Protect energy-promoting mitochondria for longer healthier life

Improving energy directly – NAD+ and CoQ10

How can we directly improve energy production?

You may (or probably may not!) remember from school biology that the production of energy involves the fiendishly complex Krebs Cycle. But don’t worry – we’ll keep it as simple as needed!

NAD+

Food is broken down into glucose which enters the cell and then the mitochondria. Within the mitochondria, the B3 vitamin nicotinamide (also called nicotinic acid) enables it to be converted to a co-enzyme molecule called NAD+, which is a vital input into the Krebs Cycle.

Eventually the whole process produces ATP – the energy molecule that we need huge amounts of to function.

So, nicotinamide is a precursor to NAD+ and therefore essential to the process of creating ATP. But other B vitamins are involved, too. Which is why optimum levels of all B complex vitamins are essential to energy, as is magnesium.

But that’s not the whole story. Because there is another part of the Krebs Cycle.

CoQ10

Another co-enzyme called CoQ10 is an essential part of that and, therefore, vital for energy production. (For biology nerds like me, this second part of the Krebs Cycle is called the Electron Transport Chain.)

Both NAD+ levels and CoQ10 levels decline with age (Ref). CoQ10 levels also decline with statin use so many doctors recommend that statin users supplement with CoQ10 (Ref).

The evidence for supplementing with CoQ10 to increase energy on its own is mixed (Ref) – but it is an antioxidant and has a supporting role to play in a truly comprehensive healthy ageing and cardio-support supplement (Ref).

The evidence for boosting NAD+, however, is strong (Ref). Indeed, Scientific American calls NAD “the linchpin of energy metabolism.”

The question, though, is how to increase it to boost flagging energy levels?

Can you supplement with NAD+?

It is true that NAD+ is a critical step in the process that creates energy (Ref). In addition, NAD+ indirectly supports DNA repair, and is involved in turning key genes called sirtuin genes on and off (Ref).

Sirtuins support the creation of new healthy mitochondria and the regeneration of cells – and are deeply involved in longevity. Indeed, sirtuins were the subject of a major 2017 paper in Biogerontology titled: Sirtuins, a promising target in slowing down the ageing process.

So, nicotinamide increases NAD+ which activates sirtuins. We’ll meet sirtuin genes again in a later part on genetic rejuvenation.

To return to NAD+, the body has an increasing demand for energy and NAD+ as we get older – at precisely the time when levels of NAD+ begin to fall. The result is that by middle age levels of NAD+ may be about half what they were in your early twenties.

So, energy levels decline, which impairs key biological functions. When the body is deficient in NAD+, it is rather like a battery that is running low on power.

NAD+ is unstable – supplement with vitamin B3, its precursor

Consequently, there has been a significant recent interest in supplements that boost NAD+. Because increasing NAD+ will not only increase ATP and therefore energy, but also helps repair DNA.

But you cannot supplement directly with NAD+ because the molecule is unstable and breaks down before cells have a chance to absorb it.  So you should supplement with the precursor of NAD+. Which is vitamin B3.

Which form of vitamin B3 to use? There are several!

There are several forms of vitamin B3, each slightly different in chemical form. And they each work differently. These are as follows.

VITAMIN B3 as NIACIN
But supplementing with niacin causes skin flushing at therapeutic doses.

VITAMIN B3 as NICOTINAMIDE (also known as niacinamide). Abbreviated name NAM.

Nicotinamide is the most common form of vitamin B3 in traditional vitamin supplements. It has decades of research behind it and is inexpensive. Indeed, it is a regular treatment for a type of skin cancer and a 2020 review (Ref) reports:

“Numerous data suggest that nicotinamide may offer therapeutic benefits in neurodegenerative disorders, including Alzheimer's Disease.”

In addition, nicotinamide (NAM) is known to activate an enzyme (called PARP1) in healthy cells which supports DNA repair (Ref), and it inhibits an enzymatic process in cancerous cells (Ref).

Nicotinamide (NAM) even seems to improve body composition. A 2020 study (Ref) published in Cell Metabolism showed that supplementing with nicotinamide (NAM) produced a decrease in whole-body fat percentage and increased muscle mass. Indeed, visceral fat (the most dangerous type of fat around the organs) was decreased by a quarter. Liver fat was also significantly decreased.

So, you’ll want some B3 as nicotinamide (NAM) in a supplement. But not too much – as we will explain soon.

VITAMIN B3 as NICOTINAMIDE MONONUCLEOTIDE. Abbreviated name NMN. 

There is a third B3 version called NMN (Nicotinamide Mononucleotide).

The problem is that it has currently been banned as a supplement by the US FDA (Food and Drug Administration) – which recently issued this notice:

“NMN is excluded from the dietary supplement definition under section 201(ff(3)(B)(ii) of the FD&C Act (21 U.S.C. § 321(ff)(3)(B)(ii)) and may not be marketed as or in a dietary supplement.”

That means it cannot be sold without prescription in the USA. Maybe because there is not yet a safety dossier supporting it – or maybe because Big Pharma is protecting its future use as a drug. You make up your own mind!

On the other hand, the FDA action implies that the principle of boosting NAD+ levels with a safe NAD+ precursor does indeed have a beneficial effect.

