Nicotinamide Riboside Optimum Dosage

dosageNicotinamide Riboside (NR) is a form of vitamin B3 closely related to Niacin that is showing great promise for it’s ability to raise  NAD+ levels in older humans, back to the levels normally found in youth to prevent and repair damage to various organs in the body.

NAD+ (Nicotinamide Adenine Dinucleotide) is a key co-enzyme that enables the mitochondria to power and repair damage in every cell of our bodies.

WHAT IS THE MAXIMUM SAFE DOSAGE

There have been numerous studies of Nicotinamide Riboside (NR) supplementation in mice that showed no negative side effects in Human Equivalent Dosages (HED) of 2.1 to 17 grams per day

The FDA recently granted Nicotinamide Riboside GRAS (Generally Recognized as Safe) status on the basis of this clinical study, which showed “no observed adverse effect level was 300 mg/kg/day.”

screen-shot-2016-10-17-at-2-25-43-pmUsing the chart here from the  FDA guidelines for calculating this to HED of 2880 mg for a 130lb person.

With the FDA required 10x safety factor, that would equate to a dose of 288 mg per day for a 130lb human.

That is likely the limit on what sellers will recommend, but many people have been taking 500-1,000mg a day with no noticeable side effects.

The 10x safety factor required by the FDA results in a safe dosage of 288 mg a day, although many people take much more and few if any side effects are reported at 1,000 mg a day or less

WHAT DOSAGE IS MOST EFFECTIVE

FIRST PUBLISHED RESEARCH ON NR IMPACT TO NAD+ IN HUMANS

The first published research to date that measures the NR supplementation increase in NAD+ levels in humans by Dr Charles Brenner is also documented in the Phd dissertation by Samuel AJ Trammel at the University of Iowa.

His research included several studies of supplementation with NR on Mice and Humans, with the most relevant being the 2 human tests.

Experiment #1
In the first experiment, one Human subject was given a single dose 1,000 mg of NR each morning for 7 days. Blood levels of NAD+ and metabolites were 9 times the first day and every 24 hours thereafter.

screenshot-2016-09-08-09-20-24

From the results shown in chart above, we see NAD+ levels did not rise until 4 hours after ingesting, peaked at around 8 hours. They remained elevated but seemed to be declining slightly at 24 hours.

Experiment #2
The second experiment involving human subjects included 12 individuals that were given 3 doses of 100,300, or 1,000 mg of NR with a washout period of 7 days between doses. Blood levels of NAD+ were recorded at 1, 2, 4, 8, and 24 hours.

nr_nad_24-hours

nr_nad_chart

100 mg per day
This chart shows 100mg per day (purple) elevates NAD+ levels around 4 hours, dropping significantly by 8 hours and continuing to decline throughout the 24 hours.

300 mg per day
The numbers in this line (red) look a little flaky here – elevated at 4 hours, lower at 8 hours, then rising in linear fashion to reach maximum at 24 hours, perhaps due to some data error partially attributed to small sample size.

It appears that the 300mg dosing achieved the same maximum NAD+ increase as the 1,000 mg dosage at the 24 hour mark.

1,000 mg per day
This line (black) looks very similar to the first test with one subject given 1,000 mg daily. Increased NAD+ noted at 4 hours, with maximum increase reached around 8 hour. It appears NAD+ levels remain at maximum through 24 hours.

We can see that at all dosages the NAD+ levels were elevated within 4 hours.

One thing we don’t see in the second experiment is the effect of second dose 24 hours later. The 300mg dose was slower to reach maximum NAD+ levels in the blood, but equal to the 1000mg dose at 24 hours.

Perhaps the cumulative effect of a second 300 mg dose at 24 hours would show an average NAD+ increase equal to 1,000 mg dose.

Do other Metabolites of NAD+ matter?
The author notes that supplementation with Nicotinamide Riboside elevates the level of many NAD+ metabolites at different rates:

“Because every NAD+ metabolite can be converted to one or more other metabolites, snapshots of the levels of NAD+ , nicotinamide (Nam) or any other NAD+ metabolite without assessment of the NAD+ metabolome on a common scale has the potential to be misleading.”

NAAD is much higher in the 1000mg subjects. However, the first study implies there is a limit to the possible increase of NAD+. Despite repeated usage over seven days, NAD+ tops out.

The second study shows that at 24 hours, NAD+ is elevated by approximately the same amount in the 300mg and 1,000mg test subjects.

The fact that NAAD is higher in 1,000mg group (and potentially available for conversion to NAD+ if needed) doesn’t seem critical if NAD+ is already maxed out at 24 hours and another dose is imminent.

Conclusion: The maximum effect appears to be achieved at some dosage well below 1,000 mg per day.

Note: Subjects in this study were healthy and between 30-55 years of age. Older, sicker subjects might benefit from higher dosages. The Elysium Basis testing with older individuals (below) will hopefully shed more light on this.

SECOND STUDY OF NR EFFECT – ELDERLY PATIENTS TAKING ELYSIUM HEALTH BASIS

niagen_basis_elysiumResearch to prove Benefits and Safety for Elysium Health Basis brand of Nicotinamide Riboside

This recently complete, but not yet published study tracked 120 elderly subjects (60-80yrs age) over 8 weeks monitored blood and heart parameters to ensure safety.

They also measured NAD+ levels and several physical performance tests.

Completed in July 2016 but not yet published, it was sponsored by Elysium Health, manufacturer of Basis Nicotinamide Riboside.

A single capsule of BASIS is 250 mg of Chromadex NIAGEN brand of Nicotinamide Riboside, along with 50 mg of Chromadex Pterostilbene.

Participants received either placebo, 1, or 2 capsules of BASIS

Although not yet published, Elysium Health did issue a press release that states that the single dose (250 mg of NIAGEN) resulted in a 40% increase in blood NAD+ levels that was maintained throughout the 8 weeks of the study.

The 500 mg dosage resulted in an increase that was “significantly higher” than the 250 mg dose, and reached 90% at one of the 4 checkpoints (4 weeks).

Since the increase from the 500 mg dosages reached a plateau at 4 weeks, and dropped afterwards, implies that a higher dosage probably would not be any more effective.

This rather speculative interpretation agrees with the results in Study #1 that the most effective dosage is higher than 250 mg, but perhaps lower than 500 mg per day.

Conclusion: Most people will require more than 250 mg of NIAGEN per day to realize the maximum possible increase in blood NAD+ levels, with 500 mg likely being sufficient.

 

SUMMARY

Further testing with larger sample sizes and more data points is underway that will give a much better estimate on the most effective dosage. For now, some conclusions on dosage we see are:

  • A single dose of NR does increase NAD+ levels
  • NAD+ levels remain elevated 24 hours after a single dose.
  • There is an upper limit on the increase of NAD+ levels achievable through NR supplementation
  • Maximum NAD+ elevation is maintained at a dosage between 300mg and 500mg – likely close to 500mg per day
  • It appears that a single daily dose may be just as effective as 2 or 3 smaller dosages.

Note: All discussion above is related to increased NAD+ levels only. No claims to health benefits in humans from supplementation with NR have yet been proven and are not implied here.