But I am confident in the exact contents of my own capsules.

 

Please give the practice a call or email if you'd like to discuss this further.