NMN has also NOT been approved as a Novel Food by EFSA (European Food Safety Authority) or the UK regulatory authorities. So NMN is being withdrawn from sale in the UK and Europe, too.

OPTIMAL VERSION VITAMIN B3 as NICOTINAMIDE RIBOSIDE. Abbreviated name NR.

Fortunately, there is a fourth form of B3 called Nicotinamide Riboside or NR. NR is found naturally at small levels in fruits, milk and vegetables.

Nicotinamide Riboside (NR) is niacin (for which there is a huge amount of safety data) bound to a sugar molecule (ribose) and the form to be used in supplements has been patented. It has and is being extensively researched as a highly effective NAD+ activator.  There are currently 67 human clinical trials testing NR for a variety of conditions – all related to healthy ageing. (Ref.)

NR IS approved as a food by the US FDA, by EFSA, the Australian TGA and in the UK as a ‘novel food’ because it has extensive safety and effectiveness research behind it. Crucially, Nicotinamide Riboside (NR) has been awarded a GRAS (Generally Recognised As Safe) certification by the FDA.

NR is needed to make NAD+, the fuel that creates energy and repairs damaged DNA. NAD+ also helps stem cells to live longer and replicate more – important as. stem cell levels decline over time.

Recent review articles have strongly supported the use of NR as a precursor to NAD+, and confirmed its superiority to other B3 versions. This includes a 2020 article in the Journal Nutrients (Ref.):

"Accumulating evidence on NR's health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative and metabolic disorders.

"At the current time, NR is emerging as a leading candidate due to its bioavailability, safety, and strong ability to raise NAD+ content compared to other precursors."

You can see from the following illustration that Nicotinamide Riboside (NR) is converted into natural NMN before it enters into the cell and creates NAD+.

Once NR is in the cell, it improves the functioning of your mitochondria, reduces inflammation, improves vascular health and improves metabolism – which is why intake of NR has been linked to easier weight control. (Ref.)

Numerous studies show that the NR pathway has a beneficial effect on healthy ageing. Ref. Ref.

But you’ll see that Nicotinamide (NAM) can also be indirectly converted into NAD+. So why not just use NAM – because it is cheaper?

Why not use the cheaper NAM instead of NMN? Because NAM can reduce the expression of vital sirtuins

NAD+ activates sirtuins. Sirtuins are a very important group of enzyme proteins directly involved in regulating ageing, repairing DNA, helping supress tumour formation and regulating life span in many organisms from simpler life forms to humans.

Too much nicotinamide (NAM) can actually reduce the expression of sirtuins. This is because NAD+ is converted into NAM in order to “activate” the sirtuins. But research shows that if there is too much NAM already present, this can hinder this conversion of NAD+ into NAM, and thus proper sirtuin functioning (Ref.)

In addition, high dose nicotinamide NAM can impair the expression of several important genes. (Ref.)

So, intake of nicotinamide NAM as a supplement should be kept below 40 - 50mg a day. [It is 24 mg in NutriShield.]

Because of its different chemical composition, NR, however, is safe at doses up to and including 250mg a day. It actually SUPPORTS sirtuin activity

Although activating NAD+ is important, there is no one magic bullet to delay ageing. Protecting your mitochondria, increasing NAD+ and energy are just individual pieces of a big jigsaw.

Activity levels, mitochondria and maintenance of muscle and energy

We all know that exercise is vital for health. It’s equally vital to maintain mitochondrial health, NAD+ levels and slow ageing.

An article in Cell Metabolism in 2016 summarised all the evidence and concluded:

“Physical inactivity and sedentary behaviour have a deleterious effect on human health that is comparable to smoking.

“Thus, physical activity and prescribed exercise are potent counter-measures against … aging and together play a major role in the prevention of the most deadly chronic diseases modern humans face, including cardiovascular diseases, metabolic diseases, cancer, pulmonary diseases, immune dysfunction, musculoskeletal disorders, and neurological disorders”.

Intriguingly, the authors introduce the idea of “exercise snacking”.

An example: 3 short (3 minute) bouts of fast paced walking before breakfast, mid-day and dinner. These 9 minutes coupled with the 7 minute a day strength exercises illustrated in the book Delay Ageing would be a realistic minimum.

A 2022 study in Nature Ageing and titled Healthy aging and muscle function are positively associated with NAD+ abundance in humans concluded:

“NAD+ abundance positively correlated with average number of steps per day and mitochondrial and muscle functioning. Our work suggests that a clear association exists between NAD+ and health status in human aging”.

Interestingly, the same article noted that boosting NAD+ helped alleviate dry eye – a macular degeneration. Just another example of how all is connected.

Thanks for reading

I spend my time researching the new science of healthy, successful ageing.  And how to extend health span rather than just lifespan.

I hope you got value from this part of the 5-part series. Links to the other 4 parts are:

Longer Healthier Life Part 1: Protect Energy-Promoting Mitochondria

Longer Healthier Life Part 2: The Right Nutrients Can Protect Your DNA

Longer Healthier Life Part 3: Clear Zombie Cells to Stay Healthy

Longer Healthier Life Part 4: Switching On Good Protective Genes

Longer Healthier Life Part 5: Defeating Inflammation and Boosting Your Immune System

And if you enjoyed it, please send the link of this article to any friend or family member who might benefit.

Colin Rose