NAD Supplements: A review

If you have been experiencing a decline in your fitness levels, longer recovery periods, trouble sleeping, and a lack of energy you may have discovered the world of NAD+ boosters. There are many different types of NAD+ boosters so this is your guide to what the research says, and which are most effective.  

In broad terms there are 4 different methods that are utilized by NAD+ boosters.

1.       Precursor Supplements

2.      Pure NAD Supplements

3.      Sublingual & Intravenous NAD Infusion

4.     Transdermal NAD Patches

A Whole-Systems approach to restoring NAD+ production

Any approach you take to restoring youthful NAD+ levels should be based on the research surrounding NAD+ decline and ageing. Research has identified what causes NAD+ decline as we age. The decreased capability of the cell to manufacture and recycle NAD+ coupled with the increased consumption of NAD+ by inflammatory proteins causes a progressive decrease in cellular NAD levels.

Therefore, when addressing this issue, you must take a whole-systems approach. By inhibiting the largest consumers of NAD+ (CD38) and increasing production (by fixing the Salvage pathway) you can restore your cells ability to make and recycle NAD+ just like it did when you were young.

A recent paper from the Buck Institute of Ageing highlighted that simply supplying the cell with more precursors (additional raw materials) is like trying to fix a leaking sink by simply adding more water. Yes, the sink may temporarily refill but the issue of the leak remains. To cause a robust increase in cellular NAD+ you need to fix the leaks!  

Boosting with Precursors (NR / NMN)

The most popular and common method of boosting NAD+ levels is to take NAD+ precursors such as NR and NMN. These do increase cellular NAD+ levels however, the boost they give is only modest and temporary. This approach doesn’t address the underlying issues within the cell that cause the decrease in NAD+ levels (they don’t fix the leak they simply add in more water!) The small increase in cellular NAD+ that they promote is not enough to lift NAD+ back to the youthful levels that older cells need for rejuvenation.

In order to appreciate why precursors alone aren’t sufficient to raise cellular NAD+ levels we must understand how youthful cells produce NAD+.

Our cells make nearly all the NAD they need via the salvage pathway which recycles 'waste' nicotinamide back into fresh NAD which can be used by the cell. When the Salvage Pathway works with youthful efficiency it makes nearly all of the NAD we need and very little precursor material is required to 'top up' cellular NAD production.

Older cells lose this recycling capacity, allowing a build-up of nicotinamide which must then be methylated and excreted from the cell. Over time this leads to a decline in NAD+ levels as the cells are unable to effectively recycle all the waste nicotinamide back into NAD+.

If the broken salvage pathway is the leak in our sink, simply adding more precursors will not fix the problem.  The modest NAD+ boost provided by precursors is soon used up by the cell and turned into waste nicotinamide. Waste that cannot be recycled back into fresh NAD+.

 ‘Pure’ NAD Supplements  

You may have seen tablets or powders which contain ‘pure NAD’ and are advertised as directly boosting NAD levels. The most notable problem is that NAD+ is a large unstable molecule with low bioavailability. Bioavailability is the amount of NAD+ that makes it through metabolism and reaches the bloodstream. Unfortunately, the majority of NAD+ is broken down by the gut and the liver meaning very little actually reaches the circulation or its target cells. Also due to its large size NAD+ struggles getting through the protective cell walls. For this reason, the cells manufacture NAD+ inside the cell, right where it is needed.

Therefore, anything that claims to be pure NAD is likely a waste of your time and money and will have little impact on your cellular NAD+ levels.

Sublingual and Intravenous NAD Infusion

To circumvent the issue of metabolism and get the NAD+ directly to the cells where it is needed, methods such as intravenous (IV) infusions and sublingual NAD have become popular. They have the benefit of bypassing the digestive tract and the liver to combat the low bioavailability of NAD+.

Despite getting the NAD+ into the bloodstream either via IV infusion or by absorption under the tongue they fail to address the problem of getting the NAD+ through the protective cell walls. The NAD+ molecule is still too large to pass from the blood into the majority of cells where it is needed, it simply remains in the blood not providing the advertised benefits.

Transdermal Patches

Transdermal patches are the latest attempt at avoiding the issues with bioavailability. Combining ease of use (you simply stick the patch on your body and wait) with the direct delivery to the bloodstream. The issue with patches is that the skin is a fantastic barrier allowing only small molecules to enter the body. Additionally, these patches use NR or NMN which have the same issues as precursor tablets described above, or pure NAD+ which has difficulties entering the cell.

Before jumping in and committing a substantial amount of your money to a supplement that claims to boost your cellular NAD+ be sure to check the scientific credibility. The types of supplements mentioned in this article simply do not provide the benefits they claim and are ineffective methods to increase NAD+ levels long term. The best method to rejuvenate older cells is to take a multitarget approach and fix the underlying problems in the cell so that it can manufacture NAD+ in the same way it once did.

To learn more about NAD supplements.

References

• Trammell, S. A., Schmidt, M. S., Weidemann, B. J., Redpath, P., Jaksch, F., Dellinger, R. W., ... & Brenner, C. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature communications, 7, 12948.

• Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., ... & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature communications, 9(1), 1-11.

• Yoshino, J., Baur, J. A., & Imai, S. I. (2018). NAD+ intermediates: the biology and therapeutic potential of NMN and NR. Cell metabolism, 27(3), 513-528.