NAD+ is a co-enzyme, meaning it acts as catalyst or helper for very many essential biological processes Link to reference, such as:

♦ Converting food into energy
♦ Repairing damaged DNA
♦ Strengthening the immune system and cellular defence
♦ Setting your body’s internal clock or circadian rhythm

However, the amount of NAD+ in your body naturally falls with age – typically by 50% in middle age.

Low NAD+ levels have been linked to ageing itself and health concerns like diabetes, heart disease, and Alzheimer’s disease. Conversely raising NAD+ levels has become a major target for healthy ageing.

Studies show that nicotinamide riboside raises blood NAD+ levels by as much as 250% and that it is more readily used by your body than other NAD+ precursors Link to reference. Nicotinamide riboside is found in trace amounts in cows’ milk, yeast and beer. But average intake from food sources is below 1 mg a day. Studies indicate that the level needed to counteract the decline in NAD+ production is above 200mg a day.

Broad health effects of NR include 'good' gene activation

Research until recently was mainly on animal models Link to reference, but has now been extended to humans. This body of research has found that raising NAD+ levels may not only help reverse signs of ageing, including muscle mass Link to reference, but can help lower the risk of many age related diseases, including cardio/heart issues.

In particular, improving NAD+ via Nicotinamide Riboside has been shown to increase the activity of a family of genes called sirtuins that are seen to improve lifespan in mammals Link to reference. Sirtuins are confirmed in human studies as helping repair damaged DNA Link to reference, reducing inflammation and ensuring normal brain function as we get older. Link to reference

Heart Health

Heart disease is still the world’s leading cause of death and linked strongly to ageing. Ageing blood vessels become thicker, stiffer and less flexible. In turn that leads to raised blood pressure levels.

In human trials, Nicotinamide Riboside was seen to raise NAD+ levels, help reduce stiffness in the aorta and lower systolic blood pressure in middle aged and older adults at risk of high blood pressure. Link to reference

Body clock effect?

NAD+ helps regulate your body’s internal clock, so taking Nicotinamide Riboside might help treat jet lag or sleep issues. Although clinical evidence is limited, it may be worth trying on your next long-haul flight. Link to reference

Apigenin is a natural phyto-nutrient found in many plant foods, but the highest concentrations are in chamomile, dried parsley and onions. Consequently, the average person’s intake is about 3-4 mg a day. The threshold level to affect NAD+ levels is 30mg a day.

Apigenin is an anti-inflammatory and known to offer a range of health benefits, including supporting heart and brain health. Therefore, it is now seen to be an important healthy anti-ageing supplement.

Let’s start, however, with why Apigenin should be combined with Nicotinamide Riboside to increase NAD+ levels.

Apigenin slows the loss of NAD+

If you look at this illustration of how NR enters the cell to create NAD+ you’ll also see a molecule called CD 38 on the surface of that cell.

CD 38 is an enzyme, which is a protein that accelerates chemical reactions.

CD 38 is used by cells to counteract inflammation. Because inflammation increases with age, the level of the CD 38 enzyme increases as you get older to combat this inflammation. But this then consumes more and more NAD+.

Essentially, as CD38 goes up, NAD+ goes down. Link to reference 1  and Link to reference 2.

So, if we could help stop CD38 from depleting NAD+, this would be a second, indirect, but important way to improve available energy in our cells.

At the same time as you’ll be making more NAD+, you’ll also be using less.

Fortunately, we have discovered how to do that.

In the last decade, scientists have discovered that apigenin is the most potent, natural, way helps reduce the activity of CD 38. Link to reference.

Apigenin therefore helps prevent CD38 from consuming or depleting NAD+.  This obviously supports the maintenance of NAD+ levels, which in turn conserves cellular energy levels, which in turn supports healthy ageing. Link to reference 1 and Link to reference 2 and Link to reference 3

Combining Apigenin with Nicotinamide Riboside is a twin anti-ageing strategy

So, by helping to reduce the consumption or drain on NAD+ (with apigenin) and simultaneously boosting the production of NAD+ (with NR) you can not only increase, but maintain, higher levels of NAD+ and hence cellular energy.

It’s a powerful, twin anti-ageing strategy that has been validated in clinical trials.

Finally, note that CD 38 activity is higher in obese people, while lower CD 38 activity appears to protect against obesity. Anecdotal evidence seems to show that people taking NR with apigenin find it easier to maintain weight.

Apigenin has other major benefits

There is some indication that apigenin may reduce anxiety levels in patients with anxiety disorder. This is probably because apigenin is particularly abundant in chamomile. Link to reference

Even more significantly, however, the Journal of the American Diabetes Association concluded that CD 38 inhibitors like apigenin have a positive effect on the pre-diabetic condition known as metabolic syndrome. Link to reference Apigenin helps this condition by improving insulin sensitivity, lowering blood sugar levels and thus – coupled with other lifestyle changes – may contribute to reducing the risk of diabetes.

Experimental studies suggest apigenin is an anti-cancer agent

An even more important potential benefit is that apigenin may help reduce the risk of cancer. This is an effect reported in multiple studies – which is why so many drug companies are investigating apigenin. Link to reference.

Apigenin appears to selectively target cancer cells and has been shown to have anti-tumour properties. Link to reference 1 and Link to reference 2

For these reasons, apigenin has been used as an adjunct to drugs in treating liver and other cancers Link to reference.

It has also been used in high doses to address a rare form of uterine cancer. Link to reference.

Yet more studies show that apigenin may possibly have a role in prostate health. Link to reference 1 and Link to reference 3

There is even some evidence that apigenin may help suppress the initiation of cancer itself. Link to reference

Myeloma Research reports that several CD 38 drugs are in use or in clinical trials for multiple myeloma. Link to reference

There is no suggestion that apigenin on its own can prevent or treat cancer – and the dose levels in these trials were considerably higher than in a nutraceutical supplement designed to increase NAD+. Nevertheless, a daily intake of apigenin seems a safe and positive element in an overall healthy ageing regime.

Brain health too

Two recent meta-reviews on Google Scholar Link to reference and the US National Library of Medicine Link to reference concluded that apigenin could have a role in maintaining long term brain health.

The role of apigenin would be to add support to other lifestyle actions known to reduce the risk of cognitive decline – including a largely plant based diet and exercise.

Boosting bio-availability of apigenin is important

One limitation of apigenin – in common with most polyphenols – is that its absorption and hence bioavailability is not high. The combination of piperine – a black pepper extract – with polyphenols does significantly improves their absorption. So, you would ideally consume apigenin together with a supplement like NutriShield which already contains piperine.

NutriShield also contains polyphenols from curcumin, grapeseed, green tea and betaine. They all act against inflammation – and lowering inflammation is another way in which less CD 38 is consumed.

Grapeseed extract is especially interesting because it down-regulates CD 38 and up-regulates the anti-ageing gene SIRT-1, which results in higher levels of NAD+. Link to reference

Your body prioritises its allocation of available energy – created through your metabolism. It will, above all, prioritise allocating energy for the brain and heart.

Even at rest, a body needs energy for hundreds of processes. These include breathing, heartbeat, brain activity, sending blood through the body, keeping hormone and temperature levels even, immune function and growing and repairing cells.

So, you may or may not feel much more muscle energy, but you can be sure that the extra energy from boosting NAD+ is translated into improvements that support your health.